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Cited by 159Psychedelics and Drug StudiesPosttraumatic Stress Disorder ResearchPsychotherapy Techniques and Applications

RETRACTED ARTICLE: Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials

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Jerome, Lisa, Feduccia, Allison A., Wang, Julie B., Hamilton, Scott, Yazar-Klosinski, Berra, Emerson, Amy, Mithoefer, Michael C., Doblin, Rick·2020·Psychopharmacology
DOI 10.1007/s00213-020-05548-2PMC PMC7351848
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Abstract

Rationale: Posttraumatic stress disorder (PTSD) is a chronic condition that has wide-ranging negative effects on an individual’s health and interpersonal relationships. Treatments with long-term benefits are needed to promote the safety and well-being of those suffering from PTSD. Objectives: To examine long-term change in PTSD symptoms and additional benefits/harms after 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD. Methods: Participants received two to three active doses of MDMA (75–125 mg) during blinded or open-label psychotherapy sessions with additional non-drug therapy sessions. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale for DSM IV (CAPS-IV) at baseline, 1 to 2 months after the last active MDMA session (treatment exit), and at least 12 months post final MDMA session (LTFU). A mixed-effect repeated-measures (MMRM) analysis assessed changes in CAPS-IV total severity scores. The number of participants who met PTSD diagnostic criteria was summarized at each time point. Participants completed a long-term follow-up questionnaire. Results: There was a significant reduction in CAPS-IV total severity scores from baseline to treatment exit (LS mean (SE) = − 44.8 (2.82), p < .0001), with a Cohen’s d effect size of 1.58 (95% CI = 1.24, 1.91). CAPS-IV scores continued to decrease from treatment exit to LTFU (LS mean (SE) = − 5.2 (2.29), p < .05), with a Cohen’s d effect size of 0.23 (95% CI = 0.04, 0.43). The number of participants who no longer met PTSD criteria increased from treatment exit (56.0%) to LTFU (67.0%). The majority of participants reported benefits, including improved relationships and well-being, and a minority reported harms from study participation. Conclusions: PTSD symptoms were reduced 1 to 2 months after MDMA-assisted psychotherapy, and symptom improvement continued at least 12 months post-treatment. Phase 3 trials are investigating this novel treatment approach in a larger sample of participants with chronic PTSD. Trial registration: clinicaltrials.gov Identifier: NCT00090064, NCT00353938, NCT01958593, NCT01211405, NCT01689740, NCT01793610

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  • Study participants have reported improved relationships following MDMA-assisted therapy for PTSD.

    “Study participants have also reported improved relationships following MDMA-assisted therapy for PTSD (Jerome et al. 2020).”

    From Authenticity and Love Drugs: Insights from Psychedelic Therapy (2026) · cites this paper as Jerome et al. 2020

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Research works printed but not linked: 43

