Drug Testing and Analysis
July 1, 2014
Simon D. Brandt, Leslie A. King, Michael Evans‐brown
164 citations
The new drug phenomenon over the past decade has been driven by the commodification of a wide range of psychoactive substances not controlled under drug laws, sold openly as 'legal highs', 'bath salts', or 'research chemicals' by entrepreneurs and criminal groups, especially via the Internet. In Europe, the rate of appearance of new psychoactive substances (NPS) averaged one new substance every 5–6 days, with 81 detected in 2013, 74 in 2012, 49 in 2011, and 41 in 2010. The number of Internet shops selling these substances rose from 170 in 2010 to 693 in 2012 and 651 in 2013. Many substances were originally synthesized years ago, some as failed pharmaceuticals, and their re-discovery has fueled the market.
Drug Testing and Analysis
July 1, 2011
Leslie A. King, Andrew T. Kicman
99 citations
This special issue introduces new psychoactive substances (NPS), formerly called 'designer drugs' or 'legal highs', defined as narcotic or psychotropic drugs not scheduled under UN conventions but posing comparable public health threats. The article traces their evolution from 1980s fentanyl derivatives and MPTP-contaminated α-prodine causing Parkinson's disease, through phenethylamines like MDMA and hallucinogens, to piperazines, cathinones (e.g., mephedrone), synthetic cannabinoids ('Spice'), and diverse recent compounds. Over half of the approximately 170 substances reported to the EMCDDA since 1997 appeared after 2006. Manufacturing shifted from clandestine labs to legitimate chemical suppliers, with internet sales. The authors note that little is known about their harmful properties, and uncontrolled experimentation risks future public health crises.
Drug Testing and Analysis
November 4, 2013
Yan Ni Annie Soh, Simon Elliott
97 citations
Thirteen new psychoactive substances (NPS) were tested for stability in human blood and plasma stored at room temperature. Most remained stable for at least 21 days, but 4-MEC became undetectable in blood within 14 days and lost 54% in plasma, with a breakdown product (dihydro-4-MEC) also found in a real case sample. AMT produced several breakdown products that also appeared in vivo. The findings indicate that additional compounds observed in forensic casework are likely metabolites rather than instability products. This is the first published stability data for these emerging substances, and presumptive metabolites for 25C-NBOMe and AH-7921 are reported.
Drug Testing and Analysis
July 28, 2014
Jordi Riba, Ethan H. Mcilhenny, José Carlos Bouso et al.
96 citations
When N,N-dimethyltryptamine (DMT) is taken orally, it produces no psychedelic effects and no DMT appears in urine, because monoamine oxidase (MAO) breaks it down almost completely into indole-3-acetic acid (97% of recovered compounds). By contrast, smoking DMT yields full psychoactivity, with unmetabolized DMT and DMT-N-oxide rising to 10% and 28% of recovered compounds, while indole-3-acetic acid drops to 63%. An inverse relationship between the ratio of these metabolites and subjective effects indicates that smoking shifts metabolism from efficient MAO-dependent breakdown to less efficient CYP-dependent pathways, enabling psychoactivity.
Drug Testing and Analysis
April 19, 2012
Jordi Riba, Ethan H. Mcilhenny, Marta Valle et al.
91 citations
Ayahuasca, an Amazonian tea containing β-carboline alkaloids (harmine, harmaline, tetrahydroharmine) and the psychedelic DMT, is used worldwide, but its metabolism in humans had not been systematically studied. In 10 healthy men given freeze-dried ayahuasca (1.0 mg DMT/kg), less than 1% of DMT was excreted unchanged; about 50% was recovered as indole-3-acetic acid, 10% as DMT-N-oxide, and total DMT plus metabolites reached 68%. Harmala alkaloids were excreted as O-demethylated and conjugated metabolites, but recoveries varied from 9% to 65%. The findings indicate alternative metabolic routes for DMT beyond monoamine-oxidase and that O-demethylation plus conjugation is important but not the only pathway for harmala alkaloids.
