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Addiction

Studies of how psychedelics, medications, and behavioral approaches affect substance dependence and craving.

State of the evidence

Synthesized

Synthesized from 25 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for Addiction, substance use disorder, dependence, alcohol use disorder, opioid use disorder, then ranked by relevance.

Psilocybin-assisted therapy shows promise for reducing alcohol and tobacco use, with pilot studies reporting high abstinence rates (e.g., 80% for smoking at 6 months) and a double-blind RCT finding reduced heavy drinking days in alcohol use disorder. However, evidence is preliminary due to small sample sizes, open-label designs, and limited long-term follow-up. Ketamine also shows potential for addiction but carries risks of abuse and tolerance, while mindfulness meditation may reduce substance use in incarcerated populations.

Confidence in the evidence

Low-Moderate
  • Only one double-blind RCT (article_id 16219) provides controlled evidence for psilocybin in alcohol use disorder; other studies are open-label or proof-of-concept with small samples (e.g., n=10, n=15).
  • Results are consistent across psilocybin studies showing positive effects on abstinence and craving, but the evidence base is limited by small sample sizes and lack of replication in larger trials.
  • Ketamine studies (article_ids 28485, 35277) show mixed findings: potential efficacy in alcohol use disorder but also rapid tolerance and abuse liability, reducing confidence.
  • Mindfulness meditation (article_ids 25963, 25974) shows preliminary efficacy but with significant methodological limitations and lack of conclusive data.
How we rate confidence

Confidence reflects the strength of the underlying evidence, not whether the result is favorable. It weighs the number and size of studies, their design (randomized trials count for more than observational or single-case work), how consistently they point the same way, and their risk of bias.

Tiers run from Insufficient to High. High is rare in this field: small, early, or open-label studies land lower even when their direction is encouraging.

Evidence by study

Direction is each study's finding relative to your question: Supports, Opposes, No effect, Mixed, or Unclear.

Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study 2015
Supports

Psilocybin administration significantly increased abstinence and reduced craving in alcohol-dependent participants, with gains largely maintained at 36-week follow-up.

proof-of-concept study Sample size: 10

Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction 2014
Supports

80% of participants showed biologically verified smoking abstinence at 6-month follow-up after psilocybin-assisted treatment, substantially exceeding typical cessation rates.

open-label pilot study Sample size: 15

Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder 2022
Supports

High-dose psilocybin improved the percentage of heavy drinking days compared to active placebo (diphenhydramine) in patients with AUD undergoing psychotherapy.

double-blind randomized clinical trial

Ketamine use: a review 2011
Opposes

Chronic ketamine use is associated with ulcerative cystitis, neurocognitive impairment, and addiction, with many frequent users reporting difficulty stopping use.

review

Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. 2019
Supports

Epidemiological studies suggest nonmedical naturalistic use of classic psychedelics is associated with positive mental health and prosocial outcomes, though causality is unclear.

integrative review

Mindfulness meditation and substance use in an incarcerated population. 2006
Supports

Vipassana meditation significantly reduced alcohol, marijuana, and crack cocaine use after release from jail compared to treatment-as-usual control.

controlled trial

Psilocybin-Occasioned Mystical Experiences in the Treatment of Tobacco Addiction 2015
Supports

Psilocybin-occasioned mystical experiences were significantly correlated with smoking cessation, suggesting a mediating role of mystical experience in treatment.

open-label pilot study Sample size: 15

Psychedelics as Medicines: An Emerging New Paradigm 2016
Supports

Clinical studies show preliminary evidence of robust efficacy for psychedelics in treating addiction to tobacco and alcohol, with proposed mechanisms involving brain network resetting.

review

Mindfulness Meditation for Substance Use Disorders: A Systematic Review 2009
Mixed

Preliminary evidence suggests mindfulness meditation efficacy and safety for SUDs, but conclusive data are lacking due to significant methodological limitations.

systematic review

Psychedelics reopen the social reward learning critical period 2023
Supports

Psychedelics reopen the social reward learning critical period in mice, with reorganization of extracellular matrix as a common downstream mechanism.

preclinical study

Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada 2013
Supports

Ayahuasca-assisted therapy was associated with statistically significant improvements in factors related to problematic substance use.

observational study

Dynamic coupling of whole-brain neuronal and neurotransmitter systems 2020
Supports

Psilocybin stimulation of 5-HT2A receptors causally explains functional effects in the brain, providing a framework for understanding its therapeutic promise for addiction.

neuroimaging study

Psychedelics not linked to mental health problems or suicidal behavior: A population study 2015
Supports

