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Psychedelic-assisted therapy

The clinical model pairing a psychedelic session with structured psychological support.

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 Psychedelic-assisted therapy, psychedelic therapy, assisted psychotherapy, drug-assisted therapy, then ranked by relevance.

Psychedelic-assisted therapy shows promise for conditions like depression, PTSD, anxiety, and alcohol use disorder, with several randomized controlled trials and open-label studies reporting large, rapid, and sometimes durable improvements. However, the evidence base remains limited by small sample sizes, open-label designs, and heterogeneity in protocols, so conclusions about efficacy are preliminary and require confirmation in larger, well-controlled trials.

Confidence in the evidence

Low-Moderate
  • Multiple RCTs (e.g., 16219, 16276, 19921) show positive effects, but sample sizes are small (12-103 participants per study).
  • Several key studies (e.g., 8534, 16028) are open-label, lacking blinding and control, increasing risk of bias.
  • Results are generally consistent in direction (positive) across different substances (psilocybin, LSD, MDMA, ketamine) and conditions, but heterogeneity in protocols limits comparability.
  • Long-term follow-up data (e.g., 8534, 16282, 19854) suggest durability, but are from small samples and often lack control groups.
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 with psychological support for treatment-resistant depression: six-month follow-up. 2017
Supports

Psilocybin with psychological support produced large reductions in depressive symptoms (Cohen's d = 2.2 at week 1, 2.3 at week 5) that remained significant at 6 months (d = 1.4).

open-label trial · Sample size: 20

Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. 2011
Supports

Psilocybin at 20 and 30 mg/70 kg occasioned mystical-type experiences in 72% of volunteers, with persisting positive changes in attitudes, mood, and behavior at 14 months.

double-blind dose-effect study · Sample size: 18

Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases 2014
Supports

LSD-assisted psychotherapy significantly reduced trait and state anxiety at 2 months (effect sizes 1.1 and 1.2), with reductions sustained for 12 months.

double-blind, randomized, active placebo-controlled pilot study · Sample size: 12

The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future. 2017
Unclear

This review discusses the therapeutic potential of psychedelic drugs but does not provide specific quantitative findings.

review

The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. 2010
Unclear

The abstract does not provide specific results, only the study description.

randomized controlled pilot study

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

Two administrations of high-dose psilocybin improved the percentage of heavy drinking days in patients with AUD undergoing psychotherapy compared to active placebo.

double-blind randomized clinical trial

Patients’ Accounts of Increased “Connectedness” and “Acceptance” After Psilocybin for Treatment-Resistant Depression 2017
Supports

Patients reported that psilocybin treatment promoted connection and acceptance, in contrast to conventional treatments which reinforced disconnection and avoidance.

qualitative thematic analysis · Sample size: 20

The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects. 2020
Supports

The authors propose that the subjective effects of psychedelics are necessary for their enduring therapeutic benefits, accounting for the majority of benefit.

theoretical review

LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects 2014
Supports

LSD-assisted psychotherapy led to sustained reductions in anxiety and improved quality of life at 12 months, with participants reporting insightful, cathartic, and interpersonal experiences.

qualitative content analysis with prospective follow-up · Sample size: 10

3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. 2018
Unclear

The abstract does not provide specific results, only the study description.

randomised, double-blind, dose-response, phase 2 clinical trial

Increased global integration in the brain after psilocybin therapy for depression. 2022
Unclear

The abstract does not provide specific results, only the study description.

observational

A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD) 2012
Mixed

MDMA-assisted psychotherapy did not show statistically significant reductions in clinician-rated CAPS scores (p = 0.066), but did show significant self-reported improvement on the PDS (p = 0.014).

randomized, double-blind, active-placebo controlled pilot study · Sample size: 12

Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. 2013
Supports

At a mean of 45.4 months follow-up, the majority of subjects maintained statistically and clinically significant gains in PTSD symptom relief from MDMA-assisted psychotherapy.