Drug Testing and Analysis
October 12, 2015
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
79 citations
1-Propionyl-d-lysergic acid diethylamide hemitartrate (1P-LSD), a non-controlled derivative of LSD, was characterized and tested for LSD-like effects. Using chromatographic, mass spectrometric, infrared, and nuclear magnetic resonance methods, the compound was compared to LSD. In male C57BL/6J mice, 1P-LSD produced a dose-dependent increase in head-twitch response (HTR) counts, a behavioral marker of 5-HT2A receptor activation. 1P-LSD had about 38% of the potency of LSD (ED50 = 349.6 nmol/kg vs. 132.8 nmol/kg for LSD). Pretreatment with the selective 5-HT2A receptor antagonist M100907 abolished the HTR, confirming that the response was mediated by 5-HT2A receptor activation. These results indicate 1P-LSD produces LSD-like effects in mice, consistent with classification as a serotonergic hallucinogen, though human psychoactive effects remain unknown.
Drug Testing and Analysis
May 13, 2019
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
72 citations
1-Butanoyl-LSD (1B-LSD), a new analog of lysergic acid diethylamide (LSD), was fully characterized using multiple analytical techniques including NMR, mass spectrometry, and infrared spectroscopy, allowing clear differentiation from a similar compound, 1P-ETH-LAD. In behavioral tests with C57BL/6J mice, 1B-LSD produced a dose-dependent increase in head-twitch response, a marker of serotonergic hallucinogen activity, though with only about 14% of LSD's potency (ED50 = 976.7 nmol/kg vs. 132.8 nmol/kg for LSD). This suggests 1B-LSD has LSD-like behavioral effects and may act as a pro-drug for LSD, but further research is needed to confirm psychoactive effects in humans.
Drug Testing and Analysis
October 29, 2020
Klára Gotvaldová, Kateřina Hájková, Jan Borovička et al.
69 citations
Psilocybin, psilocin, baeocystin, norbaeocystin, and aeruginascin are tryptamines structurally similar to serotonin. Psilocybin and its active metabolite psilocin are known for psychoactive effects and occur in most Psilocybe fungi. Freshly cultivated Psilocybe cubensis fruit bodies were used to monitor stability under various storage and processing conditions. Mycelium and individual parts (caps, stipes, basidiospores) were examined via ultra-high-performance liquid chromatography-mass spectrometry. No tryptamines were detected in basidiospores; only psilocin was present at 0.47 wt.% in mycelium. Stipes contained about half the tryptamine alkaloids (0.52 wt.%) compared to caps (1.03 wt.%), but results were not statistically significant due to high variability. Highest degradation occurred in fresh mushrooms stored at -80°C; lowest decay in dried biomass stored in dark at room temperature.
Drug Testing and Analysis
June 22, 2017
Sarah M.r. Wille, Camille Richeval, M. Nachon‐phanithavong et al.
68 citations
Among drivers stopped in Belgium in 2015, 7% of blood samples and 11% of oral fluid samples contained new psychoactive substances (NPS), including diphenidine, ketamine, mephedrone, and synthetic cannabinoids. Additionally, 17% of blood samples contained an analgesic drug, 10% a benzodiazepine or hypnotic, and smaller proportions antidepressants, antipsychotics, antiepileptics, or methylphenidate. Poly-drug use combining NPS with licit drugs and drugs of abuse was common. The findings demonstrate that NPS are present in the predominantly young male driving-under-the-influence population and highlight the need for on-site detection methods and further research on combined drug effects on driving ability.
