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• Published: 12 August 2021

Drug addiction: from bench to bedside

• Julian Cheron 1 &
• Alban de Kerchove d’Exaerde   ORCID: orcid.org/0000-0002-0682-5877 1  

Translational Psychiatry volume  11 , Article number:  424 ( 2021 ) Cite this article

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• Molecular neuroscience

Drug addiction is responsible for millions of deaths per year around the world. Still, its management as a chronic disease is shadowed by misconceptions from the general public. Indeed, drug consumers are often labelled as “weak”, “immoral” or “depraved”. Consequently, drug addiction is often perceived as an individual problem and not societal. In technical terms, drug addiction is defined as a chronic, relapsing disease resulting from sustained effects of drugs on the brain. Through a better characterisation of the cerebral circuits involved, and the long-term modifications of the brain induced by addictive drugs administrations, first, we might be able to change the way the general public see the patient who is suffering from drug addiction, and second, we might be able to find new treatments to normalise the altered brain homeostasis. In this review, we synthetise the contribution of fundamental research to the understanding drug addiction and its contribution to potential novel therapeutics. Mostly based on drug-induced modifications of synaptic plasticity and epigenetic mechanisms (and their behavioural correlates) and after demonstration of their reversibility, we tried to highlight promising therapeutics. We also underline the specific temporal dynamics and psychosocial aspects of this complex psychiatric disease adding parameters to be considered in clinical trials and paving the way to test new therapeutic venues.

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Introduction.

Drug addiction including smoking, alcohol and illicit drug use is indirectly or directly responsible for 11.8 million deaths each year in the world [ 1 ]. According to the Global Burden of Disease study, this number is higher than deaths from cancer and accounts for a fifth of all deaths around the world [ 1 ].

Drug addiction is defined as a chronic, relapsing disease that results from the prolonged effects of drugs on the brain. Similarly to other neuropsychiatric diseases, drug addiction is intermingled with behavioural and social aspects that are equally important parts of the disease, complicating the overall therapeutic approach. Actually, it is only recently, in the beginning of the 21st century, that we started to see “the drug-addict” as someone suffering from a disease and whose brain has been altered fundamentally by drugs [ 2 ]. Therefore, the most effective treatment approaches include biological, behavioural and social-context components. Based on the latest scientific advances, treatment and management of drug addiction patients point towards a personalised strategy [ 3 ]. However, there are very few objective and effective strategies for treating drug addiction. Without the mandatory mechanistic basic knowledge on drug addiction, the development of new therapeutic strategies is postponed.

The neurobiological circuits and mechanisms that support compulsive seeking and consumption of drugs with addictive potential are partially known. They comprise a progressive shift in the involvement of ventral to dorsal and medial to lateral striatal circuitry [ 4 , 5 ], along with molecular and cellular adaptations to drugs of abuse exposure. They include neuronal and synaptic plasticity and modifications in gene expression, in part through epigenetic mechanisms [ 6 ]. Notably, drug-induced neuronal modifications can also occur in non-pathological processes, underlying the fact that drugs of abuse hijack normal adaptive changes in the brain [ 7 ]. Indeed, laboratory and clinical observations suggest that addiction is driven by the usurpation of neuronal processes that normally serve reward-related learning and memory. Most of the modifications that have been shown to be involved in a state of addiction (modified gene transcription, epigenetics, neuronal plasticity and neurotrophic mechanisms) are also associated with physiological forms of behavioural memory in murine model such as spatial memory, fear conditioning and operant conditioning [ 7 , 8 ].

We know that only a proportion of individuals (depending of the drug type) will develop drug addiction after several exposures [ 9 ]. This individual vulnerability is probably linked to both genetic and environmental factors [ 10 ]. Drug addiction is highly polygenic, as hundreds of genetic variations combined result in variable vulnerability [ 11 , 12 ]. Several types of environmental factors have been characterised and interact with an individual genetic background [ 12 , 13 ]. Psychosocial stress is one of the factors, but the most important one, is by far, the exposure to drugs of abuse. Usually, drug abuse starts with a ‘gateway’ drug (mostly socially driven) catapulting the individual vulnerability to other drugs of abuse [ 14 ].

During the last three decades, combine effort has been dedicated to identify brain regions and molecular pathways involved in the development of addiction to drugs of abuse. Here, we will focus on experimental approaches that helped to provide a clearer picture on the physiopathology of drug addiction guiding therapeutic opportunities.

Converging actions on brain reward pathway elicit its remodelling

The circuit at the centre of the disease is the mesolimbic pathway, also referred as the reward pathway (Fig. 1 ). The mesolimbic pathway includes dopaminergic neurons in the ventral tegmental area (VTA) of the midbrain and their targets in the limbic forebrain, especially the nucleus accumbens (NAc), a major component of the ventral striatum. The GABA medium-sized spiny neurons (MSNs, ~95% of striatal neurons), which are targets of glutamatergic and dopaminergic inputs, form two pathways [ 15 ]. The dopamine D1 receptor–positive (D1R) striatonigral MSNs project to the medial globus pallidus and substantia nigra pars reticulata (direct pathway) and coexpress dopamine D1 receptors and substance P, whereas D2R striatopallidal MSNs project to the lateral globus pallidus (indirect pathway) and coexpress dopamine D2 receptor, adenosine A2A receptor and enkephalin [ 16 , 17 ]. Through different initial mechanisms, drugs of abuse increase the release of dopamine in the NAc from the VTA [ 18 , 19 , 20 ]. This VTA-NAc pathway could be seen as primum movens for the acute rewarding effects of all drugs of abuse. Regardless that drugs of abuse have distinct protein targets and mechanisms of action, in the end, the main addiction-related modifications are common to nearly all drugs of abuse and converge on the VTA and NAc with common acute functional effects [ 21 ]. It is schematically conjectured, that when stimulated by dopamine, cells in the NAc produce feelings of reward and satisfaction [ 22 ]. The physiological function of this response is to facilitate the motivation for basic biological goal-directed behaviours as survival, social interaction and reproduction. By artificially causing a build-up of dopamine in the NAc, drugs of abuse generate an artificial reward effect [ 22 ]. As all drugs of abuse increase dopaminergic transmission to the NAc after acute administration, they also produce shared modifications in the mesolimbic system after chronic exposure. They include (i) hypofunction of the dopamine pathway that is seen as a major contributor to the negative emotional symptoms associated to drug withdrawal, leading to drug craving and relapse, and (ii) drug-induced adaptations in glutamatergic afferents to the NAc [ 23 , 24 ]. Clearly, these modifications in the mesolimbic system after the exposure to drugs of abuse is oversimplified. The hypofunction of dopaminergic system hypothesis is self-fulfilling in that research work has principally focused on dopamine to the exclusion of other neurotransmitters. Actually, some drug of abuse reinforcement appears to be independent of the mesocorticolimbic dopamine system (e.g. opioids [ 25 ], nicotine [ 26 ]), but support self-administration by imitating the effect of dopamine in the nucleus accumbens [ 21 , 27 , 28 ].

Addictive drugs of different types have a common effect of increasing levels of dopamine released by neurons projecting from the ventral tegmental area (VTA). This effect is central for initial drug reinforcement. Notably, drug taking with initial reinforcement involves a potentiation of the projection from prefrontal cortex (PFC) to nucleus accumbens (NAc), while other glutamatergic projections are mostly involved in craving, like basolateral amygdala (BLA)-NAc projection, or in withdrawal/negative symptoms, like paraventricular thalamus (PVT)-NAc projection. With increasing administration of drugs of abuse and progressive shift toward compulsive abuse, the dorsal (dorso-lateral) striatum seems more and more implicated, with dopaminergic cells involved shifting progressively from the VTA to the substantia nigra pars compacta (SNc) [ 4 ]. Recently, data acquired through optogenetic dopamine neuron self-stimulation suggested prominent synaptic strengthening of the orbitofrontal cortex (OFC) to dorsal (dorso-medial) striatum projection in compulsive mice [ 31 ].

Drug addiction is conceptually defined as a three-stages cycle: (1) consumption/binge/intoxication, (2) withdrawal with its negative affect and (3) craving stage (Fig. 2 ) [ 27 ]. Animal models and human imaging studies have exposed the different brain areas involved in each of these stages. Briefly, the VTA-NAc (for reinforcement) and dorsal striatum (for stimulus-response habits) are important for the consumption/binge/intoxication stage, the extended amygdala with the hypothalamus and the brainstem in the withdrawal stage and cortical areas, the dorsal striatum, the hippocampus and the basolateral amygdala in the craving stage (Fig. 2 ).

Progression to addiction is defined as a transition between three consecutive phases [ 252 ]: (1) Recreational, sporadic drug taking, in which drug of abuse administration is occasional and one activity among many other distractions of the individual. (2) Intensified and sustained drug use, in which drug administration strengthens and becomes the principal recreational activity of the individual; at this phase drug taking becomes a habit. (3) Loss of control of drug use and addiction, in which drug seeking and taking are now the principal activity of the patient. The first phase can occur to every person as drugs of abuse hijack the same brain circuit as natural rewards. The second phase occurs only in vulnerable users. The phase of addiction seems to be due to a second vulnerable trait with loss of control and compulsivity. Three stages of addiction are described [ 27 ]: (1) Binge/intoxication stage: reinforcing effects of drugs may initially use mainly dopamine and opioid peptides in the nucleus accumbens (NAc) and involves the ventral tegmental area (VTA). Subsequently, cue–response habits develop and includes the substantia nigra pars compacta (SNc) and the dorsal striatum. (2) Withdrawal/negative affect stage: the negative emotional state of withdrawal may involve the extended amygdala with corticotropin-releasing factor (CRF), norepinephrine and dynorphin as key neurotransmitters. Main projections of the extended amygdala consist of the hypothalamus and brainstem. (3) Craving stage: this stage includes conditioned reinforcement in the basolateral amygdala (BLA) and contextual processes in the hippocampus. This is controlled by cortical areas (prefrontal cortex (PFC) and orbitofrontal cortex (OFC)). A key neurotransmitter involved in the craving stage is glutamate.

The progression of drug addiction begins with the first exposure, mostly when the drug is taken voluntarily for its recreational and hedonic effect, and progressively consolidates during repeated but still controlled drug use. While administration intensifies along with loss of control over drug intake, drug use becomes habitual and compulsive in vulnerable individuals [ 4 , 29 , 30 ] (Fig. 2 ). This progression from voluntary drug intake to habitual and compulsive use represents a progression from ventromedial to more dorsolateral regions of the striatum and from prefrontal cortex (PFC) to orbitofrontal (OFC) and more global cortical region [ 4 , 31 ] (Fig. 1 ).

Synaptic plasticity

Brain plasticity is a fascinating capacity allowing appropriate modification of the neural activity in response to new experiences and environmental stimuli [ 32 ]. Modifying the synaptic strength between neurons is widely assumed to be the mechanism by which memory is encoded and stored in the brain [ 7 ]. Hence, it is appealing to hypothesise that drugs of abuse cause long-term alterations on behaviour by changing synaptic plasticity in key brain circuits [ 4 , 7 , 32 ].

Drugs of abuse such as cocaine induce specific synaptic plasticity in the mesolimbic circuitry. One single injection of an addictive drug can already modify the excitatory synaptic strengths in the VTA. Indeed, it has been extensively shown that the AMPA/NMDA ratio is increased in VTA dopamine neurons after one dose of cocaine and that some glutamate AMPA receptor 2 (GluA2)-containing AMPA receptors (AMPARs) are exchanged for GluA2-lacking ones [ 33 , 34 ]. At the same time, NMDA receptor (NMDAR) function decreases. All these elements cause an impairment in eliciting long-term potentiation (LTP). Different types of synaptic plasticity in VTA dopamine neurons induced by rewarding and aversive experiences are comprehensively reviewed by Pignatelli and Bonci [ 35 ]. Midbrain dopamine neurons are central in the mesolimbic circuitry for both natural rewards and drugs of abuse [ 18 , 36 ]. The VTA is known to be a central hub integrating numerous inhibitory inputs as GABAergic synapses represents 50–80% of all synapses onto VTA dopamine neurons [ 37 , 38 , 39 ]. GABAergic inhibition of dopamine neurons is mediated by both fast ionotropic GABA A receptors and slow metabotropic GABA B receptors [ 40 ].

In 2017, Edwards et al. [ 41 ] showed that the principal monosynaptic projection to VTA dopamine neurons arising from the NAc [ 42 ] inhibits the firing of dopamine neurons via activation of GABA B receptors, whereas local VTA inhibitory interneurons inhibits dopamine neurons through GABA A receptors. Today, it is well established that pharmacological activation of GABA B receptors (e.g. by baclofen) reduces cue-associated cocaine craving as well as reduce cocaine use in humans [ 43 , 44 , 45 ] and it reduces rewarding and reinforcing effects of cocaine on animal models [ 46 , 47 , 48 , 49 ]. Edwards et al. report [ 41 ] indicates that the therapeutic effects of baclofen might pass through VTA dopamine neurons’ GABA B receptors. Intrathecal Baclofen is an effective and safe long-term treatment used worldwide to treat severe spasticity [ 50 , 51 ]. Oral baclofen is less effective and has significant rates of side effects, like sedation, somnolence, vertigo and headache especially when prescribed off-label for drug addiction (because higher doses are commonly used) [ 51 , 52 ] . . Indeed, contrasting results on the effect of baclofen in reducing alcohol craving [ 53 , 54 , 55 ] and cocaine dependence [ 43 , 56 ] were probably due to different severity of alcohol dependence of the enroled patients. This is way higher dose are tested and often prescribed off-label for drug addiction [ 55 ]. Thus, self-poisoning that could lead to severe toxicity and death represents one the major concern of baclofen use in drug addiction. Therefore, baclofen should be prescribed with caution and close monitoring [ 52 , 57 ].

Together with drug of abuse-induced LTP at excitatory synapses, plasticity of GABAergic inhibitory synapse in the VTA also have an impact on the firing rate of VTA neurons, at least following opioid [ 58 ] and cocaine administration [ 59 ]. Normally, NMDA activation, during excitatory LTP (induced by high-frequency stimulation), leads to the release of NO that will activate guanylate cyclase in adjacent GABAergic terminals, which in turn, leads to increase in GABA release. This presynaptic NMDA receptor-dependent GABAergic LTP heterosynaptic plasticity, is named LTP GABA . Nugent el al. [ 58 ] showed that opioids blocks LTP GABA through a disruption of the coupling between nitric oxide (NO) and guanylate cyclase. The incapability of GABAergic synapses to potentiate after morphine or cocaine administration may promote LTP of glutamatergic synapses [ 58 , 59 ]. The early loss of inhibitory control combined with potentiation of glutamatergic synapses on dopaminergic neurons might represent adaptations that increase vulnerability to addiction [ 58 , 59 ]. Furthermore, GABA A receptor modulators modify the addictive drugs effects [ 60 , 61 ], and targeting these receptors might be seen as an effective therapeutic strategy but precluded by many side effects among which dependence itself [ 62 , 63 , 64 ].

In addition to the discovery of LTP GABA , Nugent’s group showed that morphine is also able to modulate a form of postsynaptic LTD (LTD GABA ) at GABAergic synapses onto VTA dopamine neurons. Remarkably, after a single administration of morphine, LTD GABA was absent in slices from morphine-treated rats while unaffected in slices from saline-treated rats, indicating a bidirectional control of morphine on GABAergic synaptic plasticity in the VTA [ 65 ]. This absence of LTD GABA is suggested to result from an occlusion effect due to prior morphine-induced decrease in GABAergic synaptic strength through potentiation of glutamatergic transmission and mediated by endocannabinoid signalling [ 66 ]. It is also possible that morphine alters the ability of synapses to exhibit evoked LTP or LTD in the VTA. Previous experiences such as exposure to drugs of abuse, stress, visual or sensory deprivation can change the ability of synapses to undergo subsequent plasticity in response to LTP and LTD induction protocols. This concept of modification of plasticity capability is referred as metaplasticity [ 67 ].

In the NAc, chronic exposure to addictive drugs induces specific synaptic changes that are different from those of the VTA, including a decrease of the AMPA/NMDA ratio as some AMPARs are endocytosed. This leads to a depressed synapse (sometimes referred as long-term depression (LTD) like state), where NMDAR-dependent LTD is reduced or, in some experiments, abolished [ 68 , 69 ]. Highlighting the importance of temporal aspects, studies of withdrawal period after chronic administration of cocaine, showed that synaptic AMPAR levels increase during the first week of withdrawal and persist elevated for weeks [ 70 , 71 , 72 ]. It is established that cocaine challenge transiently decreases AMPAR surface expression, while AMPARs recover back to upregulated levels within a week, with a continuous increase during what is known to be the incubation of craving stage [ 73 ].

The abstinence period after withdrawal is of particular interest considering the classical progression of the disease, the chance of relapse and the opportunity for new therapeutic targets. A seemingly counterintuitive concept named ‘incubation of cocaine craving’ was introduced by Grimm et al. [ 74 ] who modelled cocaine-craving behaviour by using rats trained to press a lever to receive an injection of cocaine and were then forced in a withdrawal period where cocaine reward was no longer given. This concept of ‘incubation’ did not originate in drug addiction research but came from a four-stage model of the creative process proposed by Graham Wallas in 1926 [ 75 ]. Consistent with clinical observations in humans [ 76 , 77 , 78 ], they showed that relapse was progressively stronger over 2 months of cocaine withdrawal and suggest that a craving syndrome progresses or ‘incubates’ during the first 2 months of cocaine abstinence, and probably lasts for longer [ 74 ]. Subsequently, it was shown that this increase was due to the addition of new AMPARs lacking GluA2 and that these new receptors mediate the ‘incubation of cocaine craving’ [ 72 ]. Conrad et al. [ 72 ] showed that after extended withdrawal from cocaine, addition of synaptic AMPARs together with the increased conductance of GluA2-lacking AMPARs triggers higher sensitivity of NAc neurons to cocaine-related cues, leading to a strengthening of drug craving syndrome and relapse. In line with these results, it was suggested that as soon as abstinence is reached, the risk of relapse might be reduced if GluA2-lacking AMPARs were inactivated or removed from NAc synapses. It was thus proposed that GluA2-lacking AMPARs could be a new target for drug development for the treatment of cocaine addiction. While these calcium permeable AMPARs are also critical for the pathogenesis of numerous other neurological disorders (including epilepsy [ 79 ], fragile X syndrome [ 80 ], amyotrophic lateral sclerosis [ 81 ], Parkinson’s [ 82 ] and Alzheimer’s [ 83 ] diseases), developing drugs that specifically target them and not calcium-impermeable AMPARs, which are critical for normal CNS function, is challenging [ 84 ] (Fig. 3 ).

