Return of the lysergamides. Part VI: Analytical and behavioural characterization of 1‐cyclopropanoyl‐d‐lysergic acid diethylamide (1CP‐LSD)

Abstract

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. 1CP‐LSD also induces the head‐twitch response (HTR) in C57BL/6 J mice, indicating that it produces an LSD‐like behavioural profile. 1CP‐LSD induced the HTR with an ED50 = 430.0 nmol/kg which was comparable to 1P‐LSD (ED50 = 349.6 nmol/kg) investigated previously. Clinical studies are required to determine the potency and profile of the effects produced by 1CP‐LSD in humans.

Analytical profile of N‐ethyl‐N‐cyclopropyl lysergamide (ECPLA), an isomer of lysergic acid 2,4‐dimethylazetidide (LSZ)

“…ESI‐QTOF‐MS/MS and ESI single quadrupole mass spectra subjected to in‐source collision‐induced dissociation are shown in Figure 3; proposed product ions involving high‐resolution measurements are summarized in the Supporting Information based on the principles discussed in previous reports on related lysergamides 8–13 . A visual comparison of mass spectral data (Figure 3) revealed that the product ions formed were comparable to the ions observed during LSZ analysis, 9 although some variations were noted in the relative abundance of some of the product ions.…”

“…The electron ionization (EI) mass spectrum of ECPLA is depicted in Figure 2B) which was not detected to that extent in related lysergamides investigated previously under the conditions used. [8][9][10][11][12][13] Whilst the relative abundance of the ion was around 15% for LSZ, (Figure 3) revealed that the product ions formed were comparable to the ions observed during LSZ analysis, 9 although some variations were noted in the relative abundance of some of the product ions. For example, ions typically observed here and other related lysergamides [8][9][10][11][12][13] included ions at m/z 251, 223, 208, 197, 180, and 140.…”

“…The electron ionization (EI) mass spectrum of ECPLA is depicted in Figure 2A. Proposed fragmentation pathways are shown as Supporting Information, based on previous investigations with a range of other lysergamides 8–13 . Several fragment clusters that are commonly seen in the EI mass spectra of lysergamides (including ECPLA and LSZ) were observed, such as m/z 150–155, m/z 177–182, m/z 191–197, m/z 205–208, and m/z 219–224.…”

“…Although LSD has been a popular recreational drug since the 1960s, several other lysergamides have appeared in recent years. Most of those LSD analogs were known in the chemical and patent literature prior to their appearance as recreational drugs, but few appear to be true “designer drugs” with no existing scientific history 8–13 . ECPLA is not currently available as a recreational drug and has so far not been identified in medical or legal investigations, but the dissemination of key analytical data for ECPLA is justified as a proactive step, given the popularity of other novel LSD analogs.…”

“…Most of those LSD analogs were known in the chemical and patent literature prior to their appearance as recreational drugs, but few appear to be true "designer drugs" with no existing scientific history. [8][9][10][11][12][13] ECPLA is not currently available as a recreational drug and has so far not been identified in medical or legal investigations, but the dissemination of key analytical data for ECPLA is justified as a proactive step, given the popularity of other novel LSD analogs. The availability of analytical data for ECPLA will be useful for future forensic and clinical investigations.…”