AM2201 and Substance-Related-Disorders

Topics: Animals; Behavior, Animal; Cannabinoids; Drug Tolerance; Humans; Hypothermia; Indoles; Mental Disorders; Naphthalenes; Seizures; Substance Withdrawal Syndrome; Substance-Related Disorders

High-resolution mass spectrometry and accurate mass measurement by liquid chromatography/quadrupole-time of flight mass spectrometry (LC/Q-TOFMS) was applied to postmortem plasma and urine specimens from an autopsy of a fatal case involving synthetic cannabinoid use, resulting in the detection of three synthetic cannabinoids: MAM-2201, AM-1220, and AM-2232. We searched for their metabolites existing in postmortem plasma or urine by LC/Q-TOFMS and were able to detect N-dealkylated metabolites, defluorinated and further oxidized metabolites of MAM-2201, and some hydroxylated metabolites. Postmortem plasma concentrations of the parent drugs, N-dealkylated metabolites, and fluorinated and further oxidized metabolites of MAM-2201 were measured, and quantitation results revealed site differences between heart and femoral postmortem plasma concentrations of parent drugs and some metabolites, suggesting postmortem redistribution of the synthetic cannabinoids and their metabolites. Quantitation results suggest that defluorination is a major metabolic pathway for MAM-2201, and N-dealkylation is a common but minor pathway for the naphthoylindole-type synthetic cannabinoids in human.

Topics: Cannabinoids; Chromatography, Liquid; Designer Drugs; Forensic Toxicology; Humans; Illicit Drugs; Indoles; Male; Mass Spectrometry; Naphthalenes; Postmortem Changes; Substance-Related Disorders; Young Adult

With respect to the continuous emergence of new synthetic cannabinoids on the market since 2008, evaluation of the metabolism of these compounds and the development of analytical methods for the detection of these drugs including their respective metabolites in biological fluids have become essential. Other than JWH-018 or JWH-073, AM-2201 is one of the frequently identified synthetic cannabinoids in Korea. Recently, in our laboratory, several JWH-018 metabolites have been detected in some urine samples obtained from subjects who were arrested for the possession of herbal mixtures containing only AM-2201 or from those who confessed AM-2201 abuse. In the present study, we identified major urinary metabolites of AM-2201 and several metabolites of JWH-018, i.e., N-5-hydroxylated and carboxylated metabolites from rats administered AM-2201 and found that the metabolic profile in rats was similar to those in human subjects in this study. Analytical results of the urine samples from suspects who had a considerable possibility of AM-2201 or JWH-018 intake were also compared to distinguish between AM-2201 and JWH-018 abuse. The presence of 6-indole hydroxylated metabolites of each drug and N-4-hydroxy metabolite of AM-2201 was found to contribute to the decisive differences in the metabolic patterns of the two drugs. In addition, the concentration ratio of the N-(5-hydroxypentyl) metabolite to the N-(4-hydroxypentyl) metabolite of JWH-018 may be used as a criterion to differentiate between AM-2201 and JWH-018 abuse.

Topics: Animals; Biotransformation; Chromatography, Liquid; Humans; Illicit Drugs; Indoles; Male; Mass Spectrometry; Naphthalenes; Predictive Value of Tests; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Substance Abuse Detection; Substance-Related Disorders

An increasing number of synthetic cannabinoids have become available on the black market in recent years, and health professionals have seen a corresponding increase in use of these compounds among patients with psychiatric disorders. Unfortunately, there is almost no research available in the literature on this topic, and what little exists is based on case reports of individuals without psychiatric disorders. Synthetic cannabinoids are functionally similar to, but structurally different from, delta-9-tetrahydrocannabinol, the active principle in cannabis, and are problematic for many reasons. The psychotropic action of synthetic cannabinoids in patients with schizophrenia is unpredictable, with very diverse clinical presentations. These drugs can be much more potent than delta-9-tetrahydrocannabinol, they are readily available and difficult to detect. The gold standard for identification of synthetic cannabinoids is gas chromatography with mass spectrometry, but even this is difficult because new formulations of these designer drugs are constantly emerging. In this manuscript, we provide an overview and discussion of synthetic cannabinoids and present four cases of patients with synthetic cannabinoid intoxication who were hospitalized in our intensive psychiatric unit at the time of intoxication. All patients had a history of schizophrenia and had been hospitalized several times previously. While hospitalized, they smoked an unknown substance brought in by a visitor, which was then confirmed using gas chromatography with mass spectrometry to be the synthetic cannabinoid AM-2201. Our patients experienced predominantly psychiatric adverse clinical effects. We observed the appearance of new psychotic phenomena, without exacerbation of their previously known psychotic symptoms, as well as the occurrence or marked worsening of mood and anxiety symptoms. Despite several similar reactions, and even though they ingested the same exact substance, the clinical picture differed markedly between individual patients. We assume that the acute effects of synthetic cannabinoids in patients with schizophrenia would be different from those in persons without psychotic disorders. The reasons for this difference could be the actual symptomatology of the presenting disorder, the impact of psychopharmacotherapy, individual patient differences and probably many, as yet unknown, factors. The long-term consequences of synthetic cannabinoid use on preexisting psychotic disorders

Topics: Adult; Chromatography, Gas; Hospitalization; Humans; Illicit Drugs; Indoles; Male; Mass Spectrometry; Naphthalenes; Psychotropic Drugs; Schizophrenia; Substance-Related Disorders

New designer drugs such as K2, Spice, and "bath salts" present a formidable challenge for law enforcement and public health officials. The following report summarizes a three-year study of 1320 law enforcement cases involving over 3000 products described as vegetable material, powders, capsules, tablets, blotter paper, or drug paraphernalia. All items were seized in Arkansas from January 2010 through December 2012 and submitted to the Arkansas State Crime Laboratory for analysis. The geographical distribution of these seizures co-localized in areas with higher population, colleges, and universities. Validated forensic testing procedures confirmed the presence of 26 synthetic cannabinoids, 12 designer stimulants, and 5 hallucinogenic-like drugs regulated by the Synthetic Drug Prevention Act of 2012 and other state statutes. Analysis of paraphernalia suggests that these drugs are commonly used concomitantly with other drugs of abuse including marijuana, MDMA, and methamphetamine. Exact designer drug compositions were unpredictable and often formulated with multiple agents, but overall, the synthetic cannabinoids were significantly more prevalent than all the other designer drugs detected. The synthetic cannabinoids JWH-018, AM2201, JWH-122, JWH-210, and XLR11 were most commonly detected in green vegetable material and powder products. The designer stimulants methylenedioxypyrovalerone (MDPV), 3,4-methylenedioxy-N-methylcathinone (methylone), and α-methylamino-valerophenone (pentedrone) were commonly detected in tablets, capsules, and powders. Hallucinogenic drugs were rarely detected, but generally found on blotter paper products. Emerging designer drug products remain a significant problem and continued surveillance is needed to protect public health.

Topics: Benzodioxoles; Cannabinoids; Capsules; Central Nervous System Stimulants; Designer Drugs; Dronabinol; