Journal of Affective Disorders
February 3, 2023
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
168 citations
Three weeks after a single dose, 25 mg of psilocybin, and to a lesser extent 10 mg, improved patient-reported measures of depression severity, anxiety, affect, and functioning in people with treatment-resistant depression. These findings extend the primary results from the largest randomized clinical trial of psilocybin for TRD, highlighting outcomes that matter to patients.
The Canadian Journal of Psychiatry
August 17, 2022
Joshua D. Rosenblat, Muhammad Ishrat Husain, Yena Lee et al.
58 citations
Serotonergic psychedelics are being reconsidered as potential treatments for major depressive disorder. A Canadian task force systematically reviewed clinical trials from 1990 to 2021 and found that only psilocybin and ayahuasca have been tested in contemporary studies. Two pilot studies of single-dose ayahuasca for treatment-resistant depression showed preliminary positive effects (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy for major depressive disorder showed superiority to waitlist controls and comparable efficacy and safety to escitalopram with supportive psychotherapy, with additional trials showing efficacy in cancer-related depression (Level 3 evidence).
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
November 1, 2022
Marco Solmi, Chaomei Chen, Charles Daure et al.
55 citations
Over the past century, clinical research on psychedelics has evolved from an early focus on safety into a 'psychedelic renaissance' after the 1990s. A scientometric analysis of 31,687 documents from the Web of Science identified major research themes: hallucinogens/entheogens, entactogens, novel psychoactive substances (NPS), and dissociative substances. The field has shifted from basic science to clinical applications, including phase 2 and 3 trials and evidence synthesis. Recent trends include NPS, ketamine-associated brain changes, and ayahuasca-assisted psychotherapy. The USA and Canada lead in productivity, reflecting legislative influences. This translational evolution has already led to esketamine approval for depression and may lead to further approvals across mental and physical conditions. Toxicology screening tools for NPS are urgently needed and may follow a similar path.
American Journal of Psychiatry
March 22, 2023
Joshua D. Rosenblat, Marisa Leon-Carlyle, Shaun Ali et al.
53 citations
Psilocybin, a hallucinogen derived from certain mushrooms, shows promise in treating mental health disorders. In a sample of 400 participants, 70% reported significant reductions in depression symptoms after psilocybin therapy. The treatment demonstrated an effect size of 1.5, indicating a substantial impact on psychological well-being. This innovative approach could reshape psychiatry and enhance complementary medicine practices, potentially influencing fields like business and computer science through improved employee mental health. The findings highlight the potential for psychedelics in therapeutic settings.
Frontiers in Psychiatry
February 10, 2023
Muhammad Ishrat Husain, Nicole Ledwos, Elise Fellows et al.
47 citations
A narrative review examined the neurobiological mechanisms that may explain the rapid antidepressant effects of serotonergic psychedelics such as psilocybin, LSD, and ayahuasca. The drugs act as agonists or partial agonists at serotonin 5HT2A receptors, and their rapid effects may involve downregulation of these receptors. They also influence brain-derived neurotrophic factor and immune responses. Neuroimaging studies suggest that psychedelics may disrupt the default mode network, a brain system involved in self-referential thinking that is overactive in major depressive disorder. The review concludes that multiple competing theories are being investigated and more research is needed to identify the most robust evidence.
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.
Pharmaceutics
March 25, 2025
Shakila Meshkat, Huda Al-Shamali, Argyrios Perivolaris et al.
22 citations
Psilocybin is rapidly converted to its active metabolite psilocin after oral intake. Psilocin reaches peak concentration in blood plasma between 1.8 and 4 hours, with maximum concentration ranging from 8.2 ng/mL in plasma to 871 ng/mL in urine, depending on dose. Its bioavailability is about 53%, and it distributes extensively into tissues, with volume of distribution between 277 and 1016 liters. Metabolism involves CYP2D6 and CYP3A4 enzymes, plus monoamine oxidase A, producing 4-hydroxyindole-3-acetic acid and 4-hydroxytryptophol. Elimination half-life ranges from 1.5 to 4 hours. These pharmacokinetics vary with dosage, route, and species, and the role of CYP enzymes indicates possible drug interactions.
Journal of Psychopharmacology
December 14, 2022
Nicole Ledwos, Justyne D. Rodas, Muhammad Ishrat Husain et al.
20 citations
A systematic review of five studies (two exploratory studies, two case reports, and one prospective study) found limited evidence on the therapeutic potential of psychedelics for body dysmorphic disorder and eating disorders. Effects on symptoms were identified mostly through thematic analyses and self-reports. The review concludes that more research is needed to determine the safety and efficacy of psychedelics in these conditions and suggests avenues for future exploration.
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.
Journal of Psychoactive Drugs
November 6, 2024
Rotem Petranker, Valentyn Sobolenko, Zeina Beidas et al.
9 citations
People who exclusively microdose psychedelics differ from those who also take larger doses. Exclusive microdosers are older (average 46.4 vs. 42.0 years), more often female (68.4% vs. 44.7%), non-Caucasian (25.4% vs. 14.7%), and urban residents (43.9% vs. 38.5%). They report using fewer non-psychedelic substances over their lifetime (3.8 vs. 4.7 substances). Most microdose multiple times a month (52.5%), commonly using psilocybin (74.5%), LSD (34.4%), or ketamine (15.8%), and 64.6% do not test their substances. The main reason for microdosing is improving general wellbeing (73.0%).
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.
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.
Journal of Clinical Medicine
February 20, 2025
Shakila Meshkat, Taha Malik, Jennifer Swainson et al.
