A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)- assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD)
In a randomized, double‑blind, active‑placebo controlled pilot trial of 12 patients with treatment‑resistant chronic PTSD, MDMA‑assisted psychotherapy was safely administered with no drug‑related serious adverse events. The intervention produced significant self‑reported symptom improvement (PDS, p=0.014), a non‑significant clinician‑rated CAPS reduction at end‑of‑treatment (p=0.066) that improved by 1‑year follow‑up, and three MDMA sessions were more effective than two (p=0.016).
Authors
- Oehen, P.
- Traber, R.
- Widmer, V.
Published
Abstract
Psychiatrists and psychotherapists in the US (1970s to 1985) and Switzerland (1988–1993) used MDMA legally as a prescription drug, to enhance the effectiveness of psychotherapy. Early reports suggest that it is useful in treating trauma-related disorders. Recently, the first completed pilot study of MDMA-assisted psychotherapy for PTSD yielded encouraging results. Designed to test the safety and efficacy of MDMA-assisted psychotherapy in patients with treatment-resistant PTSD; our randomized, double-blind, active-placebo controlled trial enrolled 12 patients for treatment with either low-dose (25 mg, plus 12.5 mg supplemental dose) or full-dose MDMA (125 mg, plus 62.5 mg supplemental dose). MDMA was administered during three experimental sessions, interspersed with weekly non-drug-based psychotherapy sessions. Outcome measures used were the Clinician-Administered PTSD Scale (CAPS) and the Posttraumatic Diagnostic Scale (PDS). Patients were assessed at baseline, three weeks after the second and third MDMA session (end of treatment), and at the 2-month and 1-year follow-ups. We found that MDMA-assisted psychotherapy can be safely administered in a clinical setting. No drug-related serious adverse events occurred. We did not see statistically significant reductions in CAPS scores ( p = 0.066), although there was clinically and statistically significant self-reported (PDS) improvement ( p = 0.014). CAPS scores improved further at the 1-year follow-up. In addition, three MDMA sessions were more effective than two ( p = 0.016).
Research Summary of 'A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)- assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD)'
Introduction
Post-traumatic stress disorder (PTSD) is common and often chronic, with substantial residual morbidity despite existing psychotherapies and serotonergic medications. Earlier research shows that exposure-based psychotherapies (for example CBT, Prolonged Exposure, CPT, EMDR) have efficacy but also high drop-out rates and incomplete recovery for many patients; SSRIs approved for PTSD produce only modest symptom change. Consequently, there is a recognised need for more effective pharmacological and psychotherapeutic approaches for treatment‑resistant, chronic PTSD. This study set out to evaluate MDMA-assisted psychotherapy as a novel, catalyst-style treatment for chronic, treatment‑resistant PTSD. MDMA is hypothesised to reduce fear and enhance prosocial and integrative emotional processing via serotonergic release, modulation of amygdala and ventromedial prefrontal cortex activity, and increased oxytocin, thereby widening an "optimal arousal" window for therapeutic exposure. Oehen and colleagues designed a randomised, double-blind, active-placebo controlled pilot trial to test safety and preliminary efficacy in 12 outpatients, to assess whether low-dose MDMA (25 mg + 12.5 mg) could serve as an active placebo to improve blinding, and to test the hypothesis that three MDMA sessions are more effective than two and that symptom reductions would persist at 1 year.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- APA Citation
