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.
Comparable studies
Other randomized controlled trials on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases Patients with anxiety associated with life-threatening diseases | 2014 | Randomized controlled trial | n = 12 |
| Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users | 1994 | Double-blind, saline placebo-controlled, randomized study | n = 12 |
| Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Healthy subjects (8 women, 8 men) | 2014 | Double-blind, randomized, placebo-controlled, crossover study | n = 16 |
| Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Healthy human participants | 2018 | Double-blind, randomized, counterbalanced, cross-over study | n = 24 |
| LSD-induced entropic brain activity predicts subsequent personality change. Healthy adults | 2016 | Balanced-order, placebo-controlled study | n = 19 |
Citations in the library
Cited by 79
- Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder. Translational Psychiatry November 8, 2021
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Pharmacological, neural, and psychological mechanisms underlying psychedelics: a critical review Neuroscience & Biobehavioral Reviews September 1, 2022
- Models of psychedelic drug action: modulation of cortical-subcortical circuits Brain October 22, 2021
- Psilocybin acutely alters the functional connectivity of the claustrum with brain networks that support perception, memory, and attention. Neuroimage September 1, 2020
and 74 more in the library
Cites 24
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Pharmacopsychiatry July 1, 1998
- Serotonin research: contributions to understanding psychoses TIPS - Trends in Pharmacological Sciences August 1, 2008
- Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Biological Psychiatry November 29, 2014
and 19 more in the library