Drug Testing and Analysis
August 24, 2020
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
5 citations
N-ethyl-N-cyclopropyl lysergamide (ECPLA) produces LSD-like behavioral effects in mice and may act as a hallucinogen in humans. ECPLA is an isomer of the recreational drug LSZ. Several analytical methods—mass spectrometry, gas and liquid chromatography, nuclear magnetic resonance spectroscopy, and GC condensed-phase infrared spectroscopy—can differentiate ECPLA from LSZ. Key mass spectral differences include ion abundances at m/z 196, 207/208, 98, and 41. Electrospray ionization spectra show lysergamide-related ions, and LSZ (but not ECPLA) produces product ions at m/z 267 and 98 under the conditions used. These data support forensic and clinical detection of ECPLA.
Drug Testing and Analysis
September 1, 2011
Simon D. Brandt
5 citations
This special issue presents a variety of techniques and topics in illicit drug research, ranging from classic drugs like cocaine to internet drugs and new psychoactive substances. Raman spectroscopy is reviewed for non-destructive analysis of street drugs, including detection on fibers, fingerprints, banknotes, and in body fluids, as well as for detecting cocaine concealed in rum bottles down to 6% w/v solutions. Proton magnetic resonance spectroscopy at 3 Tesla can detect cocaine in wine bottles at 5 mM levels. Synthetic cathinones and other online-accessible drugs like GHB are reviewed for clinical effects and harm reduction. Internet products often have misleading labels; six out of seven products analyzed showed incorrect labeling.
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.
UNC Libraries
October 29, 2020
Simon D. Brandt, Maria F. Sassano, David E. Nichols et al.
4 citations
A series of N-benzylated-5-methoxytryptamine analogues and N-benzylated analogues of 2,5-dimethoxy-4-iodophenethylamine (2C-I) were synthesized and tested. Most compounds showed highest affinity for the 5-HT2 family of serotonin receptors. Substitution at the para position of the benzyl group reduced affinity, while ortho or meta substitution enhanced it. Large lipophilic groups improved affinity but often reduced functional activity. Functional potency was measured at human 5-HT2A, 5-HT2B, and 5-HT2C receptors and rat 5-HT2A and 5-HT2C receptors using intracellular calcium mobilization. Several tryptamine congeners were very potent functionally (EC50 values from 7.6 to 63 nM) but were mostly partial agonists. In mouse head twitch tests, many compounds induced the behavior, which correlated significantly with functional potency at the rat 5-HT2A receptor.
Metabolites
May 8, 2024
Fabian Frankenfeld, Lea Wagmann, Anush Abelian et al.
3 citations
Five deschloroketamine derivatives—deschloro-N-cyclopropyl-ketamine, deschloro-N-ethyl-ketamine, deschloro-N-isopropyl-ketamine, deschloro-N-propyl-ketamine, and deschloroketamine—are primarily metabolized through N-dealkylation, hydroxylation, multiple oxidations, and combinations, plus glucuronidation and N-acetylation. In total, 29 phase I and 10 phase II metabolites were detected in rat urine after a 2 mg/kg body weight dose, using liquid chromatography high-resolution tandem mass spectrometry and gas chromatography-mass spectrometry. For the LC-HRMS/MS standard urine screening approach, compound-specific metabolites were identified and confirmed in pooled human liver microsomes for all derivatives except deschloro-N-cyclopropyl-ketamine. The GC-MS approach detected only non-specific acetylated N-dealkylation metabolites.
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.
bioRxiv : the preprint server for biology
April 11, 2024
Ana Sofia Alberto-Silva, Selina Hemmer, Hailey A. Bock et al.
preprint
Three new chemical variants of MDMA—ODMA, TDMA, and SeDMA—show similar activity at serotonin and dopamine transporters but reduced activity at serotonin 5-HT2A/2B/2C receptors, which may lower the risk of off-target side effects. They also differ from MDMA in how they are broken down by the liver, with fewer metabolic pathways and no phase II metabolites. The analogs interact more weakly with certain organic cation transporters. These findings suggest the new compounds could be promising therapeutic alternatives to MDMA for conditions like PTSD, though further research is needed to confirm whether they pose lower risks.
European Journal of Pharmacology
August 15, 2019
Jason Wallach, Tristan Colestock, Julià Agramunt et al.
