Drug use disorders

Drug use disorders involve persistent difficulty regulating drug use, increasing priority given to it, and significant harm or disruption. This is a broad group of conditions, not one illness with one cause or one treatment. Opioids, cocaine and other stimulants, cannabis, benzodiazepines and other drugs act differently, carry different risks and respond to different forms of care. Alcohol and nicotine share some mechanisms with these drugs, but are not the main subjects here.

Frequent use, harmful use, physical dependence and addiction are not interchangeable. Physical dependence means the body has adapted to a drug and may develop withdrawal when it is reduced. This can happen during appropriate prescribed treatment without the impaired control and harmful pattern associated with a use disorder. The World Health Organization distinguishes harmful patterns of use from dependence, whose central features include difficulty regulating use and giving it increasing priority, sometimes alongside tolerance or withdrawal. Assessment therefore needs more than a tally of doses or a positive drug test. WHO's clinical description of mental and behavioural disorders, Review of changes in substance-use diagnoses

Exposure, inherited susceptibility and life circumstances

A disorder cannot develop without exposure, and exposure is shaped by availability, prescribing, peers, family and wider circumstances. How quickly a drug reaches the brain, how often it is taken and the size and pattern of its effects can influence reinforcement: the tendency for an experience to make the behaviour leading to it more likely. Rapid effects can be particularly reinforcing, although much of the detailed evidence concerns stimulants. The same chemical can have different reinforcing properties with different patterns of administration. None of this yields a simple dose-to-addiction formula for an individual. Review of drug delivery and addiction risk

Inherited differences also matter. Estimates often suggest that around half the variation in susceptibility across studied populations is associated with genetic differences, but this varies between drugs and populations. It does not divide an individual's problem into a genetic half and an environmental half. Many variants have small effects, some shared across substances and others more specific. A large genetic study included more than a million people of European ancestry and about 92,600 of African ancestry and identified nineteen independent genetic signals associated with general addiction risk. These signals do not establish nineteen single causes or one shared molecular fault. Large genetic study of shared addiction susceptibility

Genes may influence responses to drugs, behavioural tendencies, mental health and the environments people encounter. Genetic overlap between diagnoses does not show that one causes the other. There is also a basic research problem: comparing people with a disorder with people who have never used the drug can mix susceptibility to encountering or trying it with susceptibility to losing control once exposed. Studies of similarly exposed people with different outcomes are especially useful. Review of genetic and environmental pathways

The developmental context matters. Early use can signal opportunities to obtain drugs, pre-existing difficulties regulating behaviour or adversity, as well as exposing a developing person to harm. Childhood abuse, neglect and instability are associated with later substance problems. Stress responses, relationships, emotional regulation and social circumstances are plausible pathways, but the experiences often cluster with other disadvantages and family risks. A review of twenty reviews supports adversity as an important risk marker without establishing a single, independent trauma explanation for every disorder. Review of childhood adversity and substance misuse

Evidence from families also shows that environments can modify high inherited risk. A Swedish study examined 1,161 full-sibling and 3,085 half-sibling groups at elevated familial risk. Among full siblings, being adopted into screened homes was associated with about a 45% lower rate of recorded drug problems over time; the estimated range was roughly 31–55% lower. This is a comparison of rates, not a 45-percentage-point reduction in the probability of a disorder. Adoption was not random, and historical registry records capture a particular part of the problem, but the findings argue against treating family history as destiny. The Swedish high-risk sibling adoption study

Anxiety, depression and other mental health conditions may contribute through distress and attempts to obtain relief. They can also share causes with drug problems or arise after them. A 2026 study of 1,881 twin pairs found that associations between inward distress and later problems with the substances studied did not remain independently clear after accounting for shared family influences. Earlier difficulties with outward behaviour and regulation still predicted some alcohol and cannabis problems. This does not mean distress is unimportant, nor does a study of alcohol, nicotine and cannabis settle the causes of opioid or stimulant disorders. It shows why an appealing self-medication explanation needs to be tested rather than assumed. The prospective twin study

Learning, wanting and the effects of repetition

Drugs can produce pleasure, stimulation, relief from pain, relief from withdrawal or escape from difficult feelings. Each can reinforce use. Experiences become linked with places, people, routines, emotions and bodily sensations. Those cues can later draw attention and evoke an urge even when a person is trying to change.

