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.

Keywords: 5-HT2A receptor; LSD; lysergamides; new psychoactive substances; psychedelics.

FIGURE 1

Chemical structures of lysergic acid diethylamide (LSD) and various 1-acyl analogs that emerged as research chemicals

FIGURE 2

Electron ionization mass spectrum of 1CP-LSD

FIGURE 3

Proposed fragmentation pathways for 1CP-LSD following electron ionization

FIGURE 3

Proposed fragmentation pathways for 1CP-LSD following electron ionization

FIGURE 4

ATR-FTIR of 1CP-LSD hemitartrate. Top: Entire scan range. Bottom: Partial scan range

FIGURE 5

Electrospray ionization (ESI) quadrupole-time-of-flight tandem mass spectrum (top) and ESI single quadrupole mass spectrum of 1CP-LSD involving in-source collision-induced-dissociation (bottom). The ion observed at m/z 208.0819 appeared to be a mixture of two ions detected at m/z 208.0764 and m/z 208.0974 (Supporting Information.)

FIGURE 6

Proposed formation of product ions following ESI-QTOF-MS/MS analysis

FIGURE 6

Proposed formation of product ions following ESI-QTOF-MS/MS analysis

FIGURE 7

(A) Dose-dependent increase in head twitch response counts after administration of 1CP-LSD (*P < 0.001, significant difference vs. vehicle control (Tukey’s test)). (B) after administration of 1 and 3 mg/kg 1CP-LSD, the maximal response occurred during the 10–12 min time block [Colour figure can be viewed at wileyonlinelibrary.com]