EClinicalMedicine
September 24, 2020
B. Anderson, Alicia Danforth, Prof Robert Daroff et al.
271 citations
Psilocybin-assisted group therapy is feasible, relatively safe, and potentially effective for reducing demoralization in older long-term AIDS survivor (OLTAS) gay men, a population with high levels of demoralization and traumatic loss. In an open-label study, participants with moderate-to-severe demoralization received 8-10 group therapy visits and one psilocybin administration (0.3-0.36 mg/kg). The primary clinical outcome showed a reduction in demoralization from baseline to end-of-treatment and to 3-month follow-up, with a moderate effect size (partial eta-squared = 0.47, 90% CI 0.21-0.60). Groups may offer an efficient model for delivering psychotherapy alongside psilocybin to patients with complex needs.
Journal of Neuroscience
November 30, 2020
Danilo de Gregorio, Argel Aguilar‐valles, Katrin H. Preller et al.
258 citations
A renewed interest in hallucinogens for treating psychiatric disorders has emerged. Preclinical and clinical studies have confirmed ketamine's efficacy for depression. Emerging evidence points to psilocybin and LSD's therapeutic properties and their ability to modulate functional brain connectivity. MDMA, an entactogen, has shown usefulness for post-traumatic stress disorder. This review summarizes the pharmacology of hallucinogenic compounds, highlighting differences between psychedelic and nonpsychedelic hallucinogens and entactogens, and describes their behavioral effects in animals and humans. Together, these data substantiate the potential of these compounds for treating mental diseases.
Drug and Alcohol Dependence
February 1, 2022
Christopher R. Nicholas, Julie B. Wang, A. Coker et al.
67 citations
MDMA-assisted therapy for severe PTSD may also reduce hazardous alcohol use without increasing illicit drug use. In a randomized trial, 90 adults with severe PTSD received either MDMA-assisted therapy or placebo plus therapy. Those in the MDMA group showed a greater reduction in alcohol use scores (average decrease of 1.02 points) compared to a slight increase in the placebo group (average increase of 0.40 points). Changes in drug use scores did not differ between groups. The findings suggest MDMA-assisted therapy could serve as an integrated treatment for co-occurring PTSD and alcohol or substance use disorders.
PLoS ONE
February 25, 2022
Elliot Marseille, Jennifer Mitchell, James G. Kahn
49 citations
For patients with severe or extreme chronic PTSD, MDMA-assisted therapy (MDMA-AT) costs $11,537 per patient and generates net health care savings of $132.9 million over 30 years per 1,000 patients, while accruing 4,856 quality-adjusted life-years (QALYs) and averting 61.4 premature deaths compared with standard care. The therapy breaks even on cost at 3.8 years. A three-session MDMA regimen yields greater medical savings and health benefits than a two-session regimen. Even if no health care cost savings are assumed, the incremental cost-effectiveness ratio is $2,384 per QALY gained. MDMA-AT is cost-saving from a payer's perspective and delivers substantial clinical benefit.
Scientific Reports
August 2, 2024
Jennifer Mitchell, Nicky J. Mehtani, Mallory O. Johnson et al.
9 citations
HIV-related shame predicts substance use and poor antiretroviral adherence among people with HIV, hindering national epidemic-ending goals. In a pilot clinical trial with 12 participants, psilocybin-assisted group therapy produced a large decrease in HIV-related shame, with a median reduction of 5.5 points on the HIV and Abuse Related Shame Inventory from baseline to 3-month follow-up. However, two participants experienced a paradoxical worsening of sexual abuse-related shame after psilocybin, raising concerns about its use in patients with trauma. These preliminary results suggest potential for addressing HIV-related shame but highlight cautions.
bioRxiv (Cold Spring Harbor Laboratory)
November 7, 2024
Lorenzo Pasquini, Jakub Vohryzek, Anira Escrichs et al.
4 citations
preprint
Psilocybin induces fast and sustained improvements in mental well-being, yet its long-term mechanisms are not fully understood. Four weeks after a full dose, fronto-striatal-thalamic (FST) circuitry—involved in goal-directed behavior and motivation—shows increased dynamic activity and flexibility in healthy volunteers. Computational modeling indicates that reduced structural constraints on functional dynamics cause this increased flexibility. Long-term changes include increased bottom-up and reduced top-down information flow, mediated by serotonergic (5-HT2A) and dopaminergic (D2) receptor systems. This functional re-organization of FST circuits may represent a common mechanism underlying clinical improvements across neuropsychiatric disorders such as substance abuse, major depression, and anorexia.
Psychedelics
August 5, 2025
Elliot Marseille, Jennifer Mitchell
2 citations
A commentary on a cost-effectiveness analysis of MDMA-assisted therapy for PTSD, published after the FDA declined to approve the treatment in 2024, identifies two key limitations that reduce its relevance for healthcare decision-makers. The analysis compared MDMA therapy to placebo-based therapy instead of standard-of-care treatments, and it used a pricing strategy of $36,000 for the three MDMA doses that threatens accessibility. Alternative modeling indicates that at a price of approximately $10,500, MDMA therapy could be extremely cost-effective, around $160 per quality-adjusted life year (QALY), or even cost-saving. Future research should incorporate realistic treatment comparators, comprehensive healthcare utilization data, and pricing models balancing economic viability with public health goals.