Psychedelic substances such as psilocybin and 2C-B can significantly distort our sense of familiarity with past events, according to a new study published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. The study found that these substances impair episodic memory, particularly by causing false familiarity, especially with emotionally charged stimuli.
Episodic memory is a type of long-term memory that involves the recollection of specific events, situations, and experiences from one’s past. This form of memory allows individuals to mentally travel back in time to remember personal experiences, such as a birthday party, a vacation, or even a conversation from yesterday.
Episodic memory is supported by two key processes: recollection and familiarity. Recollection refers to the ability to recall detailed information about an event, such as where and when it occurred. Familiarity, on the other hand, is the sense of knowing that something has been experienced before without recalling specific details, like recognizing a face without remembering where you met the person.
The motivation for the study stems from the growing interest in the therapeutic potential of psychedelics, such as psilocybin and 2C-B, in treating various psychiatric disorders. Psychedelics have been shown to produce rapid and significant improvements in conditions like depression and anxiety, making them a promising avenue for mental health treatment.
However, these substances are also known to acutely impair cognitive functions, including memory. Previous research suggested that psychedelics impact episodic memory differently from other psychoactive substances, sparing or even enhancing familiarity while impairing recollection. This unique effect on memory processes raises questions about the underlying mechanisms and whether these effects are consistent across different types of psychedelics.
By investigating how psilocybin and 2C-B affect episodic memory, the researchers aimed to uncover whether the observed enhancements in familiarity and impairments in recollection are common across various psychedelics. This knowledge could provide deeper insights into the cognitive effects of these substances.
Psilocybin is a naturally occurring psychedelic compound found in certain mushrooms, known for its powerful effects on perception and consciousness by activating serotonin receptors in the brain. 2C-B is a synthetic psychedelic of the phenethylamine class that also affects serotonin receptors, known for its visual and entactogenic (emotional openness and empathy) effects, but with a distinct pharmacological profile compared to psilocybin.
“In a previous project, we found that psychedelics impaired the formation (i.e., encoding) of hippocampal-dependent recollection (i.e., detailed remembering like where/when something happened) but spared or even enhanced the formation of cortical-dependent familiarity (i.e., knowing that a stimulus was recently processed without necessarily remembering specific details like recognizing a face but not knowing how you know this individual),” said study author Manoj K. Doss, a research fellow at The University of Texas at Austin Dell Medical School.
“All other drugs that impaired recollection (e.g., GABA-A sedatives like alcohol and benzodiazepines, NMDA dissociatives like ketamine and dextromethorphan, THC) impaired the encoding of recollection, as well as familiarity (at least at higher doses), so we wanted to see if the sparing/enhancement of familiarity was a drug effect unique to psychedelics. Furthermore, psychedelics typically impair most measures of cognition, but there’s a reluctance for researchers to admit this (including researchers saying that psychedelics don’t impair memory), so we wanted to see if a cognitive process could truly be enhanced.”
The study involved 22 neurotypical young adults recruited from Maastricht University and the surrounding area. After excluding two participants who did not complete all conditions, the final sample consisted of 20 participants, evenly split between males and females, with an average age of 25 years.
All participants were experienced with psychedelics but had not used them in the past three months. The study followed a double-blind, placebo-controlled, repeated measures design with three experimental conditions: placebo, 15 mg of psilocybin, and 20 mg of 2C-B. Each participant experienced all three conditions in random order, with at least 14 days between sessions to prevent carryover effects.
Participants first attended a preparatory session to practice the memory task. On each experimental day, they consumed a capsule containing either the placebo or one of the psychedelics. Approximately three hours after administration, participants performed the encoding phase of the memory task. This involved viewing a series of images paired with descriptive labels and rating their emotional arousal. The images were drawn from standardized databases and included negative, neutral, and positive stimuli, balanced for content and emotional valence.
Memory was tested 24 hours later through a cued recollection test and a picture recognition test. In the cued recollection test, participants were shown the labels from the previous day and asked if they had seen the corresponding image. In the picture recognition test, they were shown images and asked if they had seen them before, distinguishing between “remember” (recollecting specific details) and “know” (feeling familiar without details) responses.
The study found that both psilocybin and 2C-B impaired recollection, particularly for neutral and positive images. Participants under the influence of these psychedelics were less accurate in recalling specific details of the images they had seen. More notably, the study revealed an increase in familiarity-based false alarms. Participants often reported a false sense of familiarity with images they had not seen, especially for emotionally charged images. This suggests that psychedelics may heighten the feeling of familiarity, leading to memory distortions.
“We found evidence that psychedelics enhanced familiarity, though the effects led to increased false recognition (i.e., claiming to have seen a stimulus that you did not actually see). In non-drug research, heightened familiarity (e.g., by presenting related words such as lime, orange, and grapefruit) can also lead to such false recognition (e.g., for a word like lemon),” Doss told PsyPost.
Additionally, the study found that memory performance was generally better for negative images across all conditions, which aligns with previous research indicating that emotionally negative stimuli are more memorable. However, the increase in false familiarity responses with psychedelics was more pronounced for negative and positive images compared to neutral ones. This highlights the role of emotional content in how psychedelics affect memory processes.
“Another surprising effect was that the recollection impairments we observed were most selective for neutral and positive stimuli, whereas other drugs preferentially impair the encoding of negative and positive memories,” Doss said.
While this study provides valuable insights into how psychedelics affect memory, it has some limitations. For instance, the sample size was relatively small, which may limit the generalizability of the findings. However, Doss noted that “this is the third time we’re finding idiosyncratic psychedelic effects on familiarity that are distinct from how other drugs impact familiarity. Even if this modulation of familiarity is an impairment, it was more prominent than the recollection impairments, whereas other drugs preferentially impair recollection. The impairments in recollection/hippocampal-dependent memory were also relatively small, though it’s worth noting that human and animal work reliably find such impairments.”
“Feelings of familiarity are thought to involve the fluency (i.e., the ease of information processing) with which information is processed through the cortex, resulting in less neural resources to process repeated or related information,” Doss said. “In addition to fluency producing false memories, fluency (by presenting a stimulus several times) can also result in other illusory phenomena such as liking a stimulus more (i.e., the mere exposure effect) or increasing the plausibility of a statement (i.e., the illusory truth effect). One idea might be that psychedelics enhance fluency, which could explain why people taking psychedelics together may like each other more (despite having little conversation) or think the ideas they conjure up during a psychedelic experience are true.”
“We are about to start testing this hypothesis that I’ve been calling FLUX (FLUency eXaggeration) that psychedelics enhance fluency with the help of MINDS [the Center for Multidisciplinary Investigation Into Novel Discoveries & Solutions],” he added.
The study, “Psilocybin and 4-Bromo-2,5-Dimethoxyphenethylamine (2C-B) at Encoding Distort Episodic Familiarity,” Manoj K. Doss, Pablo Mallaroni, Natasha L. Mason, and Johannes G. Ramaekers.