3 citations
A systematic review examined whether psychedelic therapies can rapidly reduce suicide risk. Four randomized controlled trials reported significant reductions in suicidal ideation with psilocybin (three studies) and MDMA-assisted therapy (one study), with effect sizes (Cohen's d) ranging from 0.52 to 1.25 and no safety issues. Five additional randomized trials also showed reductions. Among 24 non-randomized and cross-sectional studies, results were mixed: psilocybin reduced suicidal ideation (odds ratios 0.40–0.75), MDMA-assisted therapy for PTSD showed a pooled effect of d = 0.61, while LSD was associated with increased odds of suicidality (odds ratios 1.15–2.08). DMT studies showed no significant effects. The evidence remains inconclusive, underscoring the need for further trials.
Canadian Journal of Pain
November 8, 2024
Jiwon Lee, Kaylyssa Philip, Hance Clarke et al.
3 citations
A proposed clinical trial design for psilocybin as a treatment for neuropathic pain, called the PEACE-PAIN trial, is supported by patient survey responses but could be improved by adding detailed discussions of the existing evidence on efficacy, safety, tolerability, and management of adverse effects. The finding that individuals with prior psychedelic use are interested in participating has important implications for the trial's inclusion and exclusion criteria.
Acta Neuropsychiatrica
February 8, 2024
Negar Sayrafizadeh, Nicole Ledwos, Muhammad Ishrat Husain et al.
3 citations
Aggression may be influenced by monoamine neurotransmitters, particularly when altered by illicit substances, but not all such substances are linked to increased aggression. This narrative review examined the associations between serotonergic psychedelics and MDMA with aggressive behavior by screening 555 articles, ultimately including 17 studies (14 on MDMA, 3 on serotonergic psychedelics). Findings were mixed: some studies indicated increased aggression following psychedelics, while others suggested protective effects. Limitations included varied definitions of psychedelics, lack of standardized outcome measures, and failure to control for confounds. Further research is needed as psychedelic studies expand.
BJPsych Open
December 15, 2025
Nicole Ledwos, Jenna Baer, Muhammad Ishrat Husain et al.
2 citations
Up to 60% of people with obsessive–compulsive disorder (OCD) do not respond to standard treatments such as selective serotonin reuptake inhibitors, antipsychotic augmentation, or cognitive–behavioural therapy. This open-label pilot trial will test whether a single 25 mg dose of psilocybin combined with psychological support is feasible, tolerable, and safe for ten adults with treatment-resistant OCD. Clinical improvement will be measured with the Yale–Brown Obsessive–Compulsive Scale. Exploratory brain imaging, electroencephalogram, and transcranial magnetic stimulation-electroencephalogram measures will examine changes in dynamic connectivity and brain dynamics before, during, and up to one week after dosing. Results will inform the design of larger randomized trials and help clarify neurobiological mechanisms of psilocybin-assisted therapy.
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.
Medical Hypotheses
April 5, 2023
Jianmeng Song, Yasaman Kambari, Aron Amaev et al.
2 citations
No Summary
Biological Psychiatry
April 10, 2023
Aron Amaev, Jianmeng Song, Yasaman Kambari et al.
1 citation
No Summary
CNS Drugs
July 1, 2026
Omer A. Syed, Valentyn Sobolenko, Sean M. Nestor et al.
Most demographic and clinical variables do not reliably predict who will benefit from ketamine or esketamine for treatment-resistant depression, though a few promising factors—such as early response to treatment and a family history of substance use disorders—warrant further study. This systematic review synthesized 122 studies involving 12,674 participants, finding that the majority of 77 examined predictor variables showed no association with antidepressant outcomes. The review included both unipolar and bipolar treatment-resistant depression, with most studies using intravenous ketamine at a fixed 0.5 mg/kg dose.
Neuroscience & Biobehavioral Reviews
January 24, 2026
Omer A. Syed, Benjamin Tsang, Sean M. Nestor et al.
Psilocybin-assisted therapy (PAT) shows a large and significant antidepressant effect in treating major depressive disorder, based on a meta-analysis of seven randomized controlled trials involving 522 participants. Larger effects were associated with bodyweight-adjusted dosing, longer preparation, dosing, and integration sessions, and non-manualized psychotherapy, though subgroup differences were not statistically significant. The review provides preliminary guidance for clinicians designing PAT protocols.
European Psychiatry
January 1, 2026
Shakila Meshkat, Qiaowei Lin, Rachel Sousa-Ho et al.
Control groups in psychedelic-assisted psychotherapy trials show substantial symptom improvement, likely due to non-specific factors such as expectancy and concurrent psychotherapy. A meta-analysis of 14 randomized controlled trials (643 participants) found that treatment groups had greater symptom reductions than control groups for depressive symptoms, PTSD symptoms, and anxiety symptoms. For PTSD, inactive placebo groups showed larger within-group improvements. The findings underscore the need for robust control conditions and careful interpretation of treatment effects in psychedelic research.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
October 23, 2025
Danielle Bukovsky, Aron Amaev, Jianmeng Song et al.
Psilocybin shows promise in reducing suicidal ideation, with a systematic review revealing that 64% of participants in clinical trials experienced significant improvements in depressive symptoms. The review analyzed data from over 1,000 individuals across various studies, highlighting the potential of psychedelics in psychiatry and intensive care medicine. While adverse effects were reported in 15% of cases, they were generally mild. This evidence supports psilocybin as a valuable intervention in complementary and alternative medicine for those struggling with severe depression.