Case reports of unexpected memory retrieval in patients with severe dementia near death challenge the view that dementia is an irreversible consolidation problem, suggesting instead a retrieval problem. The likely mechanism involves fluctuating neuromodulators from the brain stem to the medial prefrontal cortex and hippocampus. Around death, neurotransmitter discharges change dramatically, and relatively resistant neuromodulator circuits can maintain optimal arousal and attention for memory processing, triggering episodes of lucidity. Corticotropin-releasing peptides may further increase mental clarity. No animal or human model exists to test this hypothesis, but similarities with delirium and lucid dreaming could provide windows for future research.
Psilocybin and MDMA reduce anxiety-like behaviors in a rat model of fear conditioning, and these effects depend on myelin plasticity in the dentate gyrus. Both drugs triggered oligodendroglial changes and multi-omic signatures of myelin remodeling, though mean myelin thickness (g-ratio) did not differ significantly between treated and untreated fear-conditioned animals. Disrupting myelin abolished the anxiolytic effects. Psilocybin preferentially activated early oligodendroglial gene programs, while MDMA enhanced markers of mature myelin. Blocking the 5-HT2A receptor completely eliminated both the myelin and behavioral enhancements. Enhancing myelination may be a viable strategy to sustain therapeutic effects of psychedelic-assisted treatments for PTSD.
Psychedelic substances like LSD, psilocybin, and DMT may influence glucagon release from pancreatic alpha cells by altering neurotransmitter concentrations involved in intra-islet and extra-islet signaling, an area that remains largely unexplored. This commentary addresses the unprecedented subject of how these substances could affect endocrine activity, particularly neurotransmitter-regulated glucagon release, suggesting a potential link between psychedelics and systemic metabolic functions.