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Return of the lysergamides. Part I: Analytical and behavioural characterization of 1‐propionyl‐d‐lysergic acid diethylamide (1P‐LSD)

Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal, Alexander Stratford, Simon Elliott, Khoa Hoang, Jason Wallach, Adam L. Halberstadt

Drug Testing and Analysis October 12, 2015 DOI: 10.1002/dta.1884 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Male C57BL/6J mice
Dose 0.025–0.8 mg/kg IP
Duration 30 minutes
Measures head-twitch response (HTR) counts
Topics LSD Psilocybin Serotonin
Keywords Hallucinogen Pharmacology Antagonist Receptor
Citations 79
Key findings 1P-LSD produces dose-dependent, 5-HT2A receptor-mediated head-twitch responses in mice with about 38% of the potency of LSD.

Abstract

1‐Propionyl‐ d ‐lysergic acid diethylamide hemitartrate (1P‐LSD) has become available as a ‘research chemical’ in the form of blotters and powdered material. This non‐controlled derivative of d ‐lysergic acid diethylamide (LSD) has previously not been described in the published literature despite being closely related to 1‐acetyl‐LSD (ALD‐52), which was developed in the 1950s. This study describes the characterization of 1P‐LSD in comparison with LSD using various chromatographic and mass spectrometric methods, infrared and nuclear magnetic resonance spectroscopy. An important feature common to LSD and other serotonergic hallucinogens is that they produce 5‐HT 2A ‐receptor activation and induce the head‐twitch response (HTR) in rats and mice. In order to assess whether 1P‐LSD displays LSD‐like properties and activates the 5‐HT 2A receptor, male C57BL/6 J mice were injected with vehicle (saline) or 1P‐LSD (0.025–0.8 mg/kg, IP) and HTR assessed for 30 min using magnetometer coil recordings. It was found that 1P‐LSD produced a dose‐dependent increase in HTR counts, and that it had ~38% (ED 50 = 349.6 nmol/kg) of the potency of LSD (ED 50 = 132.8 nmol/kg). Furthermore, HTR was abolished when 1P‐LSD administration followed pretreatment with the selective 5‐HT 2A receptor antagonist M100907 (0.1 mg/kg, SC), which was consistent with the concept that the behavioural response was mediated by activation of the 5‐HT 2A receptor. These results indicate that 1P‐LSD produces LSD‐like effects in mice, consistent with its classification as a serotonergic hallucinogen. Nevertheless, the extent to which 1P‐LSD might show psychoactive effects in humans similar to LSD remains to be investigated. Copyright © 2015 John Wiley & Sons, Ltd.

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Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex Human embryonic kidney 293 cells stably expressing 5-HT2ARs; wild-type and 5-HT2AR... 2003 Experimental study
Evidence for a central 5‐hydroxytryptamine receptor stimulation by lysergic acid diethylamide Rats 1968 Experimental study
Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats 2020 Preclinical study
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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