Dopamine helps the brain learn what is worth pursuing and organise motivation. It is not simply a pleasure meter. One influential account proposes that repeated exposure makes drug-related cues increasingly able to produce wanting, even when the drug is liked less. Experiments support a distinction between wanting and liking, but this theory is not a complete, proven explanation of every drug use disorder. The strength of a response can also depend on what is being measured: a person may show a muted response to a laboratory stimulant challenge while responding strongly to familiar drug cues. Review of wanting, liking and addiction

Repeated exposure can change chemical signalling, the number or responsiveness of receptors, the strength of connections between cells, and how genes are switched on or off. Some changes last after the drug has left the body. Animal experiments can manipulate these processes and establish that a particular change affects a particular behaviour in that model. Human addiction includes language, expectations, relationships and social constraints that the model cannot reproduce in full. Strong experimental evidence for a mechanism in animals is therefore a beginning for human explanation, not its completion. Review of persistent changes in brain connections

Adaptation also helps explain tolerance and withdrawal. Tolerance means that some effects diminish with repeated exposure. Withdrawal occurs when the body has adjusted to a drug and becomes unbalanced as its level falls. Symptoms and danger vary substantially between substances. Taking the drug again can relieve withdrawal, powerfully reinforcing further use, but this is only one route to persistent use.

A broader model suggests that ordinary rewards may become less effective while stress and distress become more influential. Detailed accounts involve interacting stress signals, including corticotropin-releasing factor, dynorphin and noradrenaline; much of that evidence comes from animal work. Researchers often describe a cycle of intoxication, withdrawal or negative feelings, and anticipation or craving. This organises common observations, but is not a compulsory sequence through which everyone progresses. Review of reward, stress and the addiction cycle

Attention, planning, inhibition and evaluation of consequences matter as well. Drug-related cues and immediate benefits may receive disproportionate weight while it becomes harder to hold longer-term goals in mind, particularly under stress. These are average patterns in research groups, not proof that every affected person lacks control in every situation or has permanent damage. A recent review also describes evidence of functional recovery. Review of impaired regulation and drug-related attention

Different drugs change different systems

Opioids such as heroin, fentanyl and oxycodone act strongly on a type of opioid receptor involved in pain and reward. Repeated exposure produces compensating changes in cell signalling. Experimental work on systems involving the chemical messenger noradrenaline and signals inside cells helps explain parts of opioid withdrawal. These mechanisms explain important physical adaptations, but tolerance and withdrawal alone do not explain the whole pattern of harmful, difficult-to-control use. Review of opioid adaptation and withdrawal

Cocaine blocks the recycling of several signalling chemicals, while amphetamines increase their release through somewhat different processes. Both can strongly affect dopamine-related motivation and learning. Glutamate signalling and changes in connections between cells also contribute. Studies of established stimulant problems often find reduced availability of certain dopamine receptors or a blunted response to a stimulant challenge, but findings vary, and separating earlier vulnerability from exposure effects remains difficult. Review of stimulant-related mechanisms

THC, the main intoxicating component of cannabis, partly activates cannabinoid receptors called CB1. Repeated exposure can reduce their responsiveness or availability. Small human imaging studies support adaptation in this system, but cannabis does not consistently show the same dopamine-receptor pattern reported for stimulants. It should not be forced into an identical chemical explanation. Review of cannabis use disorder

Benzodiazepines increase the effects of GABA at a particular receptor, slowing activity in relevant nerve-cell systems. With physical dependence, stopping suddenly can leave the nervous system excessively active. The detailed adaptations are not completely understood. Other drugs—including synthetic cannabinoids, GHB and GBL, gabapentinoids and dissociative drugs such as ketamine—have different targets and different patterns of toxicity and withdrawal. A general account of addiction cannot replace a substance-specific assessment. British Association for Psychopharmacology guidance on substance-use treatment

Compulsion, choice and recovery

Repeated behaviour can become habitual, but addiction is not simply a universal switch from conscious choice to automatic habit. Continued use may still be directed towards a valued immediate result: relief, stimulation, social connection or escape. Research on goal-directed behaviour and habits gives a mixed picture. People may respond to changing costs, alternatives and rewards while still finding it extraordinarily difficult to stop. Recognising that responsiveness helps explain why changing circumstances and making other sources of reward accessible can be therapeutic. Review of habits and goal-directed action

There is broad agreement that biology matters and that people deserve healthcare. The stronger claim that every addiction is defined by one distinctive brain pathology is disputed. Updated brain-based accounts include environmental influences, learning and recovery; critics argue that no single abnormality identifies all cases and warn against neglecting circumstances and agency. These are debates about how best to explain evidence, not a reason to deny either biological processes or the need for treatment. A revised account of addiction as a brain disorder, A critical perspective on the brain-disease model