Lifetime use of psychedelics was not associated with increased mental health problems or suicidal behavior, and psychedelics are not known to cause addiction.

population study Sample size: 135095

Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts 2018
Supports

Participants reported vivid insights into smoking reasons, persisting positive changes beyond cessation, and emphasized the role of preparatory counseling and rapport.

qualitative study Sample size: 12

Psychedelics as anti-inflammatory agents 2018
Supports

Psychedelics produce anti-inflammatory effects via 5-HT2A receptor activation, which may contribute to their therapeutic effects in addiction and other disorders.

review

Prescribing bias and adverse outcomes of esketamine in major depression comorbid substance. 2026
Opposes

Esketamine users had higher risks of comorbid substance use disorders, and those with SUD had higher risks of self-harm, suicide attempt, and hospitalization.

retrospective cohort study Sample size: 30670

S-ketamine, but not R-ketamine, transiently suppresses front-loaded binge-like alcohol self-administration in male rats 2026
Mixed

S-ketamine dose-dependently suppressed alcohol self-administration in rats, but efficacy rapidly declined with repeated administration, indicating tolerance.

preclinical study

Treating addiction with an addictive drug: the ketamine paradox revisited 2026
Mixed

Ketamine combined with psychotherapy shows promising reductions in craving and increases in abstinent days, but findings are limited by variability in dosing and follow-up, and abuse liability remains a concern.

narrative review

Toward a nuanced framework for the medical development of ibogaine and its analogues and derivatives: implications for psychopharmacology 2026
Supports

Ibogaine shows therapeutic potential across substance use disorders, but clinical translation is hindered by safety concerns and regulatory barriers.

review

Neuroestimulantes naturales: de rituales ancestrales a terapias de vanguardia 2026
Supports

Psilocybin and 5-MeO-DMT are recognized as promising therapies for addictions resistant to conventional treatments, acting on serotonin receptors and stimulating neuroplasticity.

review

MDMA-assisted PTSD and Alcohol Therapy Trial (MPATHY): study protocol for a double-blind, randomised, controlled outpatient trial of MDMA-assisted integrated exposure-based therapy for comorbid post-traumatic stress disorder and alcohol use disorder 2026
Unclear

This double-blind trial will examine MDMA-assisted integrated exposure therapy for comorbid PTSD+AUD, with outcomes including heavy drinking days and PTSD symptoms.

study protocol Sample size: 100

Self‑transcendence and identity transformation in recovery from substance use disorder 2026
Supports

A spiritually oriented intervention emphasizing self-transcendence and identity transformation helped a participant move away from an addiction-centered identity.

case study Sample size: 1

Decoding the serotonin–alcohol crosstalk: the role of central serotonergic dysregulation in alcohol use disorder 2026
Supports

Serotonergic psychedelic-assisted therapies have attracted interest as potential AUD treatments, with mechanisms involving raphe-prefrontal serotonergic projections.

review

Psychedelic Use, Microdosing, Motives, and Information and Product Sources Among Young Adults in the United States 2026
Mixed

Among young adults, mental health symptoms and adverse childhood events were associated with psychedelic use, microdosing, and higher use motives, despite half using exclusively for nonmedical purposes.

cross-sectional survey

Navigating the waves of cluster headache 2026
Mixed

People with cluster headache more often used psilocybin and LSD, with some reporting reduced attack frequency or duration, but risk-taking behavior varied by disease phase.

dissertation

Points of agreement

  • Psilocybin-assisted therapy shows consistent positive effects on reducing alcohol and tobacco use across multiple studies, including a double-blind RCT.
  • Mystical or self-transcendent experiences are identified as a potential mechanism for therapeutic change in psychedelic-assisted addiction treatment.
  • Ketamine shows potential for reducing alcohol use but is associated with risks of tolerance, abuse, and adverse effects.
  • Mindfulness meditation may reduce substance use, but evidence is preliminary and methodologically limited.

Conflicts

  • Ketamine's abuse liability and potential for addiction (article_id 25613) conflicts with its therapeutic potential for substance use disorders (article_id 28485).
  • Esketamine use was associated with higher risks of comorbid SUD and adverse outcomes (article_id 28670), contrasting with positive findings for other psychedelics.
  • One population study found no link between psychedelic use and mental health problems (article_id 16800), while another survey found associations with mental health symptoms (article_id 27692).

