title: Return of the lysergamides. Part I: Analytical and behavioural characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD).
abstract: 1-Propionyl-d-lysergic acid diethylamide hemitartrate (1P-LSD) has become available as a 'research chemical' in the form of blotters and powdered material. This non-controlled derivative of d-lysergic acid diethylamide (LSD) has previously not been described in the published literature despite being closely related to 1-acetyl-LSD (ALD-52), which was developed in the 1950s. This study describes the characterization of 1P-LSD in comparison with LSD using various chromatographic and mass spectrometric methods, infrared and nuclear magnetic resonance spectroscopy. An important feature common to LSD and other serotonergic hallucinogens is that they produce 5-HT2A -receptor activation and induce the head-twitch response (HTR) in rats and mice. In order to assess whether 1P-LSD displays LSD-like properties and activates the 5-HT2A receptor, male C57BL/6 J mice were injected with vehicle (saline) or 1P-LSD (0.025-0.8 mg/kg, IP) and HTR assessed for 30 min using magnetometer coil recordings. It was found that 1P-LSD produced a dose-dependent increase in HTR counts, and that it had ~38% (ED50  = 349.6 nmol/kg) of the potency of LSD (ED50  = 132.8 nmol/kg). Furthermore, HTR was abolished when 1P-LSD administration followed pretreatment with the selective 5-HT2A receptor antagonist M100907 (0.1 mg/kg, SC), which was consistent with the concept that the behavioural response was mediated by activation of the 5-HT2A receptor. These results indicate that 1P-LSD produces LSD-like effects in mice, consistent with its classification as a serotonergic hallucinogen. Nevertheless, the extent to which 1P-LSD might show psychoactive effects in humans similar to LSD remains to be investigated. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Brandt
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St. James Hospital, Dublin 8, Ireland.
authors.forename: Pierce V
authors.initials: PV
authors.lastname: Kavanagh
authors.affiliation: State Bureau of Criminal Investigation Schleswig-Holstein, Section Narcotics/Toxicology, Mühlenweg 166, D-24116, Kiel, Germany.
authors.forename: Folker
authors.initials: F
authors.lastname: Westphal
authors.affiliation: Synex Ltd, 483 Green Lanes, N13 4BS, London, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Stratford
authors.affiliation: ROAR Forensics, Malvern Hills Science Park, Geraldine Road, WR14 3SZ, UK.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Elliott
authors.affiliation: Department of Chemistry and Biochemistry, University of the Sciences, 600 South 43rd Street, Philadelphia, PA, 19104, USA.
authors.forename: Khoa
authors.initials: K
authors.lastname: Hoang
authors.affiliation: Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, 600 South 43rd Street, Philadelphia, PA, 19104, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Wallach
authors.affiliation: Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0804, USA.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Halberstadt
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D006213:Hallucinogens / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D008238:Lysergic Acid Diethylamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D006213:Hallucinogens; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D008238:Lysergic Acid Diethylamide
keywords: 5-HT2A receptor; LSD; lysergamides; new psychoactive substances; psychedelics