Return of the lysergamides. Part II: Analytical and behavioural characterization of N⁶‐allyl‐6‐norlysergic acid diethylamide (AL‐LAD) and (2’S,4’S)‐lysergic acid 2,4‐dimethylazetidide (LSZ)

Abstract

Lysergic N,N-diethylamide (LSD) is perhaps one of the most intriguing psychoactive substances known and numerous analogs have been explored to a varying extent in previous decades. In 2013, N6-allyl-6-norlysergic acid diethylamide (AL-LAD) and (2’S,4’S)-lysergic acid 2,4-dimethylazetidide (LSZ) have appeared on the ‘research chemicals’ / new psychoactive substances (NPS) market in both powdered and blotter form. This study reports the analytical characterization of powdered AL-LAD and LSZ tartrate samples and their semi-quantitative determination on blotter paper. Included in this study was the use of nuclear magnetic resonance spectroscopy, gas chromatography mass spectrometry (MS), low and high-resolution electrospray MS(/MS), high performance liquid chromatography diode array detection and GC solid-state infrared analysis. One feature shared by serotonergic psychedelics, such as LSD, is the ability to mediate behavioral responses via activation of 5-HT2A receptors. Both AL-LAD and LSZ displayed LSD-like responses in male C57BL/6J mice when employing the head-twitch response (HTR) assay. AL-LAD and LSZ produced nearly identical inverted-U-shaped dose-dependent effects, with the maximal responses occurring at 200 µg/kg. Analysis of the dose-responses by nonlinear regression confirmed that LSZ (ED50 = 114.2 nmol/kg) was equipotent to LSD (ED50 = 132.8 nmol/kg) in mice, whereas AL-LAD was slightly less potent (ED50 = 174.9 nmol/kg). The extent to which a comparison in potency can be translated directly to humans requires further investigation. Availability of both chemical and pharmacological data obtained from NPS as they appear on the market provides important data to research communities that are interested in various aspects related substance use and forensic identification.

Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM‐775)

“…Figure provides the solid‐state infrared (IR) spectrum of the main LSM‐775 isomer II following elution from the GC column. A key feature that differentiated LSM‐775 from the lysergamides reported previously was detected at 1115.6 cm −1 , which may reflect the C‐O stretch correlated with the morpholine ring.…”

“…Ergoline‐related fragments ions and fragment clusters that have also been observed with other lysergamides (e.g. m/z 151– m/z 154 or m/z 178– m/z 181) were also detected (Supporting Information). Figure provides the solid‐state infrared (IR) spectrum of the main LSM‐775 isomer II following elution from the GC column.…”

“…As shown in the insert of Figure A, analysis by GC–MS revealed the detection of a second, minor peak that exhibited a similar mass spectrum, thus, indicating the potential presence of a diastereomer. Whether the presence of the extra peak was artificially induced by GC conditions, as reported previously for lysergic acid 2,4‐dimethylazetidide (LSZ) or whether it reflected a contaminant present in the powdered sample could not be established unambiguously. However, as shown below, a second peak was also detected under HPLC single quadrupole MS conditions (HPLC‐Q‐MS) using single ion monitoring (SIM), which suggested that the diastereomer may have been present in the sample.…”

“…The EI mass spectrum associated with the major GC peak (Figure B, isomer II) reflected the identity of the correctly configured LSM‐775. Suggested EI‐MS fragmentation pathways for LSM‐775 have been provided as Supporting Information, which followed similar principles discussed previously for other lysergamides, such as 1P–LSD, AL‐LAD, LSZ, ETH‐LAD, and 1P–ETH‐LAD . Fragments associated with LSM‐775 specifically included m/z 337 (highly abundant molecular ion), m/z 294 and m/z 279.…”

Genie in a blotter: A comparative study of LSD and LSD analogues' effects and user profile

“…LSD analogues and LSD share the same lysergic backbone. However, they present slight variations in their chemical structure, such as AL‐LAD's modification at the N6 position (Brandt et al, ). These lysergide derivatives act as an agonist of the 5‐HT2A receptor (Brandt et al, ), generally considered the mediator of hallucinogenic effects behaviourally and subjectively (Geyer & Vollenweider, ).…”