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Analytical and behavioral characterization of 1-hexanoyl-LSD (1H-LSD)
Simon D Brandt1, Pierce V Kavanagh2, Sarah Gare3
1School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.
Drug Testing and Analysis
|July 5, 2024
Summary
Researchers characterized 1-hexanoyl-LSD (1H-LSD), a novel lysergic acid diethylamide (LSD) derivative. 1H-LSD demonstrated similar potency to ALD-52 in a mouse head-twitch response assay, suggesting it acts as an LSD prodrug.
Area of Science:
- Neuroscience
- Pharmacology
- Medicinal Chemistry
Background:
- Lysergic acid diethylamide (LSD) derivatives are explored for therapeutic potential and receptor probing.
- Some novel LSD derivatives have emerged as recreational drugs, necessitating their detection and characterization.
- The N1-position of the ergoline scaffold in LSD is a common site for modification, leading to various N1-acyl derivatives like 1-acetyl-N,N-diethyllysergamide (1A-LSD, ALD-52).
Purpose of the Study:
- To analytically characterize a novel N1-acyl LSD derivative, 1-hexanoyl-LSD (1H-LSD).
- To evaluate the in vivo behavioral effects of 1H-LSD using the mouse head-twitch response (HTR) assay.
- To compare the potency of 1H-LSD with existing LSD analogs like ALD-52.
Main Methods:
- Analytical characterization of 1H-LSD using standard laboratory techniques.
- In vivo assessment of 1H-LSD's behavioral effects in C57BL/6J mice via the head-twitch response (HTR) assay.
- Determination of the median effective dose (ED50) for 1H-LSD in the HTR assay.
Main Results:
- 1H-LSD was successfully characterized analytically.
- 1H-LSD induced the head-twitch response (HTR) in mice.
- The median effective dose (ED50) of 1H-LSD was determined to be 192.4 μg/kg (387 nmol/kg), indicating approximate equipotency to ALD-52.
Conclusions:
- 1H-LSD functions as a prodrug, likely hydrolyzed to LSD in vivo, similar to other N1-acylated analogs.
- The study provides valuable data on the pharmacological profile of 1H-LSD.
- Further investigation is needed to determine if 1H-LSD has entered the research chemical market or is being used recreationally.
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