Drug Testing and Analysis
June 6, 2016
S. Brandt, P. Kavanagh, F. Westphal et al.
62 citations
Two new psychoactive substances, AL-LAD and LSZ, which are analogs of LSD, were analytically characterized using multiple techniques including NMR, mass spectrometry, and infrared analysis. In male mice, both compounds produced LSD-like behavioral responses in a head-twitch assay, with dose-dependent effects peaking at 200 µg/kg. LSZ was equipotent to LSD (ED50 = 114.2 nmol/kg vs. 132.8 nmol/kg), while AL-LAD was slightly less potent (ED50 = 174.9 nmol/kg). The direct translation of these potency comparisons to humans requires further study. Providing chemical and pharmacological data on emerging substances aids research communities focused on substance use and forensic identification.
Drug Testing and Analysis
May 10, 2017
S. Brandt, P. Kavanagh, F. Westphal et al.
44 citations
Two new lysergamides, ETH-LAD and 1P-ETH-LAD, were characterized using multiple analytical techniques including GC-MS, mass spectrometry, infrared analysis, HPLC, and NMR. 1P-ETH-LAD had not previously been described in scientific literature. When incubated with human serum at 37°C, 1P-ETH-LAD converted to ETH-LAD over time, suggesting it may act as a pro-drug. 1P-ETH-LAD remained detectable in serum after 24 hours. This work provides analytical data for clinicians and toxicologists who may encounter these substances on the new psychoactive substances market.
Drug Testing and Analysis
August 29, 2017
Torsten Passie, Udo Benzenhöfer
43 citations
From the 1940s to the 1960s, the United States military explored mescaline and related compounds such as MDA, MDMA, and MDE as potential truth drugs for interrogation and behavior manipulation, following earlier German tests with mescaline. After animal testing, some derivatives were given to patients at the New York State Psychiatric Institute. During tests in 1952–53, an unwitting patient died, a fact kept secret. Subsequent secret animal studies in 1953–54 identified several mescaline derivatives for further human testing. By 1955, military focus shifted to LSD, though interest in mescaline-like compounds persisted for their ability to alter mood and habit without disrupting cognition. Whether any were used operationally remains unclear but probable.
Drug Testing and Analysis
July 16, 2016
Andrea E. Steuer, Michael Poetzsch, Lorena Stock et al.
41 citations
A new microflow liquid chromatography tandem mass spectrometry method was developed to quantify LSD and its metabolites in human plasma, enabling detection limits of 0.01 ng/mL and separation within three minutes. In a controlled pharmacokinetic study, elimination half-lives of iso-LSD (median 12 h) and LSD metabolites (median 9, 7.4, 12, and 11 h for oxo-HO-LSD, HO-LSD, HO-LSD-gluc, and nor-LSD, respectively) exceeded that of LSD (median 4.2 h). However, screening for these metabolites to extend detection windows in plasma is not constructive because their concentrations are very low.
Drug Testing and Analysis
March 16, 2020
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
38 citations
1-Cylopropanoyl-LSD (1CP-LSD), a new lysergamide-based designer drug, was analyzed using multiple chemical and spectroscopic methods. Incubation with human serum converted 1CP-LSD into LSD, suggesting it may act as a prodrug for LSD in the body. In mice, 1CP-LSD induced a head-twitch response (HTR) with an ED50 of 430.0 nmol/kg, comparable to 1P-LSD (ED50 = 349.6 nmol/kg), indicating an LSD-like behavioral profile. The study includes analysis of blotters and pellets, and detected artificially induced degradation products during GC-MS analysis. Clinical studies are needed to determine its potency and effects in humans.
Drug Testing and Analysis
October 5, 2012
Simon Elliott, Simon D. Brandt, Sally Freeman et al.
36 citations
5-(2-Aminopropyl)indole (5-IT) and 3-(2-aminopropyl)indole (α-methyltryptamine, AMT) are isomeric substances that are difficult to differentiate under routine analytical conditions, especially without reference material. Subtle differences in mass spectral and UV conditions can facilitate their differentiation. Analyses included 1H and 13C NMR, GC-EI/CI ion trap MS, and several U/HPLC-DAD and HPLC-MS methods. AMT was detected in a number of fatal intoxications, and there is a potential risk of misidentification when dealing with both substances.