prospective long-term follow-up study · Sample size: 19

Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxiety. 2020
Supports

Psychological flexibility fully mediated the effect of mystical and insightful experiences on decreases in depression and anxiety following a psychedelic experience.

cross-sectional survey study · Sample size: 985

MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. 2019
Supports

MDMA-assisted psychotherapy produced significantly greater reductions in CAPS-IV scores than control (between-group difference -22.0, p < 0.001, Cohen's d = 0.8), with 54.2% of the active group no longer meeting PTSD diagnostic criteria.

pooled analysis of six phase 2 randomized controlled trials · Sample size: 103

Changes in trauma symptoms of discrimination after MDMA-assisted psychotherapy for posttraumatic stress disorder. 2026
Supports

MDMA-assisted therapy significantly reduced trauma symptoms of discrimination by 38% (Cohen's d = 1.28, p = .046), though the sample size was very small.

preliminary study · Sample size: 5

Mystical Experiences as Catalysts in Ketamine-Assisted Psychotherapy: A Case Study 2026
Supports

Greater therapeutic gains in ketamine-assisted psychotherapy followed sessions with higher mystical-type experience scores, with the patient attributing improvements to the psychological and spiritual impact.

case study · Sample size: 1

Making a case for using MDMA-assisted psychotherapy for borderline personality disorder and complex PTSD: a descriptive systematic review of the literature 2026
Supports

Most of the 24 included studies reported reduced PTSD symptoms post-intervention, with some noting decreased dissociative symptoms at higher MDMA doses.

descriptive systematic review · Sample size: 335

Reframing distress in oncology: the potential of psychedelic-assisted therapy. 2026
Supports

Recent trials in advanced cancer populations report improvements in anxiety, depression, pain-related distress, and quality of life following one or two dosing sessions of psychedelic-assisted therapy.

review

The purpose of the psychosocial protocol in the psychedelic-assisted therapy: A scoping review 2026
Unclear

This review categorizes psychosocial protocols used in psychedelic research, noting limited reporting and heterogeneity as methodological challenges.

scoping review

Navigating ‘k-land’: a qualitative exploration of participants’ experiences of ketamine-assisted psychotherapy for methamphetamine use disorder 2026
Supports

Participants in ketamine-assisted psychotherapy for MAUD described reduced emotional and cognitive reactivity and translation of psychological shifts into behavioral change.

qualitative study embedded in open-label pilot trial · Sample size: 14

Ketamine-assisted psychotherapy for posttraumatic stress disorder: a systematic review and individual participant data meta-analysis of predictors of treatment effects. 2026
Supports

Greater improvement in PTSD symptoms was associated with more psychotherapy sessions (β = 1.03 per session) and more ketamine sessions (β = 1.15 per session), but most included studies were of poor quality.

systematic review and individual participant data meta-analysis · Sample size: 533

Music Playlist Use in Clinical Trials of Psychedelic Assisted Psychotherapy: A Systematic Review 2026
Unclear

There is considerable variation in music selection and use in psychedelic-assisted psychotherapy trials, with no standardized protocol.

systematic review

Integrating psychedelic-assisted psychotherapy into addiction care in the Czech Republic: Clinical evidence, safety, and regulatory developments 2026
Supports

The strongest direct evidence for psychedelic-assisted therapy in addiction treatment comes from a limited number of randomized and controlled studies, suggesting cautious clinical potential rather than established effectiveness.

narrative review

Attitudes and perceptions of psychedelic therapy among clinical trial participants with alcohol use disorder: a mixed-method study 2026
Supports

64.3% of participants were willing to participate in a psychedelic therapy trial, with willingness significantly associated with higher expectations of research success.

mixed-method study · Sample size: 112

Points of agreement

  • Psychedelic-assisted therapy (with psilocybin, LSD, MDMA, and ketamine) is associated with large, rapid reductions in symptoms of depression, anxiety, and PTSD across multiple studies.
  • Subjective effects (e.g., mystical-type experiences, psychological flexibility) are consistently linked to therapeutic outcomes.
  • Improvements often persist for months to over a year after treatment, as shown in several follow-up studies.
  • The therapy is generally well-tolerated with no serious adverse events reported in the reviewed studies.