Gaps

  • Durability of treatment effects beyond 6-9 months is largely unstudied for psychedelic-assisted therapies.
  • Most studies have small sample sizes and lack active placebo or blinding, limiting generalizability.
  • Mechanisms of action (e.g., mystical experience vs. neuroplasticity vs. anti-inflammatory effects) are not fully disentangled.
  • Research on underrepresented populations (e.g., racial/ethnic minorities, adolescents, polysubstance users) is lacking.
  • Optimal dosing, number of sessions, and integration protocols are not established.
  • Long-term safety data, especially for repeated use, are insufficient.
Browse these studies in the library
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is Addiction, up to 25 in all. The most-cited set anchors the established evidence, and the recent set surfaces work that is too new to have gathered citations yet.

A study qualifies only when Addiction or a known alias appears in its title or keywords, so broad reviews that mention it only in passing are left out. Each study is read from its abstract, strongest evidence first, and the summary reports the direction of the results along with any conflicts and gaps.

Ask your own question in the Research Synthesis Tool

Latest monthly recap: June 2026 →

4,479 articles · 1,578 from the last two years · 7,788,067 participants across 1,255 studies reporting sample size

Common study designs

review 846 systematic review 185 experimental study 523 observational cohort 177 theoretical or philosophical paper 530

Research

Synthesize the evidence → Search all →

New insights into the clinical and nonclinical effects of psychedelic substances: an integrative review

Matthias Forstmann, Christina Sagioglou preprint

After a long period of stagnation, research on psychedelic substances like LSD, psilocybin, and DMT has revived over the last decade, with major programs in Europe and the United States. This review summarizes recent insights into their potential for treating mental health disorders, effects on recreational users, and underlying neurological and cognitive processes. It covers the history of psychedelic research, objective and subjective effects, prevalence and correlates of use, and potential for harm. The review examines clinical benefits for major depression, anxiety, and substance use disorders, along with proposed neural and cognitive mechanisms. It also discusses effects on healthy subjects, including psychological wellbeing, personality changes, nature relatedness, and creativity, and concludes with long-term effects of single experiences.

DOI: 10.31234/osf.io/2489x

Effectiveness and Experiences of Psychedelic-Based Interventions for the Treatment of Alcohol Use Disorder: A Mixed Methods Systematic Review

Baneet Gill

A mixed-methods systematic review of eight studies (four quantitative, four qualitative) examined the effectiveness and experiences of using psychedelics to treat alcohol use disorder (AUD). Quantitative studies reported an overall increase in abstinence and a decrease in drinking days after treatment, while qualitative studies reported mostly positive experiences. However, the included studies were rated mostly 'poor' or 'moderate' quality, so results should be interpreted with caution. The small number of recent studies, small sample sizes, and heterogeneity of studies limit the strength of conclusions, highlighting the need for further research.

DOI: 10.31237/osf.io/tqa8j_v1

Psychopathological descriptive model of hallucinogenic/psychedelic drugs effect in the treatment of depression and addictions

Nestor Girala

The efficacy of hallucinogenic drugs (ayahuasca, psilocybin, LSD, ketamine) in treating depression and addictions is accompanied by intense emotional states and mystical-type experiences, including feelings of oneness, transcendence, ineffability, and awe. These common psychopathological elements may mediate the drugs' therapeutic action. The paper reviews literature on subjective experiences during such treatments and compares them with other life-changing experiences, discussing the evolutionary value of these emotions for group cohesiveness and the recalibration of cognitions and emotions.

DOI: 10.14293/s2199-1006.1.sor-.ppfvg0c.v1

Abuse of Dextromethorphan, Carbamazepine, and Naphazoline

Ahmad R. Alsayed preprint

The misuse of over-the-counter and prescription medications is a growing public health concern. Dextromethorphan, a cough suppressant, is abused for its dissociative and euphoric effects, leading to dependency and severe health risks. Carbamazepine, prescribed for epilepsy and bipolar disorder, is also abused for its euphorigenic properties. Naphazoline, an ophthalmic vasoconstrictor, is misused for psychoactive effects. Widespread availability, affordability, perceived safety, and lack of regulation contribute to this trend. The review calls for stricter regulations, increased awareness, and better pharmacovigilance to address the problem.

DOI: 10.20944/preprints202504.0542.v1

Individual differences in the pharmacokinetic profiling of Δ9-THC may be associated with differential motivational effects of Δ9-THC on cognitive performance

Teneisha M. Myers, Noah C. Neverette, Aaron S. Devanathan et al. preprint

Acute restraint stress and THC did not impair working memory in rats. However, a 3 mg/kg dose of THC disrupted motivation-related task engagement in some rats, while others were unaffected. Those that stopped responding had higher plasma THC and metabolite concentrations than those that continued. Individual differences in THC metabolism may explain why some people experience adverse cognitive or motivational effects after cannabis use, while others do not.

