Psilocybin and 2C-B at Encoding Distort Episodic Familiarity.

Two psychedelics, psilocybin and 2C-B, impair the encoding of detailed recollections and distort feelings of familiarity for emotional memories. In a double-blind, placebo-controlled study with 20 participants, both drugs reduced estimates of recollection and familiarity the next day, but increased false alarms based on familiarity, especially for negative and positive images. The drugs also tended to impair metamemory for negative and neutral memories while enhancing it for positive ones, though these effects were less reliable. The similar pattern across both substances suggests a shared neurocognitive mechanism among psychedelics that may underlie other phenomena.

Study at a glance

Abstract

As research on psychedelics (hallucinogenic serotonin receptor 2A 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). In a double-blind, placebo-controlled, within-participants study (N = 20), we tested the acute effects of 2 distinct psychedelics, psilocybin and 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 2 separate memory tests for these pictures. 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, because 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 enhanced estimates of metamemory for positive memories, although these effects were less reliable in additional analyses. Despite differences in their chemistry, pharmacology, and subjective effects, both psilocybin and 2C-B distorted episodic familiarity, suggesting a common neurocognitive mechanism across psychedelics that may drive other phenomena.