DNA is packaged inside nuclei with the help of histones. These are positively charged proteins that strongly adhere to negatively charged DNA and form complexes called nucleosomes. Each nucleosome is composed of DNA wound around histone octomers (H2A, H2B, H3 and H4). Nucleosomes fold up to form chromatin fibre, which forms loops compressed and folded to produce fibres, which are coiled into the chromatid of a chromosome. Only by loosening compacted chromatin, the DNA of a specific gene can be made accessible to transcription. Some of these drug-induced modifications at the chromatin level are extremely stable and sustain the drug of abuse-induced long-term behaviours. Among them, histone post-translational modifications (PTMs) are known to be causally involved in drug-induced behaviours [ 194 ]. PTMs include acetylation (Ac), methylation (Me), phosphorylation (P), ADP ribosylation (PolyADP-R) and dopaminylation (DA), among a growing list of newly discovered modifications [ 162 , 172 ]. For example, while ubiquitylation (Ub) of H2A is known to be a key interactor of H3 methylation [ 253 ], its supposed role in drug addiction is still unknown. At this epigenetic level, some drugs were demonstrated to have an influence on drug-induces behaviours such as histone deacetylase (HDAC), bromodomain and DNA methyltransferase inhibitors. Locus-specific epigenome editing is now encouraging as a new field of investigation as it might help to the discovery of new specific and causal drug of abuse targets. Overview of the tetrapartite glutamatergic synapse composed of a medium spiny neuron (MSN), a glutamatergic projection, a glial cell and the extracellular matrix (ECM). Here, we focused on synaptic potentiation after drug of abuse administration with the addition at the post-synaptic membrane of glutamate AMPA receptor 2 (GluA2) lacking AMPA receptors (AMPARs). This mechanism might be reduced by metabotropic glutamate receptor 1 (mGluR1) positive allosteric modulator or more directly by GluA2-lacking AMPARs antagonists. In the same way, it was also shown that presynaptic mGluR2 agonists can potentially abolish drug seeking and impair craving incubation. Optogenetically-inspired 12 Hz deep brain stimulation (DBS) in the nucleus accumbens can also be a promising novel therapeutic for addiction. Finally, ceftriaxone, N-acetylcysteine, and inhibitor of matrix metalloproteases 9 (MMP-9), mainly through their action on glial cell and the ECM, are very interesting molecules that may be added in the addiction therapeutic arsenal.

Inspired by previous work performed in the VTA showing that metabotropic glutamate receptor 1 (mGluR1) LTD induces removal of GluA2-lacking AMPARs from synapses [ 33 , 34 ], Loweth et al. [ 85 ] demonstrated that synaptic GluA2-lacking AMPAR decrease could be accomplished by in vivo evoked mGluR1 LTD in the NAc. More importantly, their group showed that after prolonged cocaine or methamphetamine withdrawal, systemic injection of a mGluR1 positive allosteric modulator attenuated the expression of incubated craving by reducing GluA2-lacking AMPARs in the NAc [ 85 , 86 ]. These results suggest a strategy in which abstinent methamphetamine or cocaine users could use a systemically active compound to protect themselves against cue-induced relapse.

These latter studies were conducted without differentiating between D1 receptor D1R MSNs and D2R MSNs. In 2014, Pascoli et al. [ 87 ] demonstrated that this increase in the strength of excitatory afferents was exclusively related to D1R MSNs. Interestingly, the type of drug-evoked plasticity involved is also dependent on the input. It has been shown that even in the same D1R MSN a synapse connecting the PFC to the NAc increases its strength by inserting GluA2-lacking AMPARs whereas a synapse connecting the ventral hippocampus to the NAc increases the AMPA/NMDA ratio by inserting GluA2-containing AMPARs [ 87 ].

Besides operant self-administration, all these long-term synaptic modifications also underlie behavioural changes associated with drugs of abuse, such as locomotor sensitisation [ 88 , 89 ]. Locomotor sensitisation is a behavioural protocol used to model drug-induced behaviour [ 90 , 91 ]. In rodents, repeated cocaine injection induces gradually increased locomotor activity; after 5 days of consecutive injections, the locomotor response reaches a ceiling level. This state lasts for months after cocaine withdrawal [ 91 ]. As an experimental model, locomotor sensitisation is linked with increased tendency to self-administer psychostimulants [ 92 , 93 ] and with reinstatement of previously extinguished self-administration [ 94 , 95 ]. Whereas the existence of psychomotor sensitisation in humans is discussed [ 96 , 97 ], it is a key aspect of vulnerability to drug addiction and relapse, specifically drug craving or compulsive drug-seeking behaviour [ 91 , 98 , 99 ]. Still, locomotor sensitisation can be dissociated from the rewarding effect of a drug of abuse and conditioned place preference or self-administration are more appropriate experimental paradigms to test this aspect [ 100 , 101 , 102 ]. Even if drug-induced locomotor sensitisation is unclearly present in humans, as an animal model it offers a clear readout to understand the mechanisms by which drugs of abuse induce long-term brain modifications [ 91 ].

Furthermore, it has been elegantly demonstrated that optogenetic stimulation of the excitatory projections to the NAc is able to reverse cocaine and alcohol-evoked plasticity [ 87 , 88 , 89 ]. Briefly, applying a NMDAR or mGluR1-dependent LTD on cortico-accumbal glutamatergic synapses, before a drug of abuse administration, diminishes its effect. In another study, Luscher’s team took advantage of the knowledge, obtained from optogenetic in vivo experiment in rodents, to implement a novel deep brain stimulation (DBS) protocol that abolishes behavioural sensitization to cocaine (and thus that would be efficient during the relapse phase) [ 103 ]. Basically, the idea is to manipulate synaptic plasticity in the NAc to reverse pathological synaptic transmission and its associated behaviours following exposure to drugs of abuse. In this study, as a therapeutic use of optogenetic tools in humans is for now inapplicable [ 104 ], the authors reversed cocaine-evoked plasticity and thus drug-induced behaviours by using DBS instead of optogenetic. Indeed, DBS is routinely used in clinic and a new DBS protocol can easily be translationally implemented to the human therapeutics [ 105 , 106 ]. They refined the classical high-frequency DBS protocol (that has no sustained effect on cocaine sensitization, probably because it does not affect synaptic plasticity) by applying a low frequency stimulation (12 Hz to equal the one used in the optogenetic endocannabinoid- dependent LTD protocol) in the NAc together with the administration of a D1R antagonist necessary to unmask the mGluR-dependent LTD in D1R MSNs as demonstrated previously [ 107 ] (Fig. 3 , see section on clinical treatment for broader discussion on DBS).

Kalivas’ group showed in 2009 [ 108 ] that after extended withdrawal from chronic cocaine self-administration, cocaine-induced metaplasticity at the excitatory synapses in the NAc that impairs the ability of PFC stimulation to produce LTP or LTD in NAc MSNs. They also showed that N-acetylcysteine reverses cocaine-induced metaplasticity, allowing the induction of both LTP and LTD and that N-acetylcysteine decreases cocaine-relapse in a rodent model. We are currently awaiting the results of a randomised and control study that is testing newly detoxified (and therefore abstinent) hospitalised patients who received a 3–4 week course of treatment, in order determine if N-acetylcysteine can be a useful medication candidate to avoid relapse in patients with cocaine dependence (NCT03423667).

GABAergic D1R and D2R MSNs, equally compose and are mosaically intermingled throughout the striatum [ 109 ]. As explained above, D1R and D2R MSNs send axonal projections outside the striatum, forming the two main output pathways, respectively the direct and indirect pathways [ 16 , 17 ]. In a certainly oversimplified model, the activation of the D1R MSNs result in facilitation of locomotion, reward, and reinforcement while the activation of D2R MSNs result in opposing effects [ 110 , 111 , 112 , 113 ]. In addition to the long-range projections, these neurons form short-range synaptic connections with one another within the striatum, and because they consist of inhibitory collaterals, a mechanism known as lateral inhibition [ 114 , 115 , 116 , 117 ]. Interestingly, these connections are not symmetrical, with D2R MSNs forming more synaptic connections on D1R MSNs [ 115 , 117 ]. Through this previously understudied collateral transmission, Dobbs et al. [ 115 ] presented a novel mechanism by which cocaine exerts its stimulant effect: cocaine, by blocking DAT receptors enhance levels of dopamine and subsequently activating D2Rs, causes a suppression of lateral inhibition and thus disinhibition of D1R MSNs in the NAc which in turn promotes locomotion [ 115 ]. Furthermore, Alvarez’ group suggested that constitutive low D2R levels, through imbalanced lateral inhibition, might pre-sensitised D1R MSNs, facilitate behavioural plasticity to repeated cocaine and promotes an addiction vulnerable phenotype [ 116 ].

The characterisation of the role of glia and the extracellular matrix (ECM) in drug-induced synaptic plasticity is an exciting emerging field of drug addiction research as it comes with promising new therapeutic possibilitiess [ 118 , 119 , 120 ]. Mulholland et al. [ 118 ] summarised and emphasised the role of the ECM and of astroglial cells in the regulation of synaptic plasticity. Of great interest, restoring downregulated glutamate transporter 1 (EAAT2) with ceftriaxone reduces drug seeking in animal models [ 121 , 122 ]. Matrix metalloproteases (MMP) are important regulators of the ECM and contribute to synaptic plasticity [ 123 ]. Inhibiting their activity result in suppression of the reinstatement of cocaine conditioned place preference [ 124 ] and selectively inhibiting MMP-9 prevents cue- and cocaine-induced reinstatement of cocaine self-administration [ 119 ]; these results open additional therapeutic possibilities with the use of inhibitors of MMP-9 as an innovative targeted approach [ 119 , 124 , 125 ] (Fig. 3 ). Still, at our knowledge, there are no randomised controlled study currently investigating these ECM-related drugs.

Drugs of abuse-induced modifications in glutamatergic nuclei targeting the NAc, or the VTA and essential part of the reward circuit, are less studied than cortico-striatal synapses despite the fact that they play a crucial role in the development of drug addiction. Indeed, in the OFC and PFC, chronic alcohol exposure significantly increases LTP in pyramidal neurons [ 126 , 127 ]. Kazanetz et al. [ 128 ] showed that repeated cocaine injections impair endocannabinoid-LTD and mGluR2/3-LTD in the PFC. They postulated that this might mechanistically participate in the induction of a postsynaptic, observed LTP-like phenomenon with an enhanced AMPA/NMDA ratio. It was also demonstrated that neurons of the infralimbic cortex present a decrease in mGluR2 [ 129 ]. In addition, alcohol-dependent rats exhibit an escalation of ethanol seeking, which was abolished by restoring mGluR2 expression in the infralimbic cortex via viral-mediated gene transfer [ 129 ]. Notably, mGluR2 agonist was shown to impair the incubation of cocaine craving [ 130 ] and to attenuate reinstatement of cocaine-seeking [ 131 , 132 ](Fig. 3 ). Recently, Caprioli et al. [ 133 ] extensively reviewed preclinical studies on allosteric modulators of mGluRs on animal models of drug addiction and their potential translational implications. The results reviewed [ 133 ] indicate an remarkable effect of allosteric modulators of presynaptic mGluR2 and possibly mGluR7, supporting the idea that these compounds should be tested as potential medications for addiction treatments.

Besides the PFC, other brain regions appear to be key areas in drug addiction as the paraventricular thalamus (PVT) - a central hub for cortical, sensory and limbic information [ 134 , 135 , 136 , 137 , 138 , 139 , 140 ]. In 2016, Zhu et al. [ 141 ] showed that chronic morphine administration potentiates excitatory synapses between the PVT and D2R MSNs via insertion of GluA2-lacking AMPARs. Remarkably, in vivo optogenetic depotentiation at these synapses abolishes morphine withdrawal symptoms. In a recent paper, projections from the PVT to the NAc were shown to be critical for augmentation of heroin seeking in food-restricted rats [ 142 ] (Fig. 1 ). Actually, Otis et al. [ 143 ] demonstrated that the PVT is an integrative hub for reward seeking behaviour and that PVT-NAc neurons integrate different inputs from the PFC and the lateral hypothalamus to precisely guide reward seeking behaviour. In a recent review, De Groote et al. [ 140 ] focused on the new advances in the understanding of the roles of the PVT-NAc connections in motivated behaviours, highlighting their implications in drug addiction.

Drug addiction-related genes and transcriptomic regulation

Modifications in gene expression contribute to the long-lasting effect sustaining drug addiction; thanks to gene-expression arrays, RNA-sequencing and candidate gene approaches, the specific genes and their regulatory transcriptomic mechanisms involved in drug addiction development and maintenance are now better understood.

Drug addiction-related genes

For example, the use of conditional gene knockout in mice emphasises the importance of monoamine membrane transporters (dopamine transporter, and serotonin transporter) [ 144 , 145 ] and of mGluRs [ 146 , 147 ]. As new animal models of drug addiction, these approaches are also useful to better characterise fine-tuning of important pathways involved in addiction. For example, a scaffold protein known as Maged1 has been shown to be involved in cocaine reward and reinforcement [ 148 ]. We demonstrated that Maged1 inactivation impairs drug-evoked dopamine release and glutamatergic synaptic plasticity in the NAc. Inactivation of Maged1 in mice was able to abolish behavioural sensitization to cocaine as well as cocaine conditioned place preference and operant self-administration behaviours [ 148 ]. This sole genetic alteration, causally linked to a strong alteration of drug-induced behaviours, impairs (at least) two core neuronal mechanisms leading to addictive behaviours: (1) cocaine-evoked release of dopamine in the NAc and (2) NAc plasticity, with a reduced AMPA/NMDA ratio and a resistance to LTD. Actually, it seems that, after Maged1 inactivation, the excitatory synapses in the NAc shift to a depressed state. Our hypothesis is that, in line with the previously discussed in vivo optogenetic induced LTD, this impairment could be a key factor for the significant decrease in sensitization to psychostimulants [ 87 , 103 , 148 ]. Actually, it seems that placing neurons in a state of ‘presensitization’ is able to prevent drug-induced sensitization itself [ 148 , 149 ]. Our group is now trying to understand what are the cellular and molecular pathways directly altered by Maged1 inactivation and responsible for this strong anti-addictive drug phenotype. Remarkably, the promoter of Maged1 was found in a list of 213 promoters that co-precipitate with acetylated histones and with the activated form of cAMP response element binding protein (CREB) after chronic drug taking [ 150 ]. In line with this result, preliminary and unpublished results from our laboratory point out a specific epigenetic mechanism, in parallel with an alteration of synaptic plasticity in excitatory projection to the NAc, that would link Maged1 to its major effect on drug-induced behaviours. This selected gene approach is of great interest in refining our knowledge of pathways hijacked by addictive drugs. Using cell sorting of D1R MSNs and D2R MSNs as described previously [ 151 ], our group also identified the G-protein-regulated inducer of neurite outgrowth 3 (GPRIN3) in both MSN populations but strikingly more expressed in D2R MSNs [ 149 ]. The GPRIN family (GPRIN1, GPRIN2 and GPRIN3) are Gαi/o-regulated proteins suggested to intermediate the communication between GPCRs and the sequential intracellular target [ 152 ]. Indeed, GPRIN1 and GPRIN2 have been described as alternative (to adenylyl cyclase) mediators of GPCRs signalling but GPRIN3 had a much less defined role [ 152 , 153 ]. To understand the role of GPRIN3 in the pathophysiology of the D2R-indirect pathway, we induced a D2R-MSNs-specific knockdown (KD) of GPRIN3 using small hairpin RNA and lentiviruses [ 151 , 154 ]. We first observed a significant increase in distal branching, the points of convergence between glutamate and dopamine synapses in MSNs [ 155 ] and also key targets of cocaine, which itself promotes increase in distal branching in the NAc of mice [ 156 , 157 , 158 , 159 ]. Thus, we tested the cocaine acute effect and locomotor sensitization and observed a decrease in cocaine-induced hyperlocomotion after inactivation of GPRIN3 using a CRISP/Cas9 approach. The significant increase in distal branching in GPRIN3 D2R-MSNs KD corroborates our hypothesis that the lack of GPRIN3 induces a ‘presensitization process’, able to change the targets of cocaine and therefore altering its effects [ 149 ]. Finally, we provide the first evidence that GPRIN3 partners with D2R in the striatum and modulates cocaine-induced behaviours [ 149 ].

Transcriptomic and epigenetic regulations

Epigenetics is a broad field and has multiple definitions that comprise several biochemical mechanisms (including DNA methylation and histone modifications) sustaining modifications in gene expression throughout the lifecycle of an organism without mutations of the DNA itself [ 160 , 161 , 162 ]. Epigenetics can be considered as the process through which environment (and normal development) interacts with an individual’s genome to determine all phenotypic traits, in health and disease. Stable modifications in gene expression are also said to be ‘epigenetic’, because they are heritable in the short term (through mitosis) [ 160 ] and in some cases trans-generationally, thus, providing a potential mechanism for environmental influences to be passed from parents to offspring [ 163 , 164 , 165 ]. Handel and Romagopalan [ 163 ] mentioned that “epigenetics allows the peaceful co-existence of Darwinian and Lamarckian evolution”. Such trans-generational epigenetic inheritance of drug addiction vulnerability remains debatable [ 161 ], but has been increasingly studied for the last 20 years [ 166 , 167 ]. Some epigenetic changes are very stable, an thus mediate both drug addiction susceptibility and drug-induced brain alterations that underlie the development of drug addiction [ 161 ].

As the NAc is seen as the central hub of drug addiction, with the notion that chronic drug use induces long-lasting structural, electrophysiological and transcriptional changes in the NAc, researchers are mostly targeting epigenetic modifications in NAc cells. Still, considering initial reports of cocaine-induced epigenetic modifications [ 168 , 169 ], it might be relevant to study further epigenetic changes in other regions such as glutamatergic inputs to the NAc, and further in the VTA, as they are implicated in the physiopathology of drug addiction [ 170 , 171 ] as mentioned above.

To date, the three main epigenetic mechanisms consist of (1) DNA methylation, (2) action of the non-coding RNAs and (3) histone post-translational modifications (PTMs). As an illustrative example, we will focus here only on histone PTMs. PTMs of histone residues on their N-terminal tails, that protrude from the nucleosome core, control chromatin condensation and the switch between euchromatin and heterochromatin and thus DNA-accessibility and gene expressions. PTMs include acetylation, methylation, phosphorylation, ADP ribosylation, ubiquitylation and sumoylation, among a growing list of newly discovered modifications [ 162 , 172 ].