Recovery can involve reversal of some adaptations, new learning, changed relationships and opportunities, and possibly new patterns of brain organisation. Much detailed evidence about the last possibility comes from animals. Persistent memories or vulnerability do not mean relapse is inevitable, and recovery need not require every measured biological feature to return to an earlier state. Review of the biology of recovery

Brain studies also have limits. Differences observed after years of use can reflect previous vulnerability, drug exposure, withdrawal, sleep problems, adversity, other illnesses or several substances used together. A 2025 analysis of 51 brain-imaging studies found some recurring links between responses to drug cues and treatment outcomes, but small studies, differing methods and selective reporting limit their use for predicting an individual's progress. Genetic studies remain uneven in ancestry representation, and imaging studies and other reviews of addiction often draw heavily on alcohol and nicotine. Multiple reviews can recycle the same small set of original studies. Review of brain responses to cues and treatment outcomes

Better research will follow people before substantial exposure, compare similarly exposed people with different outcomes, test competing explanations directly and study recovery outside specialist clinics as well as within them. It also needs more diverse populations and realistic combinations of substances. For now, no brain scan, dopamine measurement, genetic result or history of adversity can by itself establish a person's cause, prognosis or best treatment.

Opioid use disorder: continuing treatment saves lives

For opioid use disorder, methadone and buprenorphine are the principal established medicines for ongoing treatment. They reduce withdrawal and craving and help stabilise life without the repeated fluctuations associated with uncontrolled use. Effective treatment requires an adequate clinical regimen, reliable access and a plan that a person can sustain. Choice should consider previous treatment, preferences, other illnesses, other medicines and how care can be delivered. England's recommendations on methadone and buprenorphine

A large 2021 review found that death rates were substantially lower while people were receiving opioid agonist treatment—the name for treatment with medicines such as methadone and buprenorphine—than while they were outside it. Across observational studies, the overall comparison was approximately eleven versus twenty-four deaths per thousand person-years, with a rate ratio of 0.47 and a plausible range of 0.42–0.53. In ordinary language, the observed death rate was about half as high during treatment. These are not predictions that half of untreated individuals will die. Differences in engagement and circumstances can influence observational comparisons, but the consistency and scale of the evidence make retaining people in treatment a central priority. Review of opioid treatment and mortality

Methadone tends to retain more people in treatment on average. A 2023 review included 32 randomised trials and 69 observational studies; in trials reporting six-month retention, the proportion retained on buprenorphine was about 76% of that retained on methadone, with a range of 67–85%. These comparisons largely concerned buprenorphine taken under the tongue, not every newer formulation. Buprenorphine has advantages in breathing-related safety, particularly when tolerance is uncertain or other medical risks matter. The average retention advantage for methadone does not settle the best choice for every individual. Review comparing methadone and buprenorphine

Weekly or monthly buprenorphine injections can reduce the burden of daily medication and dispensing visits. They do not automatically outperform other formulations for every purpose. A 2026 emergency-department trial involving 1,994 unique participants found no significant improvement in engagement with treatment after seven days when a seven-day injection was compared with treatment taken under the tongue. Both groups received help connecting with ongoing care. That result concerns a specific short-term intervention and should not be treated as a verdict on all long-acting formulations. The emergency-department buprenorphine trial

Naltrexone works differently: it blocks opioid effects. It requires an opioid-free period before initiation, which can be difficult to complete safely. In the 570-person X:BOT trial, about 72% of those assigned extended-release naltrexone successfully started it, compared with 94% assigned buprenorphine–naloxone. Over twenty-four weeks, relapse occurred in about 65% and 57% respectively when everyone assigned to treatment was counted. Results were more similar among those who actually started, but excluding people who could not start hides an important practical disadvantage. Naltrexone remains a reasonable option for selected people who prefer it and can complete the required withdrawal safely. The X:BOT comparative trial

There is no universal time limit after which useful opioid medication must stop. Treatment should continue according to benefit, risk and preference. Counselling and practical support can be valuable, but their absence or a person's decision not to attend should not block access to medication. Detoxification alone does not provide a sufficient long-term plan. After a period without opioids, tolerance falls, so returning to a previously familiar amount can cause overdose. Stopping treatment therefore needs careful planning and continuing access to help. ASAM's opioid-use-disorder treatment guideline

For a small group with severe continuing heroin problems despite well-delivered oral treatment, supervised injectable diamorphine can be considered in specialist services. It requires careful selection, dedicated facilities and monitoring. It is a specific later option, not a replacement for offering accessible, effective oral treatment first. UK guidance on supervised injectable opioid treatment

