The journal of pain
October 1, 2022
Robert H. Dworkin, Brian T Anderson, Nick Andrews et al.
22 citations
Psychedelic substances have been used historically for spiritual and mystical experiences, and recent interest focuses on their potential to treat chronic pain. Clinical trials support psychedelics' effectiveness for psychiatric conditions, but studies on chronic pain—such as cancer pain, phantom limb pain, migraine, and cluster headache—are few and mostly uncontrolled. Risks are relatively rare with careful patient screening and supervision. Key challenges include identifying mechanisms of action, selecting appropriate pain conditions, designing rigorous trials with proper control groups, minimizing unblinding bias, and accounting for patient mindset and setting. Evidence-based recommendations are needed for future research to yield informative results.
Neuroscience and Biobehavioral Reviews
November 1, 2023
Sophia Linguiti, Jacob W Vogel, Valerie J Sydnor et al.
15 citations
A systematic review of 91 fMRI studies on acute psychedelic effects found substantial methodological heterogeneity. Only 51 unique samples were used across the 91 papers, and 54% of studies did not meet current standards for correcting Type I errors or controlling motion artifacts. Psilocybin and LSD consistently modulated connectivity along the sensorimotor-association cortical axis. Ketamine consistently increased activation in the dorsomedial prefrontal cortex. The review calls for future adoption of pre-registration, standardized processing and statistical testing, and data sharing to improve rigor.
Nature Mental Health
May 1, 2026
S. Parker Singleton, Brooke L. Sevchik, Analiese Lahey et al.
2 citations
A living systematic review and meta-analysis of 15 randomized controlled trials (801 participants) found that psilocybin-assisted therapy substantially reduces depressive symptoms compared to control conditions, with a standardized mean difference of −0.90 (Hedges’ g). The analysis included 12 trials (585 participants) in the primary model. Many studies had small sample sizes or risk of bias. The review is maintained as a living resource with an open-data database and online dashboard that will be updated as new evidence emerges.
bioRxiv (Cold Spring Harbor Laboratory)
October 22, 2024
Pablo Mallaroni, S. Parker Singleton, Natasha L. Mason et al.
2 citations
preprint
A double-blind, placebo-controlled crossover study with 22 healthy volunteers compared the acute brain effects of the psychedelic phenethylamine 2C-B (20 mg) and the tryptamine psilocybin (15 mg) using 7T resting-state functional MRI. Both compounds reduced connectivity within brain networks and broadly increased connections between networks and between subcortical and cortical regions. Compared to psilocybin, 2C-B caused less reduction in between-network connectivity but increased connectivity in transmodal regions. Both drugs similarly increased brain complexity. The neural effects aligned with differences in monoaminergic and serotonergic receptor binding beyond 5-HT2A, suggesting 2C-B's distinct pharmacology shapes its functional brain dynamics.
medRxiv Preprint Server
March 27, 2026
Brooke L. Sevchik, S. Parker Singleton, Analiese Lahey et al.
preprint
A living systematic review and meta-analysis of six randomized controlled trials with 286 participants found that MDMA-assisted therapy reduces PTSD symptoms more than control conditions (Hedges' g = -0.71). More dosing sessions and higher cumulative doses were linked to larger effects. MDMA also led to higher response (risk ratio 1.35) and remission (risk ratio 2.25) rates. Most studies had low risk of bias per Cochrane guidelines, though issues like expectancy and functional unblinding remain. The evidence was rated low certainty using GRADE, and the authors note more trials are needed.
medRxiv
August 16, 2025
S. Parker Singleton, Brooke L. Sevchik, Analiese Lahey et al.
preprint
Psilocybin-assisted therapy produces substantial reductions in depressive symptoms compared to control conditions, according to a systematic review and meta-analysis of 12 randomized controlled trials with 711 participants. The pooled effect size was large (Hedges' g = –0.91), and effects appeared rapidly and remained consistent over several weeks. However, many studies had small sample sizes or risk of bias, and waitlist-controlled or crossover designs contributed heterogeneity. The review provides a living open data resource that will be updated as new evidence emerges.