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.
JAMA Psychiatry
December 1, 2023
Sanjay J. Mathew, Manish K. Jha, Amit Anand
8 citations
Electroconvulsive therapy (ECT) and ketamine are both used to treat treatment-resistant depression (TRD), but recent reports highlight important considerations when comparing them. This viewpoint examines key issues from several recent studies, including differences in how quickly each treatment works, their side effects, and the practical challenges of administering them. ECT remains highly effective but requires anesthesia and can cause memory problems, while ketamine offers rapid relief but its long-term effects and optimal dosing are still being studied. The authors suggest that neither treatment is clearly superior for all patients, and the choice depends on individual circumstances and preferences.
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.
BMC Psychiatry
January 4, 2026
Carl D. Marci, Kruti Joshi, Stevan Geoffrey Severtson et al.
2 citations
Among 163 patients with treatment-resistant depression treated with esketamine nasal spray in real-world US settings, depressive symptoms improved significantly over six months. Average PHQ-9 scores dropped by 3.2 points within the first three months and by 4.4 points between three and six months after starting treatment. The proportion of patients with moderately severe or severe depression fell from 55.8% at baseline to 37.1% at three months and 25.0% at six months, while the share with minimal or mild depression increased. These findings suggest esketamine, approved in 2019 for treatment-resistant depression, is effective outside clinical trials.
medRxiv Preprint Server
April 10, 2021
Agnes Norbury, Sarah B. Rutter, Abigail B. Collins et al.
1 citation
preprint
In a small randomized clinical trial, repeated doses of ketamine improved PTSD symptoms more than midazolam. Brain scans showed that symptom improvement was linked to increased communication between the ventromedial prefrontal cortex and amygdala when viewing emotional faces, especially in those who received ketamine. Ketamine-related improvement was also predicted by decreased activity in the dorsal anterior cingulate during emotional conflict and increased resting-state connectivity between the ventromedial prefrontal cortex and anterior insula. Further analysis indicated that ketamine specifically strengthened the prefrontal cortex's ability to inhibit amygdala responses to threatening social cues, suggesting a normalization of brain circuits involved in fear regulation.