  1. Baggott MJ, Kirkpatrick MG, Bedi G, de Wit H (2015) Intimate insight: MDMA changes how people talk about significant others. J Psychopharmacol 29:669–677 25922420 10.1177/0269881115581962 PMC4698152 · DOI
  2. Batelaan NM, Bosman RC, Muntingh A, Scholten WD, Huijbregts KM, van Balkom A (2017) Risk of relapse after antidepressant discontinuation in anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder: systematic review and meta-analysis of relapse prevention trials. BMJ (Clinical research ed) 358:j3927 28903922 10.1136/bmj.j3927 PMC5596392 · DOI · Paper page
  3. Bedi G, Phan KL, Angstadt M, de Wit H (2009) Effects of MDMA on sociability and neural response to social threat and social reward. Psychopharmacology 207:73–83 19680634 10.1007/s00213-009-1635-z PMC3328967 · DOI · Paper page
  4. Bedi G, Cecchi GA, Slezak DF, Carrillo F, Sigman M, de Wit H (2014) A window into the intoxicated mind? Speech as an index of psychoactive drug effects. Neuropsychopharmacology 39:2340–2348 24694926 10.1038/npp.2014.80 PMC4138742 · DOI
  5. Bershad AK, Miller MA, Baggott MJ, de Wit H (2016) The effects of MDMA on socio-emotional processing: does MDMA differ from other stimulants? J Psychopharmacol 30:1248–1258 27562198 10.1177/0269881116663120 PMC8753974 · DOI · Paper page
  6. Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney DS, Keane TM (1995) The development of a clinician-administered PTSD scale. J Trauma Stress 8:75–90 7712061
  7. Carhart-Harris RL, Wall MB, Erritzoe D, Kaelen M, Ferguson B, De Meer I, Tanner M, Bloomfield M, Williams TM, Bolstridge M, Stewart L, Morgan CJ, Newbould RD, Feilding A, Curran HV, Nutt DJ (2014) The effect of acutely administered MDMA on subjective and BOLD-fMRI responses to favourite and worst autobiographical memories. Int J Neuropsychopharmacol 17:527–540 24345398 10.1017/S1461145713001405 · DOI · Paper page
  8. Carhart-Harris RL, Murphy K, Leech R, Erritzoe D, Wall MB, Ferguson B, Williams LT, Roseman L, Brugger S, De Meer I, Tanner M, Tyacke R, Wolff K, Sethi A, Bloomfield MA, Williams TM, Bolstridge M, Stewart L, Morgan C, Newbould RD, Feilding A, Curran HV, Nutt DJ (2015) The effects of acutely administered 3,4-methylenedioxymethamphetamine on spontaneous brain function in healthy volunteers measured with arterial spin labeling and blood oxygen level-dependent resting state functional connectivity. Biol Psychiatry 78:554–562 24495461 10.1016/j.biopsych.2013.12.015 PMC4578244 · DOI
  9. Cipriani A, Williams T, Nikolakopoulou A, Salanti G, Chaimani A, Ipser J, Cowen PJ, Geddes JR, Stein DJ (2018) Comparative efficacy and acceptability of pharmacological treatments for post-traumatic stress disorder in adults: a network meta-analysis. Psychol Med 48:1975–1984 29254516 10.1017/S003329171700349X · DOI
  10. Dolder PC, Muller F, Schmid Y, Borgwardt SJ, Liechti ME (2018) Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects. Psychopharmacology 235:467–479 28551715 10.1007/s00213-017-4650-5 PMC5813072 · DOI · Paper page
  11. Edmond T, Rubin A (2004) Assessing the long-term effects of EMDR: results from an 18-month follow-up study with adult female survivors of CSA. J Child Sex Abus 13:69–86 15353377 10.1300/J070v13n01_04 · DOI
  12. Feduccia AA, Mithoefer MC (2018) MDMA-assisted psychotherapy for PTSD: are memory reconsolidation and fear extinction underlying mechanisms? Prog Neuro-Psychopharmacol Biol Psychiatry 84:221–228 10.1016/j.pnpbp.2018.03.003 29524515 · DOI · Paper page
  13. Feduccia AA, Holland J, Mithoefer MC (2018) Progress and promise for the MDMA drug development program. Psychopharmacology 235:561–571 29152674 10.1007/s00213-017-4779-2 · DOI
  14. Feduccia AA, Jerome L, Yazar-Klosinski B, Emerson A, Mithoefer M, Doblin R (2019) Breakthrough for trauma treatment: safety and efficacy of MDMA-assisted psychotherapy compared to paroxetine and sertraline. Front Psychiatry 10:1–7 31572236 10.3389/fpsyt.2019.00650 PMC6751381 · DOI · Paper page
  15. Gamma A, Buck A, Berthold T, Liechti ME, Vollenweider FX (2000) 3,4-Methylenedioxymethamphetamine (MDMA) modulates cortical and limbic brain activity as measured by [H 2 15 O]-PET in healthy humans. Neuropsychopharmacology 23:388–395 10989265 10.1016/S0893-133X(00)00130-5 · DOI · Paper page
  16. Gasser P, Holstein D, Michel Y, Doblin R, Yazar-Klosinski B, Passie T, Brenneisen R (2014) Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. J Nerv Ment Dis 202:513–520 24594678 10.1097/NMD.0000000000000113 PMC4086777 · DOI · Paper page
  17. Gorman I, Belser AB, Jerome L, Hennigan C, Shechet B, Hamilton S, Yazar-Klosinski B, Emerson A, Feduccia AA (2020) Posttraumatic growth after MDMA-assisted psychotherapy for posttraumatic stress disorder. J Trauma Stress 33:161–170 32073177 10.1002/jts.22479 PMC7216948 · DOI · Paper page
  18. Grof S (2008) LSD psychotherapy: 4th edition. Multidisciplinary Association for Psychedelic Studies, Santa Cruz
  19. Hogberg G, Pagani M, Sundin O, Soares J, Aberg-Wistedt A, Tarnell B, Hallstrom T (2008) Treatment of post-traumatic stress disorder with eye movement desensitization and reprocessing: outcome is stable in 35-month follow-up. Psychiatry Res 159:101–108 18336919 10.1016/j.psychres.2007.10.019 · DOI
  20. Javidi H, Yadollahie M (2012) Post-traumatic stress disorder. Int J Occup Environ Med 3:2–9 23022845
  21. Johnson DR, Rosenheck R, Fontana A, Lubin H, Charney D, Southwick S (1996) Outcome of intensive inpatient treatment for combat-related posttraumatic stress disorder. Am J Psychiatry 153:771–777 8633688 10.1176/ajp.153.6.771 · DOI
