MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study

Mitchell, Jennifer; Bogenschutz, Michael P.; Lilienstein, Alia; Harrison, Charlotte; Kleiman, Sarah E.; Parker-Guilbert, Kelly; G., Marcela Ot’alora; Garas, Wael; Paleos, Casey; Gorman, Ingmar; Nicholas, Christopher R.; Mithoefer, Michael C.; Carlin, Shannon; Poulter, Bruce; Mithoefer, Ann T; Quevedo, Sylvestre; Wells, Gregory; Klaire, Sukhpreet; Kolk, Bessel van der; Tzarfaty, Keren; Amiaz, Revital; Worthy, Ray; Shannon, Scott; Woolley, Joshua; Marta, Cole J.; Gelfand, Yevgeniy; Hapke, Emma; Amar, Simon; Wallach, Yair; Brown, Randall; Hamilton, Scott; Wang, Julie B.; Coker, Allison; Matthews, Rebecca; Boer, Alberdina de; Yazar‐Klosinski, Berra; Emerson, Amy; Doblin, Rick

doi:10.1038/s41591-021-01336-3

Cited by 514 publications

(486 citation statements)

References 37 publications

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“…Conversely, there is accumulating clinical data indicating a transdiagnostic antidepressant [ 3 , 5 , 6 ], anxiolytic [ 11 , 76 ], and anti-addictive [ 8 – 10 ] therapeutic action of higher doses of psilocybin administered in the context of psychological support. Results from ongoing phase 2 RCTs [ 77 , 78 ] will determine whether psilocybin therapy will progress to phase 3 trials and likely follow esketamine/ketamine and MDMA therapy for PTSD [ 79 ] into the psychiatric clinic.…”

Section: Discussionmentioning

confidence: 99%

Psychedelic perceptions: mental health service user attitudes to psilocybin therapy

et al. 2021

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Introduction Despite the rapid advance of psychedelic science and possible translation of psychedelic therapy into the psychiatric clinic, very little is known about mental health service user attitudes. Objectives To explore mental health service user attitudes to psychedelics and psilocybin therapy. Methods A questionnaire capturing demographics, diagnoses, previous psychedelic and other drug use, and attitudes to psychedelics and psilocybin therapy was distributed to mental health service users. Results Ninety-nine participants completed the survey (52% female, mean age 42 years). The majority (72%) supported further research, with 59% supporting psilocybin as a medical treatment. A total of 27% previously used recreational psilocybin, with a male preponderance (p = 0.01). Younger age groups, those with previous psychedelic experience, and those with non-religious beliefs were more likely to have favourable attitudes towards psilocybin. A total of 55% of the total sample would accept as a treatment if doctor recommended, whereas 20% would not. Fewer people with depression/anxiety had used recreational psychedelics (p = 0.03) but were more likely to support government funded studies (p = 0.02). A minority (5%) of people with conditions (psychosis and bipolar disorder) that could be exacerbated by psilocybin thought it would be useful for them. One fifth of the total sample viewed psychedelics as addictive and unsafe even under medical supervision. Concerns included fear of adverse effects, lack of knowledge, insufficient research, illegality, and relapse if medications were discontinued. Conclusions The majority supported further research into psilocybin therapy. Younger people, those with previous recreational psychedelic experience, and those with non-religious beliefs were more likely to have favourable attitudes towards psilocybin therapy.

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Section: Discussionmentioning

confidence: 99%

Psychedelic perceptions: mental health service user attitudes to psilocybin therapy

et al. 2021

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“…The selfreport BDI scale, the outcome measure used in these trials, is not a blinded outcome measure thus expectancy effects are more likely to have contributed to findings. A recent, phase 3 RCT investigating MDMA therapy for PTSD by the same group demonstrated MDMA therapy was effective in reducing depressive mood symptoms (as measured by the BDI-II) (Mitchell et al, 2021).…”

Section: Novel Treatment Approachesmentioning

confidence: 99%

“…In 2017, MDMA was granted this designation for its use in psychotherapy for the treatment of PTSD. As of September 2020, The Multidisciplinary Association for Psychedelic Studies (MAPS) have completed one of two planned phase 3 randomized, double-blind, placebo-controlled, multi-site clinical trials to assess the safety and efficacy of MDMA-assisted psychotherapy in participants with PTSD (Mitchell et al, 2021;Multidisciplinary Association for Psychedelic Research, 2020). Psilocybin therapy has been designated in the same 'breakthrough' category for both the treatment of MDD and TRD (COMPASS Pathways, 2018;Feduccia et al, 2019;Nichols, 2020).…”

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confidence: 99%

Psilocybin and MDMA for the treatment of trauma-related psychopathology

Bird

Modlin

Rucker

2021

International Review of Psychiatry

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This review examines the role of trauma in psychiatric morbidity and analogous psychoneurobiological changes. Trauma is a necessary criterion for Post-Traumatic Stress Disorder (PTSD), however, trauma history is highly correlated with a variety of psychiatric conditions. Some evidence suggests that Major Depressive Disorder (MDD) is the most common psychiatric condition that arises following trauma. Approximately 50% of PTSD cases present with co-morbid MDD. Overlapping symptomatology and neurobiology between these conditions underlie the debate over whether these phenomena result from problematic nosology or whether comorbid MDD þ PTSD is a distinct phenotype of trauma-related psychopathology. Regardless, similar treatment approaches have been employed historically, with varying success. The drug-assisted psychotherapy treatment model, which combines pharmacological and psychotherapeutic approaches, is currently being trialled as a novel treatment approach in psychiatry. Both psilocybin-and 3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy have received Food and Drug Administration 'breakthrough therapy' designation for the treatment of resistant MDD and PTSD, respectively. This paper reviews the therapeutic rationale of both psilocybin and MDMA for treating both trauma-related MDD and PTSD.

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“…The first Phase III randomized controlled trial of 3,4-methyl enedioxy methamphetamine (MDMA) supported the efficacy of this drug for the treatment of posttraumatic stress disorder (PTSD). 1 This 18-week study (MDMA n = 46, Placebo n = 44) involved three drug administration sessions combined with a supportive psychotherapy. From a baseline PTSD severity score of approximately 44 on the Clinician Administered PTSD Scale for DSM5, MDMA produced a 24.4-point (55.5%) reduction in PTSD severity, which was significantly greater than that seen with placebo (13.9 points, 31.5% reduction).…”

Section: Main Textmentioning

confidence: 99%