Co-use of MDMA with psilocybin/LSD may buffer against challenging experiences and enhance positive experiences
Hannes Kettner, Stephen Ross, Richard J. Zeifman, Broc A. Pagni, Austin J. Mallard, Daniel E. Roberts, David Erritzøe, Robin Carhart-Harris
Scientific Reports August 22, 2023 DOI: 10.1038/s41598-023-40856-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Prospective convenience sample Peer reviewed |
|---|---|
| Sample size | 698 |
| Population | Individuals with plans to use psilocybin or LSD |
| Interventions | Psilocybin LSD MDMA |
| Dose | low (but not medium–high) dose of MDMA |
| Topics | LSD MDMA Psilocybin |
| Keywords | Hallucinogen Grief Clinical psychology Gratitude |
| Citations | 31 |
| Key points | Co-use of a low dose of MDMA with psilocybin or LSD was associated with significantly less intense challenging experiences (grief, fear) and greater self-compassion, love, and gratitude, but not with changes in mystical-type experiences or compassion. |
Abstract
Abstract Psilocybin and lysergic acid diethylamide (LSD) experiences can range from very positive to highly challenging (e.g., fear, grief, and paranoia). These challenging experiences contribute to hesitancy toward psychedelic-assisted psychotherapy among health care providers and patients. Co-use of 3,4-Methylenedioxy methamphetamine (MDMA) with psilocybin/LSD anecdotally reduces challenging experiences and enhances positive experiences associated with psilocybin/LSD. However, limited research has investigated the acute effects of co-use of MDMA and psilocybin/LSD. In a prospective convenience sample ( N = 698) of individuals with plans to use psilocybin/LSD, we examined whether co-use of MDMA with psilocybin/LSD ( n = 27) is associated with differences in challenging or positive experiences. Challenging experiences were measured using the Challenging Experiences Questionnaire and positive experiences were measured using the Mystical Experience Questionnaire and single-item measures of self-compassion, compassion, love, and gratitude. Potentially confounding variables were identified and included as covariates. Relative to psilocybin/LSD alone, co-use of psilocybin/LSD with a self-reported low (but not medium–high) dose of MDMA was associated with significantly less intense total challenging experiences, grief, and fear, as well as increased self-compassion, love and gratitude. Co-use of psilocybin/LSD and MDMA was not associated with differences in mystical-type experiences or compassion. Findings suggest co-use of MDMA with psilocybin/LSD may buffer against some aspects of challenging experiences and enhance certain positive experiences. Limitations include use of a convenience sample, small sample size, and non-experimental design. Additional studies (including controlled dose–response studies) that examine the effects and safety of co-administering MDMA with psilocybin/LSD (in healthy controls and clinical samples) are warranted and may assist the development of personalized treatments.
Comparable studies
Other observational and cohort studies on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Human participants | 2016 | Observational cohort | |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. USA adult respondents from the National Survey on Drug Use and Health (2008-2012) | 2015 | Observational cohort | n = 190,000 |
| Psychedelics not linked to mental health problems or suicidal behavior: A population study Randomly selected United States adults | 2015 | Observational cohort | n = 135,095 |
| Whole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD. Healthy human participants | 2018 | Observational study with computational modeling |
Citations in the library
Cited by 30
- Measuring psychotherapeutic processes in the context of psychedelic experiences: Validation of the General Change Mechanisms Questionnaire (GCMQ) Journal of Psychopharmacology May 1, 2024
- Preliminary evidence for the importance of therapeutic alliance in MDMA-assisted psychotherapy for posttraumatic stress disorder. European Journal of Psychotraumatology 2024
- Psychedelics for the Treatment of Psychiatric Disorders: Interpreting and Translating Available Evidence and Guidance for Future Research. American Journal of Psychiatry 2025
- Effects of Psychedelics in Older Adults: A Prospective Cohort Study. American Journal of Geriatric Psychiatry May 19, 2024
- Co-use of psychedelics with other substances: Findings from the global psychedelic survey. Journal of Psychopharmacology May 1, 2025
and 25 more in the library
Cites 72
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Frontiers in Pharmacology January 17, 2018
and 67 more in the library