Return of the lysergamides. Part VII: Analytical and behavioural characterization of 1‐valeroyl‐ d ‐lysergic acid diethylamide (1V‐LSD)

Abstract The psychopharmacological properties of the psychedelic drug lysergic acid diethylamide (LSD) have attracted the interest of several generations of scientists. While further explorations involving novel LSD‐type compounds are needed to assess their potential as medicinal drugs, the emergence of novel derivatives as recreational drugs has also been observed. 1‐Valeroyl‐LSD (also known as 1‐valeryl‐LSD, 1‐pentanoyl‐LSD, 1V‐LSD, or “Valerie”) is a new N1‐acylated LSD derivative that recently appeared on the online market, and it could be viewed as a higher homolog of ALD‐52, 1P‐LSD, and 1B‐LSD. The present study included the analytical characterization and involved various methods of mass spectrometry (MS), gas and liquid chromatography (GC and LC), nuclear magnetic resonance (NMR) spectroscopy, GC–solid‐state infrared (GC‐sIR) analysis, and Raman spectroscopy. The in vivo activity of 1V‐LSD was assessed using the mouse head‐twitch response (HTR), a 5‐HT2A‐mediated head movement that serves as a behavioral proxy in rodents for human hallucinogenic effects. Similar to LSD and other psychedelic drugs, the HTR induced by 1V‐LSD was dose dependent, and the median effective dose for 1V‐LSD was 373 nmol/kg, which was about a third of the potency of LSD (ED50 = 132.8 nmol/kg). Lysergamides containing the N1‐substituent typically act as weak partial agonists at the 5‐HT2A receptor and are believed to serve as prodrugs for LSD. 1V‐LSD is also likely to be hydrolyzed to LSD and serve as a prodrug, but studies to assess the biotransformation and receptor pharmacology of 1V‐LSD should be performed to fully elucidate its mechanism of action.