ACS Chemical Neuroscience
September 30, 2018
Julian Maier, Felix P. Mayer, Simon D. Brandt et al.
15 citations
Aminorex and its analogues are psychostimulants that interact with monoamine transporters, sharing pharmacological similarities with amphetamines and cocaine. Some of these substances, originally failed pharmaceuticals, have reemerged as new psychoactive substances (NPS) for recreational use. Consumption of certain analogues, such as 4-methylaminorex and 4,4'-dimethylaminorex, has been linked to adverse events including death. This review covers the historical background, pharmacodynamic and pharmacokinetic properties, and misuse of these drugs as adulterants. It highlights the dangers of the NPS market, where users often lack knowledge of the pharmacology, potency, or identity of active ingredients.
Drug Testing and Analysis
May 7, 2022
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
14 citations
The lysergamide 1P-AL-LAD is characterized and tested in vitro and in mice. In pooled human liver microsomes, 1P-AL-LAD converts to AL-LAD as the most abundant metabolite, supporting the idea that it acts as a prodrug. Fourteen metabolites are detected, including hydroxylation and deacylation products. In mice, 1P-AL-LAD produces a dose-dependent increase in head twitch response, a behavioral proxy for human hallucinogenic effects, with an inverted U-shaped dose-response curve. Its median effective dose is 491 nmol/kg, almost three times less potent than AL-LAD (174.9 nmol/kg). The prodrug mechanism likely explains its activity despite N1-substitution disrupting 5-HT2A receptor activation.
Drug Testing and Analysis
February 1, 2018
Tristan Colestock, Jason Wallach, Matt Mansi et al.
14 citations
A new dissociative anesthetic, 3-MeO-PCMo, a morpholine analogue of 3-MeO-PCP, was synthesized and characterized along with five related compounds. All six arylcyclohexylmorpholines were analyzed using chromatographic, mass spectrometric, and spectroscopic techniques, allowing differentiation of positional isomers. In vitro binding studies in rat forebrain preparations showed moderate affinity for the N-methyl-D-aspartate receptor (NMDAR), with 3-Me-PCMo having the highest affinity, followed by 3-MeO-PCMo. 3-MeO-PCMo had affinity comparable to ketamine and approximately 12-fold lower than PCP. These findings support anecdotal reports of dissociative effects from 3-MeO-PCMo in humans.
Drug Testing and Analysis
July 1, 2010
Simon D. Brandt, Sharon A. Moore, Sally Freeman et al.
14 citations
An impurity profile was established for a synthetic route to the hallucinogen N,N-dimethyltryptamine (DMT) using reductive amination of tryptamine with formaldehyde and reduction by sodium cyanoborohydride. Seven compounds were detected and quantified, including DMT and several byproducts. Replacing sodium cyanoborohydride with sodium borohydride almost exclusively produced tetrahydro-β-carboline instead of DMT. Detection limits ranged from 21.5 to 87.7 ng mL⁻¹, and quantification limits from 24.6 to 88.3 µg mL⁻¹, with linearity from 20.8 to 980 µg mL⁻¹. The method is useful for forensic and pharmaceutical analysis of DMT.
Drug Testing and Analysis
September 11, 2015
Jason Wallach, Tristan Colestock, Brian Cicali et al.
13 citations
Fifteen N-alkyl-arylcyclohexylamines, including compounds related to the dissociative substances 3-MeO-PCP, 3-MeO-PCE, and 3-MeO-PCPr, were synthesized and characterized. Analytical methods such as gas chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy were used. Positional isomers of methoxy-substituted arylcyclohexylamines were readily distinguishable under various analytical conditions. The work provides previously unreported analytical data to aid in identifying newly emerging research chemicals.
Drug Testing and Analysis
May 22, 2021
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
12 citations
Lysergic acid diethylamide (LSD) is a potent psychoactive substance of clinical interest, and its analogs, including N-methyl-N-isopropyl isomer (MIPLA), have appeared on the street market. This report describes analytical methods to differentiate MIPLA from LSD and the N-methyl-N-propyl isomer (LAMPA) under routine conditions. Gas chromatography-solid phase infrared spectroscopy was particularly helpful. GC-electron ionization-tandem mass spectrometry of the m/z 72 iminium ion distinguished the three isomers on mass spectral grounds alone. Derivatization with BSTFA improved GC separation. LC-Q-MS and in-source collision-induced dissociation differentiated MIPLA and LAMPA based on distinct m/z 239 ion ratios. An alternative LC-MS/MS method improved separation but LSD co-eluted with iso-LSD; comparing ion ratios at m/z 324.2 > 223.2 and 324.2 > 208.2 facilitated differentiation. Two blotters contained 180 and 186 μg MIPLA per blotter.
Drug Testing and Analysis
June 1, 2015
John D. Power, Pierce V. Kavanagh, John O'Brien et al.
