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Sean M. Nestor

Sunnybrook Health Science Centre

4 papers in the library · 2 citations · publishing 2023-2026

Papers

Adverse events associated with classic psychedelics and MDMA: a real-world population-based study using the WHO pharmacovigilance database (VigiBase)

Psychiatry Research December 29, 2025 Omer A. Syed, Sean M. Nestor, M.ishrat Husain et al. 1 citation

Adverse event reports for classic psychedelics and MDMA in the WHO global pharmacovigilance database VigiBase show that most reports were for MDMA (1,573) and LSD (394), with fewer for psilocybin (56), DMT (18), and mescaline (15). The most common adverse events were psychiatric, particularly substance abuse and dependence. Overdose reports made up 1.1 to 1.7% of total adverse events. Pregnancy-related and congenital disorders were rare. Compared to acetaminophen, LSD and MDMA were associated with significantly greater odds of reported alcohol abuse, substance use disorder, and substance dependence, and these odds were also greater than those for oxycodone. This exploratory analysis provides a first look at real-world safety data, though findings are limited by potential underreporting and co-use of other substances.

Engaging Mood Brain Circuits with Psilocybin (EMBRACE): a study protocol for a randomized, proof-of-principle, placebo-controlled and crossover, neuroimaging trial in depression

Research Square December 28, 2023 Joshua M. Poulin, Gregory E. Bigford, Krista L. Lanctôt et al. 1 citation

About one third of people with depression do not fully respond to standard treatments, and psilocybin may offer a rapid-acting alternative. This registered trial will randomize 36 adults with major depressive or persistent depressive disorder to receive either 25 mg psilocybin or an active placebo (100 mg niacin), then cross over three weeks later so that all participants receive psilocybin. Using serial neuroimaging, the study will test whether psilocybin acutely alters cerebral blood flow and functional brain activity in mood-related networks compared to placebo, and whether those changes persist subacutely. Clinical scales and serum biomarkers will also be collected to explore relationships with treatment response.

Clinical Predictors of Antidepressant Effects of Ketamine and Esketamine in Treatment-Resistant Unipolar and Bipolar Depression: A Systematic Review

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.

Methodological moderators of psilocybin-assisted therapy in depression: A systematic review and meta-analysis

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.