Oehen, P., Traber, R., Widmer, V., & Schnyder, U. (2013). A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)- assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD). Journal of Psychopharmacology, 27(1), 40-52. https://doi.org/10.1177/0269881112464827
References (4)
Papers cited by this study that are also in Blossom
Dumont, G., Sweep, F., van der Steen, R. et al. · Social Neuroscience (2009)
Johansen, P. Ø., Krebs, T. S. · Journal of Psychopharmacology (2009)
Liechti, M. E., Gamma, A., Vollenweider, F. X. · Psychopharmacology (2001)
Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T. et al. · Journal of Psychopharmacology (2010)
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Thal, S. B., Wieberneit, M., Sharbanee, J. M. et al. · Journal of Humanistic Psychology (2023)
Ponomarenko, P., Seragnoli, F., Calder, A. et al. · Journal of Psychopharmacology (2023)
Breeksema, J. J., Kuin, B. W., Kamphuis, J. et al. · Journal of Psychopharmacology (2022)
Price, C., Feduccia, A. A., DeBonis, K. · Journal of Clinical Psychopharmacology (2022)
Vizeli, P., Straumann, I., Duthaler, U. et al. · Frontiers in Pharmacology (2022)
Belser, A. B. · Frontiers in Psychology (2022)
Argento, E., Goldenberg, S., Deering, K. et al. · Drug and Alcohol Dependence (2022)
Oehen, P., Gasser, P. · Frontiers in Psychiatry (2022)
Marseille, E., Mitchell, M. J., Khan, J. G. · PLOS ONE (2022)
Pantoni, M. M., Kim, J. L., Van Alstyne, K. R. et al. · Psychopharmacology (2022)
Maples-Keller, J. L., Norrholm, S. D., Burton, M. et al. · Journal of Psychopharmacology (2022)
Reckweg, J., Uthaug, M. V., Szabo, A. et al. · Journal of Neurochemistry (2022)
Gasser, P. · Current Topics in Behavioral Neurosciences (2022)
Schenberg, E. E., Gerber, K. · Transcultural Psychiatry (2022)
Aday, J. S., Heifets, B. D., Pratscher, S. D. et al. · Psychopharmacology (2021)
Smith, K. W., Sicignano, D. J., Hernandez, A. V. et al. · Journal of Clinical Pharmacology (2021)
Chaliha, D., Mamo, J. C., Albrecht, M. et al. · Current Neuropharmacology (2021)
Ponte, L., Jerome, L., Hamilton, S. et al. · Journal of Traumatic Stress (2021)
Bathje, G. J., Fenton, J., Pillersdorf, D. et al. · Journal of Humanistic Psychology (2021)
Studerus, E., Vizeli, P., Harder, S. et al. · Journal of Psychopharmacology (2021)
Palhano-Fontes, F., Gorman, I., Nielson, E. M. et al. · Frontiers in Psychology (2021)
Bouso, J. C., Ona, G., Dos Santos, R. G. et al. · Advances in Experimental Medicine and Biology (2021)
Morgan, L. · Annals of General Psychiatry (2020)
Wolfson, P. E., Andries, J., Feduccia, A. A. et al. · Scientific Reports (2020)
Marseille, E., Kahn, J. G., Yazar-Klosinski, B. et al. · PLOS ONE (2020)
Gill, H., Gill, B., Chen-Li, D. et al. · Expert Review of Neurotherapeutics (2020)
Varker, T., Watson, L., Gibson, K. et al. · Journal of Psychoactive Drugs (2020)
Luoma, J. B., Chwyl, C., Bathje, G. J. et al. · Journal of Psychoactive Drugs (2020)
Jerome, L., Feduccia, A. A., Wang, J. B. et al. · Psychopharmacology (2020)
Mason, N. L., Kuypers, K. P. C., Reckweg, J. et al. · Neuropsychopharmacology (2020)
Chi, T., Gold, J. A. · Journal of the Neurological Sciences (2020)
Berquist, M. D., Leth-Petersen, S., Kristensen, J. L. et al. · Drug and Alcohol Dependence (2020)
Gorman, I., Belser, A. B., Jerome, L. et al. · Journal of Traumatic Stress (2020)
Searchfield, G. D., Poppe, T. N. E. R., Durai, M. et al. · International Journal of Neuroscience (2020)
