Frontiers in Psychiatry
May 14, 2024
Zijia Yu, Lisa Burback, Olga Winkler et al.
38 citations
A scoping review of 24 articles found that four psychedelic drugs—ayahuasca, psilocybin, LSD, and the entactogen MDMA—consistently alter brain functional connectivity in healthy individuals. The drugs decreased connectivity within the default mode network and increased sensory and thalamocortical connectivity. These neurophysiological changes correlated with subjective experiences such as altered consciousness, mood elevation, and mystical experiences, suggesting a brain network basis for the drugs' psychological effects. The review provides a potential neural mechanism for psychedelics' subjective effects but notes that direct clinical evidence is needed to advance therapeutic outcomes.
Psychiatry and Clinical Neurosciences
October 1, 2024
Shakila Meshkat, Fatemeh Gholaminezhad, Eric Vermetten et al.
24 citations
A systematic review of 20 studies with 2,959 participants found that psilocybin's effects on cognitive function are mixed. Global cognitive function and processing speed remained mostly unchanged in healthy individuals, while improvements in sustained attention, working memory, and executive function were reported in patients with treatment-resistant depression. Emotional processing and empathy were positively modified, especially in these patients, but cognitive empathy and social cognition were not significantly altered. Cognitive flexibility and creative cognition initially declined but could improve over time. Psilocybin improved semantic associations and associative learning, but effects on episodic and verbal memory were less pronounced than with other cognitive enhancers.
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.
Neuroscience and biobehavioral reviews
June 1, 2025
Shakila Meshkat, Gunjan Malik, Richard J Zeifman et al.
11 citations
Psilocybin-assisted psychotherapy may reduce alcohol consumption and help with smoking cessation, especially for alcohol and tobacco use disorders. In a systematic review of 16 published studies, most focused on alcohol or tobacco use, and over half used psilocybin combined with psychotherapy. Doses ranged from microdosing to 20–40 mg per 70 kg. Alcohol use disorder studies reported fewer heavy drinking days and higher abstinence rates, with brain scans showing normalized activity. Tobacco use disorder studies found high smoking abstinence rates, with mystical experiences predicting long-term success. Findings for other substance use disorders were mixed. The evidence is preliminary; larger clinical trials are needed.
Psychiatry and clinical psychopharmacology
August 11, 2025
Reinhard Janssen-Aguilar, Shakila Meshkat, Huda F Al-Shamali et al.
4 citations
Posttraumatic stress disorder (PTSD) is a severe condition that can be difficult to treat, prompting interest in innovative therapies. This systematic review of 94 studies evaluated interventional treatments including neuromodulation, rapid-acting pharmacotherapies like intravenous ketamine and esketamine, and psychedelic-assisted psychotherapies. Randomized controlled trials showed response rates ranging from 12.5% to 80% for transcranial magnetic stimulation, 17% to 67% for intravenous ketamine, and 50% to 87% for MDMA-assisted therapy. Most treatments were well tolerated with only mild, transient adverse effects. The review highlights variability in efficacy, safety, and tolerability across treatments, reflecting differences in patient populations, protocols, and comorbidities. While symptom improvement is observed, sustained efficacy varies, underscoring the need for maintenance strategies.
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.
Psychopharmacology
July 1, 2026
Sarah Ann Smith, Haseeb Mohammad, Lik Hang N Lee et al.
A review of 20 studies examined whether psychedelic drugs can affect social cognition in people with psychiatric or neurodevelopmental disorders that involve cognitive impairment. The drugs studied were ketamine, MDMA, psilocybin, LSD, and ayahuasca, tested in depressive disorders, anxiety disorders, autism spectrum disorder, and post-traumatic stress disorder. Findings included neural activation patterns suggesting that ketamine and psilocybin may modulate processes relevant to social perception, especially facial emotion processing, in depressive disorders. MDMA was linked to improvements in self-reported psychosocial functioning, self-awareness, and self-compassion in participants with PTSD. Direct evidence of improved social-cognitive functioning remains limited.
European Psychiatry
January 1, 2026
Shakila Meshkat, Qiaowei Lin, Rachel Sousa-Ho et al.
Control groups in psychedelic-assisted psychotherapy trials show substantial symptom improvement, likely due to non-specific factors such as expectancy and concurrent psychotherapy. A meta-analysis of 14 randomized controlled trials (643 participants) found that treatment groups had greater symptom reductions than control groups for depressive symptoms, PTSD symptoms, and anxiety symptoms. For PTSD, inactive placebo groups showed larger within-group improvements. The findings underscore the need for robust control conditions and careful interpretation of treatment effects in psychedelic research.
Progress in neuro-psychopharmacology & biological psychiatry
April 2, 2025
Viktoriia Kurkova, Olga Winkler, Andrew Greenshaw et al.
A scoping review of 10 studies out of 11,734 publications examined whether psychedelic-assisted psychotherapy (PAP) can help people recover from moral injury—deep distress from morally challenging experiences. None of the studies focused specifically on moral injury; they involved psilocybin, MDMA, or LSD for conditions such as PTSD, alcohol use disorder, depression, and anxiety. Across these studies, PAP was associated with rapid, sustained increases in self-compassion, self-forgiveness, and self-acceptance, along with reduced demoralization and lower drinking scores. The authors suggest PAP holds promise for treating moral injury, especially when it co-occurs with PTSD, but conclude that direct research is needed.