Drug testing and analysis
January 1, 2014
Hamilton Morris, Jason Wallach
240 citations
More than 30 dissociative compounds have been used non-medically over the past 60 years, starting with PCP in the 1950s and later including ketamine and dextromethorphan. At least 14 PCP derivatives were sold illicitly from the 1960s to the 1990s. The Internet transformed the drug market, shifting from gray-market vendors to online research chemical suppliers. The first dissociative research chemical, 4-MeO-PCP, appeared in 2008, and the market now includes at least 12 dissociatives, nearly half previously unknown in scientific literature. Methoxetamine achieved widespread international use. This historical account presents the first complete portrait of the underground dissociative market, alongside legal, technological, and scientific developments driving its evolution.
Drug testing and analysis
January 1, 2012
Steven A Barker, Ethan H Mcilhenny, Rick Strassman
143 citations
Three indole alkaloids with varying psychedelic activity—DMT, bufotenine, and 5-MeO-DMT—have been reported as naturally occurring in humans. A critical review of 69 studies from 1955 to 2010 examined their detection in blood, urine, and cerebrospinal fluid. The review evaluates the methods and criteria used, highlighting strengths and weaknesses of past approaches. It notes shortcomings in existing data given recent findings and suggests future directions for research on these endogenous psychedelics.
Drug testing and analysis
January 1, 2014
Claudio Vidal Giné, Iván Fornís Espinosa, Mireia Ventura Vilamala
135 citations
New psychoactive substances (NPS) are increasingly used as adulterants in controlled drugs, a phenomenon that has received little attention. Analysis of 173 samples submitted to a drug checking service from 2009 to 2012 identified 24 different NPS—including phenethylamines, substituted cathinones, tryptamines, and methoxetamine—in products believed to be MDMA, amphetamine, ketamine, cocaine, mescaline, or methamphetamine. The most common NPS adulterant was 2C-B, followed by 4-FA. Sixty-nine distinct substance combinations were found: 20 involved a controlled drug mixed with an NPS, and 49 involved one or more NPS replacing the intended drug entirely. These combinations pose substantial risks to users, highlighting the need for better knowledge of their toxicity and the dangers of NPS entering illegal markets. Drug checking services and early-warning systems can help reduce harm.
Drug testing and analysis
January 1, 2012
Paulo César Ribeiro Barbosa, Suely Mizumoto, Michael P Bogenschutz et al.
112 citations
Ayahuasca, a psychedelic brew traditionally used by Amazonian peoples, has spread to urban areas worldwide, raising concerns about potential health risks. A review of 15 studies from the PubMed database examined the emotional, cognitive, and physical health effects of ayahuasca use after acute effects subsided. The accumulated data suggest that ayahuasca use is safe and may even be beneficial under certain conditions. However, methodological bias in the reviewed studies may have contributed to the preponderance of beneficial effects and the few adverse effects reported. The data do not yet allow definitive conclusions about ayahuasca's effects on mental and physical health, but some studies point toward beneficial outcomes.
Drug testing and analysis
January 1, 2016
Piotr Adamowicz, Joanna Gieroń, Dominika Gil et al.
87 citations
New psychoactive substances (NPS) appeared in 112 of 1,058 analyzed forensic cases from 2012–2014, with 75 cases in 2014 alone. The overall prevalence of NPS (15.1–17.6%) was similar to that of amphetamine alone (15.1–16.5%). Cathinones made up 88% of the NPS detected, most frequently 3-MMC, α-PVP, and pentedrone. In 35% of cases, a single NPS was the only drug found; two or more NPS appeared in 19% of cases; and most cases (65%) involved NPS alongside conventional drugs such as amphetamines, cannabinoids, cocaine, or benzodiazepines. NPS were often found in drivers' blood, posing a challenge for toxicologists due to limited data on their effects on psychomotor performance.
