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.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
January 1, 2025
Zitong Wang, Brett Robbins, Ryan Zhuang et al.
15 citations
In a rodent model of chronic stress, psilocybin reduced behavioral despair and cognitive impairments. Twenty-two male Wistar rats were exposed to predator odor and social instability; those given psilocybin showed improvements in memory and mood-related behaviors compared to sham-treated stressed animals. The benefits appear to involve the endocannabinoid system dampening overactivity of the hypothalamic-pituitary-adrenal axis. The results suggest psilocybin may hold promise as an early intervention for stress-related mental health disorders.
Journal of substance use and addiction treatment
August 1, 2025
Reinhard Janssen-Aguilar, Shakila Meshkat, Ilya Demchenko et al.
12 citations
Ketamine may offer short-term benefits for treating substance use disorders, including alcohol, cocaine, opioid, and cannabis use disorders. In alcohol use disorder, it reduced withdrawal symptoms and the need for benzodiazepines. For cocaine use disorder, it decreased craving and increased abstinence rates. In opioid use disorder, high-dose ketamine combined with psychotherapy improved abstinence and reduced craving. For cannabis use disorder, it reduced weekly use and increased confidence in abstinence. However, the evidence is limited by small sample sizes and a lack of randomized trials. Larger, well-controlled studies are needed to determine optimal dosing, mechanisms, long-term efficacy, and risks before broader clinical use can be recommended.
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.
Scientific reports
February 22, 2024
Ethan V Hagen, Melike Schalomon, Yanbo Zhang et al.
11 citations
LSD at low concentrations (1.5, 15, and 150 µg/L) acutely reduced high mobility in zebrafish, and the two lowest concentrations also decreased swimming velocity. However, after repeated daily exposure for ten days followed by a seven-day withdrawal period, no significant differences in anxiety-like behavior, boldness, or locomotion were observed between any LSD-treated group and controls. These results suggest that while LSD can produce acute behavioral effects at very low doses, tolerance may develop with repeated administration, and no lasting behavioral changes persist after withdrawal.
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.
Scientific reports
May 26, 2025
Zitong Wang, Brett Robbins, Ryan Zhuang et al.
4 citations
Psilocybin showed a significant and sustained beneficial effect on behavioral despair and cognitive impairment in a rat model of treatment-resistant depression. The treatment increased thyroid-stimulating hormone (TSH) levels without significantly affecting the hypothalamic-pituitary-adrenal (HPA) axis. Psilocybin countered stress-induced TSH reductions, suggesting TSH may serve as a proxy marker of therapeutic response, though its causal role in mood regulation remains unclear. Changes in cannabinoid receptor type I (CB1R) after psilocybin administration suggest potential modulation of the endocannabinoid system, but causal links remain unconfirmed. These findings highlight psilocybin's potential to treat treatment-resistant depression through previously unexplored biological pathways.
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.
Psychiatry research
September 1, 2026
Isis Lunsky, Gilmar Gutierrez, Xena Wang et al.
Postpartum depression (PPD) is common and harmful if untreated, with few effective prevention strategies. Ketamine and esketamine are rapid-acting antidepressants showing promise for PPD. This review searched five databases for peer-reviewed randomized controlled trials, pilot studies, and observational studies examining ketamine or esketamine for PPD prevention during pregnancy or postpartum, for both cesarean and vaginal deliveries. A network meta-analysis and narrative synthesis were used. Thirty-six studies were identified; five included vaginal delivery, thirty included cesarean section, and one did not specify delivery mode. Results suggested that ketamine and esketamine were well tolerated and may reduce PPD risk. However, data quality was low to very low, so results should be interpreted cautiously. More high-quality studies are needed.
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.
Journal of Military Veteran and Family Health
February 1, 2026
Ian Stefanuk, Kaitlin Chivers-Wilson, Rakesh Jetly et al.
A retrospective chart review of 56 Veterans who completed a program combining sublingual ketamine therapy with a transdiagnostic intensive outpatient program (IOP) found significant reductions in symptoms of depression, anxiety, and posttraumatic stress, along with improved quality of life. Clinically meaningful improvements were most notable among those with moderate to severe baseline symptoms. The intervention is thought to enhance neuroplasticity and emotional learning while increasing treatment engagement and long-term resiliency. The lack of a control group limits the findings, and further research is needed to validate the results and adapt the model for Veterans.
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.
Research Square
May 6, 2025
Zitong Wang, Brett Robbins, R. L. Zhuang et al.
In an animal model of treatment-resistant depression, psilocybin produced a significant and lasting reduction in behavioral despair and cognitive impairment. The compound increased thyroid-stimulating hormone levels without altering the hypothalamic-pituitary-adrenal axis, countering stress-induced TSH reductions that may serve as a proxy marker of therapeutic response. Changes in cannabinoid receptor type I after psilocybin administration suggest possible modulation of the endocannabinoid system, though causal links remain unconfirmed. These findings highlight psilocybin's potential to treat treatment-resistant depression through targeting previously unexplored biological pathways.
Psychedelic Medicine
April 28, 2025
Shakila Meshkat, Howell Fang, Rachel Sousa-Ho et al.
Low-dose psilocybin, given as 1–3 mg or 0.1–0.2 g of dried mushrooms, shows limited and inconsistent evidence for treating mental disorders. In two randomized controlled trials for treatment-resistant depression, 18% of participants receiving 1 mg showed a significant response, 8% achieved remission, and depression scores improved by −5.4 points at week 3, but only 10% maintained improvement by week 12. Another trial reported no significant improvement with 1–3 mg, though 12% achieved anxiety remission and 16% depression remission. A trial comparing 25 mg to 1 mg plus escitalopram found higher response rates with the higher dose. The evidence is constrained by few well-designed studies comparing low-dose psilocybin to placebo.
The International Journal of Neuropsychopharmacology
February 1, 2025
Zitong Wang, Yanbo Zhang, Xin‐min Li
Psilocybin at 1.0 mg/kg reduced depressive-like behavior and cognitive impairment in stressed Wistar rats but not in treatment-resistant Wistar-Kyoto rats. It downregulated ACTH and corticosterone in Wistar rats, upregulated TSH and melatonin in both strains, and increased BDNF levels in blood and brain regions including the prefrontal cortex, amygdala, hippocampus, and hypothalamus. Psilocybin also upregulated CB1R and TrkB, activated Akt, ERK, and mTOR pathways, and increased 2-AG levels across brain regions. The findings suggest psilocybin mitigates stress-induced HPA axis dysregulation by modulating BDNF signaling mediated by the endocannabinoid system, offering insights into antidepressant mechanisms.