  22. Kadel R, Kip K (2012) A SAS macro to compute effect size (Cohen’s d) and its confidence interval from raw survey data. Proceedings of the annual southeast SAS users group conference
  23. Kessler RC, Ames M, Hymel PA, Loeppke R, McKenas DK, Richling DE, Stang PE, Ustun TB (2004) Using the World Health Organization health and work performance questionnaire (HPQ) to evaluate the indirect workplace costs of illness. J Occup Environ Med 46:S23–S37 15194893 10.1097/01.jom.0000126683.75201.c5 · DOI
  24. Kirkpatrick MG, Baggott MJ, Mendelson JE, Galloway GP, Liechti ME, Hysek CM, de Wit H (2014) MDMA effects consistent across laboratories. Psychopharmacology 231:3899–3905 24633447 10.1007/s00213-014-3528-z PMC4161650 · DOI
  25. Kline AC, Cooper AA, Rytwinksi NK, Feeny NC (2018) Long-term efficacy of psychotherapy for posttraumatic stress disorder: a meta-analysis of randomized controlled trials. Clin Psychol Rev 59:30–40 29169664 10.1016/j.cpr.2017.10.009 PMC5741501 · DOI
  26. Lee DJ, Schnitzlein CW, Wolf JP, Vythilingam M, Rasmusson AM, Hoge CW (2016) Psychotherapy versus pharmacotherapy for posttraumatic stress disorder: systemic review and meta-analyses to determine first-line treatments. Depress Anxiety 33:792–806 27126398 10.1002/da.22511 · DOI · Paper page
  27. Merz J, Schwarzer G, Gerger H (2019) Comparative efficacy and acceptability of pharmacological, psychotherapeutic, and combination treatments in adults with posttraumatic stress disorder: a network meta-analysis. JAMA Psychiatry PMC6563588 31188399
  28. Mithoefer M (2017) A manual for MDMA-assisted psychotherapy in the treatment of posttraumatic stress disorder; Version 8.1, http://www.maps.org/research/mdma/mdma-research-timeline/4887-a-manual-for-mdma-assisted-psychotherapy-in-the-treatment-of-ptsd PMC8453707 34114250
  29. Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Martin SF, Yazar-Klosinski B, Michel Y, Brewerton TD, Doblin R (2013) 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. J Psychopharmacol 27:28–39 23172889 10.1177/0269881112456611 PMC3573678 · DOI
  30. Mithoefer MC, Grob CS, Brewerton TD (2016) Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA. Lancet Psychiatry 3:481–488 27067625 10.1016/S2215-0366(15)00576-3 · DOI
  31. Mithoefer MC, Mithoefer AT, Feduccia AA, Jerome L, Wagner M, Wymer J, Holland J, Hamilton S, Yazar-Klosinski B, Emerson A, Doblin R (2018) 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. Lancet Psychiatry 5:486–497 29728331 10.1016/S2215-0366(18)30135-4 · DOI · Paper page
  32. Mott JM, Mondragon S, Hundt NE, Beason-Smith M, Grady RH, Teng EJ (2014) Characteristics of U.S. veterans who begin and complete prolonged exposure and cognitive processing therapy for PTSD. J Trauma Stress 27:265–273 24948535 10.1002/jts.21927 · DOI
  33. Nagy LM, Morgan CA 3rd, Southwick SM, Charney DS (1993) Open prospective trial of fluoxetine for posttraumatic stress disorder. J Clin Psychopharmacol 13:107–113 8463442 10.1097/00004714-199304000-00004 · DOI
  34. 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). J Psychopharmacol 27:40–52 23118021 10.1177/0269881112464827 · DOI
  35. Ot’alora GM, Grigsby J, Poulter B, Van Derveer JW 3rd, Giron SG, Jerome L, Feduccia AA, Hamilton S, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R (2018) 3,4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: a randomized phase 2 controlled trial. J Psychopharmacol 32:1295–1307 PMC6247454 30371148
  36. Posner K, Oquendo MA, Gould M, Stanley B, Davies M (2007) Columbia Classification Algorithm of Suicide Assessment (C-CASA): classification of suicidal events in the FDA’s pediatric suicidal risk analysis of antidepressants. Am J Psychiatry 164:1035–1043 17606655 10.1176/ajp.2007.164.7.1035 PMC3804920 · DOI · Paper page
  37. Schnurr PP (2007) The rocks and hard places in psychotherapy outcome research. J Trauma Stress 20:779–792 17955539 10.1002/jts.20292 · DOI
  38. Solomon Z, Shklar R, Mikulincer M (2005) Frontline treatment of combat stress reaction: a 20-year longitudinal evaluation study. Am J Psychiatry 162:2309–2314 16330595 10.1176/appi.ajp.162.12.2309 · DOI
  39. Steenkamp MM, Litz BT, Hoge CW, Marmar CR (2015) Psychotherapy for military-related PTSD: a review of randomized clinical trials. JAMA 314:489–500 26241600 10.1001/jama.2015.8370 · DOI · Paper page
  40. Swift JK, Callahan JL (2011) Decreasing treatment dropout by addressing expectations for treatment length. Psychother Res 21:193–200 21271460 10.1080/10503307.2010.541294 · DOI
  41. van der Kolk BA, Spinazzola J, Blaustein ME, Hopper JW, Hopper EK, Korn DL, Simpson WB (2007) A randomized clinical trial of eye movement desensitization and reprocessing (EMDR), fluoxetine, and pill placebo in the treatment of posttraumatic stress disorder: treatment effects and long-term maintenance. J Clin psychiatry 68:37–46 17284128 10.4088/JCP.v68n0105 · DOI
  42. Young MB, Norrholm SD, Khoury LM, Jovanovic T, Rauch SAM, Reiff CM, Dunlop BW, Rothbaum BO, Howell LL (2017) Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA). Psychopharmacology 234:2883–2895 28741031 10.1007/s00213-017-4684-8 PMC5693755 · DOI · Paper page
  43. Zimmermann P, Biesold KH, Barre K, Lanczik M (2007) Long-term course of post-traumatic stress disorder (PTSD) in German soldiers: effects of inpatient eye movement desensitization and reprocessing therapy and specific trauma characteristics in patients with non-combat-related PTSD. Mil Med 172:456–460 17521089 10.7205/MILMED.172.5.456 · DOI

