Psilocybin and 2C-B at Encoding Distort Episodic Familiarity.
Manoj K. Doss, Pablo Mallaroni, Natasha L. Mason, Johannes G. Ramaekers
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging October 1, 2024 DOI: 10.1016/j.bpsc.2024.06.008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled, within-participants study Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Healthy human participants |
| Interventions | Psilocybin 2C-B |
| Duration | 1-day (encoding during acute drug effects, memory test the following day) |
| Topics | Psilocybin |
| Keywords | 2c-b Episodic memory Familiarity Metamemory Psychedelics hallucinogens Entheogens Psychoactive drugs Memory recall Remembrance Recollection Neuroscience brain science Neural processing Cognitive science |
| Citations | 7 |
| Key points | Both psilocybin and 2C-B impaired recollection and familiarity estimates during encoding while increasing familiarity-based false alarms for emotional stimuli, indicating a common psychedelic effect on episodic memory. |
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.
Comparable studies
Other randomized controlled trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety | 2016 | Randomized controlled trial | n = 51 |
| Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression | 2016 | Double-blind, placebo-controlled, crossover trial | n = 29 |
| Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Hallucinogen-naïve adults reporting regular participation in religious or spiritual... | 2006 | Double-blind study | n = 36 |
| Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression | 2021 | Randomized controlled trial | |
| Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... | 2020 | Randomized controlled trial | n = 24 |
Citations in the library
Cited by 8
- How Psychedelics Modulate Multiple Memory Mechanisms in Posttraumatic Stress Disorder. Drugs November 1, 2024
- Psychedelics and autobiographical memory - six open questions. Psychopharmacology March 17, 2025
- Ayahuasca enhances the formation of hippocampal-dependent episodic memory without impacting false memory susceptibility in experienced ayahuasca users: An observational study. Journal of Psychopharmacology April 1, 2025
- Metacognitive Feelings of Epistemic Gain are Central to the Understanding of Psychedelic-Induced Mystical-Type Experiences Cognitive Therapy and Research March 29, 2025
- Preliminary validation and refinement of the psychedelic aesthetic experience questionnaire Frontiers in Psychology September 15, 2025
and 3 more in the library
Cites 26
- Serotonin research: contributions to understanding psychoses TIPS - Trends in Pharmacological Sciences August 1, 2008
- Emotions and brain function are altered up to one month after a single high dose of psilocybin. Scientific Reports February 10, 2020
- Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder. Translational Psychiatry November 8, 2021
- Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs). Neuropharmacology December 1, 2015
- Pharmacokinetics and Pharmacodynamics of Oral Psilocybin Administration in Healthy Participants Clinical Pharmacology & Therapeutics December 12, 2022
and 21 more in the library