Database

This long-term follow-up (n=12) of participants with moderate-to-severe major depressive disorder who received MDMA-assisted therapy (two dosing sessions integrated with nine psychotherapy sessions) found significant reductions in depression severity and functional impairment at seven months compared to baseline, with improvements maintained from the post-treatment assessment and no increases in suicidal ideation.

Psychedelic research in November examined microdosing outcomes, brain criticality and plasticity mechanisms, and clinical applications for depression, PTSD, and end-of-life care.

This computational modelling study simulated the effects of LSD and psilocybin on whole-brain models of patients with disorders of consciousness, finding that both psychedelics shifted brain activity closer to criticality with greater effects in minimally conscious state patients, whilst treatment response correlated with structural connectivity in unresponsive wakefulness syndrome and baseline functional connectivity in minimally conscious state.

This secondary analysis of an RCT (n=59) comparing two doses of psilocybin (25mg) plus placebo versus two doses of 1mg psilocybin plus daily escitalopram found that both treatments produced comparable reductions in negative bias in facial expression recognition, though decreased misclassification of positive faces as negative was associated with lower depression scores only in the escitalopram group.

This secondary analysis of an open-label study (n=30) of male Veterans with traumatic brain injury found that greater intensity of mystical experiences during magnesium-ibogaine treatment was associated with larger reductions in PTSD severity both immediately and one month post-treatment, as well as greater reductions in peak alpha frequency at one month.

This open-label study (n=9) found that an encapsulated DMT-harmala alkaloid product (pharmahuasca) produced dose-dependent mystical experiences that exceeded those reported in most previous ayahuasca studies and were associated with beneficial persisting psychological effects in healthy volunteers.

This secondary analysis of two placebo-controlled studies (n=27) found that DMT shifts brain oscillations away from criticality towards subcritical regimes in alpha and adjacent frequency bands, increasing entropy whilst reducing complexity, with these shifts in theta and alpha bands correlating with the intensity of self-dissolution experiences.

This secondary analysis (n=26) of adults with treatment-resistant depression from an open-label psilocybin-assisted psychotherapy trial found statistically significant improvements in processing speed and executive function at two weeks post-treatment, with gains on Trail Making Tests remaining significant after adjusting for depressive symptoms; however, reliable change indices showed that the proportion of participants achieving meaningful improvement (4.2–12.5%) did not exceed chance expectations, suggesting observed gains may reflect practice effects rather than genuine procognitive benefits.

This preclinical rat study (n=24; 8 rats per group) shows that a single dose of psilocybin (1.0 mg/kg) or the selective 5-HT2A receptor agonist 25CN-NBOH (1.5 mg/kg) reduces immobility in the forced-swim test, with effects persisting for at least three months. Electrophysiology of medial prefrontal cortex (mPFC) Layer 5 neurons reveals long-lasting functional, but not structural, plasticity—characterised by changes in resting membrane potential, neuronal firing rates, and excitatory synaptic input. In contrast, dendritic spine density and gene-expression markers related to synaptic structure remain unchanged, indicating enduring functional alterations rather than persistent structural modifications.

This qualitative study (n=40) of healthy males following a double-blind placebo-controlled trial of LSD microdosing (10µg every third day for 6 weeks) found participants reported effects across emotions and mood, social life, mindfulness, cognition and creativity, and physiological domains, with key themes including openness to experiences and bidirectionality of effects, alongside reports of changes in anxiety suggesting important considerations for patient selection and dose optimisation.