European Neuropsychopharmacology
August 7, 2023
Natacha Perez, Florent Langlest, Luc Mallet et al.
85 citations
A systematic review and dose-response meta-analysis of seven double-blind randomized placebo-controlled trials involving 489 adults with depression found that the optimal daily dose of psilocybin to reduce depression scores varies by population. The 95% effective dose (ED95) was 8.92 mg/70 kg for secondary depression, 24.68 mg/70 kg for primary depression, and 36.08 mg/70 kg when combining both subgroups. Dose-response associations were significant for all groups except a bell-shaped curve appeared for secondary depression. Higher doses were linked to increased side effects including physical discomfort, blood pressure increase, nausea, headache, and risk of prolonged psychosis. The analysis indicates that treatment-resistant depression requires higher doses than primary or secondary depression.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
November 1, 2022
Marco Solmi, Chaomei Chen, Charles Dauré 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.
Molecular psychiatry
March 1, 2025
Michel Sabé, Adi Sulstarova, Alban Glangetas et al.
39 citations
A systematic review and meta-analysis assessed the risk of psychedelic-induced psychosis in people with schizophrenia. Among population studies, the incidence was 0.002%; in uncontrolled trials, 0.2%; and in randomized controlled trials, 0.6%. In uncontrolled trials that included individuals with schizophrenia, 3.8% developed long-lasting psychotic symptoms. Of those who experienced psychedelic-induced psychosis, 13.1% later developed schizophrenia. The evidence suggests schizophrenia might not be an absolute exclusion for clinical trials on psychedelics for treatment-resistant depression and negative symptoms, but low study quality and limited data warrant a conservative approach until more research is done.
Current neuropharmacology
January 1, 2024
Michel Sabé, Chaomei Chen, Wissam El-Hage et al.
25 citations
A scientometric analysis of 42,170 publications on posttraumatic stress disorder (PTSD) from 1945 to 2022 identified four major research trends: war veterans and refugees, treatment of PTSD/neuroimaging, evidence syntheses, and somatic symptoms of PTSD. The largest cluster focused on evidence synthesis for genetic predisposition and environmental exposures leading to PTSD. War-related trauma research has shifted from battlefield in-person exposure to drone operator trauma and is being outpaced by civilian trauma research, including the COVID-19 pandemic, postpartum, and grief disorder. Recent trends show a burst in PTSD treatment research involving Mhealth, virtual reality, and psychedelic drugs. The USA dominates collaboration networks, with a recent surge of publications from China. Compared to other psychiatric disorders, there is a lack of high-quality randomized controlled trials for pharmacological and nonpharmacological treatments.
JAMA psychiatry
February 1, 2025
Daniel T Myran, Michael Pugliese, Jennifer Xiao et al.
23 citations
People who had an emergency department visit involving hallucinogen use were more likely to be diagnosed with a schizophrenia spectrum disorder within three years compared with the general population (3.99% vs 0.15%). After accounting for other substance use and mental health conditions, the risk remained elevated: they were about 3.5 times as likely as the general population, 4.7 times as likely as those with an alcohol-related ED visit, and 1.5 times as likely as those with a cannabis-related ED visit. The rate of hallucinogen-related ED visits rose 86% between 2013 and 2021.
Eur Neuropsychopharmacol
November 7, 2025
Mikkel Højlund, Helin Y. Kafali, Begüm Kırmızı et al.
12 citations
A living systematic review with meta-analysis examined the efficacy, safety, and all-cause discontinuation of serotonergic psychedelics and MDMA for treating mental disorders. The review found that these substances show promise in reducing symptoms of conditions such as depression, anxiety, and post-traumatic stress disorder, with some evidence supporting their therapeutic potential. However, the authors note that the overall quality of evidence is limited by small sample sizes, short follow-up periods, and methodological concerns. Safety profiles varied, with most adverse events being mild to moderate, though serious adverse events were reported in some studies. The review emphasizes the need for larger, more rigorous trials to confirm these findings.
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.
JAMA Network Open
April 1, 2025
Jenna Matsukubo, Sarah Dickson, Jennifer Xiao et al.
7 citations
As of May 2024, 57 psilocybin dispensaries operated in Canada, located in 15 of 42 major cities (35.7%) and concentrated in Ontario and British Columbia. Most stores (61.4%) were part of a chain, 91.2% had an online presence, and all sold dried mushrooms, with many also offering microdosing capsules, chocolates, and gummies. 65.2% sold products mimicking popular food brands. Among stores with websites, 86.4% claimed mental health benefits such as alleviating anxiety, yet warnings about driving, pregnancy, or history of psychosis were rare (9.1%, 13.6%, and 31.8% respectively). The findings suggest a need for greater regulatory measures to protect the public.
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.
Asian journal of psychiatry
June 26, 2025
Adi Sulstarova, Luise Scheuerlein, Silvia Monari et al.
