Co-use of MDMA with psilocybin/LSD may buffer against challenging experiences and enhance positive experiences
In a prospective convenience sample (N = 698; n = 27 co‑users), co‑use of a low dose of MDMA with psilocybin/LSD was associated with reduced overall challenging experiences—especially grief and fear—and increased self‑compassion, love and gratitude, while mystical‑type experiences and compassion were unchanged. The authors caution the small, non‑experimental convenience sample and recommend controlled dose–response studies to assess safety and therapeutic potential.
Authors
- Richard Zeifman
- Robin Carhart-Harris
- David Erritzoe
Published
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.
Research Summary of 'Co-use of MDMA with psilocybin/LSD may buffer against challenging experiences and enhance positive experiences'
Introduction
Classic psychedelics such as psilocybin and LSD produce experiences that can range from profoundly positive to highly challenging (for example, fear, grief and paranoia). These challenging experiences are reported in both clinical and non-clinical contexts and are a common source of reluctance among clinicians and potential patients for psychedelic-assisted therapies. Anecdotal reports and recreational practices describe co-use of MDMA with psilocybin or LSD (commonly called “hippy flipping” or “candy flipping”) as a way to reduce challenging experiences and enhance positive effects, but empirical data on the acute effects of such co-use are limited. A recent controlled study examined LSD plus a medium-high MDMA dose and found no acute differences, but that trial used a restricted, screened sample, a single MDMA dose, and did not assess some positive-affect outcomes that MDMA might influence. L. and colleagues therefore set out to examine, in a prospective convenience sample of people planning to use psilocybin or LSD in naturalistic settings, whether self-reported co-use of MDMA (categorised as none, low, or medium–high dose) was associated with differences in acute challenging experiences (measured by the Challenging Experience Questionnaire) and positive experiences (measured by the Mystical Experience Questionnaire and single-item ratings of self-compassion, compassion, love and gratitude). The study aimed to account for plausible confounds and to provide exploratory evidence about whether co-use buffers against adversity or enhances positive affect during psychedelic experiences.
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Zeifman, R. J., Kettner, H., Pagni, B. A., Mallard, A., Roberts, D. E., Erritzoe, D., Ross, S., & Carhart-Harris, R. L. (2023). Co-use of MDMA with psilocybin/LSD may buffer against challenging experiences and enhance positive experiences. Scientific Reports, 13(1). https://doi.org/10.1038/s41598-023-40856-5
References (56)
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Show all 56 referencesShow fewer
Holze, F., Gasser, P., Müller, F. et al. · Biological Psychiatry (2023)
Lake, S., Lucas, P. · Psychedelic Medicine (2023)
Larsen, J. K. · History of Psychiatry (2016)
Simonsson, O., Hendricks, P. S., Chambers, R. et al. · Journal of Affective Disorders (2023)
Roseman, L., Haijen, E. C. H. M., Idialu-Ikato, K. et al. · Journal of Psychopharmacology (2019)
Griffiths, R. R., Hurwitz, E. S., Davis, A. K. et al. · PLOS ONE (2019)
Gashi, L., Sandberg, S., Pedersen, W. · International Journal of Drug Policy (2021)
Bouso, J. C., Andión, O., Sarris, J. et al. · PLOS Global Public Health (2022)
Cohen, S. · Journal of Nervous and Mental Disease (1980)
Strassman, R. J. · Journal of Nervous and Mental Disease (1984)
Niles, H., Fogg, C., Kelmendi, B. et al. · BMC Palliative Care (2021)
Reynolds, L. M, Stack, A., Akroyd, A., Sundram, F. et al. · International Journal of Environmental Research and Public Health (2021)
Corrigan, K., Haran, M., Mccandliss, C. et al. · Irish Journal of Medical Science (2021)
Barrett, F. S., Johnson, M. W., Griffiths, R. R. · Personality and Individual Differences (2017)
Carhart-Harris, R. L., Roseman, L., Haijen, E. C. H. M. et al. · Journal of Psychopharmacology (2018)
Haijen, E. C. H. M., Kaelen, M., Roseman, L. et al. · Frontiers in Pharmacology (2018)
Aday, J. S., Davis, A. K., Mitzkovitz, C. M. et al. · ACS Pharmacology and Translational Science (2021)
Nayak, S., Gukasyan, N., Barrett, F. S. et al. · Pharmacopsychiatry (2021)
Kuc, J., Kettner, H., Rosas, F. E. et al. · Psychopharmacology (2021)
Carhart-Harris, R. L., Murphy, K., Leech, R. et al. · Biological Psychiatry (2015)
Dolder, P. C., Müller, F., Schmid, Y. et al. · Psychopharmacology (2017)
Bedi, G., Hyman, D., De Wit, H. · Biological Psychiatry (2010)
Studerus, E., Gamma, A., Vollenweider, F. X. · PLOS ONE (2010)
Feduccia, A. A., Mithoefer, M. C. · Progress in Neuro-Psychopharmacology and Biological Psychiatry (2018)
Kamboj, S. K., Kilford, E. J., Minchin, S. et al. · Journal of Psychopharmacology (2015)
Straumann, I., Ley, L., Holze, F. et al. · Neuropsychopharmacology (2023)
Stauffer, C., Anderson, B. T., Ortigo, K. M. et al. · ACS Pharmacology and Translational Science (2020)
Traynor, J. M., Roberts, D. E., Ross, S. et al. · Focus (2022)
Murphy, R., Murphy-Beiner, A., Kettner, H. et al. · Frontiers in Pharmacology (2022)
Wagner, A. C. · Frontiers in Psychology (2021)
Griffiths, R. R., Johnson, M. W., Richards, W. A. et al. · Journal of Psychopharmacology (2017)
Kettner, H., Rosas, F. E., Timmermann, C. et al. · Frontiers in Pharmacology (2021)
Trope, A., Anderson, B. T., Hooker, A. R. et al. · Journal of Psychoactive Drugs (2019)
Jones, G. M., Nock, M. K. · Scientific Reports (2022)
Bouso, J. C., Doblin, R., Farré, M. et al. · Journal of Psychoactive Drugs (2008)
Peill, J. M., Trinci, K. E., Kettner, H. et al. · Journal of Psychopharmacology (2022)
Spriggs, M. J., Kettner, •. H., Carhart-Harris, •. R. L. · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity (2020)
Watts, R., Kettner, H., Gandy, S. et al. · Psychopharmacology (2022)
Zeifman, R. J., Wagner, A. C., Watts, R. et al. · Frontiers in Psychiatry (2020)
MacLean, K. A., Leoutsakos, J. S., Johnson, M. W. et al. · Journal for the Scientific Study of Religion (2012)
Agin-Liebes, G. I., Zeifman, R. J., Luoma, J. B. et al. · Journal of Psychopharmacology (2022)
Davis, A. K., Barrett, F. S., Griffiths, R. R. · Journal of Contextual Behavioral Science (2020)
Ross, S., Bossis, A. P., Guss, J. et al. · Journal of Psychopharmacology (2016)
Zeifman, R. J., Wagner, A. C., Monson, C. M. et al. · Journal of Affective Disorders (2023)
Erritzoe, D., Smith, J. M., Fisher, P. M. et al. · Journal of Psychopharmacology (2019)
Nygart, V., Pommerencke, L. M., Carhart-Harris, R. L. et al. · Frontiers in Psychology (2021)
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