Among these PTMs, the most studied is the acetylation of H3 and H4, that is increased in the NAc after chronic exposure to drugs of abuse [ 150 , 173 , 174 ]. This increase in global acetylation levels is the result of drug-induced alterations in the balance of histone acetyltransferase and histone deacetylase (HDAC) function and is associated with gene activation. CREB-binding protein, a histone acetyltransferase critical to memory processes [ 175 ], is required for cocaine-induced increases in histone acetylation in the NAc [ 176 ].

Fifteen years ago, Tsankova et al. [ 177 ] showed that imipramine, a monoamine reuptake inhibitor used for decades to treat depression, was effective through histone remodelling in depression and highlight the therapeutic potential for chromatin regulation with histone methylation and deacetylation inhibitors in depression. Nevertheless, like with synaptic plasticity (see above), discovering a drug that would interfere with epigenetic mechanisms and thus decrease drugs of abuse effect faces temporal aspects issues [ 173 , 176 , 178 , 179 , 180 , 181 , 182 ]. Indeed, timing has a strong impact considering conflicting results obtained after experimental manipulations of histone acetylation. An acute administration of HDAC inhibitors systemically or directly into the NAc, promotes behavioural responses to the drugs. However, prolonged administration decreases cocaine behavioural effects. In 2013, adding a new layer of complexity, Kennedy et al. provided comprehension to this time-dependent regulation [ 183 ]. Remarkably, they showed that prolonged intraNAc administration (but not acute administration) of a HDAC inhibitor attenuated cocaine behavioural effects by inducing a form of repressive histone methylation. This study showed, for the first time, cross-talk among different types of histone modifications [ 183 ]. Besides cross-talk between different epigenetic modifications, multiple modifications work in parallel and there is often a decoupling between an observed modification at a specific locus and its final transcription [ 161 ]. Decoding these chromatin marks will be a future challenging field. Like with HDAC inhibitors, there are promising findings based on the use of DNA methyltransferases inhibitor [ 184 , 185 ] (Fig. 3 ). Though, the main issue with these new potential treatments for drug addiction is their lack of specificity. One of the key challenge for the pharmaceutical industry will be to generate small molecules with more specific targets [ 6 ].

While histone acetylation and methylation are increasingly studied, an important field of future investigation will be to understand the other drug-induced histone PTMs. It already seems that chronic cocaine alters levels of histone phosphorylation [ 174 , 186 , 187 ], and poly-ADP ribosylation [ 188 ]. Recently, an unexpected role for the intracellular dopamine in VTA has been revealed, showing that DA interacts with chromatin to initiate a new form of epigenetic regulation called dopaminylation [ 189 ] (see Table 1 for a summary of cocaine-related epigenetic modifications).

Further studies showed that histone PTMs that occur in the NAc after chronic drug administration are locus specific [ 150 , 190 , 191 ]. Even though, drugs of abuse alter global levels of multiple histone PTMs, such as increased histone acetylation or decreased methylation in the NAc, genome-wide studies have confirmed that a greater number of genomic sites show increased acetylation [ 150 ] or decreased methylation [ 190 , 191 ]. Conversely, hundreds of genes show opposite or no changes in these same PTMs after drug exposure. What defines whether, and in which direction, a specific gene is modified in the context of a global histone PTM is an intriguing and unsolved question [ 161 ]. These genome-wide studies (ChIp on chip or ChIpSeq) are nowadays fundamental to understand where PTMs and other epigenetic modifications are deposited. This will be fundamental to guide new therapeutics.

Actually, with new tools such as zinc finger proteins (ZFPs) DNA-binding domains and, more recently, RNA-guided CRISPR/dCas9 (drastically easier to design) [ 192 , 193 ], it is now possible to control epigenetic modifications at a single gene in a specific type of cell in a specific brain region [ 162 ]. Heller et al. demonstrated that gene-targeted epigenetic editing (targeted to the Fosb [ 194 ] and Cdk5 [ 195 ] locus with ZFP technology) can alter drug-related behaviours [ 194 , 195 ]. This represents crucial evidence that gene-specific changes to the epigenome are not simply correlated, but rather causal, in regulating transcriptional responses to drugs of abuse administrations. These new results of “causal epigenomics” are very encouraging as they open the way to precise translational therapeutic approaches for drug addiction and other CNS diseases.

Linking epigenetics and synaptic plasticity

Today, most studies investigate synaptic plasticity and epigenetic as two distinct fields and it is not clear how these research topics are connected to each other. Understanding how epigenetics is connected to synaptic plasticity is an emerging research issue [ 6 ].

Of course, bridging epigenetic mechanisms with synaptic plasticity is not limited to drug addiction field. For example, in 2011, Monsey et al. [ 196 ] elegantly demonstrated that DNA methylation and histone H3 acetylation regulate auditory fear conditioning and its related synaptic plasticity in the amygdala. In 2014, Massart et al. [ 197 ] suggested that sleep deprivation induces epigenetic modification (alteration in DNA methylation and hydroxymethylation) that triggers synaptic plasticity modifications by changing expression of plasticity related genes.

Regarding drug addiction, some epigenetic marks seem fundamental and upstream as illustrated by HDAC inhibitors effect on drug-induced synaptic and behavioural modifications [ 178 , 198 , 199 , 200 ]. Additionally, Maze et al. [ 201 ] demonstrated morphological plasticity induced by cocaine through the histone methyltransferase G9a. Again advocating for causal epigenetic, Authement et al. [ 66 ] demonstrated that HDAC inhibition locally in the VTA is sufficient to reverse epigenetic modifications and synaptic plasticity changes after morphine administration.

Two transcription factors implicated in addiction exemplify this bridging attempt: CREB and ∆FosB (a truncated form of the FosB gene) are both activated by several drugs of abuse [ 202 ]. CREB activation occurs in both subtypes of NAc MSNs (D1R and D2R), while ∆FosB activation is limited to D1R MSNs in response to all drugs of abuse except for opioids, which remarkably induce the protein in both MSNs [ 203 ]. Expression of active CREB in NAc MSNs increases their excitability [ 204 ] and underlies drug-induced long-term synaptic plasticity and associated changes in dendritic spine plasticity [ 205 ]. ∆FosB is also linked to synaptic plasticity but evokes contrasting effects on the two MSN subtypes, with increased AMPA receptor function induced in D1R MSNs and decreased AMPA receptor function induced in D2R MSNs [ 206 ]. Renthal et al. [ 150 ] unravelled CREB and ∆FosB target genes and observed that these genes are mainly involved in neuronal excitability and synaptic function. Moreover, as already briefly discussed above, CREB and ∆FosB action have also been related to multiple epigenetic regulations, including histone acetylation and methylation [ 150 ]. Besides, a novel mechanism for bridging the gap between epigenetic control of transcription and synapse plasticity might be seen in microRNAs [ 207 ]. The most studied miRNA in the context of synaptic plasticity is miR-132 and is known to be CREB-dependent [ 208 ]. In the striatum, miR-212 targets the epigenetic regulator methyl CpG binding protein 2 (MeCP2). MeCP2 acts as a transcriptional repressor through recruitment of histone deacetylases to methylated DNA segments [ 209 , 210 ].

Clinical treatments for drug addiction

Besides psychosocial interventions [ 211 ] such as cognitive behavioural therapy, the most widely used treatment for drug addiction involves agonist-like medication, a solution inadequately called replacement or substitution therapy [ 212 ]. This type of treatment has been successfully implemented in the daily practice for opioid use disorder (e.g.: methadone, buprenorphine) [ 213 ] and tobacco use disorder (e.g.: nicotine patch or gum, varenicline) [ 214 ]. Currently, this agonist-like treatment is also promising for psychostimulant use disorder [ 215 ]. Still, considering the addictive drug-like effect, the risk of abuse, misuse and diversion, replacement therapy should be prescribed with caution [ 215 , 216 ].

Recently, a randomised and control study on a cocaine vaccine failed to show an effectiveness but instead raised an important issue: immunised subjects may have increased their cocaine use to overcome the competitive anti-cocaine antibody inhibition [ 217 ]. Even though significant improvements have been developed for immunopharmacotherapies for psychostimulant addiction over the last decade, very few candidates have been evaluated so far in clinical trials [ 218 ]. These considerations are some of the reasons why other treatments for drug addiction should emerge with the help of neurobiological research [ 219 ].

Following successful subthalamic nucleus DBS for Parkinson’s disease [ 220 , 221 , 222 ], DBS was investigated for diverse psychiatric diseases including depression [ 223 ], obsessive-compulsive disorder [ 224 ] and Tourette syndrome [ 225 ]. Today, indications for DBS are enlarging, with several positive case reports and small cases series that studied NAc DBS for drug addiction. The first studies showing potential positive effects on drug addiction were reports on application of NAc DBS primarily intended for other medication-refractory neuropsychiatric disorder where a comorbid drug addiction was unexpectedly resolved [ 226 , 227 ]. For DBS treatment in drug addiction, it seems that clinical empirical results led to further bench investigations and refinement [ 88 , 103 , 228 , 229 , 230 , 231 ], or at least, clinical and animal studies evolved in parallel with poor connectivity between the two.

Afterwards, many case reports and small cases series studied NAc DBS being used primarily for drug addiction, all showing encouraging decreases in drug use [ 232 , 233 , 234 , 235 , 236 , 237 ]. However, these studies are limited by their descriptive nature, inconstant follow-up, multiple publication bias, small patient numbers and lack of blinded stimulation and standardised outcome measures. At this stage, additional preclinical and clinical research are needed to clarify the role of DBS in the treatment of drug addiction [ 237 ]. Currently, randomised and control clinical studies are conducted (NCT01245075).

In a recent review, Sanna et al. [ 238 ] highlighted how repetitive transcranial magnetic stimulation (rTMS) confirms the hypodopaminergic hypothesis of drug addiction. While enhancing dopaminergic function through direct or indirect pharmacological approaches does not significantly alleviate symptoms, in numerous studies, and has not yielded a single FDA-approved medication [ 239 ], rTMS might indirectly modulate the dopaminergic system. Many rTMS studies stimulate the dorsolateral PFC [ 240 , 241 ] that projects to the VTA and thus induces an increase in dopamine release in the synaptic cleft in the NAc [ 55 , 242 , 243 ]. Nevertheless, considering the heterogeneity of methods used in rTMS studies during the last 10 years [ 238 ], protocols and guidelines, were recently suggested by an international network of experts in neuromodulation and addiction to improve homogeneity of studies [ 244 ]. From this report, it is clear that multiple technical details for optimal stimulation need further investigations that might be achieved through preclinical studies. For example, low frequency (but not high-frequency) rTMS before methamphetamine exposure in rats blocked drug-induced conditioned place preference [ 245 ]. Being non-invasive, with insignificant side effects, rTMS could be seen as a great opportunity for drug addiction treatment. We are currently waiting for the results of a randomised and control study that aims at determine if, in heavy alcohol users, a single session of TMS can lower a patient’s craving and brain response to alcohol cues (NCT02939313).

Interesting views of clinical treatments for drug addiction are discussed in some other reviews [ 212 , 215 , 216 , 219 ]. The clinical impact of new treatments also depends on their translation into clinical practice which is mainly promoted by the pharmaceutical industry [ 219 ]. Indeed, even when an effective treatment is identified through basic research, it is commonly challenging to translate it to clinical practice, as illustrated by naltrexone as a treatment of alcoholism [ 219 ]. Another example of problematic translation to clinic is illustrated by modafinil, a treatment that has been reported to attenuate cocaine euphoria but for which larger clinical randomised and controlled studies showed controversial results [ 246 , 247 ].

Future directions

Drug addiction is a brain disease strongly influenced by environment and psychosocial aspects. The psychosocial conditions in which it has developed are extremely important. Exposure to conditioned cues can be a central issue in causing drug cravings and relapses, even after successful treatment, and thus they have to be minimised [ 2 , 74 , 77 ]. The pathophysiological aspects are particularly unsteady. For instance, as discussed in this review and in other ones [ 73 , 248 ], synaptic plasticity is dynamically altered after psychostimulant administration, so that a treatment could have opposite effects depending on timing aspects of the administration protocol. In addition, a prolonged treatment may involve compensatory mechanisms, giving unexpected results (e.g.: when HDAC inhibitors and psychostimulants are both administered acutely, they have synergistic effects through hyperacetylation and thus transcriptional activation of psychostimulant-regulated target genes. Conversely, when a drug of abuse is given in the context of chronic HDAC inhibitor, compensatory mechanisms may promote acetylated histone to the promoters of genes responsible for inducing histone methylation and thus chromatin condensation and gene repression, all of which, in turn, gave opposite effect [ 183 ]). Thus, the evolution through the different stages of the disease has to be taken into account [ 249 ] and treatment must follow them. These two aspects have to be incorporated in a holistic treatment strategy. Besides, studying combination of different cutting-edge approaches, with animal models of addiction, such as targeted rTMS or DBS with more systemic epigenetic modulation might show a better restoration of altered synaptic transmission and decrease the probability of relapse in drug addiction. Basically, drug addiction is a disease that seems to be difficult to treat preventively but it is more conceivable to help patients that would be in an abstinence stage not to experience relapse of their disease. As addiction is chronic and relapsing, a good treatment outcome is a significant reduction of drug administration and long periods of withdrawal, with only sporadic relapses [ 2 ].

It is clear that the main issues for optimal therapeutic management of this specific psychiatric disease belong to its dynamic complexity, diverse temporal evolution and undeniably psychosocial aspects. In this review, we focused mostly on the effects of drugs of abuse on synaptic plasticity and epigenetic modifications. Nowadays, these two subfields are mostly studied separately and the understanding of how these two main addictive drug-induced brain modifications interact might be fundamental for addiction research [ 6 ]. Indeed, argument for clinical trials for new treatments emerge from fundamental behavioural studies that should be implemented in a global approach to the addicted patient.

Conclusions

Here, we highlight, from a vast fundamental literature (mainly based on rodent models), promising therapeutics that would potentially treat drug addiction. Based on effect, on synaptic plasticity and epigenetic mechanisms, treatments such as GluA2-lacking AMPAR antagonists [ 72 , 84 ], mGluR1 positive allosteric modulator [ 85 ], NAc 12Hz-DBS [ 103 ] (in line with other promising neuromodulation therapeutics such as rTMS or transcranial direct current stimulation [ 250 ]), N-acetylcysteine [ 108 ], HDAC inhibitors [ 183 ] or even (in very early stages of investigation) CRISPR/dCas9 epigenetic editing [ 194 , 195 ] could be potential candidates for human randomised clinical trials (Fig. 3 ).

Finally, it is fundamental to consider the specific clinical aspects of the disease that would help to develop a personalised-treatment strategy. Indeed, after going from the bench to the bedside it will also be essential to assess the reversed route.

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Acknowledgements

We thank Michele Zoli, Romain Icick and Daniel Rial for helpful comments and corrections on the manuscript. Julian Cheron is supported by a fellowship of the FRS-FNRS (Belgium). Alban de Kerchove d´Exaerde is a Research Director of the FRS-FNRS. FRS-FNRS (Belgium). Fondation Simone et Pierre Clerdent, Fondation ULB, supported this study.

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Cheron, J., Kerchove d’Exaerde, A.d. Drug addiction: from bench to bedside. Transl Psychiatry 11 , 424 (2021). https://doi.org/10.1038/s41398-021-01542-0

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How do we understand the value of drug checking as a component of harm reduction services? A qualitative exploration of client and provider perspectives

• Lissa Moran 1 ,
• Jeff Ondocsin 1 , 2 ,
• Simon Outram 1 ,
• Daniel Ciccarone 2 ,
• Daniel Werb 3 , 4 ,
• Nicole Holm 2 &
• Emily A. Arnold 1  

Harm Reduction Journal volume  21 , Article number:  92 ( 2024 ) Cite this article

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Mortality related to opioid overdose in the U.S. has risen sharply in the past decade. In California, opioid overdose death rates more than tripled from 2018 to 2021, and deaths from synthetic opioids such as fentanyl increased more than seven times in those three years alone. Heightened attention to this crisis has attracted funding and programming opportunities for prevention and harm reduction interventions. Drug checking services offer people who use drugs the opportunity to test the chemical content of their own supply, but are not widely used in North America. We report on qualitative data from providers and clients of harm reduction and drug checking services, to explore how these services are used, experienced, and considered.

We conducted in-depth semi-structured key informant interviews across two samples of drug checking stakeholders: “clients” (individuals who use drugs and receive harm reduction services) and “providers” (subject matter experts and those providing clinical and harm reduction services to people who use drugs). Provider interviews were conducted via Zoom from June-November, 2022. Client interviews were conducted in person in San Francisco over a one-week period in November 2022. Data were analyzed following the tenets of thematic analysis.

We found that the value of drug checking includes but extends well beyond overdose prevention. Participants discussed ways that drug checking can fill a regulatory vacuum, serve as a tool of informal market regulation at the community level, and empower public health surveillance systems and clinical response. We present our findings within three key themes: (1) the role of drug checking in overdose prevention; (2) benefits to the overall agency, health, and wellbeing of people who use drugs; and (3) impacts of drug checking services at the community and systems levels.

This study contributes to growing evidence of the effectiveness of drug checking services in mitigating risks associated with substance use, including overdose, through enabling people who use and sell drugs to test their own supply. It further contributes to discussions around the utility of drug checking and harm reduction, in order to inform legislation and funding allocation.

The opioid crisis in the U.S. consists of multiple overlapping and inter-related waves of surging opioid exposure, dependency, overdose, and death rates. Each wave has emerged from different eras of an evolving drug market and multiple intersecting contextual factors such as trends in pharmaceutical manufacturing and prescription, socioeconomic inequities, and positive supply shocks of both licit and illicit opioids [ 1 , 2 , 3 ]. Though its history can be traced back to the 1980s and 1990s, the past decade has redefined the crisis [ 4 ].

By the time the U.S. Department of Health and Human Services (HHS) declared the opioid crisis a public health emergency in 2017 [ 5 ], a wave of unprecedented magnitude had been on the rise for nearly 4 years, marked by the rapid proliferation of fentanyl and synthetic analogues into the drug market [ 4 , 6 ]. Even as mortality from heroin and prescription opioids leveled off or decreased, opioid overdose and death rates rose precipitously [ 6 ]. From 2018 to 2021, the rates of opioid overdose deaths in the U.S. nearly doubled, and by 2021, roughly 9 out of every 10 opioid overdoses in the country (88%) were fentanyl-related [ 7 ].

