Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
March 1, 2022
Deborah Rudin, John D McCorvy, Grant C Glatfelter et al.
18 citations
Derivatives of (2-aminopropyl)indole and (2-aminopropyl)benzofuran are new psychoactive substances with stimulant effects. This study characterized six isomers of the sulfur-based analog (2-aminopropyl)benzo[β]thiophene (APBT) in vitro and three isomers in vivo. APBTs inhibited monoamine reuptake and induced transporter-mediated substrate release, similar to MDMA, but did not stimulate locomotion in mice. Instead, they acted as full agonists at 5-HT2 receptor subtypes and induced head-twitch responses, indicating psychedelic-like activity. Replacing oxygen with sulfur enhanced serotonin transporter release potency and 5-HT2 receptor activity, shifting the profile toward psychedelic and entactogenic effects with minimal psychomotor stimulation, suggesting potential for drug-assisted psychotherapy.
Drug testing and analysis
January 1, 2017
Simon D Brandt, Pierce V Kavanagh, Geraldine Dowling et al.
16 citations
Many N,N-dialkylated tryptamines have psychoactive properties in humans, and the number of derivatives has grown across research areas. Some are used in medicinal products, others as recreational drugs, and sometimes these uses overlap. 5-Methoxy-N,N-diallyltryptamine (5-MeO-DALT) recently emerged as a new psychoactive substance, while 4-acetoxy-DALT and unsubstituted DALT have been detected only recently. This report describes the analytical characterization of 17 N,N-diallyltryptamines (DALTs), including 15 prepared via microwave-accelerated synthesis. The compounds were characterized using NMR, GC-MS, mass spectrometry, photodiode array detection, and GC solid-state infrared analysis. The resulting spectral data are provided to help researchers identify newly emerging substances and explore clinical and non-clinical uses.
Drug testing and analysis
January 1, 2018
Kelly B Texter, Rachel Waymach, Pierce V Kavanagh et al.
9 citations
When the new psychoactive substance bk-2C-B is heated in a simulated meth pipe, it breaks down into at least twelve different products, some of which could be inhaled. A closely related compound, bk-2C-I, produced similar breakdown products, plus two additional ones. The toxicity of these pyrolysis products is unknown, raising concerns about potential harm from smoking or inhaling these substances.
Drug testing and analysis
January 1, 2025
Pierce V Kavanagh, Folker Westphal, Benedikt Pulver et al.
8 citations
A novel LSD derivative, 1-dodecanoyl-LSD (1DD-LSD), was synthesized and tested in mice to see if it produces LSD-like effects. The compound induced a head-twitch response in C57BL/6J mice with a median effective dose of 2.17 mg/kg (3.60 μmol/kg). LSD was 27-fold more potent than 1DD-LSD under similar conditions. Other homologues, such as ALD-52 and 1-propanoyl-LSD, also showed considerably higher potency, suggesting that hydrolysis of the 1-dodecanoyl moiety may be less efficient in vivo. The increased lipophilicity of 1DD-LSD might cause it to be sequestered in fat, reducing enzymatic hydrolysis. Further studies are needed to assess its activity in humans and its potential as a long-acting prodrug for LSD.
Drug testing and analysis
March 1, 2023
Pierce V Kavanagh, Folker Westphal, Benedikt Pulver et al.
7 citations
A new lysergamide, 1cP-AL-LAD, was analyzed using chromatographic, mass spectrometric, and spectroscopic methods. A powdered sample from an online vendor contained 17 impurities, including AL-LAD and 1P-AL-LAD (confirmed by reference standards) and tentatively identified compounds such as 1-acetyl-AL-LAD and oxidation products of the N6-allyl group and ergoline ring. The substance was also found in blotter paper samples sold online for recreational use. These findings provide analytical data for researchers interested in lysergamide chemistry.
Drug testing and analysis
December 3, 2024
Simon D Brandt, Pierce V Kavanagh, Sarah Gare et al.
5 citations
1-(2-furoyl)-lysergic acid diethylamide (1F-LSD, SYN-L-005) is a novel analog of the recently detected recreational drug 1-(thiophene-2-carbonyl)-LSD (1T-LSD). Both substances are N1-acylated LSD derivatives that bind to the 5-HT2A receptor, the primary site of action for psychedelic drugs. In C57BL/6J mice, 1F-LSD and 1T-LSD induced the head-twitch response, a 5-HT2A-mediated behavior, and were hydrolyzed to LSD after administration. These findings indicate that both compounds exhibit LSD-like properties and likely act as prodrugs for LSD, releasing the active drug in the body.
Drug testing and analysis
February 1, 2024
Simon D Brandt, Pierce V Kavanagh, Folker Westphal et al.
5 citations
N-ethyl-N-isopropyllysergamide (EIPLA), an isomer of the psychedelic lysergamide ETH-LAD, shows LSD-like properties in preclinical tests. Mass spectrometry, chromatography, and NMR spectroscopy distinguished EIPLA from ETH-LAD by their structural features. Blotter extracts contained 96.9 ± 0.5 μg and 85.8 ± 2.8 μg of EIPLA base. In mice, EIPLA induced head-twitch responses (ED50 = 234.6 nmol/kg), about half the potency of LSD (ED50 = 132.8 nmol/kg), consistent with serotonergic psychedelic effects. Analytical data are provided to aid forensic and clinical identification.
Drug testing and analysis
April 1, 2025
Simon D Brandt, Pierce V Kavanagh, Sarah Gare et al.
4 citations
A newly developed LSD derivative, 1-hexanoyl-LSD (1H-LSD), was characterized analytically and tested in mice using the head-twitch response assay, a behavioral proxy for psychedelic activity. 1H-LSD induced head-twitch responses with a median effective dose of 192.4 μg/kg, making it roughly as potent as the known analog 1A-LSD (ALD-52) under similar conditions. Like other N1-acylated LSD derivatives, 1H-LSD is expected to be hydrolyzed to LSD in the body, acting as a prodrug. It is not yet known whether this compound has appeared on the recreational drug market or in research chemical supplies.
Toxicology
March 1, 2026
Lea Wagmann, Simon D Brandt, Pierce V Kavanagh et al.
Three recently identified psychedelics and entactogens—3-APBT, 5-APBT, and 6-APBT—activate serotonin 2 receptor subtypes and cause head-twitch responses in mice. Their toxicokinetics, metabolism, and monoamine oxidase (MAO) inhibition were characterized using liquid chromatography-high-resolution tandem mass spectrometry. Metabolites were identified in urine from male Wistar rats over 24 hours after oral administration (2 mg/kg) and in incubations with pooled human liver S9 fraction (25 µM). Hydroxylation, primarily catalyzed by CYP1A2, CYP2D6, CYP3A4, and CYP3A5, was the main phase I biotransformation; phase II reactions included N-acetylation, glucuronidation, and sulfation. All three isomers strongly inhibited MAO-A (IC50: 5-APBT 0.4 µM, 6-APBT 0.6 µM, 3-APBT 4 µM) but only weakly inhibited MAO-B (IC50 23-49 µM). Clinically relevant MAO-A inhibition and associated interaction risks cannot be excluded.