Psilocybin for Substance Use Disorders (SUD)

196 papers and 41 clinical trials exploring psilocybin as a treatment for substance use disorders (sud).

Blossom tracks 196 papers and 41 clinical trials examining psilocybin as a treatment for substance use disorders (sud). Psilocybin acts primarily as a 5-ht2a agonist (prodrug to psilocin). The papers and trials below are sorted by recency, and reported adverse events and dosing protocols are summarised in the linked overviews.

Psilocybin Substance Use Disorders (SUD)Adverse events Dose summary Clinical guidelines

CompoundClassic Psychedelic

Psilocybin

Psilocybin is a naturally occurring tryptamine psychedelic that acts as a prodrug to psilocin, a potent 5-HT2A receptor agonist. It is the furthest advanced psychedelic in clinical development, with two positive Phase III trials in treatment-resistant depression and expanding regulated access in Australia, Germany, and US states.

Full Psilocybin profile

IndicationAmong the world’s largest preventable health burdens

Substance Use Disorders (SUD)

Addiction is one of the oldest hopes for psychedelic medicine, going back to LSD trials for alcoholism in the 1950s. Today psilocybin is the workhorse, with positive trials in alcohol, tobacco and cocaine use disorders, and the cross-substance signal is real. But the picture is mixed rather than settled: a major alcohol trial was null, the studies are small, and almost all of them struggle to keep patients unaware of whether they got the drug. This page is the hub; alcohol, opioid and tobacco use disorders have their own dedicated pages.

Full Substance Use Disorders (SUD) profile

Safety summary

Psilocybin for Substance Use Disorders (SUD): adverse events

Psilocybin safety reports for Substance Use Disorders (SUD) most often include headache, nausea, anxiety, insomnia among the source-backed named adverse events currently normalized in Blossom.

12 source papers|156 named AE rows|Top events: headache, nausea, anxiety

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Dose summary

Psilocybin for Substance Use Disorders (SUD): dose summaries

Psilocybin clinical studies for Substance Use Disorders (SUD) include 22 structured dose rows across 16 linked trials. Common source-reported dose patterns include 25 mg, 0.1 mg/kg, 0.3 mg/kg. Interpret these as descriptive trial protocols, not treatment recommendations.

34 source papers|22 dose rows|Patterns: 25 mg, 0.1 mg/kg, 0.3 mg/kg

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Clinical guidelines

Psilocybin clinical practice guidance

Blossom tracks 30 trial-anchored clinical guidelines for psilocybin, covering screening, dosing-session facilitation, safety, and integration competencies relevant to substance use disorders (sud) research.

30 guidelines|Psilocybin protocol family

View Psilocybin guidelines

Academic Research

196 papers

Open Accessindividual

Epigenome-wide association study of psilocybin-induced methylome changes in alcohol use disorder

This longitudinal randomised study (n=37) in detoxified patients with alcohol use disorder examined DNA methylation changes after psilocybin 25 mg versus placebo and found one psilocybin-linked methylation site, plus broader changes related to depression and drinking measures. The changes involved genes and pathways linked to neuroplasticity and immune function.

Published: May 26, 2026
Journal: Translational Psychiatry
Authors: Urban, M. M., Zillich, L., Rieser, N. M., Herdener, M., Spanagel, R., Vollenweider, F. X., Preller, K. H., Meinhardt, M. W.

Open Accessindividual

Psilocybin in the Treatment of Cocaine Use Disorder A Randomized Clinical Trial

This randomised quadruple-blind placebo-controlled clinical trial (n=40) found that a single 25 mg/70 kg dose of psilocybin, given with psychotherapy, increased cocaine-free days and delayed relapse compared with diphenhydramine in people with cocaine use disorder.

Published: May 7, 2026
Journal: JAMA Network Open
Authors: Hendricks, P. S., Lappan, S. N., Shelton, R. C., Lahti, A. C., Cropsey, K. L., Johnson, M. W., Bradley, M., Simonsson, O., Davis, L. L., Grossman, D. H., Ortiz, C. E.