In California, home to the highest number of opioid-related deaths in the U.S. [ 8 ], the opioid overdose death rate curve from 2011 to 2021 tells a harrowing story. The third wave was later to arrive in California than the national average, but its onset was rapid and dramatic. Opioid overdose death rates more than tripled from 2018 to 2021, and synthetic opioid (e.g., fentanyl) deaths increased 7.2 times, responsible for 37% of opioid overdose deaths in 2018, and 86% just three years later [ 9 ].

In response, the California Department of Public Health has committed to the expansion and promotion of policies, programs, and services to combat the overdose epidemic, with a special focus on harm reduction and drug checking strategies [ 10 ].

Drug checking services

Drug checking services (DCS) have garnered particular interest as an expansion of harm reduction strategies, as they offer the opportunity for people who use drugs to test the chemical content of their own supply [ 11 , 12 ]. In doing so, people who use drugs may be afforded the possibility of changing their use behavior to remove or reduce the likelihood of harm [ 13 , 14 ]. Multiple DCS have been operating in Europe for years—particularly in venues known for high rates of recreational drug use like music festivals [ 14 , 15 ]—but are less common in North America. In the U.S. and Canada, DCS have emerged primarily in response to the needs of marginalized people who use opioids, and operate predominantly within the context of frontline services [ 16 , 17 , 18 ].

Though not mainstream or broadly implemented, studies from North America indicate that DCS are generally acceptable among people who use drugs [ 19 , 20 ], and report that both service users and providers have expressed desire for better access to DCS, legal protections for those providing and using drug checking, and advanced technologies that provide information on drug concentrations—not just drugs present—at the point of care [ 21 , 22 , 23 , 24 ]. Several studies explore the potential impact of drug checking when used at various points along the supply chain [ 25 , 26 ], with findings that suggest feasibility, acceptability, and uptake of DCS among drug sellers [ 27 ], noting particular importance to drug sellers who are embedded in their community and hold long-term trusted relationships with customers [ 28 , 29 ].

Arguably the most common and well-known drug checking modality in North America are fentanyl testing strips (FTS), or lateral flow assays, which were originally designed for the clinical use of detecting fentanyl in urine samples, but have been publicly available for several years for modified use with drug samples [ 30 , 31 , 32 , 33 ]. FTS have been a powerful tool to combat accidental fentanyl exposure: they are small, portable, relatively accessible, and detect fentanyl in minute concentrations that could still be enough to trigger an overdose in an opiate-naïve individual [ 31 , 34 ]. They have been found to be particularly useful for outreach and street use [ 13 , 25 , 35 ]. That said, FTS are not useful in the same way for those who intend to use fentanyl, where the overdose risk is not in the presence of fentanyl, but in the concentration and presence of additional adulterants like sedatives [ 36 ].

Drug checking technology has advanced, and continues to advance, such that a greater amount can be known about the chemical components of a drug sample in a shorter period of time, in a broader array of environments [ 37 ]. Multiple drug checking modalities can inform people who use drugs about the presence of unexpected adulterants, such as benzodiazepines and xylazine, among others. Technologies that offer the greatest specificity and sensitivity include Gas Chromatography Mass Spectrometry and High-Performance Liquid Chromatography, which can detect the presence and concentrations of a wide array of chemicals present in even small amounts in a sample, but must be used in a laboratory setting by a trained technician [ 37 ]. More flexible technologies have emerged, like Fourier-Transform Infrared Spectroscopy (FTIR) [ 38 ], which is semi-portable, and returns information on the main chemical components of a drug sample (above 5% concentration) in a matter of minutes [ 31 ]. Paper spray mass spectrometry is more expensive than FTIR but is just as fast, and provides quantitative results [ 39 ]. Today, multi-technology-based drug checking services are available in some areas as standalone programs, or as added components to existing harm reduction centers [ 30 , 40 ].

These innovations continue to advance amidst complex and evolving social, legal, political, and funding conditions [ 11 , 21 , 41 , 42 ]. Legally, drug checking can be complicated as a public service, requiring the handling and, often, exchange of illicit drug material, of which possession and distribution is often criminalized [ 21 ]. Harm reduction initiatives more broadly—DCS, syringe access services, naloxone distribution, HIV/HCV testing, wound care, supervised consumption sites, and medications for opioid use disorder (MOUD), among others—can at times be unpopular socially and politically, as stigma associated with addiction and drug use combined with concerns about the goals and practices of harm reduction can generate powerful community pushback [ 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. Legislators and policymakers at local, state, and federal levels who rely on constituent support may therefore shy away from supporting various harm reduction strategies, despite endorsement from public health officials and robust evidence showing that harm reduction improves the health, survival, and recovery potential for people who use drugs, without compromising community safety [ 48 , 49 ]. At the same time, California was one of several states to bring lawsuits against opioid manufacturers, distributors, and pharmacy chains, alleging that they played an active and/or negligent role in the genesis and exacerbation of the opioid crisis [ 50 ]. Of the $43.3 billion in settlement funds that have been awarded thus far, California may receive nearly $4 billion [ 51 ]. These funds are specifically earmarked for activities that are to include “prevention, intervention, harm reduction, treatment and recovery services.” [ 52 ].

As the opioid crisis reaches an unprecedented magnitude and strategies to address it are at once both a priority and a topic of controversy, we aimed to explore the value of drug checking services and their role within harm reduction more broadly. In this study, we report on qualitative data from providers and clients of harm reduction and drug checking services, to explore how these services are used, experienced, and considered. We aim to contribute to an existing qualitative evidence base exploring the value and utility of drug checking services, particularly as data are leveraged to inform political narratives, legislation, and funding allocation.

For this study, we conducted in-depth semi-structured key informant interviews across two samples: a “provider” sample and a “client” sample. The “provider” sample consisted of individuals providing clinical and harm reduction services to people who use drugs, as well as drug checking subject matter experts such as researchers and program heads. The “client” sample consisted of individuals who use drugs and were receiving harm reduction services at an agency where multiple forms of drug checking were included in the services provided.

From June to November 2022, two authors (DC & LM) conducted in-depth semi-structured key informant interviews with 11 providers—8 working in the U.S., 2 working in Canada, and one working in both countries. Included in the sample were 2 clinical providers, 4 researchers, and 5 harm reduction service providers [Table  1 ].

We employed purposive sampling of known providers first, then snowball sampling, contacting additional potential participants at informants’ recommendation. All potential participants were contacted via email and invited to participate. If the participant agreed, an appointment was made for the interview to take place over Zoom. Interviews lasted between approximately 45 and 60 min, and solicited provider perspectives on the state of the drug market in their area, the perceived needs of and challenges faced by their local client population, and their attitudes and experiences with drug checking methods and programs and integrating such programs into existing services. Verbal consent was collected at the outset of the interviews, which were then recorded. Audio from the recordings was isolated and transcribed using a secure third-party professional transcription service. All transcripts were deidentified and researchers created unique anonymous ID numbers for each participant. Participating providers were offered an honorarium of $100 in the form of a gift card. The study protocol was reviewed by the University of California San Francisco Institutional Review Board (IRB #22-36262).

Client participant ( n  = 13) recruitment and data collection took place over a one-week period in November 2022 [Table  2 ].

We employed a non-random convenience sample, recruiting from four harm reduction programs in San Francisco, where clients were approached either by interviewers (NH & JO) or program staff who had been instructed on eligibility requirements. Eligible participants were at least 18 years of age, and currently using fentanyl, heroin, or methamphetamine. Clients were excluded from eligibility if they were intoxicated or otherwise unable to provide informed consent. Given that current drug use was an eligibility requirement, we assessed “intoxicated” as an inability to respond to simple questions, providing responses that are incoherent or unintelligible, or if the participant indicates that they are too high to continue. Potential participants who were eligible and interested were then formally verbally consented and interviewed on-site. Client interviews explored participants’ history of drug use and experiences with harm reduction services, as well as their awareness of, attitudes about, and experiences with various drug checking modalities. Interviews lasted approximately 30–60 min and were recorded, then submitted to the same external third-party transcription service being used for provider interviews. Participants were provided a $25 cash incentive as a token of appreciation for their time and expertise, and were provided unique ID numbers to anonymize their data. This study protocol, distinct from the protocol covering provider interviews, was reviewed and approved as well by the UCSF IRB (#22-36640).

Client interview transcripts were uploaded to Dedoose, a qualitative analytic program [ 53 ]. Four analysts (EA, LM, SO, and JO), two of whom were involved in data collection (LM & JO), read transcribed interviews from both client and provider data sets and drafted summaries which were then systematically reviewed as a team. Following the tenets of thematic analysis and adopting the framework developed by Miles and Huberman (1994) [ 54 ], the team collaboratively identified cross-cutting themes from interview summaries, covering areas of concordance, discordance, and particular importance, as well as exemplar and negative cases. Once major themes and sub-themes were identified and articulated, authors drafted analytic memos which consolidated and explored in detail each major theme.

Following publication of an article focused on findings from the provider data set [ 55 ], further analysis of the client data set included the development of a formal coding scheme (SO), based on a priori codes extracted from the interview guide, as well as codes reflecting themes and sub-themes identified in the summarizing process and further refined via ongoing weekly analytic meetings. Coding was led by the primary qualitative analyst [SO] with secondary coding by client interviewer and author [JO]. The application of codes was discussed regularly among all team members, focusing on discrepancies between primary and secondary coders, insights developed, and the potential emergent themes. Discrepancies occurred approximately 10% of the time, and these were resolved through group consensus in accordance with established qualitative research methods [ 56 ].

Through key informant interviews, we captured diverse perspectives on how existing and emerging drug checking services are being used, and their potential for future impact within the harm reduction suite of services.

We present our findings within three key themes: (1) the role of drug checking in overdose prevention; (2) benefits to the overall agency, health, and wellbeing of people who use drugs; and (3) impacts of drug checking services at the community and systems levels.

The role of drug checking in overdose prevention

Service providers and clients expressed varying opinions on the extent to which information from drug checking services would prevent overdose and, indeed, whether overdose prevention is the appropriate metric by which drug checking’s impact should be measured. Clients reported diverse experiences and perspectives on how they use (or don’t use) drug checking, and expectations for their own future use.

Fentanyl test strips

Almost all client participants reported having had some experience with fentanyl testing strips (FTS), either using them personally or seeing others use them. Attitudes about FTS varied. Some expressed concern that they are difficult to use correctly or that they have heard they may be unreliable (prone to false positives or negatives):

We were using them constantly when they were telling us that all the drugs had fentanyl in them. But then we found out that if you don’t put enough water on speed, that it can come up positive because of some chemical. [Client, 40, female].

Others reported relying on them heavily and using them often:

I’ve just got to have that insurance that there’s no fentanyl in [my drugs]. … I have a drawer. Like that? That’s all full of test strips. Usually every time I come to a needle exchange, if they have them, I grab as many as I can and just put them in the drawer. [Client, 43, male].

Spectrometry

Although many had not heard of spectrometry, spectroscopy, or anything beyond FTS, once it was described what a range of drug checking services could look like, clients were interested and excited about the possibilities. Some expressed interest in using mobile or site-based spectroscopy, but were concerned about their safety, one expressing worry about “ judgment from the community ” or bystanders taking videos and calling the police, another wondering if they would be an “ easy target ” for law enforcement harassment. Those who reported having used FTIR as part of their harm reduction visits, however, had positive things to say:

Interviewer: And how do you feel about that testing service at the van? Participant: I think it’s remarkably great. Interviewer: yeah? Participant: Yeah. They answered my questions, exactly what I wanted to know. [Client, 66, male]

Some participants described high percentages of testing experiences coming back with a positive or unexpected result, like a client who said that he’d used the FTIR mobile service four times with meth from four different suppliers, and “ only one came back pure .”

Using drug checking results

What participants reported doing with the results of checking their drugs varied as well. Some participants spoke about specific situations where drug checking prompted them to avoid buying contaminated drugs.

Actually I just used [drug checking] yesterday. Luckily, I didn’t buy the heroin I was going to, because it tested for fentanyl . [Client, 32, male]

Other community members expressed disinterest in checking drugs, often citing a lack of realistic options for using test results in a way that made sense for them. One participant stated directly that they didn’t want to test because they didn’t want to have to not use drugs if they got a result they didn’t like:

What if it comes up with fentanyl in it? Then I bought it but I can’t do it? They’re not going to take it back, the people I bought it from. I mean even if I get them to write me a receipt, you know? [Client, 49, male]

Another client said that she was interested in drug checking generally, but wouldn’t bother if she only had a little bit and was relying on it to keep her from getting sick:

If I was trying to [check my drugs], I would do it when I had enough to do that, you know. Because if I was dope sick and I only had two hits of fentanyl, I probably would not [test]. [Client, 24, female]

Data from service provider interviews echoed these dynamics. We heard from provider participants that, broadly, drug checking services prevent overdose directly some of the time, but not all the time, by way of individual behavior change on a case-by-case basis. One provider—a clinician with a lengthy career in addiction medicine and harm reduction—echoed doubts about how common it would be for a patient to make use choices based on drug checking results, broadening the focus to personal harm reduction behavior change rather than abstinence behavior alone:

And then the question is, what do you do about it? I’ve had a patient who is, like, yeah, I tested it. It was positive for fentanyl. I go, well, what did you do? Well, we just used anyway because it’s all we had. And we had, like, the Narcan out, and I – I just felt really sleepy afterwards. … So I guess that’s the other question – if you do drug testing and it isn’t what you expect, like, you can’t take it back to the dealer and say, hey, this isn’t – I want a refund; right? So what do you do with that information? And if, you know, if you’re in withdrawal and you really need to use that drug, like, what kind of safeguards are you going to take if you decide, yeah, I’m going to go ahead and use this; right? [Clinician, U.S.]

Other service providers similarly drew a distinction between drug checking sparking behavior change that prevents overdose versus behavior change that reduces the risk of death from overdose, situating drug checking services as a set of tools that dovetail with existing personal harm reduction strategies.

The reality is, you know, people still are using their drugs. Now, a large proportion of people who use our service say that they’ll do something differently after, you know, accessing our service, so they maybe will do a test dose first, or start, like, start with a smaller dose, or use with a friend, or use at an SCS [supervised consumption site]. [Direct service provider, Canada].

Overdose prevention versus overdose rates

Interestingly, many service providers when asked for their perspective on the role of drug checking services in overdose prevention expressed concern about a gulf between the overdose prevention they observe at the service level versus what they see represented in population-level data.

Will drug checking save a life? Absolutely. Yes, for sure. Will it, at a population level, drop overdose rates? I don’t know the answer to that. [Researcher, U.S.]

Participants offered multiple explanations for this. One described challenges inherent in proving prevention, while another explained how population overdose rates can obscure the impact of drug checking programs when they operate within a rapidly-changing drug supply:

It will be very hard to prove within these prevention paradoxes. I think prevention is one of those things that is so important, but within our scientific frameworks … preventable events are so rare and on the grand scheme of things, they’re really hard to prove. … But will [DCS] save lives? Yeah. [Clinician, U.S.] The numbers aren’t showing [an overall decrease in overdose], right, because at the same time, even though we’re offering this service, the supply is just getting worse and worse, so overdose rates are rising. [Direct service provider, Canada].

Not every participant who commented on this gulf found it to be wide or troubling, but instead remarked on it as a neutral distance between two related but distinct constructs, one of which is a measure of what outcomes drug checking information could yield, and the other of which is a fundamental right to that information.

It’s really a great question if we’re going to see things pan out in the numbers. I certainly hope so and I certainly think so, but I think that we just have the right to know what we’re putting into our bodies, regardless of what outcome measures are. We deserve to know what’s in our drugs . [Direct service provider, U.S.]

Similarly, a direct service provider offered a structural perspective on overdose prevention, decoupling the value of drug checking services from overdose outcomes, prioritizing instead the intrinsic value of equipping people with critical information about what they are putting in their body and the importance of empowering people to make decisions with as much information as possible.

I don’t really know if [drug checking] is going to decrease the rate of overdose. In my mind, the problems that contribute to overdose are prohibition, law enforcement harassment, and everything that surrounds that that creates a shitty drug supply and then prevents people from investigating it. But what [drug checking] does do, again, is this piece around like, people should know that they can find out there’s more in their drug. … I think that it just enables people to make better educated decisions around their substance use and to understand their bodies better . [Direct service provider, U.S.]

Benefits to the overall agency, health, and wellbeing of people who use drugs

Drug checking services offer users the tools to independently identify risks in the drug supply and make decisions about what to do with that information in the short and long term. Many of the service providers interviewed for this study, when asked how drug checking would impact overdose rates, gave some version of a reframed response, repositioning the focus from the drug use decisions themselves to the importance of information in fortifying the overall agency, health, and wellbeing of people who use drugs.

The provider quoted in the above section went on to reflect on the intrinsic value of giving people information, arguing that it contributes to essential experiences of bodily autonomy and health equity:

What’s really important to me as well is just sort of building this momentum around people feeling entitled to bodily autonomy and seeing that [drug checking] is a part of [that], and having folks know that, yeah, they fucking deserve to have this information. They are entitled to know what is in their stuff. And so, that’s not the only piece to health equity and justice around substances and substance use, but I think that it’s a significant piece. [Direct service provider, U.S.]

Knowledge of what is in their drugs can also confirm users’ internal experience. One provider, who had piloted an early drug checking intervention in a major metropolitan area in the U.S., believed that drug checking for people who use drugs offers confirmation of the embodied experience of their substance use, which in this provider’s experience was often regarded with skepticism by health workers:

I think that people are able to connect experiences that they’re feeling in their body with real information. And I think that actually validates the really organic knowledge and experiential knowledge of drug users as the true experts about drugs. You know, when we were doing our project in [city] and fentanyl was not everywhere [yet]—almost 100% of the time, if someone brought us a sample and said, “I think this has fentanyl in it,” it was true. … It validates experience where people’s experiential knowledge is not really validated by an educational system. It’s always this kind of thing where public health people are telling drug users what’s true. And drug checking sort of validates that drug users actually know what’s true, and we’re just using science to confirm it.” [Direct service provider, U.S.]

Client interviews echoed this theme. Several clients recounted experiences that illustrated how navigating the drug market is becoming increasingly difficult, and that drug checking provides an important tool that they can pair with their own instincts and expertise as they try to keep themselves safe.

