Role of the 5-HT2A Receptor in Acute Effects of LSD on Empathy and Circulating Oxytocin
Friederike Holze, Isidora Avedisian, Nimmy Varghese, Anne Eckert, Matthias E. Liechti
Frontiers in Pharmacology July 13, 2021 DOI: 10.3389/fphar.2021.711255 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Placebo-controlled, double-blind, random-order, crossover design Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Healthy subjects |
| Interventions | LSD ketanserin |
| Dose | 25, 50, 100, and 200 µg LSD; 200 µg LSD combined with 40 mg ketanserin |
| Topics | LSD Serotonin |
| Keywords | Empathy Ketanserin Oxytocin receptor Hallucinogen Placebo Receptor antagonist Ritanserin 5-HT Receptor Pharmacology |
| Citations | 66 |
| Key points | LSD dose-dependently increased emotional empathy, and this effect was not blocked by the 5-HT2A receptor antagonist ketanserin, whereas LSD-induced oxytocin release was reduced by ketanserin. |
Abstract
The psychedelic lysergic acid diethylamide (LSD) has experienced a revival in research, including clinical trials that evaluate LSD-assisted psychotherapy. LSD induces perceptual alterations and influences emotion processing in ways that may support psychotherapy. Here, we investigated the effects of LSD on emotional empathy and mediating role of the serotonin 5-hydroxytryptamine-2A (5-HT 2A ) receptor by administering 25, 50, 100, and 200 µg LSD alone and 200 µg LSD combined with pretreatment with the 5-HT 2A receptor antagonist ketanserin (40 mg) using a placebo-controlled, double-blind, random-order, crossover design in 16 healthy subjects. The Multifaceted Empathy Test (MET) was used to assess the effects of LSD on emotional empathy. Plasma oxytocin levels were also measured. LSD dose-dependently increased implicit and explicit emotional empathy, with the highest 200 µg LSD dose having a significant effect compared with placebo. The 200 µg dose of LSD also moderately increased plasma oxytocin levels compared with placebo. Ketanserin reduced the LSD-induced elevations of oxytocin but not the LSD-induced increases in emotional empathy. These findings confirm that LSD enhances empathy, and this effect may be partially independent of its primary action on 5-HT 2A receptors to induce subjective psychedelic effects. In contrast, LSD-induced oxytocin release may depend on 5-HT 2A receptor stimulation, which is consistent with the psychedelic effect of LSD. Further studies are needed to investigate whether LSD may also enhance empathy and potentially produce therapeutic effects in patients who have deficits in empathy and impairments in social functioning.
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 58
- Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects Neuropsychopharmacology February 25, 2022
- Pharmacological, neural, and psychological mechanisms underlying psychedelics: a critical review Neuroscience & Biobehavioral Reviews September 1, 2022
- Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants. Neuropsychopharmacology October 1, 2023
- A neurobiological perspective on social influence: Serotonin and social adaptation Journal of Neurochemistry March 11, 2022
- Examining Psychedelic-Induced Changes in Social Functioning and Connectedness in a Naturalistic Online Sample Using the Five-Factor Model of Personality Frontiers in Psychology November 25, 2021
and 53 more in the library
Cites 36
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later Journal of Psychopharmacology May 30, 2008
- Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases The Journal of Nervous and Mental Disease March 4, 2014
- Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Biological Psychiatry November 29, 2014
and 31 more in the library