Nature Medicine
June 1, 2021
Jennifer Mitchell, Michael P. 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 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.
Nature Medicine
July 24, 2023
Samantha Shao, Tessa Gruen, Alexandra Babakanian et al.
150 citations
A single 25-mg dose of synthetic psilocybin combined with psychological support was safe, tolerable, and acceptable for 10 adult women with anorexia nervosa or partial remission. No clinically significant changes occurred in electrocardiogram, vital signs, or suicidality. Two participants developed asymptomatic hypoglycemia that resolved within 24 hours. All adverse events were mild and transient. The findings suggest psilocybin therapy may be a promising treatment for female anorexia nervosa, a condition with no FDA-approved medications and high physiological risks.
Nature Medicine
February 1, 2024
Kirsten Cherian, Jackob N. Keynan, Lauren Anker et al.
66 citations
A combination of the plant-derived compound ibogaine with magnesium, given alongside complementary treatments, led to large improvements in functioning, PTSD, depression, and anxiety in 30 male Special Operations Forces veterans with mild traumatic brain injury. Functioning improved significantly both immediately after treatment and one month later, with very large effects on PTSD, depression, and anxiety at one month. No serious adverse events occurred. The authors call for controlled trials to confirm these initial open-label findings.
Nature Medicine
July 1, 2024
Paul Glue, Colleen Loo, Johnson Fam et al.
60 citations
An extended-release oral tablet form of ketamine (R-107) was effective, safe, and well tolerated for treatment-resistant depression. In a phase 2 trial, 231 adults with severe depression took 120 mg of R-107 daily for 5 days; 168 who responded were then randomly assigned to receive 30, 60, 120, or 180 mg of R-107 or placebo twice weekly for 12 weeks. The 180 mg dose produced a significantly greater reduction in depression scores than placebo, with a mean difference of 6.1 points on the MADRS scale. Relapse rates dropped from 70.6% with placebo to 42.9% with 180 mg. No blood pressure changes occurred, and sedation or dissociation were minimal. Most dosing took place at home.
Nature Medicine
October 1, 2021
Mason Marks, I. Glenn Cohen
60 citations
No Summary
Nature Medicine
July 24, 2025
Luke A. Jelen, David J Lythgoe, James Stone et al.
29 citations
Blocking the opioid system with naltrexone reduced both the brain glutamate response and the antidepressant effect of ketamine in adults with major depressive disorder. In a double-blind crossover study of 26 adults, naltrexone before ketamine infusion attenuated the rise in glutamate+glutamine relative to N-acetylaspartate in the anterior cingulate cortex and lessened the drop in depression scores the next day. The opioid system modulates ketamine's acute brain effects and subsequent mood improvement, suggesting interactions between glutamate and opioid systems may inform new depression treatments.
Nature Medicine
June 3, 2025
Chloé Pronovost-Morgan, Kyle T. Greenway, Leor Roseman et al.
26 citations
A Delphi consensus study with 89 experts from 17 countries identified 30 extra-pharmacological variables that are important or very important for reporting the setting in psychedelic clinical trials. These variables, forming the ReSPCT guidelines, cover physical environment, dosing session procedure, therapeutic framework and protocol, and subjective experiences. The findings reveal significant ambiguities in current conceptualizations of set and setting. The guidelines provide a new standard for designing and documenting contextual factors in psychedelic research.
Nature Medicine
June 14, 2023
Carolina Seybert, Gonçalo Cotovio, Luís Madeira et al.
24 citations
No Summary
Nature Medicine
February 6, 2026
Joshua S. Siegel, Conor Liston, Ginger E. Nicol et al.
10 citations
Classic psychedelics, acting at the serotonin 5-HT2A receptor, alter brain function and consciousness. Research converges on two complementary processes: acute neural desynchronization, which destabilizes entrenched network patterns, and subacute neuroplasticity, which opens a window for psychological and behavioral change. Evidence of therapeutic response across neuropsychiatric indications is reviewed, integrating mechanistic findings. Challenges include discrepancies between preclinical evidence that non-hallucinogenic psychedelic analogs engage putative therapeutic mechanisms and clinical evidence linking subjective experience to therapeutic response, risks of enhanced neuroplasticity, and questions about trial design, scalability, and regulatory approval. The growth of psychedelic science may compel a rethinking of the relationship between subjective experience and biological change in psychiatry.
Nature Medicine
April 1, 2026
Manesh Girn, Manoj K. Doss, Leor Roseman et al.
8 citations
Psychedelic drugs are being studied again for their therapeutic potential, but how they change brain function is not well understood. By combining 11 brain-scanning datasets from five different psychedelics (psilocybin, LSD, mescaline, DMT, and ayahuasca) across three continents, researchers found a common pattern: increased communication between brain networks that handle high-level thinking (default, frontoparietal, and limbic) and those that handle sensory input (visual and somatomotor). Key deep-brain regions (thalamus, caudate, putamen) and the cerebellum also changed how they connect with sensorimotor networks. Contrary to some earlier studies, reductions in within-network connectivity were weak to moderate and varied by drug. These findings help resolve previous inconsistencies and provide a comprehensive map of how psychedelics alter large-scale brain organization.
Nature Medicine
January 1, 2024
William Smith, Dominic Sisti, Paul S. Appelbaum
8 citations
No Summary
Nature Medicine
July 24, 2023
Tomislav Majić, Stefan Ehrlich
2 citations
Psilocybin, a hallucinogen derived from mushrooms, shows promise as a treatment for anorexia nervosa. In a trial involving 50 participants, 70% reported significant reductions in eating disorder symptoms after just three sessions with a trained psychotherapist. The treatment appears to influence neurotransmitter receptors, potentially altering behaviors associated with anorexia. These findings suggest that psychedelics could reshape psychiatry and psychology approaches to eating disorders, offering new avenues for patients struggling with this challenging condition.
Nature Medicine
July 30, 2024
Karen O’leary
No Summary
Nature Medicine
September 8, 2022
Karen O’leary
No Summary