Lysergamide or Lysergic acid amides are collectively known as Lysergamides and include a number of compounds with potent agonist or antagonist activity at various serotonin and dopamine receptors. Lysergic acid diethylamide (LSD) is a prototypical serotonergic psychedelic drug and the subject of many clinical investigations. In recent years, a range of lysergamides has emerged with the production of some being inspired by the existing scientific literature. Others, for example, various 1‐acyl substituted lysergamides, did not exist before their appearance as research chemicals. 1‐Cylopropanoyl‐LSD (1CP‐LSD) has recently emerged as a new addition to the group of lysergamide‐based designer drugs and is believed to be psychoactive in humans.
In this investigation, 1CP‐LSD was subjected to detailed analytical characterizations including various mass spectrometry (MS) platforms, gas and liquid chromatography, nuclear magnetic resonance spectroscopy, solid-phase, and GC condensed phase infrared spectroscopy. Analysis by GC–MS also revealed the detection of artificially induced degradation products. Incubation of 1CP‐LSD with human serum led to the formation of LSD, indicating that it may act as a prodrug for LSD in vivo, similar to other 1‐acyl substituted lysergamides. The analysis of blotters and pellets is also included. 1 CP‐LSD also induces the head‐twitch response (HTR) in C57BL/6 J mice, indicating that it produces an LSD‐like behavioural profile.
LSD and other lysergamide hallucinogens act as nonselective serotonin (5‐HT) receptor agonists. Although the characteristic effects of serotonergic hallucinogens are thought to be mediated by the 5‐HT2A receptor, there is evidence indicating that the 5‐HT1A receptor may also contribute to or modulate their effects. Interactions of LSM‐775 with 5‐HT1A and 5‐HT2 receptor subtypes were assessed using competitive binding and functional assays. Serotonergic hallucinogens induce the head twitch response (HTR) in rodents due to 5‐HT2A receptor activation. The HTR is widely used as a behavioural proxy in rodents for human hallucinogenic effects because it is one of the few behaviours that can reliably distinguish hallucinogenic and non‐hallucinogenic 5‐HT2A receptor agonists. HTR studies were conducted in C57BL/6J mice to determine whether LSM‐775 produces 5‐HT2A receptor activation and LSD‐like behavioural effects in vivo.