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Analytical and behavioral characterization of 1-dodecanoyl-LSD (1DD-LSD).

Pierce V. Kavanagh, Folker Westphal, Benedikt Pulver, Simon Elliott, Alexander Stratford, Adam L. Halberstadt, Simon D. Brandt

Drug Testing and Analysis 2025 DOI: 10.1002/dta.3691 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Preclinical study Peer reviewed
Population C57BL/6J mice
Intervention 1-dodecanoyl-LSD (1DD-LSD)
Dose 2.17 mg/kg
Topics LSD
Keywords Head‐twitch response New psychoactive substances Psychedelics hallucinogens Psychedelic drugs Entheogens Pharmacology drug research Drug studies Pharmaceutical science LSD Derivatives Lysergamides LSD Analogs LSD Variants
Citations 8
Key points 1DD-LSD induced the head-twitch response in mice with a median effective dose of 2.17 mg/kg, but LSD was 27-fold more potent.

Abstract

1-Acetyl-N,N-diethyllysergamide (1A-LSD, ALD-52) was first synthesized in the 1950s and found to produce psychedelic effects similar to those of LSD. Evidence suggests that ALD-52 serves as a prodrug in vivo and hydrolysis to LSD is likely responsible for its activity. Extension of the N1-alkylcarbonyl chain gives rise to novel lysergamides, which spurred further investigations into their structure-activity relationships. At the same time, ALD-52 and numerous homologues have emerged as recreational drugs ("research chemicals") that are available from online vendors. In the present study, 1-dodecanoyl-LSD (1DD-LSD), a novel N1-acylated LSD derivative, was subjected to analytical characterization and was also tested in the mouse head-twitch response (HTR) assay to assess whether it produces LSD-like effects in vivo. When tested in C57BL/6J mice, 1DD-LSD induced the HTR with a median effective dose (ED50) of 2.17 mg/kg, which was equivalent to 3.60 μmol/kg. Under similar experimental conditions, LSD has 27-fold higher potency than 1DD-LSD in the HTR assay. Previous work has shown that other homologues such as ALD-52 and 1-propanoyl-LSD also have considerably higher potency than 1DD-LSD in mice, which suggests that hydrolysis of the 1-dodecanoyl moiety may be comparatively less efficient in vivo. Further investigations are warranted to determine whether the increased lipophilicity of 1DD-LSD causes it to be sequestered in fat, thereby reducing its exposure to enzymatic hydrolysis in plasma and tissues. Further clinical studies are also required to assess its activity in humans and to test the prediction that it could potentially serve as a long-acting prodrug for LSD.

Comparable studies

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Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission Male mice 2021 Multidisciplinary experimental study with in vivo electrophysiology, optogenetics, behavioral paradigms, molecular biology, and conditional knockout mice
A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. Mice and cultured rat cortical neurons 2023 Preclinical study

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