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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

3,725 articles · 1,378 from the last two years · 4,837,720 participants across 988 studies reporting sample size

Common study designs

review 699 systematic review 159 experimental study 432 randomized controlled trial 142 theoretical or philosophical paper 401

Research

Synthesize the evidence → Search all →

Sensing minimal self in a sentence that involves the speaker

Ryoko Uno, Shu Imaizumi preprint

Variations in sentence structure can alter a speaker's sense of minimal self—specifically, the sense of agency and ownership over their own actions and perceptions. In experiments using Japanese sentences, the sense of agency was significantly lower when actions or perceptions were absent from the first-person subject's expression. The sense of ownership was significantly lower when both action and perception were absent, and varied by context when action was absent but perception remained. These findings suggest that linguistic choices affect the felt experience of selfhood, bridging the narrative self and the embodied minimal self.

DOI: 10.31234/osf.io/3qa25

Sensing minimal self in sentences involving the speaker

Ryoko Uno, Shu Imaizumi preprint

The way a sentence is structured can influence a speaker's sense of agency and ownership—key components of the minimal self. In an experiment with Japanese sentences, participants rated their sense of agency and ownership as if they had uttered each sentence. Agency was significantly lower in sentences lacking causation or perception compared to those including them, and higher for perceiver-prominent sentences than for perceiver-stimulus-prominent ones. Ownership was also significantly lower when causation or perception was absent, though its relationship with sentence type varied by perceived stimulus. These findings indicate that linguistic structure measurably affects embodied self-experience, supporting cognitive linguistic theories about subjective construal.

DOI: 10.31234/osf.io/3qa25_v3

A chromosome level reference genome of Diviners sage (Salvia divinorum) provides insight into salvinorin A biosynthesis

bioRxiv (Cold Spring Harbor Laboratory) • Scott A. Ford, Rob W. Ness, Moonhyuk Kwon et al. preprint

A chromosome-level genome assembly of the diviners sage plant, which produces the hallucinogen salvinorin A, has been produced. The genome is about 541 million base pairs, diploid, and comparable to other sage species. Two gene clusters involved in diterpene biosynthesis were identified, including a gene that forms the dihydrofuran ring early in the salvinorin A pathway. Other enzyme classes likely involved in later steps are scattered across the genome. Most of these genes are not activated by methyl jasmonate treatment. This high-quality genome sequence will help uncover the remaining steps in salvinorin A biosynthesis and support exploration of its medical potential for chronic pain, addiction, and post-traumatic stress disorder.

DOI: 10.1101/2024.09.08.611878

The cultural evolution of shamanism

Manvir Singh • 35 citations

Shamanism—including medicine-men, mediums, and prophets—is a near-universal feature of human societies, especially among hunter-gatherers, and is often considered the first profession, the earliest institutionalized division of labor beyond age and sex. This paper proposes a cultural evolutionary theory explaining why shamanism consistently develops and exhibits recurrent features worldwide, why it professionalizes early even without other specialization, and how social conditions shape its form. The theory argues that shamanism adapts to people's intuitions by convincing observers that a practitioner can influence unpredictable, significant events. The shaman ostensibly transforms during initiation and trance, violating folk-intuitions of humanness to assure group-members of interaction with invisible forces controlling uncertain outcomes. Entry requirements persist because credibility depends on transformation, unlike problems with identifiable solutions where credibility hinges on results.

DOI: 10.31235/osf.io/bemhx

The God receptor: naturalistic, psychotic and entheogenic neurocognition in the origins and phenomenology of spiritual and religious thought

Bernard Crespi, Nancy Yang, Sam Doesburg preprint

The human brain does not contain a single region or network dedicated to spiritual or religious thought. Instead, religious and spiritual cognition may arise from the widespread effects of a specific receptor, the HT2A receptor, which influences perception, emotion, and cognition across many brain areas. The hypothesis is supported by integrating fMRI and lesion studies with data on HT2A receptor distribution, activation in psychedelic experiences, psychiatric conditions, and stress. If true, understanding the neuroscience of spirituality will require studying how adaptive and hyperactivated HT2A receptor signaling interacts with predictive coding and other brain systems.

