A Single Dose of LSD Does Not Alter Gene Expression of the Serotonin 2A Receptor Gene (HTR2A) or Early Growth Response Genes (EGR1-3) in Healthy Subjects
This double-blind, placebo-controlled crossover study (n=15) investigated whether a single dose of LSD (100 µg) alters gene expression in whole blood as a marker of tolerance. Results show no significant changes in the expression of the 5-HT2A receptor gene or early growth response genes (EGR1-3) at 1.5 or 24 hours post-administration.
Authors
- Matthias Liechti
- Stefan Borgwardt
- Patrick Dolder
Published
Abstract
Rationale
Renewed interest has been seen in the use of lysergic acid diethylamide (LSD) in psychiatric research and practice. The repeated use of LSD leads to tolerance that is believed to result from serotonin (5-HT) 5-HT2A receptor downregulation. In rats, daily LSD administration for 4 days decreased frontal cortex 5-HT2A receptor binding. Additionally, a single dose of LSD acutely increased expression of the early growth response genes EGR1 and EGR2 in rat and mouse brains through 5-HT2A receptor stimulation. No human data on the effects of LSD on gene expression has been reported. Therefore, we investigated the effects of single-dose LSD administration on the expression of the 5-HT2A receptor gene (HTR2A) and EGR1-3 genes.
Methods
mRNA expression levels were analyzed in whole blood as a peripheral biomarker in 15 healthy subjects before and 1.5 and 24 h after the administration of LSD (100 μg) and placebo in a randomized, double-blind, placebo-controlled, cross-over study.
Results
LSD did not alter the expression of the HTR2A or EGR1-3 genes 1.5 and 24 h after administration compared with placebo.
Conclusion
No changes were observed in the gene expression of LSD’s primary target receptor gene or genes that are implicated in its downstream effects. Remaining unclear is whether chronic LSD administration alters gene expression in humans.
Research Summary of 'A Single Dose of LSD Does Not Alter Gene Expression of the Serotonin 2A Receptor Gene (HTR2A) or Early Growth Response Genes (EGR1-3) in Healthy Subjects'
Introduction
LSD has regained interest for psychiatric research and clinical applications, yet several pharmacological effects remain incompletely understood. One notable phenomenon is the rapid development of tolerance to LSD's psychological and physiological effects with repeated dosing; early human and animal work implicates adaptations at the serotonin 5-HT2A receptor as a likely mechanism. Preclinical studies also report that acute LSD increases expression of immediate early genes such as EGR1 and EGR2 in rodent cortex via 5-HT2A receptor stimulation, and repeated dosing can reduce 5-HT2A receptor binding in frontal cortex. Liechti and colleagues set out to examine whether a single oral dose of LSD alters transcription of the 5-HT2A receptor gene (HTR2A) and early growth response genes (EGR1-3) in humans. Because direct measurement of brain gene expression in healthy people is not feasible, the investigators used peripheral whole blood mRNA as a cautious biomarker for central transcriptional responses. Their hypothesis was that LSD would acutely alter HTR2A expression and increase EGR1 and EGR2 expression in humans in a manner analogous to rodent findings.
Expert Research Summaries
Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.
Full Text PDF
Full Paper PDF
Pro members can view the original manuscript directly in the browser.
Study Details
- Study Typeindividual
- Journal
- Compounds
- Topic
- Authors
- APA Citation
Dolder, P. C., Grünblatt, E., Müller, F., Borgwardt, S. J., & Liechti, M. E. (2017). A Single Dose of LSD Does Not Alter Gene Expression of the Serotonin 2A Receptor Gene (HTR2A) or Early Growth Response Genes (EGR1-3) in Healthy Subjects. Frontiers in Pharmacology, 8. https://doi.org/10.3389/fphar.2017.00423
Related Papers
References (19)
Papers cited by this study that are also in Blossom
Carhart-Harris, R. L., Kaelen, M., Bolstridge, M. et al. · Psychological Medicine (2016)
Carhart-Harris, R. L., Muthukumaraswamy, S., Roseman, L. et al. · PNAS (2016)
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)
Gonza ´lez-Maeso, J., Weisstaub, N. V., Zhou, M. et al. · Neuron (2007)
Kraehenmann, R. ;., Pokorny, D. ;., Vollenweider, L. ;. et al. · Psychopharmacology (2017)
Lebedev, A. V., Kaelen, M., L€ Ovd En, M. et al. · Human Brain Mapping (2016)
Liechti, M. E. · Neuropsychopharmacology (2017)
Liechti, M. E., Dolder, P. C., Schmid, Y. · Psychopharmacology (2016)
Show all 19 referencesShow fewer
Nichols, D. E. · Pharmacological Reviews (2016)
Passie, T., Halpern, J. H., Stichtenoth, D. O. et al. · CNS Neuroscience and Therapeutics (2008)
Preller, K. H., Herdener, M., Pokorny, T. et al. · Current Biology (2017)
Rickli, A., Moning, O. D., Hoener, M. C. et al. · European Neuropsychopharmacology (2016)
Schmid, Y., Enzler, F., Gasser, P. et al. · Biological Psychiatry (2015)
Strajhar, P., Schmid, Y., Liakoni, E. et al. · Journal of Neuroendocrinology (2016)
Tagliazucchi, E., Roseman, L., Kaelen, M. et al. · Current Biology (2016)
Vizeli, P., Liechti, M. E. · Journal of Psychopharmacology (2017)
Wacker, D., Wang, S., Mccorvy, J. D. et al. · Cell (2017)
Cited By (4)
Papers in Blossom that reference this study
Agnorelli, C., Spriggs, M. J., Godfrey, K. et al. · Preprints (2024)
Schindler, E. A. D., Wallace, R. M., Sloshower, J. A. et al. · Frontiers in Pharmacology (2018)
Nichols, D. E. · ACS Chemical Neuroscience (2018)
Nichols, D. E., Grob, C. S. · Forensic Science International (2018)
Your Personal Research Library
Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.