The Fabric of Meaning and Subjective Effects in LSD-Induced States Depend on Serotonin 2A Receptor Activation.
Katrin H. Preller, Marcus Herdener, Thomas Pokorny, Amanda Planzer, Rainer Kraehenmann, Philipp Stämpfli, Matthias E. Liechti, Erich Seifritz, Franz X. Vollenweider
Current Biology February 6, 2017 DOI: 10.1016/j.cub.2016.12.030 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Healthy human volunteers |
| Interventions | Lysergic acid diethylamide (LSD) Ketanserin |
| Topics | LSD Serotonin |
| Keywords | Dopamine Ketanserin Meaning Music Personal relevance Serotonin 2a receptor |
| Key findings | Ketanserin fully blocked LSD's general subjective effects and inhibited the LSD-induced attribution of personal relevance to previously meaningless stimuli, while modulating processing of meaningful stimuli in cortical midline structures. The authors argue this points to a crucial role of the serotonin 2A receptor and cortical midline regions in generating and attributing personal relevance, with potential implications for treating psychiatric disorders marked by altered relevance attribution. |
Abstract
A core aspect of the human self is the attribution of personal relevance to everyday stimuli enabling us to experience our environment as meaningful [1]. However, abnormalities in the attribution of personal relevance to sensory experiences are also critical features of many psychiatric disorders [2, 3]. Despite their clinical relevance, the neurochemical and anatomical substrates enabling meaningful experiences are largely unknown. Therefore, we investigated the neuropharmacology of personal relevance processing in humans by combining fMRI and the administration of the mixed serotonin (5-HT) and dopamine receptor (R) agonist lysergic acid diethylamide (LSD), well known to alter the subjective meaning of percepts, with and without pretreatment with the 5-HT2AR antagonist ketanserin. General subjective LSD effects were fully blocked by ketanserin. In addition, ketanserin inhibited the LSD-induced attribution of personal relevance to previously meaningless stimuli and modulated the processing of meaningful stimuli in cortical midline structures. These findings point to the crucial role of the 5-HT2AR subtype and cortical midline regions in the generation and attribution of personal relevance. Our results thus increase our mechanistic understanding of personal relevance processing and reveal potential targets for the treatment of psychiatric illnesses characterized by alterations in personal relevance attribution.
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 337
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future. Neuropsychopharmacology April 26, 2017
- Global Street Food: la cocina de la calle Diseño interior 2009
- Predicting Responses to Psychedelics: A Prospective Study Frontiers in Pharmacology November 2, 2018
- Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Elife October 25, 2018
and 332 more in the library
Cites 19
- Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. American Journal of Psychiatry 2003
- The Pharmacology of Lysergic Acid Diethylamide: A Review CNS Neuroscience & Therapeutics November 11, 2008
- Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Biological Psychiatry November 29, 2014
- Activation of Serotonin 2A Receptors Underlies the Psilocybin-Induced Effects on Oscillations, N170 Visual-Evoked Potentials, and Visual Hallucinations Journal of Neuroscience June 19, 2013
- Stress Sensitivity, Aberrant Salience, and Threat Anticipation in Early Psychosis: An Experience Sampling Study Schizophrenia Bulletin February 1, 2016
and 14 more in the library