International Review of Psychiatry
June 5, 2020
Ben Carter, Rebecca Strawbridge, Muhammad Ishrat Husain et al.
45 citations
A network meta-analysis of 27 randomized trials found that NMDA-targeting medications (e.g., ketamine) are markedly more effective than placebo for augmenting treatment-resistant depression (effect size 0.91). Antipsychotics, mood stabilizers, and other pharmacological augmenters were also compared, but NMDA therapies had the highest probability of being effective. No psychological augmentation trials could be included due to the lack of a common comparator. The evidence is limited by few trials, heterogeneity, and inconsistent safety reporting.
BJPsych Open
July 1, 2023
Muhammad Ishrat Husain, Nicole Ledwos, Elise Fellows et al.
41 citations
A proof-of-concept randomized controlled trial will test whether combining the psychedelic psilocybin with risperidone, a drug that blocks the serotonin 2A receptor, can block psilocybin's psychedelic effects while preserving its antidepressant action in adults with treatment-resistant depression. Sixty participants will be randomly assigned to receive psilocybin plus risperidone, psilocybin alone, or placebo plus risperidone, all with 12 hours of manualized psychotherapy. Feasibility and tolerability will be assessed through recruitment, retention, and adverse events. If successful, this approach could make psilocybin therapy more acceptable and accessible by eliminating the need for a psychedelic experience and continuous monitoring.
Psychedelic Med (New Rochelle)
March 12, 2024
Alexander Wen, Nikhita Singhal, Brett D. M. Jones et al.
36 citations
Blinding is especially difficult in randomized controlled trials of psychedelics because these drugs produce noticeable changes in consciousness. This systematic review of 50 papers from 48 clinical trials published between 1963 and January 2023 found that most studies were double-blinded, used within-subjects designs, and employed inert placebos. The majority did not report on whether blinding procedures were successful, and in those that did, blinding failed. To reduce unblinding and expectancy effects, the authors recommend using active placebos and dose-response or active comparator designs.
Journal of Affective Disorders
July 18, 2025
Mary E. Kittur, Mingyao Liu, Brett D. M. Jones et al.
12 citations
Psilocybin therapy shows promise for rapid and lasting clinical benefits when paired with psychological support, but the field lacks standardized therapeutic guidelines. A systematic review of 22 recent trials across conditions like depression, substance use, and obsessive-compulsive disorders found broad consistency in the structure of therapy sessions—before, during, and after psilocybin administration. However, trials varied widely in therapeutic intensity, diagnostic adaptations, and use of evidence-based psychotherapies. Fewer than half reported standardization measures such as manualized procedures, specific training, or adherence monitoring. These gaps undermine replicability and generalizability, and until support protocols are clearly defined, mechanistic understanding and clinical adoption will remain limited.
Journal of Psychoactive Drugs
August 24, 2023
Stanley Wong, An Yi Yu, Nicholas Fabiano et al.
11 citations
Interest in psychedelic therapies for mental and substance use disorders has grown, but evidence for non-psilocybin serotonergic psychedelics remains limited. A scoping review of mescaline, ibogaine, ayahuasca, DMT, and LSD identified 77 studies: 43 on LSD, 24 on ayahuasca, and 5 each on DMT, ibogaine, and mescaline. Reported benefits included improved mood, anxiety, insight, reduced substance use, better relationships, and fewer vegetative symptoms. Adverse effects were psychological, neurological, physical, and gastrointestinal; serious events like homicide and suicide appeared in LSD studies. The review concludes there is only low-level evidence supporting the safety and efficacy of these substances for mental and substance use disorders.
Psychiatry Research
January 1, 2022
Joshua D. Di Vincenzo, Orly Lipsitz, Nelson B Rodrigues et al.
11 citations
A small proportion of people with treatment-resistant depression experience clinically significant worsening of symptoms during a course of intravenous ketamine, but the rate is very low—between 1.83% and 5.49% across infusion time points—and similar to that seen with conventional antidepressants. In a retrospective analysis of 164 adults (142 with unipolar depression and 22 with bipolar depression) who received four ketamine infusions over two weeks, no individuals with bipolar depression reported worsening. The findings suggest that symptomatic worsening with ketamine is uncommon, though the study's uncontrolled, single-center design limits certainty.
