1. Academic Validation
  2. 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)

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)

  • Drug Test Anal. 2017 Jan;9(1):38-50. doi: 10.1002/dta.1985.
Simon D Brandt 1 Pierce V Kavanagh 2 Folker Westphal 3 Simon P Elliott 4 Jason Wallach 5 Tristan Colestock 6 Timothy E Burrow 7 Stephen J Chapman 8 Alexander Stratford 9 David E Nichols 10 Adam L Halberstadt 11
Affiliations

Affiliations

  • 1 School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
  • 2 Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St. James Hospital, Dublin 8, Ireland.
  • 3 State Bureau of Criminal Investigation Schleswig-Holstein, Section Narcotics/Toxicology, Mühlenweg 166, D-24116, Kiel, Germany.
  • 4 ROAR Forensics, Malvern Hills Science Park, Geraldine Road, WR14 3SZ, UK.
  • 5 Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, 19104, USA.
  • 6 Department of Chemistry and Biochemistry, University of the Sciences, 600 South 43rd Street, Philadelphia, PA, 19104, USA.
  • 7 Department of Chemistry, University of Toronto, St. George Street, Toronto, ON, M5S 3H6, Canada.
  • 8 Isomer Design, 4103-210 Victoria Street, Toronto, ON, M5B 2R3, Canada.
  • 9 Synex Ltd, 67-68 Hatton Garden, N13 4BS, London, UK.
  • 10 Division of Chemical Biology and Medicinal Chemistry, University of North Carolina, Genetic Medicine Building 120 Mason Farm Road, Chapel Hill, NC, 27599, USA.
  • 11 Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0804, USA.
Abstract

Lysergic acid N,N-diethylamide (LSD) is perhaps one of the most intriguing psychoactive substances known and numerous analogs have been explored to varying extents in previous decades. In 2013, N6 -allyl-6-norlysergic acid diethylamide (AL-LAD) and (2'S,4'S)-lysergic acid 2,4-dimethylazetidide (LSZ) 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 (NMR) spectroscopy, gas chromatography-mass spectrometry (GC-MS), low and high mass accuracy 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 behavioural responses via activation of 5-HT2A receptors. Both AL-LAD and LSZ displayed LSD-like responses in male C57BL/6 J 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. Chemical and pharmacological data obtained from NPS may assist research communities that are interested in various aspects related to substance use and forensic identification. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords

5-HT2A receptors; LSD; lysergamides; new psychoactive substances; psychedelics.

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