Database

This systematic review (s=45) on psychedelic-assisted psychotherapy for mental disorders finds that psychological interventions are reported with low completeness and high heterogeneity. It also finds that MDMA studies are more homogeneous, with greater procedural detail.

This systematic review (2024) and meta-analysis (s=44) finds that medium/high doses of LSD yield higher ratings of visionary restructuralisation than psilocybin. It also reports that psychedelics strengthen between-network functional connectivity and diminish within-network connectivity, and that LSD induces more inositol phosphate formation at the 5-HT2A receptor than DMT or psilocin, while receptor selectivity differences remain negligible.

This perspective article (2024) for investigators at academic medical centres in the United States provides recommendations for establishing psychedelic research programs. It highlights challenges including funding, regulatory approvals, sourcing controlled substances, preparing study spaces, managing controlled substances, and engaging the local community, and offers strategies to anticipate and surmount these obstacles.

This double-blind randomized trial (n=30) finds that psilocybin therapy significantly reduces symptoms of depression in clinicians after frontline work during the COVID-19 pandemic. Psilocybin (25mg) showed greater reductions in depression (MADRS scores) and PTSD symptoms compared to the niacin control, though PTSD findings were not statistically significant.

In the November recap, we explore the neuroplasticity mechanisms of psychedelics, their therapeutic applications for mental health conditions like OCD and fibromyalgia, safety considerations, and the significant role of user experiences in therapeutic outcomes.

This review (2024) examines the effects of classic psychedelics (e.g., LSD, psilocybin, DMT) and non-classic psychedelics (e.g., ketamine, MDMA) on neuroplasticity. Drawing on preclinical and clinical studies, it discusses molecular, structural, and functional changes induced by these agents, highlighting their potential to re-open developmental windows (hyper-plasticity) and increase nervous system sensitivity to stimuli (meta-plasticity). Translating findings to humans remains challenging, but emerging tools like PET radioligands and multimodal approaches offer promise for future research.

This robustness analysis of the ESCAPE-TRD Phase IIIb trial (n=676) investigates esketamine nasal spray versus quetiapine extended release for treatment-resistant depression (TRD). Esketamine significantly outperformed quetiapine in achieving remission at week 8 (MADRS ≤10) and maintaining relapse-free status through week 32, with hazard ratios favouring esketamine (HR: 1.658–1.711, p < 0.001).

This observational study (n=24) examines the acute effects of ayahuasca on memory in experienced Santo Daime members (>500 lifetime uses). Findings show ayahuasca enhances memory accuracy and recollection while not impacting familiarity or false memory, suggesting β-carboline activity may drive selective improvements in hippocampal-dependent processes.

This randomized, double-blind, psychoactive-controlled study (n=12) compared intramuscular ketamine (35-70mg/70kg) to fentanyl (50μg) in treatment-resistant OCD patients, with 10 participants completing the trial. The study found dose-dependent reductions in OCD symptoms (Y-BOCS scores) for ketamine compared to fentanyl, with effects lasting up to 168 hours, though two participants dropped out due to dissociative effects.

This meta-analysis (s=29) examines the effects of psychedelics (including ketamine and MDMA) and two other 'psychoplastogens' on peripheral BDNF levels in humans. It finds no significant changes in BDNF levels post-administration (SMD=0.024, p=0.64), regardless of drug, dose, participant age, or psychiatric condition. Studies with better-controlled designs report smaller effect sizes, and later timepoints show minimal increases in BDNF. The authors conclude that peripheral BDNF is likely not a reliable marker of rapid neuroplasticity and recommend neuroimaging or stimulation-based methods for future research.