Analytical and Pharmacological Characterization of 1-(Furan-2-Carbonyl)-LSD (1F-LSD) and Comparison With 1-(Thiophene-2-Carbonyl)-LSD (1T-LSD).
Simon D. Brandt, Pierce V. Kavanagh, Sarah Gare, Simon Elliott, Alexander Stratford, Adam L. Halberstadt
Drug Testing and Analysis December 3, 2024 DOI: 10.1002/dta.3829 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | C57BL/6J mice |
| Interventions | 1F-LSD 1T-LSD |
| Topics | LSD |
| Keywords | LSD Research Prodrugs Psychopharmacology Head‐twitch response New psychoactive substances Psychedelics |
| Citations | 5 |
| Key points | Both 1F-LSD and 1T-LSD induce the head-twitch response in mice and are hydrolyzed to LSD in vivo, suggesting they act as prodrugs for LSD. |
Abstract
The classical psychedelic drug (+)-lysergic acid diethylamide (LSD) continues to attract considerable multidisciplinary interest, and over the last eight decades, many derivatives and analogs of LSD have been synthesized. One site on the ergoline scaffold of LSD that has been frequently modified is the N1-position, with the N1-acylated LSD derivative 1-acetyl-LSD (1A-LSD, ALD-52) being one of the earliest examples. In more recent years, several other alkylcarbonyl- and cycloalkylcarbonyl-substituted LSD derivatives have been evaluated, including several distributed as research chemicals. Although N1-substitution is detrimental for the activity of LSD at the 5-HT2A receptor (the primary site of action of psychedelic drugs), N1-acylated LSD derivatives are rapidly hydrolyzed in vivo and are believed to act as prodrugs for LSD. Recently, 1-(thiophene-2-carbonyl)-LSD (1T-LSD, SYN-L-021) was detected as a new recreational drug, signaling a move towards N1-acyl groups with an aromatic character. The present study was conducted to investigate the analytical profile and pharmacology of 1-(2-furoyl)-lysergic acid diethylamide (1F-LSD, SYN-L-005), a novel analog of 1T-LSD. The binding of 1F-LSD to the 5-HT2A receptor and other monoamine sites was assessed using radioligand binding. Furthermore, the in vivo activities of 1F-LSD and 1T-LSD were assessed in C57BL/6 J mice by comparing their biotransformation to LSD and effects on the head-twitch response (HTR), a 5-HT2A-mediated behavior. Both 1F-LSD and 1T-LSD induced the HTR in mice and were hydrolyzed to LSD after in vivo administration, indicating that both substances exhibit LSD-like properties and may serve as prodrugs for LSD.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 5
- Identification of two lysergic acid diethylamide analogs, 1-(3-(trimethylsilyl) propionyl) lysergic acid diethylamide (1S-LSD) and 1-(2-thienoyl)-6-allyl-nor-d-lysergic acid diethylamide (1T-AL-LAD), in paper sheet products distributed on the internet. Forensic Toxicology April 3, 2025
- In vitro metabolic fate of 1-[3-(trimethylsilyl)propanoyl] lysergic acid diethylamide (1S-LSD), a silicon-containing LSD analog. Forensic Toxicology July 29, 2025
- Identification and Analysis of Lysergic Acid Diethylamide Analogs, 4‐Benzoyl‐ N,N ‐Diethyl‐7‐Methyl‐4,6,6a,7,8,9‐Hexahydroindolo[4,3‐ fg ]quinoline‐9‐Carboxamide (1Bz‐LSD) and N , N ‐Diethyl‐7‐Methyl‐4‐(4‐(Trimethylsilyl)Benzoyl)‐4,6,6a,7,8,9‐Hexahydroindolo[4,3‐ fg ]quinoline‐9‐Carboxamide (1‐TMSBz‐LSD), in tablet or paper sheet products available online in Japan Drug Testing and Analysis February 18, 2026
- In Vitro Metabolism of 1‐Benzoyl‐Lysergic Acid Diethylamide (1Bz‐LSD) and Identification of a Deethylated Metabolite (1Bz‐LAE) Using a Synthesized Reference Standard Drug Testing and Analysis February 17, 2026
- Synthesis and Analytical Characterization of 1-(1,2-Dimethylcyclobutane-1-Carbonyl)-Lysergic Acid Diethylamide (1D-LSD) and Differentiation From 1-(Thiophene-2-Carbonyl)-LSD (1T-LSD). Drug Testing and Analysis August 27, 2026
Cites 19
- Structural Features for Functional Selectivity at Serotonin Receptors Science March 21, 2013
- D‐Lysergic acid diethylamide (LSD): A review of its present status Clinical Pharmacology & Therapeutics March 1, 1965
- Return of the lysergamides. Part I: Analytical and behavioural characterization of 1‐propionyl‐d‐lysergic acid diethylamide (1P‐LSD) Drug Testing and Analysis October 12, 2015
- Return of the lysergamides. Part V: Analytical and behavioural characterization of 1‐butanoyl‐d‐lysergic acid diethylamide (1B‐LSD) Drug Testing and Analysis May 13, 2019
- 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 Testing and Analysis June 6, 2016
and 14 more in the library