I can look at it and I can be like, “Wait a minute, we might want to test that.” Because speed and fentanyl are different. They actually look different than the other one, so when I start seeing traces of fentanyl being in the speed, I go, “We need to check that before we do any of it.” And, hey, sometimes I’m wrong. [Client, 43, male] The [meth] that was in the medicine bottle [tested positive for fentanyl], yeah. But I kind of knew it was going to because I packed a bowl right before and if it’s dirty … yeah, the color starts changing wrong right away. [Client, 43, male] I like that [drug checking] gives us some certainty of what’s in the drug … like with the heroin, there was stuff in that that just did not feel good. I’d love to know what they were cutting that stuff with. We used to joke it was shoe polish because it was so dark and dirty, but it’s really important what you put in your body . [Client, 48, female]

Our client data further provide evidence that people who use drugs are making health-related decisions for themselves and care about their own health and wellbeing. Woven throughout community member interviews were examples of health-seeking decision-making in users’ everyday lives, demonstrating agency in considering health behaviors and expressing both implicitly and explicitly a desire to care for themselves. Examples of these pro-health micro-decisions include choosing not to smoke out of foil (it’s “ not healthy to smoke out of ” and “ it’s going to give us Alzheimer’s or something ”) or reducing smoking marijuana due to a “ sensitive ” respiratory system. One informant laid out explicitly their hopes for their future, shaped too by an acute awareness of the risks of the current drug market:

I don’t want to be a statistic out here. I want to go back to regular life and experience all the rest of the highs that there still are out there before I die. I want to jump out of an airplane, or take a balloon ride, or ride more rollercoasters. … I don’t want to limit myself to one freaking high. … it’s not worth it anymore at all. … You’d never OD on meth before. Meth and weed were two things you just didn’t overdose on. If you did too much, you passed out and you slept it off and that was it. Now, no matter what drugs you’re doing, every time you use, it’s a 50–50 chance that you could die. [Client, 49, female]

These excerpts from client interviews highlight the demand among potential DCS users for strategies that contribute to their agency, health, and wellbeing, even within the context of continued drug use in the short- or long-term.

Impacts of drug checking services at community and systems levels

In addition to use at the individual level, participants talked extensively about the ways that they experience and imagine DCS having an impact at community and systems levels. They described the ways that drug checking could facilitate upstream regulation of the drug market, how the information and transparency made possible by checking drugs can fill a policy and regulatory vacuum, and how drug checking can empower public health surveillance systems and clinical response.

Community level regulation of the drug market

Multiple informants, both service providers and clients, reflected on the use—or potential use—of drug checking as a grassroots tool to regulate the drug market.

Participants talked about using, or thinking one could use, DCS as a vetting tool for sellers or suppliers.

And if people could get their shit tested, almost every time if not every time, not only would it help them to be safer by them regulating themselves and knowing what’s in their stuff … But I feel like if they knew exactly what was in it, they could go tell their guys that they got it from, “Look, man, I’m not buying that shit anymore if it’s like that. If that shit -- if this or that’s in it or whatever. Or if you don’t, whatever, I’m not buying it from you. I’m buying it from someone else.” And that might even make them be… It’ll hold them more accountable. [Client, 32, male]

This use was so important to one participant that they expressed interest in their samples being sent for more extensive in-lab spectrometry testing that could give them greater detail about the compounds and amounts in their sample:

Hey, [a full spectrometry report] may take a week, but at least in that week, I find out if I should go back to that person or not. [Client, 43, male]

Client participants frequently referred to DCS as a tool to “keep [suppliers] honest”; that is, as informal regulatory pressure on currently unregulated illegal drug markets. Some reported that they spread the word if drugs from a supplier come up contaminated or low-grade. One participant, who uses fentanyl, reported using FTS to ensure that what they are about to buy is, indeed, fentanyl:

I keep them [FTS] around. … Then I say, “Can I test it?” and I test it in front of them. And like some of it’s turned up negative. And so I totally outed them out on the block with it. It pisses them off – it kind of keeps them honest. … When you got a bunch of test strips, I can go down the line and keep, yeah, at least trying to keep them honest, you know. I got a pile of those things right now. That’s actually what I use them for. [Client, 40, male]

Of particular value, according to our participants, was the idea that spectrometry would provide formal documentation of drugs’ contents. Analytical evidence that something was either dangerously contaminated or not what the seller claimed it to be can shift the balance of power in the transactional dynamic, placing upstream pressure on suppliers to better monitor what they are contributing to the market.

If you could get results that are on paper or on a text or on a whatever, then you could bring it to them that, “Look, dude. I’m not fucking around. You need to make this shit right or I’m not buying it anymore.” That would be a game-changer . [Client, 32, male]

From the service provider standpoint, one participant, a drug checking technician and program manager with a longstanding history in their city’s drug scene, identified similar opportunities for DCS to impact the drug market, were it made easily accessible to those at multiple points in the drug supply chain in addition to consumers.

It’s not just people who are consuming the drugs that can use the service. It’s also people who are selling them. And so, oftentimes people who are not essentially the first or second hands that are creating the substance and then moving it down the chain towards the end consumer, they don’t know what is in their product. For folks who are selling drugs, if they’re able to come and get an ingredient list, they can then kind of know what to say to folks who are buying. [Direct service provider, U.S.]

This was not discussed as just a hypothetical. One informant who sells drugs validated this use as feasible and valuable:

I want to make sure what I’m buying is what it is. … I do sell it myself, so [spectrometry]’s a good service because that’s what I want to know is the chemical balance as to how much it is and how much it isn’t and whether it’s good every time. [Client, 66, male]

Filling a policy and regulatory vacuum

In the absence of a government or regulatory body that will monitor and report on the verified contents of illicit drugs, our data suggest that drug checking services, and spectrometry in particular, may be filling a policy and regulatory vacuum.

Clients likened the idea of having access to a list of drugs present in a sample to knowing ingredients of something that they would eat.

I mean we know what’s in our food, right? The packaging is all labeled and the ingredients are listed. It’s just too important, especially with drugs. Especially because we don’t know who’s making them. We don’t know exactly where they’re coming from. And every single one is different. Every week is different. Even if you buy it from the same person all the time, they’re always having something different. Maybe you’ll have the same thing twice or three times but that’s it. [Client, 48, female]

Providers, meanwhile, explicitly framed the value of drug checking within the context of an unmet regulatory need. One service provider qualified many of their statements about drug checking services with “until prohibition goes away,” situating DCS as being necessary only in a regulatory vacuum. Another spoke more directly to the relationship between drug checking and regulation:

And with drugs, because of prohibition, we just have this unknown, unregulated supply, and people are – what they’re putting in their bodies and what they’re purchasing is obscured, right? And so, drug checking is like a series of sort of imperfect tools to help consumers of drugs regain a little bit of control in the form of information around what it is that they are using. …. And there’s a very good argument that, if we had some kind of safe, regulated supply, we wouldn’t need drug checking at all, which is true . [Direct service provider, U.S.]

Empowering public health surveillance systems and clinical response

Data from our interviews suggest that drug checking technologies and programming may also contribute meaningfully at a structural level, to public health surveillance systems and clinical response. Aggregated sample results provide real-time data about what drug compositions are trending across regions, and what the clinical implications may be for providers treating clients who use drugs [ 57 ]. One drug checking program team posted results to their website in the hopes of informing local clinicians and public health policy makers about what was circulating in the drug supply. This program manager talked about making results available “at the societal level”:

And then at the kind of societal level what we do … [is] every other week we take all of the results from the samples that we’ve checked, and we combine them, and then we put out a report and update our website about, like, what’s circulating in the drug supply. So we talk about, you know, trends in the drug supply over that period, and new drugs that have been introduced, and what those drugs could mean, that type of thing. So service doesn’t only benefit individuals, but it also benefits the larger community by being able to say, okay, this is what we’re seeing. If you can’t access the service, you still at least know, you know, what is circulating. [Direct service provider, Canada]

Community members expressed an awareness of this function. One participant cited drug checking’s role in a larger tracking network as one of the things they value most about the service:

I liked a lot about [drug checking]. One, that it was available in the first place. Two, that it was not just doing its own thing. It was part of a larger network that was keeping track of what drugs were popping up on the streets and what their makeup was. I really like that that’s happening. [Client, 30, male]

At the point-of-service level, provider informants discussed significant benefits that drug checking could provide to clinicians and other medical professionals who work closely with people who use drugs. This informant posited specifically that having more detailed knowledge about what was circulating in the drug supply could help clinicians better formulate strategies for managing opioid use disorder and transitioning patients onto MOUD:

Understanding what’s actually in the supply… allows clinicians to tailor the care that they are providing to people who use drugs. So, you know, if they know that the average amount of fentanyl in a fentanyl sample is this and they want to transition someone off the unregulated drug supply onto, like, a pharmaceutical alternative, well, what pharmaceutical alternative is actually suitable based on what they’ve been using? [Direct service provider, Canada]

This is especially critical given the significant difficulties that have been recently reported when transitioning people using fentanyl to appropriate longitudinal services [ 58 ]. A provider we interviewed who runs a mail-based drug checking service in the U.S. reported that developing a more thorough knowledge of the drug supply outside of the current surveillance panoply may provide important clinical toxicology assistance to help physicians connect health outcomes to specific substances or components of the drug supply, and more quickly provide tailored treatment:

There’s one other really big one for me, which is that it allows us to link specific physiological harms with specific chemicals. So, we’re not just talking about dope anymore. We’re talking about this component of dope causing this specific reaction. What we have been able to do is, we’ll get calls from our central hospital on campus, and they’ll say, “We have this patient with an idiosyncratic presentation. Boom, boom, boom, boom, boom, boom. Here it is. We think it might be… You know, they’ve been injecting this, this, and this. We have some of their samples. Can we get them tested?” Or if they don’t have the samples, they’re like, “This is what the symptoms are. This is where they’re from. What are you seeing about the drug supply in their area?” And I can be like, “Well, yeah, there’s been a spike in levamisole in that area or xylazine,” you know, whatever it is. And then they can get to treatment quicker because the physicians have a more specific knowledge about the ideology of the harm that they’re observing in clinic. [Researcher, U.S.]

Negative cases

While the vast majority of participant responses reflected positive experiences with or attitudes about DCS, some participants additionally expressed ambivalence or concern. Many of these perspectives are embedded within the themes reported above, but deserve reiteration: service users expressed concerns about the accuracy of drug checking technologies, their privacy and safety relative to community stigma and law enforcement, and anxiety about having to make hard choices about drug use in the face of an unexpected result. Service providers expressed concern about the “then what” of drug checking, citing constrained choices and limits to what could be realistically expected in terms of behavior change without other supports in place. Some further lamented the challenges of translating the benefits of what they were seeing in practice to what is visible to a broader audience.

Not included in the above findings, but important to note, are two additional concerns that arose in interviews. First, service users and providers cautioned that the street drug supply changes so quickly that new compounds may be showing up on the street before they are identified in spectrometry libraries, potentially limiting their ability to accurately identify contaminants. Finally, one provider, a clinician with a longstanding career in addiction medicine and harm reduction, closed their interview with a somber caution against decontextualizing drug checking from a broader commitment to multi-method harm reduction, health equity, and social justice.

[I worry that] we’re just throwing yet another technology at a much bigger problem. My fear is that people will say, oh, now we have drug checking, so now we can stop trying to dismantle, you know, structures of racism and oppression in society, right? We can stop looking for homes for people because we have this technology that’s going to prevent people from dying. … It doesn’t work that way. [Clinician, U.S.]

While the magnitude of the opioid crisis is often communicated in terms of overdose and death rates, the harms associated with opioid use—intentional or unintentional—in an unregulated drug market extend far beyond those data points alone, and so too must the strategies leveed to combat them. Our findings demonstrate that drug checking services offer diverse benefits at the individual, community, public health, and health systems levels.

Overdose prevention and beyond

If the question is, do and will these technologies contribute to overdose prevention , our findings suggest that the answer is yes, with some important caveats. The first being that, according to our participants, they do not prevent overdose all the time. Our findings reflect that individuals make complex and highly contextualized decisions regarding their use behavior each time they use drugs. Information about the chemical composition of a drug sample sometimes leads to decisions to abstain, but more often leads to decisions to engage in other types of harm reduction behaviors—like using with a friend rather than alone, making sure to have naloxone on hand, using at a supervised consumption site, alerting others to a bad batch, using a tester first, or avoiding a certain supplier in the future. Sometimes it leads to no observable behavior change at all.

Further, DCS have not been scaled up to meet the needs of everyone at risk for overdose; until it is, it is premature to discuss population-level prevention. This study does not purport DCS to be in and of themselves sufficient to prevent overdose, but they are clearly part of a continuum of services that can prevent overdose mortality.

Many participants took care to note as well that the needs of people who use drugs are not solely to avoid overdose; people navigating drug use are whole people, and the stigmatization and criminalization of drug use regulates their access to a multitude of essential needs and liberties, like health care, housing, employment, agency, and a host of social and legal protections. Access to information that contributes to agency and autonomy, and enables more informed decision-making, is an essential service regardless of other outcomes.

Of course, among harm reductionists and researchers acquainted with the diverse and dynamic ways that harm reduction functions within communities, this is not news. Our findings reflect and reinforce much of the existing evidence from studies aiming to understand the role of drug checking within the larger constellation of harm reduction and, indeed, the role of harm reduction itself.

One recent qualitative study in particular reported themes with striking similarities to the prevailing themes from our interviews. Wallace et al. [ 59 ] explored the potential impacts of community drug checking on prospective service users, finding drug checking to “increase quality control in an unregulated market,” “improve the health and wellbeing of people who use substances,” and “mediate policies around substance use.”

Our findings further add to existing evidence that links drug checking with consumer empowerment within an opaque drug market [ 25 , 26 , 29 ] and underlines the reciprocal relationship between individual agency and the adoption of harm reduction strategies [ 46 , 60 , 61 ].

Of note is the shifting context in which many existing drug checking studies, including ours, are situated. In some areas, fentanyl appears most often as an unwanted adulterant in another drug—be it a non-opioid or a less potent opioid like heroin—and DCS are used primarily for fentanyl avoidance [ 13 , 19 ]. Increasingly, however, pockets of consumers are preferring fentanyl, as seen in our San Francisco client sample and within populations reflected in recent drug checking studies. Our data echo the broader finding that drug checking technologies are likely to be used differently by fentanyl-seeking opioid users versus fentanyl-avoiding opioid users, and differently still among those using stimulants, psychedelics, or other non-opioid drugs [ 22 , 62 ].

On the subject of behavior change—whether and how drug checking can be understood to prompt changes in drug use behavior—our findings align with existing evidence showing that drug checking is at times followed by contaminated drug disposal, and at times followed by the employment of personal harm reduction techniques such as spreading information within the community [ 30 , 63 ], and reduction in polysubstance use or dosage [ 13 , 14 , 15 , 64 ]. Lacking as we do a robust methodological-empirical foundation to assess this type of causality, whether and to what extent drug checking in various contexts leads to less use or more safe use among different populations cannot be stated concretely [ 16 , 65 , 66 ]. Whether individuals change their use behavior based on drug checking results is highly informed by such matters as how limited their access to drugs is, realistic options for modified use, and their perceived relative risks of knowingly ingesting a potentially dangerous compound or compounds versus not.

The tension at the center of harm reduction policy

The role of harm reduction services within communities have long reflected a central tension: in contrast with abstinence and criminalization models, harm reduction is often socially and politically criticized as enabling drug use and making neighborhoods less safe [ 67 , 68 , 69 ], while research consistently finds harm reduction to yield positive outcomes for both service users and surrounding communities [ 70 , 71 ]. In addition to improving the health and wellbeing of people using drugs, evidence suggests that those accessing harm reduction services are more likely to ultimately seek treatment and pursue recovery [ 49 , 70 , 72 , 73 ]. Concerns about public safety, too, while in many cases expressed in good faith, have been shown to be largely misplaced: multiple studies show harm reduction programs to have no significant impact on nearby violent or property-related crime, with some findings suggesting improved indicators of public order and safety [ 48 , 49 , 74 , 75 ]. Harm reduction strategies have additionally been found to be cost-effective in the short term and cost-saving to public monies in the medium- and long-term [ 76 ]. Nonetheless, public perception of harm reduction has historically been interwoven with deeply entrenched cultural stigmas related to race and ethnicity, socioeconomics, and an imprecise moralism that positions access to health and protection as a privilege that should be earned or denied based on behavior [ 67 , 69 , 71 ].

This tension plays out most concretely in the public policy space. Even as the opioid crisis dominates public health discourse and funding is earmarked for research and programming to combat it [ 77 ], harm reduction programs on the ground are under siege. At the federal level, the House Appropriations bill for the Fiscal Year 2024 HHS budget dramatically cuts funding to HIV/AIDS programs—a budget umbrella under which many harm reduction, substance use support and treatment programs are funded [ 78 , 79 ]. In California, a $15.2 million state grant supporting syringe access services has dried up amidst an overdose crisis at its peak, with no plans for replacement [ 80 ]. In 2022, a landmark bill (SB58) that would have authorized overdose prevention programs with supervised consumption in Los Angeles, Oakland, and San Francisco was vetoed by the Governor, despite broad support and robust evidence behind it [ 81 ]. Funds for such safe consumption sites have further been excluded from receiving opioid settlement funds in San Francisco [ 82 ], and in September of 2023, a bill was put forth by the San Francisco Mayor’s office to require drug screening and mandatory treatment for anyone receiving public services [ 83 ]. This, despite the expressly articulated commitment to and acknowledged necessity of harm reduction services—services explicitly aimed at helping people who use drugs to be more safe rather than abstaining from use—highlighted in policy language across multiple levels of government and legislature [ 10 , 84 , 85 , 86 , 87 ].

It is worth noting that one of the harm reduction sites where several of this study’s client participants were receiving services was defunded shortly after we completed data collection, and since then, overdose death rates in the city have climbed [ 88 ] and public order in that area has reportedly deteriorated [ 89 ].

The framing of effectiveness is crucial in this policy environment

In light of these tensions, we offer the findings of this study as a contribution to an evidence base that may play an increasingly central role in California’s—and the nation’s—opioid crisis response. The allowable expenditures for opioid settlement funds list “evidence-informed programs to reduce the harms associated with intravenous drug use” as a focus area [ 51 ] and California’s Overdose Prevention Initiative describes its approach as being “data-driven.” [ 10 ] The proposed HHS FY2024 budget, in addition to cutting much of the funding that covers harm reduction programming, proposes the rejection of “controversial programs” while maintaining funding for “an effective opioid response.” [ 78 ] As California faces a $68 billion budget deficit [ 90 ] and supplementary federal and settlement funds are to be apportioned based on strategy effectiveness and the body of scientific evidence, the role of research comes into sharper focus. It is the strength or weakness of the evidence base—of the complexity of the research inquiry and integrity of the data—that may ultimately frame which initiatives are eligible for support.