Drug Testing and Analysis
April 22, 2019
Lewis Couchman, Anca Frinculescu, Catarina Sobreira et al.
35 citations
MDMA (Ecstasy) tablets collected in the UK between 2001 and 2018 show increasing MDMA content over time, with median free-base content exceeding 100 mg for the first time in 2018. Analysis of 412 tablets revealed dramatic within-batch content variability, with differences up to 136 mg. Dissolution testing on 247 tablets showed that tablets can be categorized as fast-, intermediate-, or slow-releasing, but no tablet characteristics predicted dissolution classification, meaning users cannot know a tablet's release profile beforehand. Within-batch variation in dissolution rate was also observed. Rapid assessment of MDMA content alone does not account for variability in remaining tablets in a batch or dissolution profiles. High-content, slow-releasing tablets may cause delayed or prolonged toxicity, increasing risk of re-dosing if absorption is delayed.
Drug Testing and Analysis
May 11, 2012
Alain Gaujac, Sandro Navickiene, Mark I. Collins et al.
33 citations
Ayahuasca, a hallucinogenic beverage traditionally used by Amazonian indigenous communities, is gaining global popularity through syncretic religions like Santo Daime and União do Vegetal. Similarly, jurema wine, originating from indigenous cultures in northeastern Brazil, is now used in urban neo-shamanic rituals and religions such as Catimbó and Umbanda. Both drinks contain N,N-dimethyltryptamine, which requires co-administration of naturally occurring monoamine oxidase inhibitors, such as β-carboline derivatives, to induce psychoactive effects in humans. This review examines the cultural use of tryptamines and β-carbolines and describes recent analytical techniques for detecting these compounds in ayahuasca, its analogues, and the plants used in preparing these beverages.
Drug Testing and Analysis
February 28, 2012
Daniel Trachsel
32 citations
Psychedelic phenethylamines range from natural mescaline to synthetic amphetamine analogues. Fluorine, widely used in medicinal chemistry, can greatly alter the psychoactivity of these compounds. An overview of over 60 fluorinated phenethylamines shows that adding fluorine may either reduce or enhance effects. For example, fluoroescaline is almost inactive, while difluoroescaline retains activity and trifluoroescaline increases potency compared to escaline. Difluoromescaline and trifluoromescaline surpass mescaline in both potency and duration.
Drug Testing and Analysis
July 5, 2017
Katharina Elisabeth Grafinger, Marianne Hädener, Stefan König et al.
31 citations
The synthetic tryptamine 5-MeO-MiPT, a hallucinogenic drug recently abused in Germany and Switzerland, was identified in a case of intoxication involving a naked, agitated, and aggressive man. Metabolites were characterized in pooled human liver microsomes, blood, and urine using LC–HRMS/MS. Seven phase I metabolites were found in vitro; four in blood and seven in urine. The most abundant metabolites resulted from demethylation and hydroxylation. Blood concentration was 160 ng/mL; urine concentration was 3380 ng/mL. Cocaine, cocaethylene, methylphenidate, and ritalinic acid were also detected in urine. Four metabolites—5-MeO-NiPT, 5-OH-MiPT, 5-MeO-MiPT-N-oxide, and OH-5-MeO-MiPT—are recommended as biomarkers for detecting consumption.
Drug Testing and Analysis
February 17, 2016
Marie Mardal, Juliet Kinyua, Pedram Ramin et al.
31 citations
Wastewater-based epidemiology can track community drug use, but biomarkers are often diluted. Pooled urine and urinated soil from festivals were screened for illicit drug excretion products. Cocaine and ecstasy-like compounds were most frequent. A method was developed to quantify their excretion products. Hydroxymethoxymethamphetamine (HMMA), MDMA, MDA, HMMA sulfate, benzoylecgonine, and cocaethylene retained 85–102% of initial concentration after 8 hours, while cocaine and ecgonine methyl ester dropped to 74% and 67%, respectively. HMMA increased over 24 hours, likely from conjugate cleavage and MDMA biotransformation. HMMA is suggested as a stable analytical target for MDMA consumption in wastewater.
