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 a number of measures of cognition in healthy volunteers. It was found that LSD sub-acutely improved visuospatial memory, phonological verbal fluency and impaired cognitive flexibility when compared to placebo suggesting that LSD-assisted therapy may provide a novel treatment in conditions involving memory and language declines.

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.”

Authors: Isabel Wießner, Rodolfo Olivieri, Marcelo Falchi, Fernanda Palhano-Fontes, Lucas O. Maia, Amanda Feilding, Draulio B. Araujo, Sidarta Ribeiro & Luís Fernando Tófoli

Summary

Psychedelics acutely impair cognitive functions, but with growing experiences with psychedelics, these impairments decline and microdoses may even exert opposing effects. This explorative study aimed at investigating the potential of psychedelics to sub-acutely change cognition.

2.1. Study design

This study used a randomized, double-blind, placebo-controlled, crossover design with two treatments and a washout period of 14 days between treatments. Half of the participants received LSD first.

2.2. Participants

Twenty-five healthy participants were recruited in a convenience sample, and one ceased participation after the first session for personal reasons. All participants consumed 3 cups of coffee a day, and one third of the sample consumed tobacco every third day to several times a day.

2.4.1. Episodic memory

The Rey-Osterrieth Complex Figure (ROCF) measures visual perception, visuoconstructional abilities and spontaneous memory retention. Participants copy a complex geometric figure on a sheet of paper, and then immediately recall and draw the figure from memory.

The 2D Object-Location Memory Task (OLMT) measures visuospatial memory consolidation. Participants learn 15 pairs of identical cards (4 x 4 cm) with pictures of animals and objects, and then recall the locations of these pairs in two consecutive learning runs and in immediate recall before drug administration.

The Rey Auditory-Verbal Learning Test (RAVLT) measures auditory-verbal memory consolidation. Participants hear a list of 15 nouns twice, recall as many nouns as possible, and recognize the 15 nouns from a larger list with phonological and semantic distractors.

The Design Fluency Task (DFT) measures design fluency by having participants draw as many different designs as possible using four lines per rectangle connecting black dots, white dots and a black and a white dot.

2.4.3. Cognitive flexibility

The Wisconsin Card Sorting Test (WCST) measures cognitive flexibility, including the formation, maintenance and shift of abstract concepts utilizing feedback. Participants assign cards to key cards according to the assumed correct dimension (colour/form/number), followed by feedback from the researcher (correct/wrong). We evaluated perseveration by evaluating perseverative responses, perseverative errors type 1, perseverative errors type 2, and perseverative errors type 3 . We calculated the percentage of total errors, conceptual level responses, perseverative responses, perseverative errors and non-perseverative errors.

2.4.4. Sustained and shifting attention

The Trail Making Test measures sustained and shifting attention and visuomotor processing speed. Participants must connect circles without lifting the pencil, in ascending order of numbers and ascending/alphabetical order switching between numbers and letters.

2.4.5. Inhibitory control

The Stroop Task measures inhibitory control, selective attention and visuoverbal processing speed. Participants must name the colours of each item as fast as possible, and the total duration to name all 24 stimuli is assessed.

2.4.6. Perceptual organization

The Block Design Test measures perceptual organization including visuospatial reasoning and visuoconstructional abilities.

2.5. Study procedures

Each session consisted of two study days, starting with baseline measurements at 7:30 a.m. and ending at 5:30 p.m. The next morning, subjects performed RAVLT and OLMT final recall, WCST, ROCF, TMT, Stroop, VFT, DFT, BDT, amongst other tasks.

2.6. Data analysis

Data were analysed with IBM SPSS Statistics (version 22). A repeated measures General Linear Model (GLM) was performed for each variable and complemented by the covariates ‘abstinence from psychedelics’ and ‘Body Mass Index’ (BMI) to assess effects of abstinence periods and drug dose.