LSD and ketanserin and their impact on the human autonomic nervous system
In a randomised, placebo-controlled crossover study using R‑peak-derived HRV, LSD predominantly increased sympathetic activity while pre-treatment with the 5‑HT2A antagonist ketanserin shifted autonomic balance towards increased parasympathetic tone. Sympathetic activation correlated positively (and parasympathetic negatively) with psychedelic intensity, and baseline HRV predicted subjective responses, suggesting trait ANS measures could serve as candidate biomarkers for LSD’s therapeutic effectiveness.
Authors
- Franz Vollenweider
- Katrin Preller
Published
Abstract
The interest in lysergic acid diethylamide (LSD) has sparked again due to its supposed positive effects on psychopathological conditions. Yet, most research focuses on the actions of LSD on the central nervous system. The interaction with the autonomic nervous system (ANS) has been neglected so far. Therefore, the aim was to assess the effects of LSD and the serotonin 2A receptor antagonist ketanserin on the ANS as assessed by heart rate variability (HRV) measures and their correlation with subjective drug‐induced effects in a randomized, placebo‐controlled crossover trial. Thus, ANS activity was derived from electrocardiogram recordings after intake of placebo, LSD or ketanserin, and LSD by calculating R‐peak‐based measures of sympathetic and parasympathetic activity. Repeated measure ANOVA and partial correlation for HRV measures and subjective experience questionnaires were performed. LSD predominantly increased sympathetic activity, while ketanserin counteracted this effect on the ANS via an increase of parasympathetic tone. Sympathetic activity was positively and parasympathetic activity negatively associated with psychedelic effects of LSD. Furthermore, Placebo HRV measures predicted subjective experiences after LSD intake. The association between trait ANS activity and LSD‐induced subjective experiences may serve as a candidate biomarker set for the effectiveness of LSD in the treatment of psychopathological conditions.
Research Summary of 'LSD and ketanserin and their impact on the human autonomic nervous system'
Introduction
Interest in lysergic acid diethylamide (LSD) has renewed because of potential therapeutic effects in psychiatric conditions, but most research has concentrated on central nervous system actions. Olbrich and colleagues note that the drug's interaction with the autonomic nervous system (ANS) has been sparsely examined in humans, and no prior study has applied heart rate variability (HRV)–based measures to quantify LSD's effects on sympathetic and parasympathetic activity. Earlier clinical observations and a few recent reports suggest LSD raises heart rate, blood pressure and pupil size—indicators of sympathetic activation—but the impact on parasympathetic function and the relationship between autonomic changes and subjective psychedelic experiences remain unclear. This study set out to characterise LSD's effects on ANS function, to test whether blocking the serotonin 2A (5-HT2A) receptor with ketanserin alters those effects, and to examine correlations between autonomic measures and subjective experiences. Using a randomised, double-blind, placebo-controlled crossover design, the investigators hypothesised that LSD would increase sympathetic activity, that ketanserin pretreatment would attenuate this effect, and that ANS measures would correlate with the magnitude of subjective psychedelic effects. They also explored whether baseline (placebo) ANS markers might predict subsequent subjective responses to LSD.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Authors
- APA Citation
Olbrich, S., Preller, K. H., & Vollenweider, F. X. (2021). LSD and ketanserin and their impact on the human autonomic nervous system. Psychophysiology, 58(6). https://doi.org/10.1111/psyp.13822
References (19)
Papers cited by this study that are also in Blossom
Barrett, F. S., Preller, K. H., Herdener, M. et al. · Cerebral Cortex (2017)
Carhart-Harris, R. L., Goodwin, G. M. · Neuropsychopharmacology (2017)
Deshon, H. J., Rinkel. M., Solomon, H. C. · Psychiatric Quarterly (1988)
Dolder, P. C., Schmid, Y., Haschke, M. et al. · International Journal of Neuropsychopharmacology (2015)
Dolder, P. C., Schmid, Y., Müller, F. et al. · Neuropsychopharmacology (2016)
Dolder, P. C., Schmid, Y., Steuer, A. E. et al. · Clinical Pharmacokinetics (2017)
Gasser, P., Holstein, D., Michel, Y. et al. · Journal of Nervous and Mental Disease (2014)
Haijen, E. C. H. M., Kaelen, M., Roseman, L. et al. · Frontiers in Pharmacology (2018)
Holze, F., Duthaler, U., Vizeli, P. et al. · British Journal of Clinical Pharmacology (2019)
Holze, F., Vizeli, P., Müller, F. et al. · Neuropsychopharmacology (2019)
Show all 19 referencesShow fewer
Kaelen, M., Barrett, F. S., Roseman, L. et al. · Psychopharmacology (2015)
Liechti, M. E. · Neuropsychopharmacology (2017)
Luckenbaugh, D. A., Niciu, M. J., Ionescu, D. F. et al. · Journal of Affective Disorders (2014)
Passie, T., Halpern, J. H., Stichtenoth, D. O. et al. · CNS Neuroscience and Therapeutics (2008)
Preller, K. H., Burt, J. B., Adkinson, B. et al. · eLife (2018)
Preller, K. H., Herdener, M., Pokorny, T. et al. · Current Biology (2017)
Rucker, J., Young, A. H., Jelen, L. A. et al. · Journal of Psychopharmacology (2016)
Schmid, Y., Enzler, F., Gasser, P. et al. · Biological Psychiatry (2015)
Studerus, E., Gamma, A., Vollenweider, F. X. · PLOS ONE (2010)
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Rosas, F. E., Mediano, P. A. M., Timmermann, C. et al. · Biorxiv (2023)
Dursun, S. M., Kelly, J. R., Gillan, C. M. et al. · Frontiers in Psychiatry (2021)
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