Conflicts

  • One pilot study (22029) found no significant clinician-rated improvement on the CAPS despite significant self-reported improvement, suggesting possible divergence between measures.
  • The quality of evidence varies widely, from open-label and qualitative studies to double-blind RCTs, leading to different levels of confidence in findings.

Gaps

  • Most studies have small sample sizes, limiting generalizability and statistical power.
  • There is a lack of large, multi-site phase 3 trials for most substances and conditions, though some are underway.
  • Heterogeneity in treatment protocols (dose, number of sessions, psychotherapy model, music use) makes cross-study comparisons difficult.
  • Long-term durability beyond 12 months is not well-established for most indications.
  • Few studies include diverse populations or examine effects on discrimination-related trauma, with most samples being predominantly white and male.
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 Psychedelic-assisted therapy, 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 Psychedelic-assisted therapy 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

2,394 articles · 1,058 from the last two years · 1,531,449 participants across 677 studies reporting sample size

Common study designs

review 553 qualitative study 99 systematic review 125 randomized controlled trial 75 theoretical or philosophical paper 328

Research

Synthesize the evidence → Search all →

Suggestions effects in psychedelics: Confounds and opportunities

Madeline Victore Stein, Devin B. Terhune • 1 citation preprint

Growing excitement about psychedelics in media and science often overlooks the influence of suggestion—where expectations and beliefs shape outcomes. Suggestion can distort experimental research on psychedelics' neurocognitive effects, yet it may also enhance therapeutic results when used deliberately. The authors call for greater attention to suggestion as both a source of bias and a potential tool to maximize benefits in psychedelic-assisted therapy.

DOI: 10.31234/osf.io/5krs4

Psychedelics and autobiographical memory – Six open questions

Samuli Kangaslampi, Morten P. Lietz preprint

Psychedelics have long been thought to enhance autobiographical memory, and revisiting such memories may be key to their therapeutic effects, yet modern research has largely overlooked this area. This review identifies six open questions: whether psychedelics boost autobiographical recall; whether recalling significant or traumatic memories is common during psychedelic experiences; whether they can produce false memories; how memories change when recalled and reconsolidated under psychedelics; what memories of the psychedelic experience itself are like; and whether autobiographical experiences under psychedelics are especially important for therapeutic outcomes. The authors present the limited current evidence for each question and propose how future studies could address them, emphasizing relevance for optimizing psychedelic-assisted therapies and avoiding harm.

DOI: 10.31234/osf.io/su7ch_v2

Assessing the Impact of Ketamine-Assisted Multimodal Therapy on Depressive Symptoms: A Longitudinal Pre-Post BDI-II Study with Exploratory Follow-Up Analysis

Anja Frank, Mario H W Scheib preprint

A multimodal therapy combining ketamine-assisted psychotherapy, repetitive transcranial magnetic stimulation, neurofeedback, and additional psychotherapy sessions substantially reduced depressive symptoms in a Spanish clinic. Among 67 patients with various diagnoses who were screened for depression, Beck Depression Inventory-II scores dropped significantly from before to after treatment, with a large effect size. Exploratory follow-up of 28 patients indicated that improvements could be sustained for months or even years. The findings suggest that integrating multiple biological and psychological interventions may offer an effective approach for treating depression in a clinical setting.

DOI: 10.31219/osf.io/4smjr_v1

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

MDMA-Based Psychotherapy in Treatment-Resistant Post-traumatic Stress Disorder (PTSD): A Brief Overview of Current Evidence

Preprints.org • Kainat Riaz, Sejal Suneel, Mohammad Hamza Bin Abdul Malik et al. • 1 citation preprint

Half of patients with post-traumatic stress disorder (PTSD) do not respond to standard pharmacotherapy or psychotherapy. A review of six phase II randomized controlled trials indicates that MDMA-assisted psychotherapy can reduce PTSD symptoms, even in treatment-resistant cases, by increasing neurohormones such as dopamine, serotonin, norepinephrine, and oxytocin and by modulating brain regions involved in fear and anxiety. The FDA has granted MDMA-assisted psychotherapy a "Breakthrough Therapy" designation. Further research is needed to determine whether the benefits outweigh the risks and whether this approach can be integrated into existing treatment options.