Fluorolintane, a 1,2-diarylethylamine sold as a 'research chemical' for dissociative effects, was studied pharmacologically for the first time alongside five related isomers. In vitro binding showed fluorolintane has high affinity for NMDA receptors (Ki = 87.92 nM) and even higher affinities for dopamine transporters (DAT) in most cases. Functional experiments in rat hippocampal slices demonstrated that fluorolintane inhibits NMDA receptor-induced field excitatory postsynaptic potentials and blocks long-term potentiation, consistent with NMDA receptor antagonism. In rats, fluorolintane disrupted prepulse inhibition (a measure of sensorimotor gating) with a median effective dose of 13.3 mg/kg, supporting anecdotal reports of dissociative effects in humans.
Analytical and Bioanalytical Chemistry
July 19, 2019
Lea Wagmann, Lilian H. J. Richter, Tobias Kehl et al.
Nine LSD derivatives—ALD-52, 1P-LSD, 1B-LSD, ETH-LAD, 1P-ETH-LAD, AL-LAD, ECPLA, LSZ, and LSM-775—are metabolized in pooled human liver S9 fractions primarily through N-dealkylation and hydroxylation, mainly catalyzed by CYP1A2 and CYP3A4. ALD-52, 1P-LSD, and 1B-LSD undergo deacylation to LSD. Many metabolites are structurally identical, complicating differentiation in urinalysis. However, after administering expected recreational doses to rats, neither parent drugs nor metabolites were detectable in urine using standard screening approaches.
Handbook of experimental pharmacology
January 1, 2018
Torsten Passie, Simon D. Brandt
Scientists and therapists have a long tradition of self-experimenting with psychoactive substances, dating back to the mid-eighteenth century. Substances producing complex effects—such as altered space/time experience, ego dissolution, and heightened insights (e.g., hallucinogens, entactogens)—have been the focus of the vast majority of these self-experiments, while those producing simple effects like euphoria or emotional blunting (e.g., cocaine, opioids) are much rarer. Self-experimenters fall into two types: exploratory, seeking expanded awareness and insight, and compensatory, aiming to cope with psychiatric symptoms or personality deficits. Scientific limitations are clear compared to double-blind, randomized, placebo-controlled trials, and adverse effects include loss of objectivity, increased risk of addiction, isolation, and problematic group dynamics.
Handbook of experimental pharmacology
January 1, 2018
Jason Wallach, Simon D. Brandt
Beyond the well-studied dissociative drugs phencyclidine (PCP) and ketamine, hundreds of related compounds have been developed since the late 1950s, some through legitimate research and others originating from clandestine chemists. The internet in the 1990s enabled global collaboration on designing novel dissociative compounds with goals like improved duration, analgesia, and reduced toxicity. These creations, marketed as "research chemicals" or "legal highs," have entered wider distribution and sometimes reached academic labs for potential clinical applications. Two structurally distinct classes of dissociative new psychoactive substances (NPS) are the 1,2-diarylethylamines (e.g., diphenidine, fluorolintane) and β-keto-arylcyclohexylamines (e.g., methoxetamine, deschloroketamine). This chapter introduces these emerging NPS and their known pharmacology.
Handbook of experimental pharmacology
January 1, 2018
Jason Wallach, Simon D. Brandt
Phencyclidine (PCP), discovered in 1956, became the model dissociative drug and later a street drug, with about 14 analogs identified as such between the 1960s and 1990s. In the 2000s, the Internet enabled communities to explore new PCP analogs, some previously unknown in scientific literature. This chapter provides an introductory overview of recent PCP-derived new psychoactive substances (NPS) and their pharmacology. Because N-methyl-D-aspartate receptor (NMDAR) antagonism underlies the subjective effects of many dissociatives, data from other analogs not currently identified as NPS are also included.
Toxicology Letters
April 15, 2017
Lea Wagmann, Simon D. Brandt, Pierce V. Kavanagh et al.
Thirteen analogs of the psychoactive substance alpha-methyltryptamine (AMT) were tested for their ability to inhibit monoamine oxidase (MAO), an enzyme that breaks down neurotransmitters. All analogs inhibited MAO-A, with IC50 values ranging from 0.049 to 166 μM, and four also inhibited MAO-B (IC50 82–376 μM). 7-Me-AMT was the most potent MAO-A inhibitor, comparable to the known inhibitors harmine and harmaline, and acted competitively. Most analogs also inhibited MAO in human liver S9 fractions. These findings suggest that MAO inhibition by these compounds could contribute to dangerous serotonin- and adrenaline-related effects, especially when combined with other drugs that block monoamine reuptake.