Stimulant use disorder: making change rewarding

For cocaine and methamphetamine problems, contingency management has the clearest established role. It provides timely, tangible rewards for agreed, verified progress, such as attending treatment or submitting samples showing no recent use. The point is to make beneficial actions rewarding now, rather than relying solely on distant promises of improved health. Reliable implementation matters. It can be combined with cognitive behavioural therapy, which develops coping skills, or community reinforcement, which helps build rewarding activities and relationships outside drug use. Structured programmes such as the Matrix approach combine several forms of support. ASAM and AAAP's stimulant treatment guideline

An analysis of fifty trials involving 6,942 people found that contingency management combined with community reinforcement improved end-of-treatment abstinence compared with usual care. The odds ratio was 2.84, with a wide range of 1.24–6.51. This is not a finding that nearly three times as many people achieve lasting recovery; odds, proportions and long-term outcomes differ. A 2024 Cochrane review of 64 trials and 8,241 people found that psychological and social treatments reduced dropout. Effects on drug use were clearer against no intervention than against usual care, while lasting abstinence was less certain. Most studies concerned cocaine, which limits automatic generalisation to methamphetamine. Comparative review of stimulant treatments, Cochrane review of psychosocial treatment

Medication findings for cocaine remain inconsistent. Medicines can have a role in selected stimulant cases, but there is no medication with the same established general role that methadone or buprenorphine has for opioid use disorder. In the ADAPT-2 methamphetamine trial, which enrolled 403 people at its initial stage, combined naltrexone and bupropion produced a weighted response rate of 13.6%, compared with 2.5% for placebo: an 11.1-percentage-point difference. Response meant at least three of four urine samples were negative during the final two weeks of a six-week treatment stage. It did not mean long-term recovery, and most participants did not meet that response definition. Naltrexone cannot simply be added to methadone or buprenorphine treatment because it blocks opioid effects and can precipitate withdrawal. The ADAPT-2 trial

A larger 2026 trial of mirtazapine randomised 344 adults with methamphetamine use disorder. At twelve weeks, the medication group reported about 2.2 additional days without methamphetamine per twenty-eight days compared with placebo; the plausible extra benefit ranged from about 0.2 to 4.2 days. Tests of oral fluid and other secondary outcomes did not show clear improvement. Drowsiness, weight gain and stopping the medicine because of adverse effects were more frequent. This is evidence of a modest possible benefit, not a general cure or a reason to abandon established psychological treatment. The 2026 mirtazapine trial

Guidelines disagree about prescribed stimulants as treatment for stimulant use disorder. The American ASAM/AAAP guideline allows selected, closely monitored use of long-acting preparations by appropriately experienced clinicians. WHO advises against dexamphetamine, methylphenidate and modafinil for cocaine or stimulant use disorders because of safety concerns, while British guidance describes insufficient evidence for amphetamine disorders and inconclusive evidence for cocaine disorders. These differences reflect uncertain benefits, safety and implementation, rather than a universally accepted first-line medication. Treating a co-occurring condition such as ADHD is a separate clinical question. WHO's psychostimulant treatment recommendation, British pharmacological guidance

Cannabis use disorder: helpful therapies, uncertain medicines

The best-supported approaches to cannabis problems combine motivational work with cognitive behavioural therapy. They help people consider what they want to change, recognise triggers, manage urges and develop other ways to cope. Contingency management can also be added, although comparisons between particular combinations remain uncertain.

A 2025 review of 22 trials involving 3,304 people found improved continuous abstinence with motivational enhancement plus cognitive behavioural therapy compared with inactive controls. The odds ratio was 2.72, with a range of 1.20–6.19. The evidence was limited by study quality and imprecision, so the number should not be read as a firm prediction for an individual. A 2026 comparison drawing on 57 studies found promising results for combinations including contingency management and approaches involving acceptance of difficult experiences, but did not establish a dependable ranking of therapies. The 2025 review of cannabis psychological treatments, The 2026 comparative review

There is no established medication treatment for cannabis use disorder. A 2025 Cochrane review of 37 trials involving 3,201 people found insufficient evidence to support routine medication use. Newer analyses have reported possible signals for cannabidiol, N-acetylcysteine or varenicline, but estimates are imprecise and compatible with no benefit. Relieving a withdrawal symptom is also different from helping someone make a durable change in cannabis use. Such medicines remain experimental for this purpose. Cochrane review of medicines for cannabis dependence

