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
June 26, 2012
Torsten Passie, H. M. Emrich, Matthias Karst et al.
114 citations
A 19-year-old male with severe PTSD symptoms, including flashbacks, panic attacks, and self-mutilation, experienced dramatic symptom reduction after smoking cannabis resin. This review examines clinical and preclinical neurobiological evidence for cannabis's effects on PTSD. Cannabis may reduce the strength and emotional impact of traumatic memories through synergistic mechanisms, potentially aiding sleep, reducing anxiety, and lessening flashback involvement. Endocannabinoid signaling systems in stress-sensitive brain regions like the hypothalamus and amygdala suggest their role in regulating stress responses. Evidence increasingly indicates cannabinoids may play a role in fear extinction and have antidepressive effects. Further studies are needed to evaluate cannabinoids' therapeutic potential in PTSD.
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
June 5, 2017
Simon D. Brandt, Pierce V. Kavanagh, Brendan Twamley et al.
56 citations
Lysergic acid morpholide (LSM-775), a structural relative of LSD, appeared on the market for new psychoactive substances in 2013, but its potency and psychoactive effects in humans have been disputed. This investigation characterized a powdered sample using multiple analytical techniques and tested its receptor activity. LSM-775 acted as a nonselective agonist at 5-HT1A and 5-HT2A receptors. In head twitch studies with C57BL/6J mice, LSM-775 did not induce the head twitch response unless 5-HT1A receptors were blocked by the antagonist WAY-100,635 (1 mg/kg, subcutaneous). The findings suggest that activation of 5-HT1A receptors by LSM-775 masks its hallucinogen-like effects, consistent with reports that it produces only weak LSD-like effects in humans.
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
May 19, 2014
Simon D. Brandt, Michael H. Baumann, John S. Partilla et al.
37 citations
A new designer drug, para-methyl-4-methylaminorex (4,4'-DMAR), was linked to 26 deaths in Europe in 2013. Laboratory analysis of samples from online vendors identified the (±)-cis isomer in at least 18 cases. The drug acts as a potent releaser at dopamine, norepinephrine, and serotonin transporters, with EC50 values of 8.6 nM, 26.9 nM, and 18.5 nM respectively. Its potency at dopamine and norepinephrine transporters rivaled that of d-amphetamine and aminorex, but it was far more potent at the serotonin transporter. This broad activity predicts serious side effects including psychosis, agitation, hyperthermia, and cardiovascular stimulation, especially at high doses or with other stimulants.
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
April 15, 2015
Gavin McLaughlin, Noreen Morris, Pierce V. Kavanagh et al.
32 citations
Three powdered samples sold online as the 'research chemical' 2-methoxydiphenidine (2-MXP) were analytically characterized and compared with synthesized isomers. Gas chromatography, high-performance liquid chromatography, mass spectrometry, nuclear magnetic resonance spectroscopy, infrared spectroscopy, and thin layer chromatography all confirmed the samples were 2-MXP. The three positional isomers (2-, 3-, and 4-MXP) could be differentiated, notably by distinct stability differences observed during in-source collision-induced dissociation of the protonated molecule under HPLC selected-ion monitoring. Additionally, matrix assisted inlet ionization Orbitrap mass spectrometry detected the protonated molecule of 2-MXP directly from a tablet surface after adding 3-nitrobenzonitrile as matrix.
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
July 15, 2014
Jason Wallach, Pierce V. Kavanagh, Gavin McLaughlin et al.
26 citations
Diphenidine, a dissociative agent sold as a 'research chemical,' and its isomer 2,2-DEP can be distinguished using gas chromatography-mass spectrometry by their unique iminium ions. The study synthesized and characterized both compounds and their pyrrolidine analogues. Two vendor samples confirmed diphenidine. In rat hippocampal slices, diphenidine (30 μM) reduced NMDA-mediated electrical signals to a similar extent as ketamine (30 μM), indicating it acts on the same receptor. This suggests 1,2-diphenylethylamines are emerging alternatives to arylcyclohexylamine-type dissociatives like PCP and methoxetamine.