Drug testing and analysis
January 1, 2014
L A King
81 citations
By 2013, nearly 100 illicit phenethylamines had been found in the European Union. Of these, nine were submitted for risk assessment by the EMCDDA, and all except MBDB were recommended for EU-wide control. The most commonly reported new phenethylamine was 2C-B, though other 2C compounds were widespread. Recent years have seen a rapid rise of phenethylamines with bulky N-substituents, such as 25I-NBOMe, and the appearance of fused ring variants like benzofurans and indanylalkylamines. Thiophene bioisosteres of amphetamine and conformationally-restricted variants have also been detected in drug seizures.
Drug testing and analysis
January 1, 2014
Lucy Burns, Amanda Roxburgh, Allison Matthews et al.
78 citations
In 2013, 44% of a sample of 654 regular ecstasy users in Australia had used a new psychoactive substance (NPS) in the past six months. The most common NPS were the hallucinogens 2C-I (14%) and 2C-B (8%). Users of NPS were younger, used a wider variety of drugs more frequently, and were more likely to rate ecstasy purity as low compared to those who did not use NPS. NPS have become a regular part of Australia's recreational drug scene, and monitoring systems need to adapt to track this rapidly changing market.
Drug testing and analysis
August 1, 2013
Dariusz Zuba, Karolina Sekuła
61 citations
Three new hallucinogenic substances—25D-NBOMe, 25E-NBOMe, and 25G-NBOMe—were identified in blotter papers seized from the drug market. These are N-(2-methoxy)benzyl derivatives of the 2C-series of phenethylamine drugs. A range of analytical methods, including gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, infrared spectroscopy, and nuclear magnetic resonance, unequivocally identified the active components. The GC-MS spectra showed very similar dominant ions at m/z = 150, 121, and 91, with other ions analogous to those of the parent 2C compounds but at low intensities. Derivatization helped determine molecular masses, and exact masses and chemical formulas were confirmed by LC-QTOF-MS. Tandem mass spectrometry confirmed the N-(2-methoxy)benzyl derivative structures, and NMR provided final structural elucidation. FTIR spectroscopy corroborated compound identities.
Drug testing and analysis
January 1, 2018
Achim T Caspar, Jonas B Gaab, Julian A Michely et al.
33 citations
Three new psychoactive tryptamines—5-MeO-2-Me-DALT, 5-MeO-2-Me-ALCHT, and 5-MeO-2-Me-DIPT—are mainly broken down in the body through O-demethylation, hydroxylation, and N-dealkylation, followed by glucuronidation or sulfation. In rats given 20 mg/kg doses, 5-MeO-2-Me-DALT produced 24 phase I and 12 phase II metabolites, 5-MeO-2-Me-ALCHT produced 24 phase I and 14 phase II metabolites, and 5-MeO-2-Me-DIPT produced 20 phase I and 11 phase II metabolites. Human liver enzyme incubations suggest the same major metabolic pathways occur in humans. CYP1A2, CYP2C19, CYP2D6, and CYP3A4 catalyze hydroxylation; CYP2C19 and CYP2D6 catalyze O-demethylation; and CYP2C19, CYP2D6, and CYP3A4 catalyze N-dealkylation. Liquid chromatography-based urine screening detected intake of all three compounds after low doses (0.1–1 mg/kg), whereas gas chromatography-based screening did not.
Drug testing and analysis
January 1, 2022
Thomas Gicquel, Romain Pelletier, Camille Richeval et al.
32 citations
Thirteen metabolites of the dissociative drug 2-fluoro-deschloroketamine (2F-DCK) were produced in vitro using human liver microsomes and HepaRG liver cells. Seven additional metabolites, including three Phase II conjugates, were identified in post-mortem bile and urine from a fatal case. Molecular networking helped compare the two in vitro models, which proved complementary. The authors propose that nor-2F-DCK (mass-to-charge 208.1137) and a hydrogenated metabolite (224.1443) are reliable markers for detecting 2F-DCK use in high-resolution mass spectrometry libraries.