When asked about the place and promise of drug checking within the broader constellation of harm reduction services, it was drug users’ humanity and right to health, more so than the public health implications, that grounded many of our participants’ responses. Their responses implicated, too, the underlying operating principle that, ultimately, people make choices that make sense for them. Whether by the hand of addiction or desire, constrained options or access, or every individual’s complex hierarchy of relative dangers and needs, people’s choices are reflections of their full humanity. Approaches to stemming the tide of this crisis cannot be effective unless they are built on respect for the individuals living it, and focused on understanding their needs.

We encourage continued research and reporting on drug checking services and emerging technologies, with an emphasis on exploring effectiveness within a broad scope, reflective of the impacts of these services on whole lives and systems.

Limitations

Many of the community members we interviewed had not heard of spectrometry or spectroscopy, and the interview represented the first time they were introduced to the technology as a concept and the first time they considered whether and how they could see themselves using it in their own lives. This limits the range of our findings among the client sample, given that much of our qualitative data speaks to hypothetical future use rather than past or current use of emerging technologies. The absence of data on client use should not be interpreted to mean that participants chose not to use DCS.

Additionally, the sampling frame for clients was limited to one setting, while providers were sampled from across North America, and the small sample size for both groups may have limited saturation. Finally, providers did not reflect all North American regions where drug checking has been implemented, nor all DCS models, limiting the generalizability of findings.

Our manuscript contributes to growing evidence of the effectiveness of drug checking services in mitigating a range of risks associated with substance use, including overdose, and offer diverse benefits at the individual, community, public health, and health systems levels. For that reason, policymakers should consider allocating resources towards its implementation and scale-up in settings impacted by overdose mortality.

Data availability

Due to ethical restrictions, the data generated and analyzed during the current study are not available to those outside the study team. Data and materials are of a sensitive nature, and participants did not consent to transcripts of their interviews being publicly available. Portions of interviews about which editors have questions or concerns may be provided upon request after any details that may risk the confidentiality of the participants beyond de-identification have been removed. Researchers who meet the criteria for access to confidential data may send requests for the interview transcripts to the Human Research Protection Program (HRPP)/IRB at the University of California, San Francisco at 415-476-1814 or [email protected].

Abbreviations

Fourier–Transform Infrared Spectroscopy

Fentanyl testing strips

US Department of Health and Human Services

Medications for opioid use disorder

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Acknowledgements

This study would not have been possible without the client participants who so generously shared insights about their lives and how they access harm reduction services, and our provider key informants and their work on behalf of people who use drugs. The authors would also like to thank the staff of the Northern California HIV/AIDS Policy Research Center who supported the project during its inception, data collection, and writing.

This research was funded by the California HIV/AIDS Research Program (CHRP) to the Northern California HIV/AIDS Policy Research Center (PI Arnold), H21PC3238. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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Lissa Moran, Jeff Ondocsin, Simon Outram & Emily A. Arnold

Family & Community Medicine, Department of Medicine, University of California, San Francisco, CA, 94143, USA

Jeff Ondocsin, Daniel Ciccarone & Nicole Holm

Centre on Drug Policy Evaluation, St. Michael’s Hospital, Toronto, ON, M5B 1W8, Canada

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Contributions

E.A.A. and D.C. conceptualized and designed the study; J.O., L.M., D.C., and N.H. were responsible for data collection, each conducting in-depth key informant interviews. L.M., J.O., S.O., and E.A.A. analyzed the data. L.M. led the writing of the original manuscript draft with significant contributions from J.O., S.O., and E.A.A. L.M., J.O., D.C., S.O., D.W., N.H., and E.A.A. were directly involved in iterative review and revision. E.A.A. provided supervision, project administration, and funding acquisition. All authors have read and agreed to the submitted version of the manuscript.

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Correspondence to Lissa Moran .

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The study was conducted in accordance with the Declaration of Helsinki and informed consent was obtained from all subjects involved in the study. The study protocol and consent procedures were reviewed and approved by the UCSF IRB (#22-36640) on 12 September 2022.

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Not applicable.

Competing interests

D.W. is a founder of DoseCheck, a commercial entity that is developing a mobile drug checking technology. D.C. reports the following relevant financial relationships during the past 12 months: (1) he is a scientific advisor to Celero Systems; and (2) he has been retained as an expert witness in ongoing prescription opioid litigation by Motley Rice, LLP. The remaining authors have no relevant financial or non-financial interests to disclose. The remaining authors have no relevant financial or non-financial interests to disclose.

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Moran, L., Ondocsin, J., Outram, S. et al. How do we understand the value of drug checking as a component of harm reduction services? A qualitative exploration of client and provider perspectives. Harm Reduct J 21 , 92 (2024). https://doi.org/10.1186/s12954-024-01014-w

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108 Drug Abuse Essay Topic Ideas & Examples

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Youth is a major demographic that is affected by addiction issues due to drug consumption. Young people are impressionable and prone to search for new sensations. Drugs can offer a sense of novelty and provide an experience they have not had before, leading to considerable appeal.

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• Drug Abuse in High School and College With respect to social work and the problem of substance abuse, research has been carried out in terms of investigating the relationship between drug abuse and poverty, the effects of drug abuse on the society.
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• Community Intervention Practices Against Drug Abuse The key features that result in successful community-based intervention on drug abuse are integrated for effectiveness and efficiency. On the other hand, drug abuse refers to the consumption of substances that elicit particular feelings and […]
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• Drug Abuse and Its Psychological Effects The purpose of this paper is to explore in more depth the psychological effects of addiction on the family and inner circle of the addict.
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• Policies for Pregnant Women With Drug Abuse Thus, out of all the offered policies, financial support for therapy is the best one, as it motivates prevention and treatment, which, in turn, causes the improvement of this situation.
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• Youth Drug Abuse Among, Education, and Policies Although drug abuse encompasses improper use of drugs disregarding the prescriptions of medical practitioners, the principal challenges of drug abuse occasion from abuse of drugs such as cocaine, heroin, and marijuana.
• Prescription Drug Abuse in the United States The combination of Ibuprofen and acetaminophen are effective for the patients, who want to reduce and control the level of pain.
• Drug Use Among Parolees and Probationers: A Comprehensive Plan To reduce drug use in probationers and the probability of a new crime, the approach to drug testing needs to be changed.
• Drug Abuse and Medicaid Program The emergence of alcohol and drug abuse as a problem and the intensification of people with mental health problems, have exposed the society to the likelihood of involvement of the population in substance abuse.
• Drug Abuse: Age, Gender and Addictive Susceptibility This incorporates the aspects of gender where males and females possess varying biological constitutions that might affect the prescribed treatments in the realms of addiction. It is important to consider the rapidity and susceptibility of […]
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• Drug Abuse Prevention Programs Additionally, it is possible to prospect the success of the program in case the required readiness from the community can be unveiled prior to the program execution.
• The Cultural Context and Ethics of Prevention of Drug Abuse The first prevention strategy outlined in the document is the involvement of young people in all levels of the prevention program establishment. Concurrently, it is crucial to relate this technique with the subject of culture […]
• Use of Psychotropic Medications in the Treatment of Drug Abuse This is because the mental illness is, literally, the one that sustains the abuse of drugs and thus after it is healed; the patient will have no reason to continue abusing the drugs.
• Drug Abuse: Awareness Amongst the Youths This project is going to carry out a public awareness campaign with the aim of educating the young people on the hazards related to the vice of drug and substance abuse. The awareness campaign is […]
• Spirituality Effect on Drug Abuse Treatment Programs The hypothesis of the study was that spirituality is appropriate in the formal treatment of addiction; the study confirmed this hypothesis.
• Drug Abuse and Religious Spirituality Concept Particularly, this high rate of relapses was determined by Olmstead et al.as a direct result of a degree of failure on the part of drug abuse treatment programs to sufficiently address the primary reason why […]
• Drug Abuse and Harmful Health Effects The principle recognizes the importance of helping drug addicts out of the activity but also sees the importance of protecting their rights to health matters if the country is to realize economic development.
• The Extent of Drug Abuse Among People in America Toronto Mayor Rob Ford Said He Lied about Crack Cocaine Use Because He Was Embarrassed Mayor lied about the use of crack cocaine The article titled “Toronto Mayor Rob Ford said he lied about crack […]
• Drug Use and Abuse in America: Historical Analysis The new law was similar to the Boggs Act of 1951 in that it employed the same formula of using perceived increase in drug use in the country.
• Drug Abuse as an Ethical Issue On the side of duties and obligations, the societal norms stipulate that individuals should be caring to other members of the society especially the children and the old.
• Drug Abuse and Society Regardless of the many intervention measures that can be adopted to solve this problem of drug abuse, the most effective intervention measure is to create awareness to youths to enable them change their behaviors and […]
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• Adolescent’s Drug Abuse and Therapy Success When one accepts to put up with negative peer pressure, they end up giving up the personal trusts and values thus the pressure becomes a form of a negative force.”Does peer pressure affect the decision […]
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IvyPanda. (2024, February 26). 108 Drug Abuse Essay Topic Ideas & Examples. https://ivypanda.com/essays/topic/drug-abuse-essay-examples/

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INSTITUTE FOR POLICY RESEARCH

Unraveling the drug crisis: providing timely data to break the cycle.

IPR’s Lori Ann Post is leading a drug data research center to combat overdose deaths

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The problem is that we're too late. Data were just released for 2021; it's 2024. It's as helpful to me today to combat drug overdose deaths to study the year 2021 as it is 1850. It's just a whole different ballgame out there.”

Lori Ann Post Demographer, epidemiologist, and IPR associate

Throughout its history, the U.S. has battled waves of widespread drug addiction. From painkiller addictions on Civil War battlefields to the 1980s era of crack cocaine, each crisis gives way to a new one.

Today, however, with new drugs constantly emerging, it's becoming harder to keep up with creating drug screenings and medicine to reverse overdoses. This lag leads to more overdose deaths, according to demographer, epidemiologist, and IPR associate Lori Ann Post.

Post emphasizes that we are not in a drug epidemic: We’re in a continuous, evolving drug crisis. Pandemics and epidemics have a clear beginning, middle, and end, she says, but the shape-shifting nature of the drug crisis leaves no end in sight.

The Ohio River Valley Corridor Regional Drug Data Research Center (ORVC-C) , led by Post, aims to keep history from repeating itself. The center aims to support prevention, harm reduction, treatment, public safety, and recovery services, and to create a drug data-sharing model for others. Currently, overdose death data lags two or three years behind.

“The problem is that we're too late. Data were just released for 2021; it's 2024,” Post said. “It's as helpful to me today to combat drug overdose deaths to study the year 2021 as it is 1850. It's just a whole different ballgame out there.”

“By the time we get the evidence we have, it's already too late and the problem has evolved, and it's a new variant of concern and has new treatment and needs,” she explained.

Approximately 107,622 drug overdose deaths were reported in 2021, up nearly 15% from 93,655 deaths in 2020. Over 75% of those deaths involved opioids. The COVID-19 pandemic is commonly blamed for the surge in overdose deaths, but Post said the rates were "skyrocketing" before the pandemic.

Since 1999, almost 645,000 people have died from overdoses involving opioids. This rise in opioid overdose deaths can be explained in waves, according to Post:

• The first wave started in the 1990s due to an increase in opioid prescriptions.
• The second wave began in 2010, marked by a sharp increase in overdose deaths involving heroin.
• The third wave began in 2013, with significant increases in overdose deaths involving synthetic opioids, particularly illicitly manufactured fentanyl.
• The fourth wave began around 2019 and is largely still driven by fentanyl with the addition of stimulants such as cocaine and methamphetamines.

Post explains that the fourth wave is further evolving into drug cocktails that are adulterated with animal tranquilizers . This wave is more dangerous than its predecessors, as these drug combinations are more lethal and reversal agents are limited to fentanyl overdoses.

The ORVC-C launched in October with $3.55 million in funding from the Bureau of Justice Assistance. It operates in the Ohio River Valley Corridor, encompassing Delaware, Illinois, Indiana, Maryland, Michigan, Ohio, Pennsylvania, Virginia, Washington, D.C., and West Virginia. These regions bear a lopsided burden of escalating rates of drug overdoses, individuals with substance use disorder, and drug/narcotic violations, Post says.

The Bureau of Justice Assistance has doubled the funding to create a second regional center extending the initial center to New England, New York, and New Jersey.

Within the center, Post established a Central Data Repository (CDR) and a Dissemination and Engagement Center (DEC). The CDR collects, analyzes, and shares comprehensive drug-related data from existing information collected by local, state, and national agencies. This covers labor, crime, public health indicators, and demographic data. The DEC fosters partnerships and produces educational materials to address needs as they arise.

Post says that the center processes data to provide actionable insights for policymakers, public health practitioners, law enforcement, and other stakeholders, while also ensuring accessibility for fellow researchers.

Streamlining the data collection process reduces administrative burdens. It also allows researchers to delve directly into addressing critical issues without unnecessary hurdles.

“The more people doing research on it, the better we're going to do,” she said. “The timelier the data is, the more relevant it is to solving drug use and preventing drug overdose deaths. That’s the whole point.”

Lori Ann Post is the Buehler Professor for Aging, director of the Buehler Center for Health Policy and Economics, and an IPR associate.

Photo credit: iStock

Published: May 10, 2024.

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Treatment of Substance Use Disorders

• Millions of Americans have a substance use disorder (SUD), and it remains an important health issue in our country.
• In 2022, more than one in six Americans aged 12 or older reported experiencing a SUD.
• With effective treatment, recovery is possible for everyone. There is strength in getting help.

What is an SUD?

A substance use disorder (SUD) is a treatable, chronic disease characterized by a cluster of cognitive, behavioral, and physiological symptoms indicating that the individual continues using the substance despite significant substance-related problems. 1 In 2022, more than one in six Americans aged 12 or older reported experiencing a SUD. 2

SUDs can lead to significant problems in all aspects of a person's life. Patterns of symptoms resulting from substance use (drugs or alcohol) can help a doctor diagnose a person with a SUD or SUDs and connect them to appropriate treatment.

For certain drug types, some symptoms are less prominent, and in some cases, not all symptoms apply. For example, withdrawal symptoms are not specified for inhalant use.

SUDs can range in severity from mild to severe and can affect people of any race, gender, income level, or social class. A SUD can be applied to the following types of drugs: 1

• Hallucinogens
• Opioids (Prescription and Illegal)
• Sedatives, hypnotics, or anxiolytics
• Stimulants and Psychostimulants
• Tobacco (nicotine)
• Other (unknown) substance

Treatment and recovery options

Addiction is a disease, not a character flaw. People experiencing SUDs have trouble controlling their drug use even though they know drugs are harmful.

Overcoming an SUD is not as simple as resisting the temptation to take drugs. Recovery may involve medication to help with cravings and withdrawal as well as different forms of therapy. It may even require checking into a rehabilitation facility.

Addiction is a treatable disease

Like many other chronic conditions, treatment is available for substance use disorders. While no single treatment method is right for everyone, recovery is possible, and help is available for patients with SUDs.

Evidence-based guidelines can assist doctors with choosing the right treatment options. These guidelines help evaluate a patient's clinical needs and situation to match them with the right level of care, in the most appropriate available setting. For more information on evidence-based guidelines visit Addiction Medicine Primer .

Recovery options

There are safe and effective ways to recover from SUDs. Finding the right treatment option can be the key to a successful recovery journey.

Outpatient counseling

Helps people understand addiction, their triggers, and their reasons for using drugs. This form of treatment can be done at a doctor’s office or via telehealth appointment.

Inpatient rehabilitation

A full-time facility provides a supportive environment to help people recover without distractions or temptations.

Behavioral health care

Trained providers who help with mental health concerns.

Medications for opioid use disorder (MOUD)

Specific conditions like opioid use disorder may require medication as the first course of treatment. MOUD can help with cravings and withdrawal symptoms. 3 MOUD is effective in helping people reduce illegal opioid use, stay in treatment longer, and reduce the risk of opioid-involved overdose. 4

MOUD medications approved by the Food and Drug Administration (FDA):

• Buprenorphine

Research has demonstrated that MOUD is effective in helping people recover from their OUD. 5 6 7 It is important to find what works best each individual.

Resource‎

Reducing stigma is important, addiction can happen to anyone.

SUD is a treatable, chronic disease that can affect people of any race, gender, income level, or social class. No one driving factor leads to SUD. Some people may use drugs to help cope with stress and trauma or to help with mental health issues. Some may develop a SUD after taking opioids that are prescribed to them by doctors. In any case, using drugs over time may cause changes in a person's brain, leading to intense cravings and continued use. 8

Some may view acknowledging and receiving treatment for an SUD as a sign of personal failure and weakness. The associated shame felt by patients and families can make it difficult to seek treatment. Finding a doctor who is comfortable discussing SUDs can help ensure long-term recovery.

Find treatment services

Use these resources to find services that fit your needs:

Mental Health and Addiction Insurance Help (HHS)

Health Center Locator (HRSA)

Behavioral Health Treatment Services (SAMHSA)

Opioid Treatment Program Directory by State (SAMHSA)

Buprenorphine Providers Locator (SAMHSA)

Learn more about recovery

SAMHSA Behavioral Health Treatment Services Locator

Rx Awareness: Real Stories

Recovery is Possible: Know the Options

What You Need to Know About Treatment and Recovery

Opioid Therapy and Different Types of Pain

Addiction Medicine Toolkit

Medication-Assisted Treatment (MAT) | SAMHSA

Decisions in Recovery: Treatment for Opioid Use Disorder

Stigma Reduction

Addiction Treatment Locator, Assessment, and Standards (ATLAS) Platform

Linking People with Opioid Use Disorder to Medication Treatment

Working Together With Your Doctor to Manage Your Pain

• American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA, American Psychiatric Association, 2013.
• Substance Abuse and Mental Health Services Administration. (2023). Key substance use and mental health indicators in the United States: Results from the 2022 National Survey on Drug Use and Health (HHS Publication No. PEP23-07-01-006, NSDUH Series H-58). Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. https://www.samhsa.gov/data/report/2022-nsduh-annual-national-report
• SAMHSA. 2022, March 22. Medications, Counseling, and Related Conditions. Retrieved from https://www.samhsa.gov/medications-substance-use-disorders/medications-counseling-related-conditions
• TIP 63: Medications for Opioid Use Disorder - Full Document | SAMHSA
• Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2014). Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. The Cochrane database of systematic reviews , 2014 (2), CD002207. https://doi.org/10.1002/14651858.CD002207.pub4
• Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2003). Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. The Cochrane database of systematic reviews , (2), CD002209. https://doi.org/10.1002/14651858.CD002209
• Fullerton, C. A., Kim, M., Thomas, C. P., Lyman, D. R., Montejano, L. B., Dougherty, R. H., Daniels, A. S., Ghose, S. S., & Delphin-Rittmon, M. E. (2014). Medication-assisted treatment with methadone: assessing the evidence. Psychiatric services (Washington, D.C.) , 65 (2), 146–157. https://doi.org/10.1176/appi.ps.201300235
• https://nida.nih.gov/publications/drugs-brains-behavior-science-addiction/drug-misuse-addiction

Overdose Prevention

Overdose prevention is a CDC priority that impacts families and communities. Drug overdose is a leading cause of preventable death in the U.S.