Drug Testing and Analysis
May 16, 2020
Christina Grumann, Kerstin Henkel, Simon D. Brandt et al.
23 citations
1P-LSD, a non-controlled alternative to LSD, acts as a prodrug that converts almost entirely into LSD in the human body. In two volunteers, oral and intravenous doses of 100 μg 1P-LSD were administered. After oral intake, only LSD was detected in serum and urine, with a terminal elimination half-life of about 6.4 hours. Intravenous 1P-LSD was detectable for only a few hours, while LSD persisted much longer. The bioavailability of LSD from oral 1P-LSD was nearly 100%. Subjective drug effects and altered states of consciousness scores were comparable to those from LSD, supporting the prodrug hypothesis. Oral administration produced higher 5D-ASC scores than intravenous.
Drug Testing and Analysis
August 30, 2016
Michael Collins, Christopher Donnelly, Shane Cameron et al.
21 citations
A red liquid seized by Australian authorities as a suspected MDMA precursor was identified as N-tert.-butoxycarbonyl-MDMA (t-BOC-MDMA), a derivative that can be converted to MDMA under acidic conditions. In simulated gastric juice, most t-BOC-MDMA converted to MDMA within 305 minutes, suggesting it could act as a pro-drug in the body. Similar t-BOC derivatives of methamphetamine, pseudoephedrine, and mephedrone were also prepared. The appearance of such derivatives on the drug market warrants monitoring.
Drug Testing and Analysis
August 9, 2012
Manuela Pellegrini, Maria Concetta Rotolo, Emilia Marchei et al.
21 citations
A liquid chromatography–tandem mass spectrometry method was developed to rapidly measure psilocybin and psilocin in Psilocybe sclerotia, known as magic truffles. After a simple methanol extraction, the alkaloids were separated on a reversed-phase column and detected using electrospray ionization tandem mass spectrometry. The method was linear over the calibration range with correlation coefficients above 0.99, detection limits of 0.3 µg per 100 mg, and quantification limits of 1 µg per 100 mg. Only psilocybin was found in the examined sclerotia, with concentrations ranging from 59.3 to 167.8 µg per 100 mg of fresh material.
Drug Testing and Analysis
November 27, 2021
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
19 citations
A new LSD derivative called 1-valeroyl-LSD (1V-LSD, or "Valerie") has appeared on the online market. It is a higher homolog of earlier derivatives like ALD-52, 1P-LSD, and 1B-LSD. The study analytically characterized 1V-LSD using mass spectrometry, chromatography, NMR, and Raman spectroscopy. In mice, 1V-LSD induced a head-twitch response, a behavioral proxy for human hallucinogenic effects, in a dose-dependent manner. Its median effective dose was 373 nmol/kg, about a third the potency of LSD (ED50 = 132.8 nmol/kg). 1V-LSD likely acts as a prodrug that is hydrolyzed to LSD, but further studies on its biotransformation and receptor pharmacology are needed.
Drug Testing and Analysis
July 5, 2016
Marcos Tascón, Fernando Benavente, Nora M. Vizioli et al.
18 citations
The β-carboline alkaloids of the harmala group (HAlks), found in plants like Peganum harmala (Syrian rue) and Banisteriopsis caapi, act as reversible monoamine oxidase type A inhibitors (MAOIs). Their levels in natural sources vary greatly, limiting clinical use and leading to recreational or ritual use, such as in Ayahuasca. This work presents a fast, simple, and robust method using capillary electrophoresis with UV detection to simultaneously quantify six common HAlks: harmine, harmaline, harmol, harmalol, harmane, and norharmane. The method was applied to analyze P. harmala seed infusion, detecting harmaline, harmine, and harmol. Validation across three instruments showed transferability and comparable performance.