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 Psychopharmacology
October 3, 2024
Charles Q. Choi, Danica E. Johnson, David Chen‐li et al.
11 citations
Posttraumatic stress disorder (PTSD) can develop after a traumatic event, causing intrusive re-experiencing, mood and cognitive changes, and altered arousal. Few treatments help patients who cannot access or do not benefit from conventional psychotherapy or pharmacotherapy. This review examines the neurobiology of PTSD and psilocybin's mechanism of action, suggesting that psilocybin may be an underexplored treatment option based on pharmacodynamic and psychoanalytic principles, though further research is needed.
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.
CMAJ
March 2, 2025
Daniel T. Myran, Jennifer Xiao, Nicholas Fabiano et al.
8 citations
People who had an emergency department visit or hospital admission involving hallucinogen use in Ontario, Canada, between 2006 and 2022 had a 2.6-fold higher risk of death from any cause within five years compared with the general population. Among 7953 individuals with such acute care, 6.1% died within five years versus 0.6% in the matched general population. Elevated risks were also seen for death from unintentional drug poisoning, suicide, respiratory disease, and cancer. These associations persisted even after excluding people with other mental or substance use disorders.
Current Treatment Options in Psychiatry
April 26, 2024
Noah Chisamore, Erica Kaczmarek, Gia Han Le et al.
8 citations
No Summary
Psychiatry Research
May 8, 2025
Noah Chisamore, Lee Phan, Roger S McIntyre et al.
7 citations
A review of pre-clinical and clinical studies on non-hallucinatory psychedelics (NHPs) for mood and anxiety disorders found five animal studies showing antidepressant-like effects, assessed via forced swim test and open field test, without the head-twitch response that indicates hallucination. One case report described a patient who inadvertently combined trazodone and psilocybin and experienced potent antidepressant effects without psychedelic effects. These preliminary findings suggest that antidepressant benefits of psychedelics may be separable from hallucinatory effects, providing impetus for rigorous clinical trials in humans.
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.
General Hospital Psychiatry
December 9, 2025
Gerasimos Konstantinou, Joshua D. Rosenblat, Sarah Hales et al.
4 citations
Psilocybin-assisted therapy shows promise for treating late-life mental health conditions such as depression, loneliness, and existential distress, where conventional medications often have limited effectiveness and poor tolerability in older adults. The review describes neurobiological mechanisms including serotonergic modulation, enhanced neuroplasticity, and disruption of maladaptive default mode network activity. Clinical trials in general adult populations report sustained improvements in depressive symptoms, existential anxiety, and social connectedness following psilocybin administration. However, older adults are underrepresented in psychedelic research, creating gaps in knowledge about dosing, safety, and long-term outcomes. Age-specific protocols are needed to address pharmacokinetic complexities, cardiovascular risks, drug interactions, and ethical challenges around informed consent in cognitively impaired patients.
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.
Journal of Affective Disorders
September 16, 2025
Sami George Sabbah, Sophie Li, Sabrina Wong et al.
2 citations
Psilocybin is linked to dynamic and temporally distinct neuroplastic changes that are associated with clinical improvement in depression. However, many studies reused overlapping datasets, had high exploratory flexibility, and risk of bias, which limits the generalizability of the results. Future research should use independent datasets, pre-registered imaging endpoints, and longitudinal designs to better understand the mechanisms of psychedelic therapy for depression.
Nature Mental Health
October 14, 2024
Danica E. Johnson, Joshua D. Rosenblat
1 citation
No Summary
Clinical Pharmacology & Therapeutics
May 28, 2026
Gia Han Le, Sabrina Wong, Danica E. Johnson et al.
The serotonin 5-HT2B receptor sits at a crossroads between potential antidepressant effects in the brain and serious heart valve risks when activated peripherally. This narrative review of preclinical and clinical literature finds that peripheral activation of 5-HT2B receptors causes valvular heart disease through cell proliferation and scarring, as seen with older drugs like fenfluramine and some dopamine agonists. In the brain, the receptor's effects are mixed: astrocytic activation may support metabolism and plasticity, while neuronal blockade can normalize dopamine and glutamate activity. Several approved antidepressant adjuncts (aripiprazole, brexpiprazole, cariprazine) antagonize this receptor without observed heart valve problems. The authors propose developing centrally selective, periphery-sparing 5-HT2B antagonists for treatment-resistant depression, with early cardiac monitoring to ensure safety.
Discover Mental Health
March 7, 2026
Nicholas Fabiano, Brendon Stubbs, David W. Lawrence et al.
More than half of people with major depressive disorder do not respond to standard treatments, prompting interest in alternatives such as exercise and psychedelics. This commentary examines how these two approaches might work together. Biologically, psychedelics briefly boost brain-derived neurotrophic factor (BDNF) signaling, while exercise provides sustained BDNF elevation; psychedelics enhance neuroplasticity mainly in the cortex, whereas exercise promotes hippocampal neurogenesis; both increase serotonin release. Psychologically, psychedelics may help people adopt exercise habits, and exercise may improve emotional resilience, potentially deepening the psychedelic experience. The authors suggest that these complementary mechanisms warrant future research on their combined efficacy, tolerability, safety, and neurobiology.
Journal of Affective Disorders
February 12, 2026
Erica Kaczmarek, Nelson Rodriguez, Noah Chisamore et al.
Anhedonia, a core symptom of depression that often resists standard treatments, may be reduced by psilocybin-assisted psychotherapy (PAP). In a secondary analysis of a randomized, waitlist-controlled trial, 30 adults with treatment-resistant depression (major depressive disorder or bipolar II disorder) received one 25 mg dose of oral psilocybin plus psychotherapy. Anhedonia severity, measured by the Snaith-Hamilton Pleasure Scale, decreased significantly at the 2-week primary endpoint, with clinically meaningful improvements persisting at 3 and 6 months. The analysis adjusted for sex and age. These preliminary results suggest PAP could be a promising intervention for anhedonia in treatment-resistant depression, though larger placebo-controlled trials are needed to confirm the findings and clarify underlying mechanisms.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
November 22, 2025
Shakila Meshkat, Noah Chisamore, Zoe Doyle et al.
A single dose of psilocybin was linked to small, temporary gains in processing speed and executive function in people with treatment-resistant depression. These cognitive improvements seemed unrelated to mood changes but did not consistently surpass the improvements expected from simply retaking the tests. The findings underscore the need for larger, controlled studies to determine whether psilocybin genuinely enhances cognition or if the observed changes stem from practice effects or mood shifts.
Neuroendocrinology
October 30, 2025
Sabrina Wong, Gia Han Le, Jens Uhlig et al.
Blocking NMDA receptors improves the function and survival of pancreatic alpha and beta cells, which may help explain why certain NMDA antagonists like ketamine, esketamine, and dextromethorphan have antidepressant effects and could also address metabolic problems often seen in depression. The findings suggest a shared mechanism linking mood regulation and pancreatic hormone control. More research is needed on how low doses of these drugs affect pancreatic function and delta cells.
Biological Psychiatry
April 9, 2025
Mary E. Kittur, L. Martínez, Brett D. M. Jones et al.
No Summary