12 citations
A substance called bk-2C-B, a cathinone analogue of the psychoactive phenethylamine 2C-B, has become available from online retailers. Its identity was confirmed through multiple analytical methods, including nuclear magnetic resonance spectroscopy, gas and liquid chromatography, and high-resolution mass spectrometry. The compound was also synthesized using the Delépine reaction. Gas chromatography-mass spectrometry showed potential for artificial formation of byproducts, but these were not seen with liquid chromatography. Analysis revealed the purchased material was a mixture of hydrochloride and hydrobromide salts, suggesting a specific synthetic route, and X-ray crystallography showed it exists as polymorphs.
Journal of chromatography. A
August 14, 2009
Cláudia P.B. Martins, Sally Freeman, John F. Alder et al.
11 citations
A purported two-step internet recipe for making the psychoactive compound DMT was tested and found to produce almost none. The second step, methylation of tryptamine, was analyzed with advanced mass spectrometry. Instead of DMT, the reaction yielded 47.4% 1-N-methyl-TMT, 21.0% TMT, 11.1% unreacted tryptamine, and a 0.5% trace of N-methyltryptamine. The work demonstrates that synthetic methods circulated online can be unreliable and produce largely unintended, non-psychoactive products.
Journal of Neurochemistry
September 1, 2024
Ana Sofia Alberto-Silva, Selina Hemmer, Hailey A. Bock et al.
10 citations
Three new chemical variants of MDMA—ODMA, TDMA, and SeDMA—show similar activity at serotonin, dopamine, and norepinephrine transporters but reduced activity at 5-HT2A/2B/2C receptors compared to MDMA. They also differ in liver metabolism, with N-demethylation as the only shared route and no phase II metabolites formed. TDMA showed faster clearance. The analogs interacted more weakly with organic cation transporters and plasma membrane monoamine transporter. These bioisosteres may offer therapeutic alternatives to MDMA with a reduced off-target profile, but further studies are needed to determine if they pose lower risks.
Microchemical Journal
March 20, 2013
Alain Gaujac, James L. Ford, Nicola M. Dempster et al.
10 citations
N,N-dimethyltryptamine (DMT) may exist in at least two polymorphic forms, explaining the wide variation in reported melting points (38–40 °C to 73–74 °C). Using X-ray powder diffraction and differential scanning calorimetry, including fast scan DSC, on DMT extracted from Mimosa tenuiflora bark or synthesized in the lab, two polymorphs were identified: Form I melts at 57–58 °C and Form II at 45–46 °C, with respective enthalpies of 91.9 ± 2.4 J g⁻¹ and 98.3 ± 2.8 J g⁻¹. Form II converts to Form I during standard DSC, but conversion is prevented at fast scanning rates (100 °C min⁻¹).
Drug Testing and Analysis
January 1, 2012
Simon D. Brandt, Ruchanok Tearavarich, Nicola M. Dempster et al.
10 citations
Thirteen new tryptamine derivatives were synthesized and analyzed to provide reference data for forensic and clinical identification. Using NMR and mass spectrometry, the compounds were characterized and distinguished from each other and from related substances. Key mass spectral fragments were identified, including an iminium ion and indole-related ions at specific mass-to-charge ratios. The work extends earlier research on similar compounds and supplies analytical standards that can help professionals identify these substances before they cause adverse health effects.
Drug Testing and Analysis
December 29, 2010
Ruchanok Tearavarich, Viwat Hahnvajanawong, Nicola M. Dempster et al.
10 citations
Twelve novel 5-ethoxy-N,N-dialkyl-tryptamines and their deuterated counterparts were synthesized using a microwave-accelerated reduction step that took 5 minutes in tetrahydrofuran at 150 °C. The resulting 24 tryptamines were characterized by nuclear magnetic resonance spectroscopy and gas chromatography ion trap mass spectrometry, revealing differential fragmentation of side-chain-related iminium ions. These compounds are intended as internal standards for bioanalytical and pharmacological assays, aiding identification of novel tryptamines from non-traditional sources, and are of immediate value in forensic, research, and public health contexts.
Forensic Science International
July 4, 2008
Simon D. Brandt, Cláudia P.B. Martins, Sally Freeman et al.
10 citations
DMT, a psychoactive compound, reacts with common laboratory solvents like dichloromethane (DCM) to form a quaternary ammonium salt, which can rearrange during analysis into products including 3-(2-chloroethyl)indole and 2-methyltetrahydro-beta-carboline. This study extends these findings to other halogenated solvents—dibromomethane and 1,2-dichloroethane—characterizing the resulting derivatives. The DCE derivative produced at least six rearrangement products. Using deuterated compounds helped clarify the rearrangement mechanisms. These solvent-derived marker molecules could help identify which solvents were used in the manufacture of controlled substances, a factor often overlooked because solvents are assumed inert.
Journal of Pharmaceutical and Biomedical Analysis
December 28, 2007
Simon D. Brandt, Cláudia P.B. Martins, Sally Freeman et al.