Open Accessindividual

Major life changes following psychedelic use: A retrospective survey among people using psychedelics naturalistically

This survey (n=581) evaluates the Psychedelic-related Major Life Changes Questionnaire (P-MLCQ) in people reporting naturalistic psychedelic use. It finds that 82.96% of participants reported major life changes in at least one domain, including goals (53.7%), values (53.53%), and spirituality (49.05%), with changes rated highly positively (M = 4.64/5). Frequency of use correlated with more changes (r = 0.34), while education level was negatively associated with the number of changes (β = -0.137).

Published: April 15, 2026
Journal: Scientific Reports
Authors: Aday, J. S., Glynos, N., Baker, A., Pouyan, N., Barron, J., Herberholz, M., Kruger, D. J., Woolley, J. D., Boehnke, K. F.

Open Accessindividual

Psilocybin or Nicotine Patch for Smoking Cessation A Pilot Randomized Clinical Trial

This pilot randomised clinical trial (n=82) found that a single dose of psilocybin (30mg/70kg) combined with cognitive behavioural therapy produced significantly higher long-term smoking abstinence rates at 6 months compared to nicotine patches plus CBT (41% vs 10%), with no serious adverse events attributed to either treatment.

Published: March 10, 2026
Journal: JAMA Network Open
Authors: Johnson, M. W., Naudé, G. P., Hendricks, P. S., Garcia-Romeu, A.

Open Accessmeta

Psychedelic medicine: mechanisms, evidence, and translation to practice

This review (2026) summarises the rapidly growing evidence for psychedelic-assisted therapies, finding the strongest support for psilocybin in treatment-resistant depression (TRD) and MDMA in post-traumatic stress disorder (PTSD). It also highlights that while these treatments are generally well tolerated in controlled settings, major challenges remain around unclear mechanisms, trial limitations, scalability, and translation into routine practice.

Published: February 23, 2026
Journal: BMJ
Authors: Jacobs, E., Zahid, Z., Hinkle, J., Nayak, S., Yaden, D. B.

Paywallindividual

A qualitative analysis of participant expectations and experiences of psilocybin-assisted psychotherapy for methamphetamine use disorder

Participants in a pilot study of psilocybin‑assisted psychotherapy for methamphetamine use disorder found the intervention acceptable and reported that confronting vividly challenging psychedelic experiences—described as “leaning into the obstacle”—fostered new self‑understandings and shifts in relationships that reduced the salience of methamphetamine. A strong therapeutic alliance, characterised by concentrated attention and intersubjective intimacy, was seen as critical to these positive changes.

Published: December 22, 2025
Journal: Addiction
Authors: Brett, J., Lea, T., Knock, E., Albert, S., Acheson, L., Siefried, K. J., Job, S.

Clinical Trials

41 trials

Not yet recruitingPhase I/II

Psilocybin Assisted Psychotherapy for Treatment Resistant Depression and Co-occurring Substance Use Disorder

This Phase I/Phase II, randomised, double-blind, quadruple-masked trial (n=50) will evaluate a single oral dose of psilocybin 5 mg, 10 mg or 25 mg, given alongside psychotherapy, in veterans and first responders with treatment-resistant depression (TRD) and co-occurring substance use disorder (SUD). The study will assess safety and tolerability, as well as whether psilocybin-assisted psychotherapy can reduce substance use severity and depressive symptoms. Participants will be assigned in parallel to one of three psilocybin dose groups and will complete two intake visits, three preparatory psychotherapy sessions, an 8 to 10 hour dosing session, and three weekly integrative psychotherapy sessions afterwards. Outcomes include adverse events, urine drug results, days of substance use, depression symptom ratings, plasma brain-derived neurotrophic factor (BDNF) during stress exposure, and resting brain functional connectivity on MRI, with repeated daily assessments across 6 weeks and follow-up through 12 weeks, including a 60-day follow-up.

