LSD acutely impairs working memory, executive functions, and cognitive flexibility, but not risk-based decision-making
Thomas Pokorny, Patricia Duerler, Erich Seifritz, Franz X. Vollenweider, Katrin H. Preller
Psychological Medicine September 10, 2019 DOI: 10.1017/s0033291719002393 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, randomized, placebo-controlled, within-subject design Peer reviewed |
|---|---|
| Sample size | 25 |
| Population | Healthy participants |
| Interventions | LSD Ketanserin |
| Dose | 100 µg LSD, 40 mg ketanserin |
| Duration | Acute effects |
| Topics | LSD |
| Keywords | Cognitive flexibility Working memory Executive functions Cognition Flexibility engineering Cognitive psychology |
| Citations | 102 |
| Key points | LSD significantly impairs executive functions, cognitive flexibility, and working memory via the 5-HT2A receptor, but does not affect decision-making or risk-taking. |
Abstract
Abstract Background Psychiatric and neurodegenerative illnesses are characterized by cognitive impairments, in particular deficits in working memory, decision-making, and executive functions including cognitive flexibility. However, the neuropharmacology of these cognitive functions is poorly understood. The serotonin (5-HT) 2A receptor might be a promising candidate for the modulation of cognitive processes. However, pharmacological studies investigating the role of this receptor system in humans are rare. Recent evidence demonstrates that the effects of Lysergic acid diethylamide (LSD) are mediated via agonistic action at the 5-HT 2A receptor. Yet, the effects of LSD on specific cognitive domains using standardized neuropsychological test have not been studied.
Methods: We examined the acute effects of LSD (100 µ g) alone and in combination with the 5-HT 2A antagonist ketanserin (40 mg) on cognition, employing a double-blind, randomized, placebo-controlled, within-subject design in 25 healthy participants. Executive functions, cognitive flexibility, spatial working memory, and risk-based decision-making were examined by the Intra/Extra-Dimensional shift task (IED), Spatial Working Memory task (SWM), and Cambridge Gambling Task (CGT) of the Cambridge Neuropsychological Test Automated Battery.
Results: Compared to placebo, LSD significantly impaired executive functions, cognitive flexibility, and working memory on the IED and SWM, but did not influence the quality of decision-making and risk taking on the CGT. Pretreatment with the 5-HT 2A antagonist ketanserin normalized all LSD-induced cognitive deficits.
Conclusions: The present findings highlight the role of the 5-HT 2A receptor system in executive functions and working memory and suggest that specific 5-HT 2A antagonists may be relevant for improving cognitive dysfunctions in psychiatric disorders.