4 citations
Psychedelic-induced psychosis is rare, occurring in less than 1% of users in controlled trials, but evidence on its treatment is limited. A systematic review of 93 cases from 1955 to 2024 found that LSD (47.3%) and MDMA (38.7%) were the most common substances involved, with an average patient age of 23.7 years and 88% male. Psychosis lasted about 1.8 weeks on average. Second-generation antipsychotics had a response rate of 91.3%, significantly higher than first-generation antipsychotics at 27%. Electroconvulsive therapy also showed a 91% response rate. Follow-up revealed 34% of patients later developed schizophrenia spectrum disorders and 20.4% bipolar disorder, though limited follow-up data constrain these findings.
Trends in psychiatry and psychotherapy
January 1, 2025
Elena Koning, Marco Solmi, Elisa Brietzke
4 citations
As psychedelics gain acceptance for mental health treatment, corporate funding of clinical trials raises concerns about conflicts of interest and biased reporting. The evidence for safety and efficacy of psychedelic-assisted psychotherapy remains early. This paper examines safety concerns associated with psychedelics, how financial stakeholders may influence the reporting of safety outcomes, and why balanced science communication is critical for public health and safety during ongoing drug reform.
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.
J Psychiatry Neurosci
July 25, 2025
Michel Sabé, Federico Seragnoli, Gabriel Thorens et al.
2 citations
A case report describes the use of serotoninergic psychedelics to treat depressive and negative symptoms in a person with schizoaffective disorder. The treatment was associated with improvements in these symptoms, suggesting a potential therapeutic benefit. The report highlights the need for further research into psychedelic-assisted therapy for this population.
Canadian Journal of Public Health
March 19, 2026
Jenna Matsukubo, Erik Loewen Friesen, Rachael MacDonald-Spracklin et al.
1 citation
Between 2024 and 2025, the number of physical psilocybin retail stores in Canada increased from 57 to 75, a 33% rise in stores per 100,000 people (0.18 to 0.24). The proportion of Canadians living within a 10-minute walk of a store rose from 1.4% to 1.7%. However, 30 of the original 57 stores closed, while 48 new ones opened, indicating rapid turnover. Two large chains operated 44% of all stores in 2025, and 97% were located in Ontario and British Columbia. In Toronto and Vancouver, 9.5% and 29.0% of residents, respectively, lived within a 10-minute walk of a store. Most stores sold dried mushrooms, microdose capsules, and infused edibles online, with 69% offering products mimicking commercial snack brands.
Schizophrenia Research
March 13, 2026
Michel Sabé, Paul Grof, Nathan B. Sackett et al.
1 citation
Serotonergic psychedelics, which are being explored for treatment-resistant depression, might also help with depressive and negative symptoms in schizophrenia spectrum disorders (SSDs). Schizophrenia and depression share some underlying brain disturbances, including problems with dopamine, glutamate, and neuroplasticity, as well as abnormal brain network connectivity. Depressive symptoms in SSDs may combine features of both disorders, and psychedelics could potentially recalibrate maladaptive brain networks. Preclinical studies show psychedelics increase dendritic spines and BDNF and restore reward sensitivity. Clinical evidence is limited: uncontrolled psychedelic use is linked to increased psychosis, but controlled administration may be tolerated in stable individuals. Only one early-phase trial with MDMA in schizophrenia is ongoing; no randomized trials have tested psilocybin or LSD in SSDs. The authors conclude that psychedelics are biologically plausible but unproven for these symptoms.
Molecular psychiatry
May 29, 2026
Mickael Eskinazi, Rayan Nasserdine, Romane M Cusin et al.
A systematic review of 23 studies examined whether serotonergic psychedelics (psilocybin, LSD, mescaline, DMT/ayahuasca) or MDMA can trigger manic or hypomanic symptoms. Rates of such symptoms ranged from 5.8% in controlled trials of psilocybin-assisted therapy for depression to 30% in naturalistic studies of people with bipolar disorder. When manic symptoms occurred, they were typically acute and self-limited. Higher risks were seen in individuals with bipolar I disorder, family vulnerability, polysubstance use, or unsupervised use. Registry data showed a 4% prevalence of later transition to bipolar disorder, with little evidence for a hallucinogen-specific signal. The authors conclude that these substances pose a low but clinically meaningful relative risk of transient mood symptoms in susceptible individuals while remaining relatively safe in controlled settings.
PLoS medicine
December 1, 2025
Daniel T Myran, Rachael MacDonald-Spracklin, Michael Pugliese et al.
Among 9.3 million people in Ontario, those who had an emergency department visit or hospitalization involving hallucinogens faced a 6-fold higher risk of a first episode of mania and a nearly 4-fold higher risk of a new bipolar disorder diagnosis over three years, compared to similar individuals without such acute care. The absolute risk was low: 1.43% of those with hallucinogen-related acute care developed mania versus 0.06% in the general population. The findings apply only to people who required acute care for hallucinogen use, not to most users, and suggest caution for individuals at risk of bipolar disorder.