Bahji, A., Forsyth, A., Groll, D. et al. · Progress in Neuro-Psychopharmacology and Biological Psychiatry (2020)
Holze, F., Vizeli, P., Müller, F. et al. · Neuropsychopharmacology (2019)
Feduccia, A. A., Jerome, L., Yazar-Klosinski, B. et al. · Frontiers in Psychiatry (2019)
Mithoefer, M. C., Feduccia, A. A., Jerome, L. et al. · Psychopharmacology (2019)
Bershad, A. K., Mayo, L. M., Van Hedger, K. et al. · Neuropsychopharmacology (2019)
Barone, W., Beck, J., Mitsunaga-Whitten, M. et al. · Journal of Psychoactive Drugs (2019)
Carlyle, M., Stevens, T., Fawaz, L. et al. · Journal of Psychopharmacology (2019)
Müller, F., Brändle, R., Liechti, M. E. et al. · Neuroscience and Biobehavioral Reviews (2019)
Vizeli, P., Meyer Zu Schwabedissen, H. E., Liechti, M. E. · ACS Chemical Neuroscience (2018)
Ot'alora G, M., Grigsby, J., Poulter, B. et al. · Journal of Psychopharmacology (2018)
Danforth, A. L., Grob, C. S., Struble, C. et al. · Psychopharmacology (2018)
Schenberg, E. E. · Frontiers in Pharmacology (2018)
Ly, C., Greb, A. C., Cameron, L. P. et al. · Cell Reports (2018)
Feduccia, A. A., Mithoefer, M. C. · Progress in Neuro-Psychopharmacology and Biological Psychiatry (2018)
Barnett, B. S., Siu, W. O., Pope Jr, H. G. · Journal of Nervous and Mental Disease (2018)
Szigeti, B., Winstock, A. R., Erritzoe, D. et al. · Journal of Psychopharmacology (2018)
Cameron, L. P., Benson, C. J., Dunlap, L. E. · ACS Chemical Neuroscience (2018)
Belouin, S. J., Henningfield, J. E. · Neuropharmacology (2018)
Papaseit, E., Torrens, M., Pérez-Mañá, C. et al. · Expert Opinion on Drug Metabolism and Toxicology (2018)
Curry, D. W., Young, M. B., Tran, A. N. et al. · Neuropharmacology (2017)
Argento, E., Strathdee, S. A., Tupper, K. et al. · BMJ Open (2017)
Kuypers, K. P. C., Puxty, D. J., Ramaekers, J. G. et al. · Frontiers in Pharmacology (2017)
Wagner, M. T., Mithoefer, M. C., Mithoefer, A. T. et al. · Journal of Psychopharmacology (2017)
Mueller, F., Lenz, C., Dolder, P. C. et al. · Translational Psychiatry (2017)
Vizeli, P., Schmid, Y., Prestin, K. et al. · European Neuropsychopharmacology (2017)
Vizeli, P., Liechti, M. E. · Journal of Psychopharmacology (2017)
Walpola, I. C., Nest, T., Leor, R. et al. · Neuropsychopharmacology (2017)
Pisano, V. D., Putnam, N. P., Kramer, H. M. et al. · Journal of Psychopharmacology (2017)
Bershad, A. K., Miller, M. A., Baggot, M. J. et al. · Journal of Psychopharmacology (2016)
Garcia-Romeu, A., Kersgaard, B., Addy, P. H. · Experimental and Clinical Psychopharmacology (2016)
Bouso, J. C., Pedrero-Pérez, E. J., Gandy, S. · Human Psychopharmacology (2016)
Amoroso, T., Workman, M. · Journal of Psychopharmacology (2016)
Grob, C. S., Mithoefer, M. C., Brewerton, T. D. · Lancet Psychiatry (2016)
Danforth, A. L., Struble, C., Yazar-Klosinski, B. et al. · Progress in Neuro-Psychopharmacology and Biological Psychiatry (2016)
Mueller, F., Lenz, C., Steiner, M. et al. · Neuroscience and Biobehavioral Reviews (2015)
Kamilar-Britt, P., Bedi, G. · Neuroscience and Biobehavioral Reviews (2015)
Baggot, M. J., Coyle, J. R., Siegrist, J. D. et al. · Journal of Psychopharmacology (2015)
Baggot, M. J., Kirkpatrick, M. G., Bedi, G. et al. · Journal of Psychopharmacology (2015)
Kamboj, S. K., Kilford, E. J., Minchin, S. et al. · Journal of Psychopharmacology (2015)
González, D., Torrens, M., Farré, M. · BioMed Research International (2015)
Stewart, L., Ferguson, B., Morgan, C. J. A. et al. · Journal of Psychopharmacology (2014)
Frye, C. G., Wardle, M. C., Norman, G. J. et al. · Pharmacology Biochemistry and Behavior (2014)
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