DOI: 10.20944/preprints202308.1847.v1

MDMA Assisted Psychotherapy Decreases PTSD Symptoms, Dissociation, Functional Disability, and Depression: A Systematic Review and Meta-Analysis

medRxiv • W. M. Green, S.b. Raut, F.l.j. James et al. • 4 citations preprint

MDMA-assisted psychotherapy improves dissociation, depression, and functional impairment in people with post-traumatic stress disorder (PTSD), but does not improve sleep quality. A systematic review and meta-analysis of randomized controlled trials found that the therapy reduces core PTSD symptoms and enhances quality of life. The evidence is limited by small sample sizes in available trials, but supports further development of MDMA-assisted psychotherapy for PTSD.

DOI: 10.1101/2023.08.17.23293955

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

Getting In Touch with Touch: The Importance of Studying Touch in MDMA-Assisted Therapy and the Development of a New Self-Report Measure

Jason B Luoma, Luke Roy Allen, Veronika Gold et al. • 1 citation preprint

MDMA is being tested as an adjunct to psychotherapy in controlled trials, including two completed Phase 3 trials, and could become a legally available medicine for MDMA-assisted therapy (MDMA-AT) within a few years. The treatment manual for MDMA-AT research considers touch an important part of therapy, but no empirical evaluation has examined how touch functions in MDMA-AT, and research on touch in psychotherapy generally is scarce. Concerns exist that touch combined with MDMA could intensify power imbalances or contribute to boundary crossings and unethical behavior.

DOI: 10.31234/osf.io/768p2

The FDA Backdoor to MDMA Rescheduling

SSRN Electronic Journal • Vincent Joralemon

The Drug Enforcement Administration (DEA) classifies MDMA as a Schedule I controlled substance, the most restrictive category under the Controlled Substances Act. However, Lykos Therapeutics (formerly MAPS PBC) has submitted a New Drug Application for MDMA-assisted therapy for PTSD. If the FDA approves this drug, it would provide the 'accepted medical use' that Schedule I drugs are statutorily denied, triggering a rescheduling process. Based on precedents like XYWAV and cannabis-derived medications, the DEA would likely reschedule only the specific FDA-approved drug product—likely to be marketed as RENSANSE—to Schedule II or III, while raw MDMA remains on Schedule I. This mechanism offers a model for incrementally relaxing federal restrictions on psychedelic substances and expanding research access.

DOI: 10.2139/ssrn.6960838

Mindfulness-Based Psilocybin-Assisted Therapy (MB-PAT) for cancer-related demoralization in Canada: the case for a hybrid group-based delivery model

Christopher P. Albertyn, Jeremie Richard, Ron Joseph Shore et al. preprint

Demoralization syndrome affects about one in five Canadians with advanced cancer, marked by helplessness, hopelessness, and loss of meaning, and is linked to a greater desire for hastened death and worse outcomes, but it is underrecognized and undertreated. Pharmacological treatments fail to address its existential roots, and psychosocial therapies are underfunded and not universally effective. Mindfulness-Based Psilocybin-Assisted Therapy (MB-PAT) combines mindfulness training with psilocybin's neuroplastic effects, but its traditional one-on-one delivery limits scalability. The authors argue that group-based MB-PAT could bridge this gap by leveraging existing group therapy infrastructure and therapist familiarity with mindfulness, offering a scalable, equity-focused model for publicly funded Canadian oncology. The Canadian Network for Psychedelic-Assisted Cancer Therapy (CAN-PACT) is highlighted as a key initiative to generate evidence and capacity.

DOI: 10.31234/osf.io/yrgkf_v1

Clinical trials

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