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

Background: Psychedelics acutely impair cognitive functions, but these impairments decline with growing experiences with psychedelics and microdoses may even exert opposing effects.

Aims: Given the recent evidence that psychedelics induce neuroplasticity, this explorative study aimed at investigating the potential of psychedelics to sub-acutely change cognition.

Methods: 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).

Results: 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).

Conclusion: 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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