Drug testing and analysis
February 1, 2019
Lea Wagmann, Simon D Brandt, Alexander Stratford et al.
26 citations
Thirteen of 17 phenethylamine-derived designer drugs (12 from the 2C-series and five FLY analogs) inhibited monoamine oxidase A (MAO-A), and 11 inhibited monoamine oxidase B (MAO-B) in an in vitro assay using heterologously expressed enzymes and hydrophilic interaction liquid chromatography-high resolution tandem mass spectrometry. For the seven drugs where MAO-A IC50 values were determined, values ranged from 10 to 125 μM; for the nine drugs with MAO-B IC50 values, the range was 1.7 to 180 μM. Because clinical information on most test drugs is lacking, a pharmacological contribution of MAO inhibition cannot be excluded, and further studies are warranted.
Drug testing and analysis
October 1, 2017
Daniel Pasin, Adam Cawley, Sergei Bidny et al.
25 citations
Twelve 2C-X, six DOX, and fourteen 25X-NBOMe hallucinogenic phenethylamines, including two deuterated derivatives, were analyzed using UPLC-QTOF-MS with collision-induced dissociation at 10, 20, and 40 eV. Common neutral and radical losses (e.g., NH3, •CH6N, C2H7N, C2H9N) and characteristic product ions were identified for each class. Novel analogues can be detected by applying neutral loss filters and extracting these common product ions, enabling detection of rapidly changing new psychoactive substances without targeted screening.
Drug testing and analysis
July 1, 2013
Dariusz Zuba, Karolina Sekuła
24 citations
A new designer drug, 2,5-dimethoxy-3,4-dimethyl-β-phenethylamine (2C-G), was identified in a powder sample seized in Poland in 2011. Mass spectrometry, infrared spectroscopy, and nuclear magnetic resonance spectroscopy were used to characterize the substance. Distinctive features in the gas chromatography-electron impact-mass spectrometry spectrum, such as an intense peak at m/z = 178 and differing intensities of ions at m/z = 165 and 180, allowed it to be distinguished from the similar compound 2C-E. Differences in ion intensities in liquid chromatography-electrospray ionization/quadrupole time of flight mass spectrometry and a unique Fourier transform infrared spectrum with characteristic doublets at 993-1014 cm⁻¹ and 1099-1124 cm⁻¹ further aided identification. The analysis demonstrates that marketing analogues of controlled substances presents a significant analytical challenge, often requiring sophisticated methods for unequivocal identification.
Drug testing and analysis
June 1, 2021
Islam Amine Larabi, Fanny Zerizer, Alice Ameline et al.
23 citations
A new ketamine analogue, deschloro-N-ethyl-ketamine (O-PCE), involved in severe intoxications and deaths, was metabolically profiled for the first time. After incubating O-PCE with human liver microsomes and analyzing urine and hair from a 43-year-old male user using high-resolution mass spectrometry, 15 metabolites were identified. Nine metabolites detected in urine extended the detection window after O-PCE itself was no longer present. The five most abundant urinary markers were 2-en-PCA-N-Glu (34%), M3 (16%), O-PCA-N-Glu (15.4%), OH-O-PCE (15%), and OH-PCE (11.9%). In hair, nine metabolites appeared; OH-PCA dominated (78%) with a metabolite-to-parent-drug ratio of 6, making it the best marker for long-term monitoring of O-PCE exposure.
Drug testing and analysis
October 1, 2019
Lea Wagmann, Nora Hempel, Lilian H J Richter et al.
20 citations
Three new psychoactive substances of the 2C-FLY series—2C-E-FLY, 2C-EF-FLY, and 2C-T-7-FLY—were studied to determine how the body metabolizes them and how they can be detected in toxicological tests. Using rat urine and human liver S9 fractions analyzed by LC-HRMS/MS, 32 metabolites were identified. Main metabolic steps were hydroxylation and N-acetylation, catalyzed by CYP2D6, CYP3A4, FMO3, NAT1, and NAT2. Deamination by MAO-A and B was also observed. Polymorphisms or drug interactions may cause interindividual differences. Standard urine screening approaches using GC-MS, LC-MSn, and LC-HRMS/MS were suitable for detecting intake, but common metabolites of 2C-E-FLY and 2C-EF-FLY must be considered when interpreting results.
