Psilocybin and 4-Bromo-2,5-Dimethoxyphenethylamine (2C-B) at Encoding Distort Episodic Familiarity

Background: As research on psychedelics (hallucinogenic 5-HT2A agonists) progresses, it is important to delineate the reliability of supposedly unique effects across this drug class. One such effect is how psychedelics impair the formation (i.e., encoding) of hippocampal-dependent recollections (retrieval of specific details) while potentially enhancing the encoding of cortical-dependent familiarity (a feeling of knowing that a stimulus has been previously experienced).

Methods: In a double-blind, placebo-controlled, within-subjects study (N = 20), we tested the acute effects of two distinct psychedelics, psilocybin and 4-bromo-2,5-dimethoxyphenethylamine (2C-B), on the encoding of emotional episodic memories. During acute drug effects, participants viewed negative, neutral, and positive pictures. The following day (while sober), participants completed two separate memory tests for these pictures.

Results: Using computational models of memory confidence, we found trends for psilocybin and 2C-B at encoding to impair estimates of recollection that were supported by other measures/analyses. Surprisingly, psilocybin and 2C-B at encoding impaired estimates of familiarity, but these impairments were likely due to a misattribution of heightened familiarity, as both drugs at encoding selectively increased familiarity-based false alarms, especially for negative and positive stimuli. Psilocybin and 2C-B at encoding also tended to impair estimates of metamemory (understanding one’s own memory) for negative and neutral memories but enhance estimates of metamemory for positive memories, though these effects were less reliable in additional analyses.

Conclusions: Despite differences in their chemistry, pharmacology, and subjective effects, both psilocybin and 2C-B distort episodic familiarity, alluding to a common neurocognitive mechanism across psychedelics that may drive other phenomena.