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A high school-based education concerning drug abuse prevention

Atoosa bonyani.

1 Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Leila Safaeian

2 Department of Research and Development, Vice Chancellery for Food and Drug, Isfahan University of Medical Sciences, Isfahan, Iran

Mojtaba Chehrazi

Alireza etedali, mahsa zaghian, farnaz mashhadian.

There is increasing evidence for declining the onset age of drug abuse worldwide. This study was conducted to investigate the effectiveness of four educational methods including lecture, presentation of poster and leaflet, presentation of video clip, and group/class discussion for life skills training and changing in knowledge and attitude of adolescents toward drug abuse.

MATERIALS AND METHODS:

In a pretest–posttest design, a sample of 897 girl and boy high school students from the first grade (14–15 years old) were involved in this cross-sectional study conducted in Isfahan, Iran. After collection of pretest questionnaires, each educational method was implemented separately for one class in one session (3 h) in each high school, and evaluation was carried out immediately after intervention through posttest questionnaires by the same students.

According to paired t -test, the video clip- and lecture-based methods were significantly efficient in changing the attitudes toward drug abuse in boy and girl students, respectively. Analysis of covariance showed significant differences between girls and boys in pretest–posttest attitude scores using group discussion-based and video clip-based methods.

CONCLUSION:

Life skills training program through lecture-based and video clip-based educational methods was considerably effective in changing the high school students’ attitude toward drug abuse and addiction.

Introduction

Drug abuse as a biological psychosocial problem threatens the human society all over the world. Opioids, alcohol, cocaine, cannabinoids, and amphetamines are the drugs which are most often abused by the people.[ 1 ] In recent years, there is an increasing rate of use for new substances such as ecstasy and some prescription drugs such as tramadol.[ 2 ] About 246 million people consumed illegal substances in 2013; among them, more than one out of 10 drug users had dependence and social problems. Drug abuse has also contributed to 0.5%–1.3% mortality among 15–64-year-old population.[ 3 ] Iran, due to vicinity with Afghanistan as the biggest drug-producing country, is at the greatest risk for drug abuse.[ 4 ] Knowledge and attitude toward substance abuse, availability of illicit drugs, and culture and society are some effective factors that have an impact on this international problem.[ 5 ] Recently, studies have noted that the onset age of drug abuse has decreased globally and teenagers are more likely vulnerable to using illegal drugs due to less information regarding serious complications of drug abuse.[ 2 ] Poor school performance, despair, cigarette-smoking parents, tension release, looking for pleasure, and modeling are some important factors associated with higher rates of drug abuse among adolescents.[ 6 ]

Therefore, there is an extensive concern to drug abuse in the societies and makes it as a priority in public health issues for governments. Different countries have taken trials and interventions at various school, family, and public level of information to change knowledge and attitude of the society toward illegal drugs and accordingly to reduce the rate of drug abuse.[ 7 ] Some effective interventions are included enhancing good decision-making ability and self-protection due to improving life skills and assertive training and also changing the knowledge and attitude by informing teenagers about abused drugs and their consequences.[ 8 ]

Various training tools including curriculum development, lecturing, large- and small-group discussion, simulation and role play, practice in using the technique, and video and film presentation have been used in the programs for drug abuse prevention education.[ 9 ] Lecture as a simple and inexpensive approach is commonly used in many training programs for increasing the students’ knowledge; however, this method has some disadvantages such as inactiveness of the learners and fast forgetting of the information.[ 10 ] Although some interactive methods such as problem-based learning and group discussion have been proposed as more beneficial approaches, the mean learning scores and retention rates in these methods have not always been more than the lecture-based method depending on the educational subject.[ 11 ]

Some new technology-based approaches such as video, computer, Internet, e-mail, and mobile phone have also been used for substance abuse prevention and treatment. However, feasibility of application, age, higher education, and income are some factors which affect the effectiveness of learning programs based on communication technology.[ 12 ]

The results of investigations have also shown that the efficiency of different interventional methods could be different according to the age, sex, developmental level, type of illegal substance, level of substance use, ethnicity, religion, and cultural, financial, and socioenvironmental context.[ 13 ] The implementation of preventive programs for drug abuse in each city may be related to the characteristics of managers, schools, and curriculum and not all preventive programs implemented in schools have been effective.[ 14 ] Moreover, most of the studies about interventional approaches in the field of drug abuse prevention in youth population have been done in high-income countries, and their effectiveness in other countries is unknown.[ 13 ]

In Iran, although there are some limited studies in young people, there is not any complete learning package and a comprehensive school-based drug abuse prevention program for high schools regarding the socioenvironmental context.[ 2 ]

Since there are limited studies about the assessment of different educational methods for substance abuse prevention in adolescents in Isfahan city and due to the influence of various factors on efficiency of different educational approaches, this study was aimed to measure and compare the effectiveness of different training tools including lecture, poster and brochure, movie, and group working in life skill training, promoting positive behavior change, reducing abuse harm, and changing the knowledge and attitude toward drug abuse in 14–15-year-old students in Isfahan.

Materials and Methods

This cross-sectional study was conducted in 10 high schools of Isfahan city in May 2016. The study population for the intervention was male and female high school students (14–15 years old). These high schools were randomly selected from a numbered list of high schools located in different geographical sites of Isfahan using the clustering method. The schools of adolescents with mental and physical disabilities were not included in this study. In each high school, 5 classes in first grade were randomly selected from the list of the classes, and all the adolescents from selected classes were included in this interventional study. The program was finally performed in a sample of 897 girl and boy students. Respondents comprised 445 girls and 452 boys aged 14–15 years. Before implementing the intervention, coordination with the school authorities was made.

This educational study was evaluated using a pretest–posttest design. The pretest measure was done before training intervention and posttest data were collected after that. Four educational methods were used for life skills training and changing in the knowledge and attitude toward drug abuse including lecture, presentation of poster and leaflet, presentation of video clip, and group/class discussion. One class was considered as control group without any intervention. Each educational method was administered separately for one of four other classes in each school, and all the students participated in the intervention program. One training session (3 h in the morning) was held for each method using school facilities. Life skills training regarding the drug abuse prevention included self-confident skills, decision-making skills, cognitive skills and self-control skills, strategies for relieving stress and anxiety, social resistance skills, and other skills which help the youth lower their risk for substance use. For change in the knowledge and attitude toward drug abuse, the educational approaches were used to create awareness among the students about misunderstandings and false information which may lead to drug abuse and to inform them about the risks and harms of using substances and their adverse consequences.

The educational materials for each method were prepared based on the international programs and national studies under supervision of some expert faculty members and also approved by the Committee of Rational Use of Drugs and also Poisoning Control Center, Vice Chancellery for Food and Drug, Isfahan University of Medical Sciences, Isfahan, Iran. The video clip contained the life stories of some user of drugs. This educational effort via drama was planned for changing attitudes toward substance abuse, encouraging the life skills training and activities regarding drug abuse prevention, and increasing awareness about the risk and protective factors associated with drug abuse. The play revealed sections directly related to the common substance abuse problems in our country. It depicted the risk factors that are associated with the development of drug abuse including copying parent's behavior and poor life skills. The play showed the negative consequences of drug abuse on activities of normal life, educations, job and relationships, and its other adverse effects including impairment of judgment, damages to many body organs, poor mental and physical health, and also criminal justice involvement. The posters and leaflets presented the similar contents through the text and images. In lecturing and group discussion, the above-mentioned goals were achieved by a presenter or interactive dialogs.

The instruction was made with senior pharmacy students, and in all high schools, the lecturer and group discussion manager were the same.

A short self-administered questionnaire comprising 32 closed-ended questions was used; and according to the final version of the questionnaire designed by Khodayari et al . for substance abuse attitude, the survey was conducted and validated in an initial pilot study among a random sample of 20 students. Its reliability was evaluated by Cronbach's alpha, and there was a suitable level of internal consistency of scales (Cronbach's alpha = 0.80). Khodayari et al . also reported the Cronbach's alpha coefficient to be 0.83.[ 15 ]

The questionnaire addressed the following issues: (1) attitudes toward the drug abuse, (2) attitudes toward the drug abuse reasons, (3) attitudes to the people abuse substances and their personality, and (4) attitudes toward consequences of drug abuse. The scoring for each question followed the Likert format, from 1 for “absolutely disagree” to 5 for “absolutely agree.” The mean score was calculated for the results, with higher scores indicating more negative attitudes toward drug abuse, and vice versa.

After gathering the pretest questionnaires, different educational methods were implemented in selected classes and evaluation of the intervention was carried out immediately after education through filling out the posttest questionnaires by the same students.

The average score in the pretest and posttest in each group was expressed as means ± standard deviation; statistical evaluation was done by paired t -test and analysis of covariance (ANCOVA) followed by Tukey post hoc test using the SPSS Software Version 18 (SPSS Ltd., Quarry Bay, Hong Kong). P < 0.05 was considered as the statistically significant levels.

Tables ​ Tables1 1 and ​ and2 2 show the comparison between the attitude toward various issues of drug abuse before and after training with four educational methods in male and female high school students, respectively. According to paired t -test, the lecture-based education resulted in significant changes in attitudes toward consequences of drug abuse in boy students ( P < 0.001) [ Table 1 ]. However, there was not significant effect on the mean score of total attitudes using lecture-based education in these students [ Table 3 ]. The video clip-based method also caused significant changes in attitudes toward consequences of drug abuse in girl students ( P < 0.001) [ Table 2 ], but significant difference on the mean score of total attitudes using video clip-based education was not observed in these students [ Table 3 ]. Evaluation of the impact of four methods on mean score of total attitudes toward drug abuse showed that video clip- and lecture-based education were efficient in changing the attitudes toward drug abuse in boys and girls, respectively ( P < 0.001 and P < 0.01) [ Table 3 ]. According to ANCOVA, there were significant differences between girl and boy students in pretest–posttest attitude scores using group discussion-based and video clip-based methods ( P < 0.05) [ Table 4 ].

Comparison of the pre- and post-test attitude scores toward drug abuse for different educational methods in male high school students

Comparison of the pre- and post-test attitude scores toward drug abuse for different educational methods in female high school students

The impact of the four educational methods on total attitude scores toward drug abuse in each gender and between male and female high school students

Analysis of covariance in attitude scores toward drug abuse for different educational methods between male and female high school students

Based on the findings of this study, the video clip- and lecture-based interventions for life skills training and preventing drug abuse were efficient in changing the attitudes toward drug abuse in boy and girl students. Comparison between girls and boys showed that among the four educational methods, the video clip-based method was more efficient in boy students and the group discussion-based method was more efficient in girl students on changing attitude toward drugs and addiction. Our results also showed that there was no significant difference at the baseline attitude between girl and boy students and they had a relatively negative attitude toward substances abuse.

In the context of the primary prevention from addiction disorder as a serious public health problem, policymakers have developed various school-, family-, and community-based approaches in different countries.[ 16 , 17 ] Life skills training is one of the most efficient interventional efforts for school- and family-based prevention.[ 8 ]

A decision for choosing the most suitable educational method depends on the aims of the preventive program or educational process, target group, and also resources available.[ 13 ] In Iran, several educational methods have been studied by the researchers for drug abuse prevention. In the study of Bahreini-Borujeni et al ., life skills training classes and education through video were more effective than training through poster and catalog and sending SMS through mobile phone in changing students’ attitude toward drug abuse.[ 18 ] Similar results have been reported by Taromiyan and Mehryar and Rabiei et al .[ 19 , 20 ] This finding contradicts the findings of Aghababae et al . because they considered the effect of sending SMS and education through catalogs and brochures on meaningful changing in attitudes of students in their study.[ 21 ] However, it seems that using multimedia materials and new educational technologies would be more effective than the text materials.[ 8 ] Small-group activities and discussion, storytelling, and role-playing scenarios are some evidence-based educational methods in life skills training programs.[ 8 , 22 ] However, the international protocols have suggested that each program should assess which interactive techniques and how often each technique could be used in substance use prevention programs.

Although focusing on lecturing the students about the hazards and adverse consequence of drug abuse may be an unsuccessful approach, an attractive and cordially lecture-based program for life skills training, especially in younger adolescents, would be an effective approach. In addition to teacher talent for faithful delivering of lessons, educational materials should be prepared based on the developmental and etiologic factors and social stimuli which are contributed in drug abuse in adolescent. Governmental intervention strategies and comprehensive efforts regarding school, family, and community should be developed for rising community awareness and achieving the effective drug abuse prevention.[ 23 ]

In the present study and also in many investigations only changes in attitudes and knowledge toward substances abuse were reported.[ 24 ] In general, life-skill training can meaningfully change some elements in drug abuse in short time, but sustainable changes in behavior and performance are needed more times and continuation of the educational programs and assessing the effectiveness of the outcome in the future.

The major limitations of this study were as follows: To attribute the differences observed merely to the difference in the implemented methods, a control group of students who did not receive the educational intervention should be considered. However, in most of the schools, there were not more than four classes in the same grade.

Sustained interventions should be implemented for gaining life skills and insight in students, but this aim requires comprehensive national planning and spending of energy and expense.

For measuring the educational impacts, it is suggested that reevaluations would be carried out at greater intervals. However, due to constraints in coordination with high schools and end of the school year, we had to hold the posttest immediately after training.

The life skills training and preventing drug abuse program through lecture-based and video clip-based educational methods were considerably effective in changing the high-school students’ attitude toward drug abuse and addiction. Among the four educational methods, the video clip-based method was more efficient in boy students and the group discussion-based method was more efficient in girl students on changing attitude toward drugs and addiction. The policymakers should determine the educational needs of different target groups and develop a consistent preventive drug abuse program through school curricula and innovative educational materials which adapted to the socioeconomic and cultural conditions in the country.

Financial support and sponsorship

This research project no. 294188 was financially supported by Vice Chancellery for Research and Technology, Isfahan University of Medical Sciences, Isfahan, Iran.

Conflicts of interest

There are no conflicts of interest.

Acknowledgments

The authors would like to thank the students, high school principals, and Vice Chancellery for Food and Drug, Isfahan University of Medical Sciences, Isfahan, Iran, who participated in this study.

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Drug-Impaired Driving: The Contribution of Emerging and Undertested Drugs

Impaired driving is often associated with alcohol use and frequently leads to accidents, injuries, and fatalities. According to the National Highway Traffic Safety Administration, one person was killed every 39 minutes in an alcohol-related crash in 2021. [1] But alcohol is not the only concern; the use of illicit drugs, legalized drugs such as cannabis, and the abuse of prescription medications may also impair a driver’s abilities. In 2022, an estimated 13.6 million people drove under the influence of illicit drugs during the prior year. [2]

In 2007, the National Safety Council (NSC) introduced testing scope and cutoff standardization for impaired driving cases and traffic fatalities to improve testing consistency. Since 2013, it has recommended that forensic toxicology labs regularly test blood for 35 of the most often encountered drugs and metabolites. Referred to as Tier I drugs ( Figure 1 ), they are now included as a testing standard in many forensic toxicology labs. [3] Furthermore, these compounds can be detected and confirmed with commonly used analytical instrumentation.

Figure 1. List of Tier I and Tier II drugs. Tier II drugs can be both individually named drugs and classes of drugs (e.g., atypical antipsychotics).

NSC also created a second drug category with significant impairment potential, termed Tier II drugs. These drugs include emerging novel psychoactive substances, prescription drugs, and traditional drugs of abuse with limited or regional prevalence, many of which require advanced instrumentation for detection. Most laboratories test for Tier I drugs, but only test for select Tier II drugs when they are regionally relevant. Therefore, the frequency and the types of Tier II substances contributing to drug-impaired driving cases and fatal crashes is not well understood.

NIJ-funded researchers from the Center for Forensic Science Research and Education examined blood samples from over 2,500 driving under the influence of drugs (DUID) cases. The goal was to create a detailed picture of both Tier I and Tier II drugs that contribute to impaired driving cases and compare results to the NSC’s recommended testing scopes. Researchers also analyzed drug presence at various blood alcohol concentrations to assess the operational impact of different testing thresholds and stop limit testing.

What is Stop Limit Testing?

If a sample meets or exceeds a pre-determined blood alcohol concentration threshold, some labs will not perform any additional drug tests. This cutoff is most commonly either 0.08% or 0.10%. [4] The  proscribed per se blood alcohol level in the U.S. across every state is 0.08% (except Utah, where it is 0.05%) . Labs that adhere to this practice will not detect other drugs that may cause or contribute to driving impairment. 

This stop limit testing can interfere with a comprehensive understanding of drug involvement in impaired driving. Why do so many labs use it?

• Toxicology labs have limited budgets and resources.
• Driving impairment can be explained by the blood alcohol concentration alone.
• A lack of enhanced penalties for drug use means there is no need to measure beyond the blood alcohol level.
• Agencies that use the laboratories’ services have requested this limit.

National Safety Council Recommendations Are Supported

Researchers estimated the frequency with which drugs contribute to the national DUID problem by testing 2,514 cases using a scope of 850 therapeutic, abused, and emerging drugs. They examined deidentified blood samples randomly selected from a pool of suspected impaired driving cases. The samples were collected from NMS Labs in Horsham, Pennsylvania, between 2017 –2020.

Of the 2,514 suspected DUID cases examined:

• The overall drug positivity (Tier I or Tier II drugs) was 79%, nearly double the 40% positive for alcohol ( Figure 2 ).
• A smaller portion of cases (23%) tested positive for both drugs and alcohol.
• Only 17% of the cases were positive for alcohol alone.
• Naturally occurring cannabinoids experienced a statistically significant increase in positivity over the four years.

Figure 2. The frequency of cases with (a) no drugs or ethanol detected (4%), (b) ethanol detected (40%), (c) drugs and ethanol detected (23%), and (d) drugs detected (79%).

Alcohol use in combination with drugs spanning multiple categories was common, as was multiple drugs used in combination. THC (the primary psychoactive component of marijuana) was most often found with ethanol (n=359), and it was frequently found with amphetamine/methamphetamine (n=146).