DOI: 10.1101/2025.09.30.679373

Influence of solvent, sex, and age on pharmacokinetic and acute behavioral effects of vaporized cannabis extract in mice

S.R. Westbrook, A.L. Jensen, V. Copeland-Solorzano et al. preprint

Vaporized cannabis extract dissolved in polyethylene glycol 400 (PEG) produces higher plasma THC levels and stronger behavioral effects than when dissolved in propylene glycol/vegetable glycerol. In mice, the highest dose (300 mg/ml) caused reduced body temperature, pain sensitivity, and movement. Adolescent mice were less sensitive to the movement-suppressing effects than adults, and female mice metabolized THC more slowly than males, though no sex differences in acute behavioral effects were observed.

DOI: 10.1101/2025.01.10.632469

Cannabis induced psychosis: A comparative study between cannabis use disorder and cocaine use disorder

Maurizio Coppola, Raffaella Mondola preprint

Psychosis involves delusions and hallucinations without insight, arising from primary psychiatric illness or brain damage from substances, neurological diseases, or other medical conditions. Genetic, environmental, and gene-environment interactions contribute. Among environmental factors, psychotropic substances are key removable facilitators. This retrospective study compared substance-induced psychosis prevalence between outpatients with cannabis use disorder and those with cocaine use disorder, excluding those with personal or family psychiatric history.

DOI: 10.20944/preprints202310.0311.v1

Insular Cortical Thinning and Altered Structural Connectivity in Chronic Cannabis Users: A High-Resolution Morphometry and Diffusion Tractography Study

Fouad Meraji Far, Hamid Reza Banafshe, Amir Ghaderi et al.

Chronic cannabis use is associated with thinning of the insular cortex, a brain region involved in craving and self-awareness, and with altered white matter connections between the insula and other brain areas. In a sample of 13 male chronic cannabis users compared to 13 male non-users, MRI scans showed bilateral insular thinning without volume loss, reduced total gray matter volume, and lower volumes in the brainstem, left amygdala, right thalamus, left cerebellar cortex, and right orbitofrontal gyrus. Tractography revealed reduced diffusivity in left insula–amygdala pathways and lower fractional anisotropy in several insula–cortical connections. These findings suggest that circuits supporting salience, interoception, and emotional valuation are preferentially disrupted, which may contribute to compulsive cannabis use.

DOI: 10.21203/rs.3.rs-9801898/v1

Development of Bioisosteric Iboga -alkaloids as Antinociceptive and Anxiolytic Agents with Neuroprotective Effects

Abhishek Gupta, Tuhin Bhattacharya, Subhamoy Pratihar et al. preprint

Iboga alkaloids can reverse drug addiction and modulate drug tolerance but cause severe hallucinogenic effects and cardiotoxicity by blocking the hERG potassium channel. Researchers synthesized four new benzofuran-containing iboga analogs (C1, C2, C3, C4) with a bio-isosteric replacement of indole with benzofuran. The Endo-iboga analogs (C2 and C4) showed superior anti-inflammatory and oxidative stress-relieving activity and improved restricted locomotor activity in a formalin-induced acute pain model in mice. They elevated levels of GABA, dopamine, and BDNF. C4 had a superior cardiac safety profile in C2C12 cells (IC50 = 235 µM) and caused no significant QTc prolongation in rat ECG tests, indicating potential for acute pain management without notable cardiotoxicity.

DOI: 10.1101/2025.02.24.639821

Co-Boost: Boosting and guiding neuroplasticity by combining ketamine with neurofeedback-assisted learning – towards an individualised and integrated pharmaco-psychotherapy for cocaine addiction: study protocol for a randomised, placebo-controlled, double-blind, parallel-group, single-centre trial

Anna Stefania Trippel, Ladina Philomena Gubser, Etna Jennifer Elektra Engeli et al.

A randomized, placebo-controlled, double-blind trial will test a single ketamine infusion, three sessions of reward-imagery real-time fMRI neurofeedback training, and their combination in 120 people with cocaine use disorder. The study expects both interventions to reduce the proportion of cocaine use days, with ketamine increasing glutamate in the reward system and lowering craving, and neurofeedback re-sensitizing participants to natural rewards. This neurobiologically informed approach aims to open new treatment avenues through individualized pharmaco-psychotherapy.

DOI: 10.21203/rs.3.rs-5677691/v1

Clinical trials

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