Analytical and behavioral characterization of 1-hexanoyl-LSD (1H-LSD).
Simon D Brandt, Pierce V Kavanagh, Sarah Gare, Alexander Stratford, Adam L Halberstadt
Drug testing and analysis April 1, 2025 DOI: 10.1002/dta.3767 via PubMed
Summary
AI-generated from the abstractA newly developed LSD derivative, 1-hexanoyl-LSD (1H-LSD), was characterized analytically and tested in mice using the head-twitch response assay, a behavioral proxy for psychedelic activity. 1H-LSD induced head-twitch responses with a median effective dose of 192.4 μg/kg, making it roughly as potent as the known analog 1A-LSD (ALD-52) under similar conditions. Like other N1-acylated LSD derivatives, 1H-LSD is expected to be hydrolyzed to LSD in the body, acting as a prodrug. It is not yet known whether this compound has appeared on the recreational drug market or in research chemical supplies.
Study at a glance
| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | C57BL/6J mice |
| Intervention | 1-hexanoyl-LSD (1H-LSD) |
| Dose | 192.4 μg/kg |
| Topics | LSD |
| Keywords | Psychedelics hallucinogens Acid research Head‐twitch response New psychoactive substances |
| Citations | 4 |
| Key finding | 1H-LSD induces the head-twitch response in mice with potency comparable to ALD-52 and is expected to act as a prodrug for LSD. |
Abstract
The development of lysergic acid diethylamide (LSD) derivatives and analogs continues to inform the design of novel receptor probes and potentially new medicines. On the other hand, a number of newly developed LSD derivatives have also emerged as recreational drugs, leading to reports of their detection in some countries. One position in the ergoline scaffold of LSD that is frequently targeted is the N1-position; numerous N1-alkylcarbonyl LSD derivatives have been reported where the acyl chain is attached to the indole nitrogen, for example, in the form of linear n-alkane substituents, which represent higher homologs of the prototypical 1-acetyl-N,N-diethyllysergamide (1A-LSD, ALD-52). In this study, 1-hexanoyl-LSD (1H-LSD, SYN-L-027), a novel N1-acyl LSD derivative, was characterized analytically using standard techniques, followed by evaluation of its in vivo behavioral effects using the mouse head-twitch response (HTR) assay in C57BL/6J mice. 1H-LSD induced the HTR, with a median effective dose (ED50) of 192.4 μg/kg (equivalent to 387 nmol/kg), making it roughly equipotent to ALD-52 when tested previously under similar conditions. Similar to other N1-acylated analogs, 1H-LSD is anticipated to by hydrolyzed to LSD in vivo and acts as a prodrug. It is currently unknown whether 1H-LSD has appeared as on the research chemical market or is being used recreationally.