10 citations
DMT, a simple tryptamine with powerful psychoactive properties, reacts with dichloromethane during work-up or long-term storage, forming the quaternary ammonium salt N-chloromethyl-DMT chloride. Analysis of this side-product by gas chromatography ion trap mass spectrometry (GC-MS) yielded only degradation products, such as 3-(2-chloroethyl)indole and 2-methyltetrahydro-beta-carboline, while HPLC detected the original salt. Because GC-MS is standard for drug fingerprinting, the presence of these degradation products could lead to erroneous conclusions about the synthetic route of a DMT sample.
The Analyst
January 1, 2005
Simon D. Brandt, Sally Freeman, Ian A. Fleet et al.
10 citations
Twelve symmetrically and 13 asymmetrically N,N-disubstituted glyoxalylamide precursors and their corresponding tryptamine derivatives were characterized using gas chromatography low-pressure chemical ionization ion trap tandem mass spectrometry with methanol as the chemical ionization reagent. In tryptamines, formation of [CH2=N+R2R3] iminium ions after beta-cleavage dominates, while dissociation into [3-vinylindole]+ is a minor pathway compared to electrospray triple quadrupole tandem mass spectrometry, where that transition is distinctively important. This method also enables differentiation between most isomeric derivatives studied.
Drug Testing and Analysis
April 30, 2019
Michael Dybek, Jason Wallach, Pierce V. Kavanagh et al.
9 citations
Six possible racemic isomers of the research chemical fluorolintane (2-F-DPPy) were synthesized and characterized. The isomers differ by the position of a fluorine substituent on the phenyl or benzyl ring of the 1,2-diarylethylamine structure. Using mass spectrometry, chromatography, nuclear magnetic resonance spectroscopy, and infrared spectroscopy, each isomer was distinguishable. A tandem mass spectrometry method analyzing the [M + H – HF]+ species produced distinct product ions for all six substances, aiding identification of positional isomers that pose challenges for stakeholders confronting new psychoactive substances.
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
April 19, 2018
Gavin McLaughlin, Michael H. Baumann, Pierce V. Kavanagh et al.
8 citations
Two new psychoactive substances, 4-methylphenmetrazine (4-MPM) and 3-methylphenmetrazine (3-MPM), have appeared on the recreational drug market following the earlier emergence of 3-fluorophenmetrazine. Analytical characterization of vendor samples confirmed the presence of 4-MPM in two samples and 3-MPM in one sample. In vitro transporter assays using rat brain synaptosomes tested the isomers' ability to inhibit uptake or stimulate release of dopamine, norepinephrine, and serotonin. The findings suggest that 2-MPM and 3-MPM will exhibit stimulant properties similar to phenmetrazine, whereas 4-MPM may display entactogen properties more similar to MDMA. Combining test purchases, analytical characterization, targeted synthesis, and pharmacological evaluation provides an effective approach for generating data on emerging substances.
Drug Testing and Analysis
August 15, 2013
Leslie A. King, István Ujváry, Simon D. Brandt
8 citations
The term 'derivative' has a precise but context-dependent meaning in chemistry, yet it appears widely in drug legislation without clear definition. Many assume only first-order derivatives—substances made in one reaction step—are covered, but this excludes substances like 2-carbomethoxytropinone, convertible to cocaine in multiple steps, which courts have ruled as controlled. The US Drug Enforcement Administration successfully argued in 1986 that buprenorphine, requiring six or more steps from thebaine, is a derivative. This ambiguity leaves the legal status of substances like 2-bromo-LSD uncertain. The authors suggest that unless qualified, the term should be avoided in future legislation.
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.
Psychopharmacology
December 7, 2022
Adam L. Halberstadt, Dino Luethi, Marius C. Hoener et al.
7 citations
A series of 4-thio-substituted phenylalkylamines, including the psychedelic drugs 2C-T-2 and 2C-T-7, were tested in mice using the head twitch response (HTR), a behavioral proxy for human psychedelic effects. Adding an α-methyl group to the parent compound 2C-T increased potency fivefold, and extending the 4-methylthio group by one to three methylene units also increased potency. Fluorination of the 4-position alkylthio chain or a 4-allylthio substituent reduced activity, and bulky 4-benzylthio groups showed little or no effect. Binding studies confirmed nanomolar affinity for 5-HT2 receptor subtypes and partial agonism at 5-HT2A, supporting classification of these compounds as psychedelic drugs.
Drug Testing and Analysis
September 1, 2024
Verena Angerer, Yasmin Schmid, Florian Franz et al.
6 citations
In six healthy volunteers, the new psychoactive substance MDAI at 3.0 mg/kg produced subjective effects comparable to 125 mg of MDMA, including increased blood pressure, but did not raise heart rate or body temperature. MDAI increased cortisol and prolactin levels, appeared in serum about 20 minutes after ingestion, and remained detectable for at least 4 days in serum and 6 days in urine. The drug was well tolerated. Further research is needed to evaluate whether MDAI might have medicinal applications.
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.