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

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.

Low-dose LSD and the stream of thought: Increased Discontinuity of Mind, Deep Thoughts and abstract flow.

RATIONALE: Stream of thought describes the nature of the mind when it is freely roaming, a mental state that is continuous and highly dynamic as in mind-wandering or free association. Classic serotonergic psychedelics are known to profoundly impact perception, cognition and language, yet their influence on the stream of thought remains largely unexplored. OBJECTIVE: To elucidate the effects of LSD on the stream of thought. METHODS: In a randomized, double-blind, placebo-controlled, crossover study, 24 healthy participants received 50 µg lysergic acid diethylamide (LSD) or inactive placebo. Mind-wandering was measured by the Amsterdam Resting State Questionnaire (ARSQ), free association by the Forward Flow Task (FFT) for three seed word types (animals, objects, abstract words). ARSQ and FFT were assessed at +0 h, +2 h, +4 h, +6 h, +8 h and +24 h after drug administration, respectively. RESULTS: LSD, compared to placebo, induced different facets of mind-wandering we conceptualized as "chaos" (Discontinuity of Mind, decreased Sleepiness, Planning, Thoughts under Control, Thoughts about Work and Thoughts about Past), "meaning" (Deep Thoughts, Not Sharing Thoughts) and "sensation" (Thoughts about Odours, Thoughts about Sounds). LSD increased the FFT for abstract words reflecting an "abstract flow" under free association. Overall, chaos was strongest pronounced (+2 h to +6 h), followed by meaning (+2 h to +4 h), sensation (+2 h) and abstract flow (+4 h). CONCLUSIONS: LSD affects the stream of thought within several levels (active, passive), facets (chaos, meaning, sensation, abstractness) and time points (from +2 h to +6 h). Increased chaos, meaning and abstract flow at +4 h indicate the utility of a late therapeutic window in psycholytic therapy.