Psychiatry research
October 1, 2024
Gilmar Gutierrez, Jennifer Swainson, Nisha Ravindran et al.
17 citations
Both intravenous ketamine and intranasal esketamine significantly reduce depressive symptoms and suicidal ideation in people with treatment-resistant major depressive disorder. In a multi-site observational study of 53 patients, those receiving IV ketamine (26 patients, average age 52.8) and those receiving IN esketamine (27 patients, average age 43.9) showed similar improvements in depression severity and suicidal thoughts. Side effects were mild and temporary, with no significant difference in risk between the two treatments. The findings suggest both therapies are effective and well tolerated for treatment-resistant depression.
Therapeutic advances in drug safety
January 1, 2025
Gilmar Gutierrez, Gustavo Vazquez, Nisha Ravindran et al.
5 citations
Intranasal esketamine, used for treatment-resistant depression, does not appear to carry significant abuse liability during an acute course of treatment. In a secondary analysis of a multicenter observational study, 23 patients with major depressive disorder reported neutral liking and no cravings for esketamine after their first dosing session, and these measures did not increase over eight sessions. Neither age, sex, baseline depression severity, side effects, nor study site influenced liking or cravings. The findings align with existing literature suggesting that acute esketamine treatment is not associated with high drug liking or cravings, though larger studies are needed.
Trials
July 3, 2024
Joshua M Poulin, Gregory E Bigford, Krista L Lanctôt et al.
3 citations
A proposed randomized controlled trial will test whether a single 25 mg dose of psilocybin, compared to a placebo, acutely alters cerebral blood flow and functional brain activity in mood-regulating networks in people with major depressive disorder or persistent depressive disorder. Fifty participants from a mood disorders clinic will be randomly assigned to receive either psilocybin or a placebo, with the placebo group later crossing over to receive psilocybin. The study will use arterial spin labelling and blood oxygenation level-dependent functional MRI to measure brain changes intraday and at three weeks. Clinical outcomes will be tracked with the Montgomery-Åsberg Depression Rating Scale and other scales. The work aims to clarify psilocybin's neuroplastic mechanisms and identify early brain-based predictors of treatment response.
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.
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.
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.