Therapeutic Advances in Psychopharmacology
September 1, 2025
Stanley Wong, Gray Meckling, Nicholas Fabiano et al.
6 citations
A systematic review and meta-analysis of nine randomized controlled trials involving 593 adults with psychiatric diagnoses found that psilocybin therapy led to a small but significant decrease in suicidal ideation compared to control conditions. No studies reported suicide attempts or deaths. The analysis showed low heterogeneity and no publication bias, though two studies had a high risk of bias. Current evidence is limited by small sample sizes, insufficient follow-up data, and inadequate assessment of blinding.
JAMA Psychiatry
April 15, 2026
Diana Orsini, Sabrina Wong, Sara Di Luch et al.
4 citations
In randomized clinical trials of psychedelic drugs for psychiatric disorders, the drugs' strong subjective effects often reveal which treatment participants or raters think they received, a phenomenon called functional unblinding. A systematic review of 112 trials found that only 29.5% assessed whether blinding was maintained, yet 57.1% cited blinding as a limitation. Blinding failure exceeded 90% in psilocybin, LSD, and ayahuasca studies and 85% in MDMA trials with inert placebos. Ketamine trials rarely assessed blinding but fared better when midazolam was used as an active comparator. No control strategy consistently preserved ideal blinding, raising concerns about the validity of efficacy estimates.
Ther Adv Psychopharmacol
October 16, 2025
Stanley Wong, Brett D. M. Jones, Mathura T. Thiyagarajah et al.
3 citations
A review of nine small clinical trials found that ayahuasca and psilocybin, when used to treat major depressive disorder and treatment-resistant depression, are associated with changes in several biological markers. These include increased serum brain-derived neurotrophic factor, decreased serum C-reactive protein, altered amygdala activation, and changes in functional connectivity between brain regions such as the ventromedial prefrontal cortex, anterior cingulate cortex, and posterior cingulate cortex. These associations suggest potential mechanisms of clinical response, but larger, longer-term studies are needed to confirm these findings.
The Journal of Clinical Psychiatry
January 8, 2025
Ali Abdolizadeh, Brett D. M. Jones, Maryam Hosseini Kupaei et al.
2 citations
A systematic review of treatments for suicidality among psychiatric inpatients aged 18–65 found that intravenous ketamine produced the most consistent rapid reduction in suicidality among 14 pharmacologic trials. Among 35 nonpharmacologic trials—including chronotherapy, neurostimulation, and psychotherapies—results were mixed, with some interventions showing potential benefit, especially for mood, personality, and trauma-related disorders. Many studies had methodological limitations such as nonrandomized designs and lack of control groups. The review calls for larger, well-designed trials to confirm effectiveness.
PLoS One
January 1, 2025
Johny Bozdarov, Brett D. M. Jones, Madeha Umer et al.
2 citations
A 10-week trial of Mindfulness-Based Boxing Therapy (MBBT) for adults with major depressive disorder or generalized anxiety disorder showed high retention (89%), attendance (84%), and satisfaction (98%). Among eight outpatients in Toronto, depression scores dropped 54%, anxiety 51%, and distress 36%, while mindfulness increased 79%. Participants reported benefits including cathartic release, improved self-esteem, and a sense of community. The authors conclude that MBBT is feasible and acceptable as an exercise-based intervention, but caution that larger randomized trials are needed to confirm clinical benefits.
Biological Psychiatry
April 9, 2025
Mary E. Kittur, L. Martínez, Brett D. M. Jones et al.
No Summary
Neuropsychopharmacology
April 16, 2024
Brett D. M. Jones, M. Ishrat Husain
The abstract indicates that the neural effects of psychedelics are primarily characterized by increased complexity in brain activity. This suggests that psychedelics alter brain dynamics by promoting more diverse and flexible patterns of neural connectivity, which may underlie their therapeutic potential and ability to induce altered states of consciousness. The focus is on complexity as a key concept for understanding how these substances affect the brain.