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
October 1, 2024
Jess L Algar, Douglas J Lawes, Adam J Carroll et al.
14 citations
Three samples brought to Australia's first fixed-site drug checking service, CanTEST, were expected to be 4F-MPH, MXE, and 3-MMC but did not match any known substances on-site. Further laboratory analysis using NMR and mass spectrometry identified them as three previously undescribed new psychoactive substances: 4F-α-PiHP, 4F-MBZP, and propylphenidine. The case illustrates how drug checking services can rapidly detect and characterize emerging compounds in the unregulated drug market, supporting harm reduction and public health monitoring.
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
June 1, 2015
John D Power, Pierce 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.
Drug testing and analysis
May 1, 2024
Rie Tanaka, Maiko Kawamura, Sakumi Mizutani et al.
11 citations
A paper-sheet product sold as containing the LSD analog 1D-LSD actually contained a different, previously unreported compound: 1-thiophenoyl LSD (1T-LSD). Using mass spectrometry and nuclear magnetic resonance spectroscopy, the compound was identified as having a thiophene-2-carbonyl group instead of the claimed 1,2-dimethylcyclobutane-carbonyl group. Each unit of the sheet contained 87–100 μg of 1T-LSD free base. The compound slowly converted to LSD in methanol-d4 during analysis. Its UV spectrum differed from other LSD analogs, and its fluorescence was much lower. The authors recommend continued monitoring of sheet products for new LSD analogs.
Drug testing and analysis
March 1, 2021
Rafael Lanaro, Sueli Moreira Mello, Kelly Francisco da Cunha et al.
10 citations
After consuming ayahuasca, alkaloids such as DMT and β-carbolines reach higher peak concentrations and overall exposure in saliva than in serum, while their mean residence time is 1.5 to 3 times longer in serum. A statistical model suggests that serum concentrations can be predicted from saliva concentrations, though individual variability is large. Saliva offers a fast, noninvasive way to detect these alkaloids and could aid in identifying recreational use of similar compounds that pose intoxication risks.
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
June 1, 2025
N Meert, J Eliaerts, F Van Durme et al.
8 citations
At a dance festival, 166 drug samples—90 tablets, 53 powders, 16 crystals, and 7 liquids—were tested on-site using Raman and Fourier transform-infrared (FT-IR) spectroscopy. Raman identified powders and crystals with high sensitivity (100% and 81%), but performed poorly on liquids (67%) and ecstasy-like tablets (41%). FT-IR achieved sensitivities above 95% across all forms. On-site MDMA doses in tablets ranged from 52 mg to 336 mg hydrochloride. Combining both techniques is recommended for rapid on-site drug identification, but optimized settings, in-house libraries, and trained operators are essential for accurate results.
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
August 1, 2024
Cui-Mei Liu, Zhen-Dong Hua, Wei Jia et al.
7 citations
Seventeen impurities characteristic of the ketamine manufacturing process were identified and characterized in 150 seized ketamine samples using ultra-high-performance liquid chromatography-quadrupole-time of flight (UHPLC-Q-TOF). Impurities were selected if present in over 10% of samples, contained at least one nitrogen, had unsaturation greater than 5, and remained stable in solvent for 48 hours. All 17 impurities shared a deschloroketamine (DCK) skeleton with additional chlorine, hydroxyl, methyl, cyclohexane, or o-chlorophenyl cyclopentyl ketone substituents. Their structures were tentatively elucidated based on the synthetic route and mass spectrometry fragmentation patterns. These impurities are routinely used for profiling seized ketamine samples to provide tactical intelligence for law enforcement.