Benzodiazepines and other drugs need their own plans

A person who has become physically dependent on prescribed benzodiazepines should not automatically be described as addicted. When reducing or stopping is appropriate, the usual approach is an individualised, gradual, clinically supervised reduction, together with care for the anxiety, insomnia or other problem for which the medicine was taken. Cognitive behavioural therapy, including therapy specifically for insomnia, can support the process. NICE recommends reductions proportionate to the current dose, generally becoming smaller as the dose falls, with flexibility when symptoms make progress difficult. This is a principle for supervised care, not a do-it-yourself schedule. NICE guidance on dependence and withdrawal from prescribed medicines

Abruptly stopping benzodiazepines after physical dependence can cause seizures or delirium. Some situations need inpatient management. The best rate of reduction is not settled by strong comparative trials; much detailed guidance relies on clinical experience and expert agreement. A plan needs to respond to the person's symptoms, health, other substances and circumstances. The joint benzodiazepine tapering guideline

For ketamine use disorder, medication evidence is largely limited to small series and individual reports. GHB or GBL withdrawal can deteriorate rapidly and requires urgent specialist assessment. Evidence does not establish a single best treatment hierarchy for these and several other less-studied substances. Synthetic cannabinoids and gabapentinoids also require attention to their own effects and risks. The absence of a well-proven medication does not mean that assessment, psychological treatment, physical healthcare and practical support have nothing to offer. British guidance on less-studied substance-use disorders

Reducing harm and making care possible

Preventing death and illness is part of treatment even while drug use continues. People at risk of opioid overdose and those around them should have access to naloxone and training in overdose response. Naloxone reverses opioid overdose; it does not treat the longer-term disorder, and emergency medical help is still necessary. Infection prevention, appropriate equipment services, testing and treatment for infections, and ordinary physical healthcare remain important. Using opioids with alcohol or other sedating drugs increases danger and needs explicit discussion in care. SAMHSA's guidance on medications for opioid use disorder

Mental healthcare, safer housing, help with employment and relationships, and continuity after hospital or residential treatment can determine whether a treatment plan is possible to follow. These are not merely extras added after a biological treatment is complete. International standards emphasise accessible, coordinated and continuing care matched to need. Most trial evidence concerns adults; adolescents, pregnancy and complex use of several substances need more specific assessment. WHO and UNODC's international treatment standards

Motivational interviewing can help a person explore uncertainty about change. A review of 93 studies found clearer benefit compared with no intervention than compared with usual care or another active treatment. The studies combined alcohol and other drugs, so the result is not equally precise for every substance. It is a useful way of engaging people, not a universally superior standalone treatment. Cochrane review of motivational interviewing

Residential rehabilitation is a setting, not a single treatment with a uniform effect. NICE suggests considering it for people seeking abstinence who have significant difficulties and have not benefited from community treatment. What happens there, the person's needs and what happens after discharge matter more than the label alone. Continuing drug use should prompt reassessment of the plan, risks and support; it should not automatically lead to discharge or forced withdrawal from effective opioid medication. NICE guidance on psychosocial treatment and residential care

What treatment research can and cannot tell us

A negative urine sample, fewer days of use, remaining in treatment, improved daily functioning and staying alive are different outcomes. A treatment can help one without clearly helping all. Retention can be particularly consequential for opioid treatment because being in treatment is associated with lower mortality. For other interventions, an early improvement in a test result does not establish lasting recovery.

Comparisons also matter. A therapy may outperform no help yet add little to already supportive care. An apparently successful medication trial may rely on a secondary outcome after the main outcome failed. People who leave studies or treatment can have worse outcomes than those who remain; analysing only completers can therefore give an overly favourable picture. Psychological treatment cannot usually be concealed from participants, and objective drug tests do not remove every effect of extra attention or expectations. Medication side effects can also reveal treatment allocation.

Many studies are small, short or restricted to selected participants. Reviews may repeatedly include the same trials, and inconsistent definitions or selective reporting can produce apparently conflicting results. Evidence for long-term functioning, health and durable remission is often thinner than evidence for short-term use or attendance. New findings from 2026 add useful possibilities but do not overturn the central treatment distinctions: ongoing medication is foundational for opioid use disorder; well-delivered contingency management is especially important for stimulant disorders; psychological treatment leads current cannabis care; and benzodiazepine withdrawal requires a careful individual plan.

The next priorities are longer and more representative comparisons, replication of promising medicines with objective as well as self-reported outcomes, better evidence for people using several substances, and studies of how to make effective treatment reliably accessible. No one programme fits every drug problem. Care works best when it addresses the specific substance, immediate risks, the function use serves, other health conditions and the practical circumstances in which change has to happen.