Nature medicine
June 1, 2021
Jennifer M Mitchell, Michael Bogenschutz, Alia Lilienstein et al.
965 citations
A phase 3 clinical trial tested MDMA-assisted therapy against placebo for severe PTSD. Participants received manualized therapy with either MDMA or placebo alongside preparatory and integrative sessions. At two months after the last session, the MDMA group showed a significantly greater reduction in PTSD symptoms (average 24.4-point drop on the CAPS-5 scale) compared to the placebo group (13.9-point drop), with a large effect size. Functional impairment also improved more with MDMA. No serious safety issues such as abuse potential, suicidality, or heart rhythm problems were observed. The findings suggest MDMA-assisted therapy is highly effective and safe for severe PTSD, including in people with common co-occurring conditions.
Nature medicine
October 1, 2023
Jennifer M. Mitchell, Marcela Ot’alora G., Bessel Van der Kolk et al.
400 citations
In a phase 3 trial, MDMA-assisted therapy reduced PTSD symptoms and functional impairment more than placebo with therapy in 104 participants with moderate to severe PTSD. The average decrease in PTSD symptom severity was 23.7 points with MDMA-assisted therapy versus 14.8 points with placebo, and functional disability improved by 3.3 versus 2.1 points. Participants were ethnoracially diverse, with 27% identifying as Hispanic/Latino and 34% as other than White. Severe side effects occurred in 9.4% of the MDMA group and 3.9% of the placebo group; no deaths or serious adverse events were reported. The treatment was generally well tolerated.
Clinical Pharmacokinetics
March 28, 2017
Randall Brown, Christopher R. Nicholas, Nicholas V. Cozzi et al.
189 citations
Psilocybin is a psychedelic tryptamine being studied for depression and substance use disorders. In an open-label study of 12 healthy adults, escalating oral doses of 0.3, 0.45, and 0.6 mg/kg were given at monthly intervals. No psilocybin was found in plasma or urine; its active metabolite psilocin had an elimination half-life of 3 hours (standard deviation 1.1). Renal clearance of intact psilocin accounted for less than 2% of total clearance, indicating no dose reduction is needed for mild-moderate renal impairment. Body weight did not predict variation in psilocin clearance. No serious adverse events occurred. A fixed 25 mg dose approximates the exposure of a 0.3 mg/kg dose.
Focus (American Psychiatric Publishing)
July 1, 2023
Jennifer M Mitchell, Michael Bogenschutz, Alia Lilienstein et al.
97 citations
A phase 3 clinical trial tested MDMA-assisted therapy for severe PTSD. In 90 participants randomized to receive either MDMA or placebo alongside therapy, those receiving MDMA showed a significantly larger reduction in PTSD symptoms, with an average decrease of 24.4 points on the CAPS-5 scale compared to 13.9 points in the placebo group. Functional impairment also improved more with MDMA. No serious safety issues like abuse potential or suicidality were observed. The treatment was effective even for patients with common co-occurring conditions such as depression or substance use history. The authors conclude MDMA-assisted therapy is a safe and highly effective treatment for severe PTSD.
Journal of Psychopharmacology
June 27, 2018
Christopher R. Nicholas, Kelsey M. Henriquez, Michele Gassman et al.
85 citations
Healthy participants given escalating doses of psilocybin (0.3, 0.45, and 0.6 mg/kg) showed a significant linear dose-related increase in Mystical Experience Questionnaire total score and the transcendence of time and space subscale, but not in the rate of complete mystical experiences. Dose 3 produced significantly higher transcendence of time and space scores than dose 1, while no dose-related differences emerged for total scores or mystical experience rate. Positive persisting effects 30 days after the last dose were significantly higher than negative ones, and a moderate increase in well-being or life satisfaction was associated with the maximum mystical experience score. Pharmacokinetic measures correlated with dose but not with mystical experience scores or rate, indicating that a complete mystical experience was not necessary for positive outcomes.
Psychedelic Medicine
December 1, 2023
Julia Malicki, Amelia Baltes, Christopher R. Nicholas et al.
7 citations
A clinical trial found that giving psilocybin together with buprenorphine to people with opioid use disorder was safely tolerated and did not interfere with buprenorphine's effectiveness or psilocybin's subjective effects. The study faced feasibility challenges that required changes to the participant pool and eligibility rules, along with strategies to improve accessibility, reduce burden, and increase generalizability.