JAMA Network Open
May 1, 2020
K. Beck, Guy Hindley, F. Borgan et al.
179 citations
Ketamine administration produces transient psychopathological effects in both healthy volunteers and patients with schizophrenia, with the nature and severity of these effects varying according to experimental factors such as dose, route of administration, and participant characteristics. The meta-analysis quantifies these outcomes, showing that ketamine reliably induces psychotic-like symptoms, dissociation, and cognitive impairments in healthy individuals, while its effects in patients with schizophrenia are more complex and may involve both symptom exacerbation and potential therapeutic benefits depending on the context.
JAMA Network Open
April 10, 2024
Akhila Yerubandi, Catherine Harrington, Joshua Caballero et al.
80 citations
A meta-analysis of six randomized, double-blind clinical trials involving 528 participants (about 51% female, median age 39.8 years) found that therapeutic single doses of psilocybin for depression and anxiety are associated with several acute adverse effects. Compared to placebo or low-dose psilocybin, psilocybin significantly increased the risk of headache (nearly double), nausea (nearly nine times), anxiety (more than double), dizziness (nearly six times), and elevated blood pressure (more than double). Psilocybin was not linked to paranoia or transient thought disorder. The adverse effects were tolerable and resolved within 48 hours, but the authors call for future studies to better manage these effects.
JAMA Network Open
March 6, 2024
Yu Chen, Yu Guo, Han Wu et al.
63 citations
A single intravenous dose of esketamine given during cesarean delivery, followed by 48 hours of patient-controlled analgesia containing esketamine, reduced early postpartum depression symptoms. On day 7 after delivery, 23% of women who received esketamine screened positive for postpartum depression (score of 10 or higher on the Edinburgh Postnatal Depression Scale) compared with 35% in the placebo group. The difference in depression scores between groups was small but statistically significant. However, by days 14, 28, and 42, there were no differences between groups in depression screening rates or score changes. Pain scores were similar between groups except for a small advantage with esketamine during movement at 72 hours. The antidepressive effect may not apply to women with low baseline depression scores.
JAMA Network Open
August 12, 2020
Matthew S. Milak, Rain Rashid, Zhengchao Dong et al.
59 citations
A single subanesthetic dose of ketamine produces an antidepressant response in patients with major depressive disorder within hours. In this randomized clinical trial of 38 adults, higher ketamine doses and blood levels correlated with greater improvement on the Hamilton Depression Rating Scale 24 hours later. However, the brain's glutamate+glutamine (Glx) response to ketamine mediated this relationship: lower Glx responses predicted better antidepressant effects. GABA levels did not correlate with antidepressant benefit. Adverse effects were linked to blood levels only in men. The findings suggest that ketamine's antidepressant mechanism involves reducing Glx levels in the ventromedial prefrontal cortex.
JAMA Network Open
December 5, 2024
Anthony L Back, Timara K Freeman-Young, Ladybird Morgan et al.
37 citations
A double-blind randomized trial tested psilocybin therapy against niacin in 30 US clinicians (physicians, advanced practice practitioners, and nurses) who developed depression, burnout, or PTSD from frontline COVID-19 pandemic work. Participants had no prepandemic mental health diagnoses but had moderate or severe depression at enrollment. After one medication session, depression symptoms (measured by the Montgomery-Asberg Depression Rating Scale) improved significantly more with psilocybin (mean decrease of 21.33 points) than with niacin (mean decrease of 9.33 points), a difference of 12.00 points. Burnout and PTSD symptoms showed numerically larger improvements with psilocybin, but these differences were not statistically significant. The findings suggest psilocybin therapy can reduce depression in this postpandemic condition.
JAMA Network Open
July 30, 2025
Fredrik Hieronymus, Evana López, Helena Werin Sjögren et al.
21 citations
In clinical trials for depression, patients given a placebo or control treatment in psilocybin trials showed significantly less improvement in depression ratings than those given control treatments in trials of SSRIs or esketamine. The meta-analysis of 17 trials found that control treatment response rates in SSRI trials were 14 percentage points higher than in psilocybin trials, and in esketamine trials were 23 percentage points higher. Dropout rates were similar for psilocybin and esketamine (5-12% active, 8-11% control) but much lower than for SSRIs (32% active, 35% control). These results suggest that psilocybin's antidepressant efficacy may be overestimated compared to SSRIs and esketamine.
JAMA Network Open
May 1, 2023
R. Price, M. Wallace, S. Mathew et al.
9 citations
Automated self-association training may extend the antidepressant effect of a single ketamine infusion beyond one month in people with treatment-resistant depression. This secondary analysis of a randomized clinical trial tested whether a computerized task designed to strengthen positive self-associations could prolong the benefits of ketamine. The results suggest that combining ketamine with this training could help maintain mood improvement for a longer period than ketamine alone.
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.
JAMA Network Open
March 10, 2026
Mw Johnson, Gideon P. Naudé, Peter S. Hendricks et al.
6 citations
A single high dose of psilocybin combined with cognitive behavioral therapy (CBT) led to significantly higher long-term smoking abstinence rates than nicotine patch treatment plus CBT. At six months, 40.5% of participants who received psilocybin had biochemically verified prolonged abstinence, compared to 10.0% of those using the nicotine patch. No serious adverse events were attributed to either treatment. The pilot trial randomized 82 psychiatrically healthy adult smokers and used an intention-to-treat analysis. The findings suggest psilocybin-assisted therapy may be a promising intervention for tobacco smoking cessation.
JAMA Network Open
May 7, 2026
Peter S. Hendricks, Sara Lappan, Richard C. Shelton et al.
4 citations
A single 25 mg dose of psilocybin, combined with psychotherapy, led to a higher percentage of cocaine-abstinent days, a greater likelihood of complete abstinence, and a longer time before the first cocaine lapse over 180 days compared with an active placebo (100 mg diphenhydramine) in a randomized, quadruple-blind trial. Among 40 participants with cocaine use disorder, 33 were men, 33 were Black, and most had low income. Psilocybin appeared safe, with no serious adverse events, and may offer a treatment for cocaine use disorder in underrepresented populations.
JAMA Network Open
April 1, 2025
Paul R. Hutson
2 citations
No Summary
JAMA Network Open
May 15, 2026
1 citation
A single 25 mg dose of psilocybin, combined with psychotherapeutic support, produced rapid antidepressant effects in people with moderate to severe recurrent major depressive disorder. Depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale, improved significantly more in the psilocybin group than in the placebo group by day 8, with benefits lasting through day 42 but not at one year. Self-reported depressive symptoms showed improvement as early as day 2 and persisted for over three months. The treatment was generally well tolerated, though two participants experienced persistent severe anxiety requiring medical attention. These findings suggest psilocybin may offer a rapid and relatively durable antidepressant effect.
JAMA Network Open
September 11, 2025
Richard B. van Breemen, Daniel Simchuk, Bjorn Fritzsche et al.
1 citation
Unregulated psilocybin mushroom edibles contain a range of active constituents beyond psilocybin and psilocin, including baeocystin, norbaeocystin, and aeruginascin, with variable concentrations across products. The analysis of these edibles reveals inconsistent labeling and dosing, posing potential risks for consumers.