Cited by

Sorted by citations

Authors
Jerome, L., Feduccia, A. A., Wang, J. B., Hamilton, S., Yazar-Klosinski, B., Emerson, A., Mithoefer, M. C., & Doblin, R.
Affiliations
  • Stanford Medicine (US)
  • Medical University of South Carolina (US)
  • Multidisciplinary Association for Psychedelic Studies (US)
Corresponding author
Jerome, Lisa
ORCID
Venue
Psychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2020-06-04
Volume
237
Issue
8
Pages
2485-2497
ISSN
  • 0033-3158 (ISSN-L)
  • 1432-2072
DOI
10.1007/s00213-020-05548-2
PMC
PMC7351848
OpenAlex
W3033913667
Cited by
159
References
22
Citations by year
2026: 4 · 2025: 20 · 2024: 30 · 2023: 42 · 2022: 41 · 2021: 21 · 2020: 1
FWCI
10.48
Type
journal article
Language
en
Status
Retracted
Update notices
retraction (2024-08-10)
Open access
Licence
Locations
  • Psychopharmacology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Multidisciplinary Association for Psychedelic Studies
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
Keywords
MDMA-assisted psychotherapy, MDMA, post-traumatic stress disorder, long-term follow-up, symptom relief, chronic PTSD, treatment harms, well-being, relationships, retracted article, pooled analysis, adverse events
MeSH terms
Adult, Combined Modality Therapy, Dose-Response Relationship, Drug, Double-Blind Method, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Psychotherapy, Surveys and Questionnaires, Stress Disorders, Post-Traumatic, Treatment Outcome, Cross-Over Studies, N-Methyl-3,4-methylenedioxyamphetamine

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