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
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
January 1, 2012
Steven A. Barker, Ethan H. Mcilhenny, Rick J. 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
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
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
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
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
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
January 1, 2014
Lucy Burns, Amanda Roxburgh, Allison J 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
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
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
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.