DOI: 10.31234/osf.io/hk3xw_v1

"Advaita, Quantum Physics, and the Nature of Consciousness: A Philosophical Dialogue"

Preprints.org • Ranjeet Kumar Verma preprint

A dialogue between Advaita Vedanta's non-dualistic consciousness and quantum physics suggests that both challenge materialist views of reality. Advaita holds that consciousness (Brahman) is the fundamental reality and the material world is illusion (Maya). Quantum phenomena such as wave-particle duality, non-locality, and the observer effect resonate with this view, implying reality is interconnected, probabilistic, and observer-dependent. The paper proposes that quantum physics may offer a scientific framework supporting Advaita's claim that consciousness is the substratum of reality, and examines how the observer effect aligns with the Advaitic principle that reality is shaped by consciousness. This contributes to philosophy of mind and science by proposing a unified, non-dual model of consciousness.

DOI: 10.20944/preprints202411.0897.v1

The Phenomenal Is Functional: A Unified Theory of Consciousness and Computation

Michael Timothy Bennett, Sean Welsh

Consciousness arises because organisms that learn to classify causes of their own sensations adapt more efficiently. The hard problem—why there is something it is like to be conscious—is resolved by showing that phenomenal consciousness (P-consciousness) emerges when an organism must classify its own interventions, creating a persistent quality across those interventions. Access consciousness (A-consciousness) emerges at a higher order when an organism must infer another's prediction of its interventions. Together they form H-consciousness, a hierarchy of causal identities that simplify the environment into classifiers of cause and affect. The authors deny that a philosophical zombie could be as capable as a P-conscious being, because learning causality requires presupposing objects, not just learning associations.

DOI: 10.36227/techrxiv.24630621

Psychedelic Therapy: A Primer for Primary Care Clinicians – Part VII. Ketamine

Viviana D. Evans, Alejandro Arenas, Kenneth Shinozuka et al. preprint

Ketamine, originally a dissociative anesthetic, is now used for treatment-resistant depression and major depressive disorder with suicidal ideation. A single intravenous infusion shows antidepressant effects within hours, with a large effect size on depression scores. It also reduces PTSD symptom severity and suicidal ideation in emergency settings. However, therapeutic effects often subside within weeks, requiring repeated doses. Risks include temporary or persistent memory impairment, cardiovascular issues, liver toxicity, and bladder inflammation. Ketamine's opioid-sparing effect improves postoperative pain management.

DOI: 10.31234/osf.io/dtb6a

Psychedelic Therapy: A Primer for Primary Care Clinicians – Part VI. 3,4-methylenedioxy-methamphetamine (MDMA)

Kenneth Shinozuka, Burton J. Tabaac, Alejandro Arenas et al. preprint

MDMA, known as a party drug in the 1980s, is emerging as a powerful treatment for PTSD. Phase III FDA trials show MDMA-assisted psychotherapy has an effect size of 0.7-0.91, two to three times larger than existing antidepressants. Within 18 weeks, 67 to 71% of patients no longer meet PTSD diagnostic criteria. The literature is biased: animal studies used doses far above human levels, and human samples often involve recreational users of multiple substances. Only six clinical trials, all by MAPS, have been conducted, but preliminary evidence suggests MDMA is much more effective than current antidepressants for PTSD.

DOI: 10.31234/osf.io/r89k3

Lysergic acid diethylamide stimulates cardiac human H 2 histamine receptors

Research Square • Ulrich Gergs, Hannes Jacob, Pauline Braekow et al. • 1 citation

LSD increases the force and rate of heart muscle contraction by activating H2-histamine receptors in humans, and also acts as a partial agonist at 5-HT4 serotonin receptors in mice. In human atrial tissue from heart surgery patients, LSD's contractile effects were blocked by cimetidine, an H2-receptor antagonist. These findings clarify the cardiac effects of LSD, which is being studied again for psychiatric uses.

DOI: 10.21203/rs.3.rs-2898645/v1

Clinical trials

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