Samples with a blood alcohol content of 0.08% or higher that were also positive for either Tier I or Tier II drugs occurred 19% of the time (n=478). Cases with blood alcohol content of 0.10% (the cutoff used most frequently by toxicology labs) were also positive for Tier I or Tier II drugs 17.3% of the time (n=434). This suggests that laboratories employing stop limit testing may miss many drug-positive cases.

“Limiting testing based on alcohol results precludes information of drug involvement in several cases and leads to underreporting of drug contributions to impaired driving,” said Mandi Moore, one of the researchers involved in the study.

The research supported NSC’s recommendations for Tier I and Tier II testing. Tier I drugs were found in 73% of suspected impaired driving cases while only 3% contained just Tier II drugs. This suggests that Tier I testing captures the vast majority of drug-involved DUID cases. However, some Tier II drugs (diphenhydramine, gabapentin, hydroxyzine, and two novel psychoactive substances) were found as often or more often than some Tier I drugs, potentially indicating their increased prevalence and a need to re-examine guidelines.

Study Limitations

The cases used in this analysis were exclusively from Pennsylvania. Therefore, they provide a geographically limited snapshot rather than a comprehensive characterization for the entire U.S. population. However, the sample size of over 2,500 cases was “suitable to meet the research goals outlined” by the researchers.

Because Tier II and novel psychoactive substances were found in relatively low frequencies, the researchers did not develop or validate additional confirmatory methods as they had previously planned.

Filling in the Big Picture Details

This work increases awareness of drugs that labs are less likely to test for and labs’ role in addressing the DUID problem. It also demonstrates how frequently DUID cases involve drugs other than alcohol. Although stop limit testing can be justified, data on both alcohol and drug use creates the clearest picture of DUID contributing factors. Current estimates of drug frequency in DUID cases are likely to be inaccurate and actual usage is likely to be higher than previously believed due to stop limit testing. Equipping labs with sufficient resources could encourage labs to eliminate stop limit testing.

About This Article

The work described in this article was supported by NIJ award number 2020-DQ-BX-0009 , awarded to the Frederic Rieders Family Renaissance Foundation.

This article is based on the grantee report “ Assessment of the Contribution to Drug Impaired Driving from Emerging and Undertested Drugs ” (pdf, 26 pages), by Amanda L.A. Mohr and Barry Logan, The Center for Forensic Science Research and Education (CFSRE) at the Frederic Rieders Family Renaissance Foundation.

[1] NHTSA.gov, accessed January 29,2024, https://www.nhtsa.gov/risky-driving .

[2] Select Illicit Drugs include the use of marijuana, cocaine (including crack), heroin, hallucinogens, inhalants, or methamphetamine. For more information, see "Table 8.35A" in  2022 NSDUH Detailed Tables, Substance Abuse and Mental Health Services Administration,  https://www.samhsa.gov/data/sites/default/files/reports/rpt42728/NSDUHDetailedTabs2022/NSDUHDetailedTabs2022/NSDUHDetTabsSect8pe2022.htm#tab8.35a .

[3] ANSO/ASB Standard 120.

[4] Amanda D’Orazio, Amada Mohr, and Barry Logan, “Updates for Recommendations for Drug Testing in DUID & Traffic Fatality Investigations, Toxicology Laboratory Survey,” Willow Grove, PA: The Center for Forensic Science Research & Education at the Frederic Rieders Family Foundation, June 28, 2020, https://www.cfsre.org/images/content/research/toxicology/Survey_Report_Final.pdf .

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Drugs, Brains, and Behavior: The Science of Addiction Introduction

Why study drug use and addiction.

Use and misuse of alcohol, nicotine, and illicit drugs, and misuse of prescription drugs cost Americans more than $700 billion a year in increased health care costs, crime, and lost productivity. 1,2,3  Every year, illicit and prescription drug overdoses cause tens of thousands of deaths (nearly 70,000 in 2018), alcohol contributes to the death of more than 90,000 Americans, while tobacco is linked to an estimated 480,000 deaths per year. 4,5  (Hereafter, unless otherwise specified,  drugs  refers to all of these substances.)

People of all ages suffer the harmful consequences of drug use and addiction:

• Teens who use drugs may act out and may do poorly in school or drop out. 6 Using drugs when the brain is still developing may cause lasting brain changes and put the user at increased risk of dependence. 7
• Adults who use drugs can have problems thinking clearly, remembering, and paying attention. They may develop poor social behaviors as a result of their drug use, and their work performance and personal relationships suffer.
• Parents'  drug use can mean chaotic, stress-filled homes, as well as child abuse and neglect. 8 Such conditions harm the well-being and development of children in the home and may set the stage for drug use in the next generation. 9
• Babies exposed to drugs in the womb may be born premature and underweight. This exposure can slow the child's ability to learn and affect behavior later in life. 10 They may also become dependent on opioids or other drugs used by the mother during pregnancy, a condition called neonatal abstinence syndrome (NAS).

How does science provide solutions for drug use and addiction?

Scientists study the effects drugs have on the brain and behavior. They use this information to develop programs for preventing drug use and for helping people recover from addiction. Further research helps transfer these ideas into practice in the community.

The consequences of drug use are vast and varied and affect people of all ages.

14.Short Essay and Article on : Drug Abuse Among students

You are worried about the menace of drug abuse among students. You want to write an article “ Drug Abuse ” among students for a local newspaper .

Ans:-                                       Drug Abuse Among students

Drugs have been used by mankind for the medical purpose since ages. But never before had the abuse of drugs causes such a worldwide concern and posed an alarming. According to a survey conducted by WHO, there are about 7 million heroin addicts. There are 4.8 million cocaine abusers and 3.4 million addicts of other narcotics. The abuse of the drug is now an international problem. Recent students in India show that 88% of the heroin addicts in India are in the age group of 14-25 years. The students of India are virtually being crippled by this menace. Children of families whose parents maintain strained relations become easy prey to drugs. To start with. The addict student takes a fill to get a thrill. Very soon. He develops a mental dependence on the thrill. He requires an increasing dose of daily Drugs affect his mind, health and morals. Physically mentally and spiritually he becomes a wreck. The gravity of the student demands the declaration of an all-out war against the menace of drugs.  In schools and colleges, students should be enlightened about the devastating effects of drugs. The government institutions and voluntary organizations should work for hand in – hand to wipe out this evil from the society in general and the student community in particular.

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Essay on drug abuse among students- 150 words.

There is no doubt that drug abuse is a serious problem among students. It has been shown to lead to poor academic performance, health problems, and even criminal behavior. However, the problem of drug abuse among students is often overlooked or downplayed. This is likely due to the fact that students are seen as being “too young” to be engaging in such behavior. The reality, however, is that drug abuse among students is a very real and serious problem. In fact, it is estimated that nearly one in four college students have used an illicit drug at least once during their time in college. This number increases when you consider non-college students of the same age group. There are many reasons why students may turn to drugs. Some do it for recreation or to relieve boredom, while others may use drugs as a way to cope with stress or anxiety. Whatever the reason, it is important to remember that drug abuse is a serious issue with potentially harmful consequences. If you or someone you know is struggling with drug abuse, you must make efforts to help the addict. It is ready deadly. 

Write an article on drug abuse among students

Here is an article on ‘Drug Abuse among Students’- 200 Words

The use of illicit drugs is a serious problem among students. According to a recent survey, nearly one in four college students have used an illegal drug at some point in their academic career. Drug abuse can lead to a variety of problems, including poor grades, health problems and even legal trouble.  There are a number of reasons why college students turn to drugs. Some students use drugs as a way to cope with the stress of school. Others may be trying to fit in with their peers or relieve boredom. Whatever the reason, drug abuse is a serious problem that can have devastating consequences.  The first step in preventing drug abuse among college students is to educate them about the risks. Students need to be made aware of the potential for addiction and the dangers of using illegal drugs. They also need to know where to go for help if they or someone they know has a problem with drugs. There are many resources available to help college students stay drug-free. Campus health centers can provide information and referrals for treatment. Student organizations like Alcoholics Anonymous and Narcotics Anonymous offer support and recovery programs.  By working together, any college can help be safe and healthy places for learning and growth.

Drug Abuse among Students Article- 250 Words

It is no secret that drug abuse among students is a serious problem. Every year, thousands of young people fall victim to addiction, and many never recover.  The statistics are staggering: according to the National Institute on Drug Abuse, nearly one in four high school students has used an illicit drug at least once. And of those who do use drugs, nearly half will go on to develop a substance use disorder.  The causes of drug abuse among students are numerous and complex. peer pressure, academic stress, and mental health issues can all contribute to substance abuse. And while there may not be a single solution to the problem, there are things that can be done to help prevent it. Education is critical. Young people need to be taught about the risks of drug use and the dangers of addiction. They also need to understand that drugs are not a shortcut to success or happiness; they will only lead to misery and despair. In addition to education, early intervention is essential. If we can identify students who are at risk for substance abuse, we can provide them with the resources they need to get help before it’s too late. This might include counseling, therapy, or even medication. Finally, we need to address the underlying causes of drug abuse among students. Peer pressure, academic stress, and mental health issues can all contribute to substance abuse. By addressing these issues head-on, we can make progress in preventing drug abuse before it starts.

Long Article on Drug Abuse Among Students

What is Drug Abuse Explain with Examples?

What is Drug Abuse- 

Drug abuse is the misuse of drugs for non-medical purposes. Drug abuse includes the use of illegal drugs, such as marijuana, cocaine, heroin, and methamphetamine, as well as the use of prescription medications for purposes other than those for which they are prescribed. People who abuse drugs may do so because they are seeking a feeling of euphoria or escape from reality.  They may also be trying to self-medicate for underlying mental health issues, such as anxiety or depression. Whatever the reason, drug abuse can lead to serious consequences, including addiction, health problems, and even death. If you or someone you know is struggling with drug abuse, there is help available. There are many treatment options available that can help you recover from addiction and lead a healthy, sober life.

What are the causes of drug abuse among students?

Here are 10 main Causes of Drug Abuse Among Students

Drug addiction is a serious problem that can have a profound impact on an individual’s life. It can lead to social isolation, job loss, financial problems, and even death. While there are many different factors that can contribute to drug addiction, there are 10 primary causes of drugs.  1.Poverty – Around the world, poverty is one of the main causes of drugs. In poor countries, many people turn to drugs to escape their difficult reality. Drugs provide a temporary escape from the problems of poverty, such as hunger, lack of shelter, and unemployment. 2.Lack of education- or no interest in studies – One of the main causes of drugs is a lack of education. When people are not educated about the dangers of drugs, they are more likely to use them. Drug education should be a part of every school’s curriculum. It is important for students to learn about the dangers of drug use so that they can make informed decisions about their own drug use. 3.Lack of family support – Lack of family support is one of the main causes of drugs. In many cases, people who start using drugs come from families where there is little or no support. This can be due to a variety of factors, including financial problems, abuse, neglect, and other issues.  4. Peer pressure – Peer pressure is one of the most common causes of drug use. Many young people feel pressure to try drugs or to keep using them because their friends are doing it. This pressure can come from friends, siblings, or even classmates. It can be hard to resist peer pressure, but it’s important to remember that you don’t have to do what everyone else is doing.  5.Curiosity – There are many different causes of drug addiction, but one of the most common is curiosity. People often start taking drugs because they’re curious about what they’ll feel like, or they want to fit in with their friends. Once someone starts taking drugs, it can be hard to stop. The chemicals in drugs change the way the brain works, and this can lead to addiction. 6. Mental health disorders – Mental health disorders are one of the most common causes of drug addiction. Many people who suffer from mental health problems turn to drugs to cope with their symptoms. Mental health disorders can include conditions such as depression, anxiety, bipolar disorder, and schizophrenia. 7. Access to drugs – There are many causes of drug addiction, but one of the most significant is access to drugs. When people have easy access to drugs, they are more likely to use them, and when they use them more often, they are more likely to develop an addiction. There are many ways that people can get access to drugs. Some people may buy them from dealers, while others may find them in their homes or in public places. Still others may get them from friends or family members who are using drugs. No matter how people get access to drugs, the bottom line is that it increases their chances of developing an addiction. If you or someone you know is struggling with drug addiction, please get help as soon as possible. There is no shame in admitting that you need help, and there are many resources available to those who want to recover from drug addiction.

8.Family history of drug use

A family history of drug use is one of the biggest risk factors for developing a drug problem. If you have a parent or other close relative who has struggled with drug abuse, you are more likely to develop problems with drugs yourself. There are several reasons why having a family member who has abused drugs can increase your risk. First, it can be genetic. If your parents struggled with addiction, you may be more likely to develop addiction yourself. This is because addiction can be passed down through families. Second, even if addiction isn’t genetic, growing up in a home where someone struggles with drugs can still have an impact. You may see firsthand how drug abuse can ruin lives and damage relationships. This can make you more likely to turn to drugs yourself when you’re faced with difficult situations later in life. If you have a family history of drug use, it’s important to be aware of the risks. Talk to your doctor about your concerns and get help if you think you might be struggling with addiction yourself. 9. Traumatic experiences – There are many different factors that can contribute to a person developing a drug addiction. One of the most significant contributing factors is exposure to traumatic experiences. Traumatic experiences can include things like abuse, neglect, witnessing violence, or losing a loved one. 10. Stress – There are many causes of drug addiction, but one of the most common is stress. When someone is under a lot of stress, they may turn to drugs to cope. This can become a vicious cycle, as the person becomes more dependent on the drugs to deal with their stress. It is important to find healthy ways to cope with stress, such as exercise, relaxation techniques, or talking to a therapist.

What are the Effects of Drug Abuse on Students

The use of drugs is a major problem on college campuses. Drug abuse can lead to academic problems, health problems, and even death. 

Here are 10 effects of drug abuse on students:

1. Drug abuse can lead to poor grades and academic problems. 2. Drug abuse can lead to health problems, including addiction, overdose, and death. 3. Drug abuse can lead to social problems, such as isolation from friends and family. 4. Drug abuse can lead to financial problems, such as staggering medical bills or the loss of scholarships and grants. 5. Drug abuse can lead to legal problems, such as arrest and imprisonment. 6. Drug abuse can lead to job loss and unemployment. 7. Drug abuse can cause relationship problems, such as the loss of trust and communication breakdowns. 8. Drug abuse can lead to mental health problems, such as anxiety, depression, and psychosis. 9. Drug abuse can cause physical health problems, such as organ damage and disease. 10. Drug abuse can cause death.

Ways of Preventing Drug Abuse

It is important to be proactive in the fight against drug abuse. 

Here are 10 ways you can help prevent drug abuse from happening in the first place:

1. Educate yourself and others about the risks of drug abuse. 2. Talk to your children about drugs at an early age. 3. Keep communication open with your children and monitor their activities. 4. Set a good example for your children by living a healthy lifestyle yourself. 5. Get involved in your child’s school and know who their friends are. 6. Help your child develop coping and problem-solving skills. 7. Encourage positive activities and interests outside of school or work. 8. Monitor your own drug use and be honest about it with your children. 9. Seek professional help if you or someone you love is struggling with drug addiction. 10. Advocate for policy changes at the local, state, and federal level to reduce drug abuse and addiction.

5 Types of Drug Abuse

There are many different types of drug abuse, and each one can have different effects on the user. 

Here are five of the most common types of drug abuse:

1. Stimulant Abuse: Stimulants are drugs that increase alertness and energy. They can include drugs like cocaine, methamphetamine, and Adderall. Stimulant abuse can lead to increased heart rate and blood pressure, anxiety, paranoia, and even psychosis. 2. Depressant Abuse: Depressants are drugs that slow down the central nervous system. They can include alcohol, barbiturates, and benzodiazepines. Depressant abuse can lead to slurred speech, impaired coordination, drowsiness, and even coma or death. 3. Hallucinogen Abuse: Hallucinogens are drugs that cause hallucinations and distorted perceptions. They can include LSD, MDMA (Ecstasy), and ketamine. Hallucinogen abuse can lead to psychotic episodes, severe anxiety, and even death. 4. inhalant Abuse: Inhalants are substances that are sniffed or inhaled to get high. They can include aerosol cans full of compressed air or Freon, spray paint cans, markers, and glue. Inhalant abuse can lead to brain damage, organ damage, seizures, and even death. 5. Narcotic Abuse: Narcotics are powerful painkillers that work by binding to opioid receptors in the brain. 

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1990 WAEC English Language Theory Write an article, for publication in a national newspaper, on the dangers of drug abuse...

Write an article, for publication in a national newspaper, on the dangers of drug abuse among youths.

Explanation

                                     THE DANGERS OF DRUG ABUSE        Drug abuse has become a matter of constant discussion on the radio, television and in the daily newspapers recently. The menace of drug abuse in our country has reached a frightening proportion and it has pervaded every sector of our society. Drugs, which are made from medicinal substance formulated by pharmacists for the cure of people's ailments, is used wrongly and abused by people across the social strata. A lot of people just walk across to the nearby chemist to their houses to buy drugs which are not prescribed for them by a pharmacist or a doctor, thus abusing the drugs.        There are lots of dangers in drug abuse In fact, many families have endangered the live of their members through self medication There are cases of many small children who lost their lives simply because their parents, out of ignorance, purchased drugs from chemists and even in the common markets without any doctor's prescription and administered such drugs on their children.       In our society nowadays. it is common to see young children with one deformity or the other. This is so because many pregnant women abuse drugs easily They simply buy drugs and use them without doctor's prescription during pregnancy. The resultant effect of this ignorant act is that most babies are born with one deformity or the other.        Drug abuse also leads to the several psychiatric cases we have around in the country. Several youths take drugs such as heroine cocaine Indian hemp which affect their brain They take these drugs ostensibly because they want to be in fashion and they want to be daring and bold Consequently. most of them constitute themselves into nuisance to the society and end up in psychiatric hospitals.       Our national prestige and honour are not spared of the gruesome effect of the social malaise called drug abuse. Many Nigerians travelling abroad are subjected to derogatory search at the points of entry into other countries. This has destroyed our international image as many Nigerians are found to be carriers and couriers of these hard drugs.        Many crimes in the country can be linked to drug abuse The high rate of criminal activities is a pointer to the danger inherent in drug abuse Armed robbers and the like operate under the influence of drugs which make them to be so daring and ruthless in their nefarious activities.        It is certain that drug abuse has posed a lot of dangers to our society and the government has to do something about it. Our people need to be enlightened about the dangerous consequences of drug abuse. Mass enlightenment campaign should be organised by the government. In addition, the government should promulgate a law which forbids the sale of drugs in the common open market and there should also be a law which forbids a chemist from selling drugs to the public without prescription paper from a doctor or a pharmacist. Religious bodies also have a role to play in educating the public about the dangers of drug abuse 

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