Started: August 1, 2026
Type: interventional
Blinding: quadruple
Randomized: Yes
Registry ID: NCT07499583

Not yet recruitingPhase III

Efficacy in Relapse Prevention: Psilocybin in Alcohol Use Disorder With Depressive Symptoms

This Phase III, randomised, triple-blind, parallel trial (n=172) will evaluate whether psilocybin-assisted psychotherapy can prevent relapse in adults with severe alcohol use disorder (AUD) and depressive symptoms after detoxification. The study will compare two administrations of high-dose psilocybin (25 mg) with two administrations of low-dose psilocybin (3 mg), given 3 weeks apart, with the main aim of reducing relapse over 6 months. Participants must have a confirmed DSM-5 diagnosis of severe AUD and a Beck Depression Inventory-II score of at least 14, with the last drink taken between day -60 and day -10 before inclusion. The primary outcomes are incidence of relapse and time to relapse at 6 months. Eligible adults of any sex will be enrolled at the Centre Hospitalier Universitaire de Nîmes, with study start planned for June 2026 and completion expected in June 2030.

Started: June 1, 2026
Type: interventional
Blinding: triple
Randomized: Yes
Registry ID: NCT07638553

Not yet recruitingPhase II

Psilocybin-Assisted Psychotherapy for the Treatment of Severe Alcohol Use Disorder

This Phase II, randomized, quadruple‑masked, parallel trial (n=36) will evaluate the safety and preliminary efficacy of psilocybin‑assisted psychotherapy in adults aged 18–65 with severe alcohol use disorder, with primary outcomes including percent heavy drinking days and adverse effects and secondary measures of cue‑induced craving and neural response by fMRI. Participants will be randomised 1:1 to a low‑dose or full‑dose psilocybin arm and will complete two supervised dosing sessions paired with a standardised psychotherapy protocol. Participants in the low‑dose arm receive oral psilocybin capsules of 10 mg at the first session with an optional escalation to 15 mg at the second session; the full‑dose arm receives 30 mg at the first session with an optional escalation to 40 mg at the second session. Dosing sessions occur in a controlled clinical setting four weeks apart with preparatory and integration sessions delivered by a dyad of trained therapists, continuous monitoring during dosing, and support from a peer recovery coach plus optional outpatient addiction treatment. Eligible participants are recruited up to 90 days after completing inpatient withdrawal management; outcomes are assessed through 48 weeks after the second dose, including percent heavy drinking days (weeks 0–24 after the first dose), adverse events at multiple post‑treatment timepoints, cue‑induced craving (baseline, 4 and 24 weeks after the second treatment), and fMRI measures one week before and one week after the second psilocybin session.

Started: May 1, 2026
Type: interventional
Blinding: quadruple
Randomized: Yes
Registry ID: NCT07296094

RecruitingPhase I

Psilocybin for Methamphetamine Addiction

Open-label, single-arm early Phase I pilot (n=20) assessing feasibility and tolerability of a single 25 mg oral psilocybin dose to promote abstinence in adults receiving residential treatment for methamphetamine dependence.

Started: March 1, 2025
Type: interventional
Blinding: none
Randomized: No
Registry ID: NCT06899594

RecruitingPhase II

Psilocybin for Opioid Use Disorder (OUD)

Double-blind, adaptive, two-stage, multi-site, Phase II randomised trial (up to 480 consented to yield 240 randomized) comparing single moderate (20 mg) and high (30 mg) doses of oral psilocybin with low-dose (1 mg) control in OUD patients on methadone.

Started: March 1, 2025
Type: interventional
Blinding: double
Randomized: Yes
Registry ID: NCT06796062

RecruitingPhase II

Psilocybin on Brain Mechanisms of Motivation in OUD

Randomised, quadruple-masked Phase II trial (n=24) comparing single low (1 mg) vs high (25 mg) PEX010 psilocybin doses to study motivation/reward and cognitive flexibility circuits in people with opioid use disorder.

Started: March 1, 2025
Type: interventional
Blinding: quadruple
Randomized: Yes
Registry ID: NCT06810310

Explore further

Search all Psilocybin papers Search all Substance Use Disorders (SUD) trials Full Psilocybin profile Full Substance Use Disorders (SUD) profile