Anxiety DisordersSubstance Use Disorders (SUD)Neurological InjuryNeurocognitive DisordersHealthy VolunteersImmunology & InflammationLSD

LSD, afterglow and hangover: Increased episodic memory and verbal fluency, decreased cognitive flexibility

This trial (n=24) investigated the effects LSD (50 μg) has on cognition in healthy volunteers. It was found that LSD sub-acutely improved visuospatial memory and phonological verbal fluency and impaired cognitive flexibility when compared to placebo.

Authors

  • Fernanda Palhano-Fontes
  • Luiz Tófoli
  • Amanda Feilding

Published

European Neuropsychopharmacology
individual Study

Abstract

Psychedelics acutely impair cognitive functions, but these impairments decline with growing experiences with psychedelics and microdoses may even exert opposing effects. Given the recent evidence that psychedelics induce neuroplasticity, this explorative study aimed at investigating the potential of psychedelics to sub-acutely change cognition. For this, we applied a randomized, double-blind, placebo-controlled, crossover study with 24 healthy volunteers receiving 50 μg lysergic acid diethylamide (LSD) or an inactive placebo. Sub-acute changes in cognition were measured 24 h after dosing, including memory (Rey-Osterrieth Complex Figure, ROCF; 2D Object-Location Memory Task, OLMT; Rey Auditory-Verbal Learning Test, RAVLT), verbal fluency (phonological; semantic; switch), design fluency (basic; filter; switch), cognitive flexibility (Wisconsin Card Sorting Test, WCST), sustained and switching attention (Trail Making Test, TMT), inhibitory control (Stroop Task) and perceptual reasoning (Block Design Test, BDT). The results show that when compared to placebo and corrected for Body Mass Index (BMI) and abstinence period from psychedelics, LSD sub-acutely improved visuospatial memory (ROCF immediate recall points and percentage, OLMT consolidation percentage) and phonological verbal fluency and impaired cognitive flexibility (WCST: fewer categories achieved; more perseveration, errors and conceptual level responses). In conclusion, the low dose of LSD moderately induced both “afterglow” and “hangover”. The improvements in visuospatial memory and phonological fluency suggest that LSD-assisted therapy should be explored as a novel treatment perspective in conditions involving memory and language declines such as brain injury, stroke or dementia.

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Research Summary of 'LSD, afterglow and hangover: Increased episodic memory and verbal fluency, decreased cognitive flexibility'

Introduction

Psychedelics such as LSD, psilocybin and ayahuasca have been investigated increasingly for psychiatric indications including mood, anxiety and substance use disorders, and there is growing interest in other applications. Previous research reports acute impairments in a range of cognitive functions during intoxication, yet findings are mixed: experienced users or low (micro) doses sometimes show preserved or improved performance, and animal and human studies have suggested psychedelic-induced neuroplasticity, neurogenesis and anti-inflammatory effects that could support memory and language functions. The main pharmacological target, the serotonin 2A (5-HT2A) receptor, is implicated in executive functions, learning and memory, but the literature leaves open questions about whether observed episodic memory changes reflect encoding, consolidation or retrieval processes and whether sub-acute (post-acute) effects might differ from acute impairments. Wießner and colleagues designed an exploratory human study to examine whether a low sub-psychedelic dose of LSD (50 μg) produces measurable sub-acute changes in diverse cognitive domains 24 hours after administration. The study aimed to test multiple aspects of episodic memory, verbal and design fluency, cognitive flexibility, attention, inhibitory control and perceptual reasoning using a randomised, double-blind, placebo-controlled, crossover design in healthy volunteers, with particular interest in whether LSD might improve specific memory or language-related processes despite acute cognitive disruptions reported elsewhere.

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Study Details

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