OPEN Foundation

Day: 18 June 2019

Return of the lysergamides. Part V: Analytical and behavioural characterization of 1-butanoyl-d-lysergic acid diethylamide (1B-LSD).

Abstract

The psychedelic properties of lysergic acid diethylamide (LSD) have captured the imagination of researchers for many years and its rediscovery as an important research tool is evidenced by its clinical use within neuroscientific and therapeutic settings. At the same time, a number of novel LSD analogs have recently emerged as recreational drugs, which makes it necessary to study their analytical and pharmacological properties. One recent addition to this series of LSD analogs is 1-butanoyl-LSD (1B-LSD), a constitutional isomer of 1-propanoyl-6-ethyl-6-nor-lysergic acid diethylamide (1P-ETH-LAD), another LSD analog that was described previously. This study presents a comprehensive analytical characterization of 1B-LSD employing nuclear magnetic resonance spectroscopy (NMR), low- and high-resolution mass spectrometry platforms, gas- and liquid chromatography (GC and LC), and GC-condensed phase and attenuated total reflection infrared spectroscopy analyses. Analytical differentiation of 1B-LSD from 1P-ETH-LAD was straightforward. LSD and other serotonergic hallucinogens induce the head-twitch response (HTR) in rats and mice, which is believed to be mediated largely by 5-HT2A receptor activation. HTR studies were conducted in C57BL/6J mice to assess whether 1B-LSD has LSD-like behavioral effects. 1B-LSD produced a dose-dependent increase in HTR counts, acting with ~14% (ED50  = 976.7 nmol/kg) of the potency of LSD (ED50  = 132.8 nmol/kg). This finding suggests that the behavioral effects of 1B-LSD are reminiscent of LSD and other serotonergic hallucinogens. The possibility exists that 1B-LSD serves as a pro-drug for LSD. Further investigations are warranted to confirm whether 1B-LSD produces LSD-like psychoactive effects in humans.

Brandt, S. D., Kavanagh, P. V., Westphal, F., Stratford, A., Elliott, S. P., Dowling, G., … & Halberstadt, A. L. (2019). Return of the lysergamides. Part V: Analytical and behavioural characterization of 1‐butanoyl‐d‐lysergic acid diethylamide (1B‐LSD). Drug testing and analysis., https://doi.org/10.1002/dta.2613
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Interaction of Sex and Age on the Dissociative Effects of Ketamine Action in Young Healthy Participants.

Abstract

Ketamine is a drug that reduces depressive and elicits schizophrenia-like symptoms in humans. However, it is largely unexplored whether women and men differ with respect to ketamine-action and whether age contributes to drug-effects. In this study we assessed dissociative symptoms via the Clinician Administered Dissociative States Scale (CADSS) in a total of 69 healthy subjects aged between 18 and 30 years (early adulthood) after ketamine or placebo infusion. Dissociative symptoms were generally increased only in the ketamine group post-infusion. Specifically, within the ketamine group, men reported significantly more depersonalization and amnestic symptoms than women. Furthermore, with rising age only men were less affected overall with respect to dissociative symptoms. This suggests a sex-specific protective effect of higher age which may be due to delayed brain maturation in men compared to women. We conclude that it is crucial to include sex and age in studies of drug effects in general and of ketamine-action in specific to tailor more efficient psychiatric treatments. Clinical Trial Registration: EU Clinical Trials Register (EudraCT), trial number: 2010-023414-31.
Derntl, B., Hornung, J., Sen, Z. D., Colic, L., Li, M., & Walter, M. (2019). Interaction of sex and age on the dissociative effects of ketamine action in young healthy participants. Frontiers in neuroscience13, https://doi.org/10.3389/fnins.2019.00616
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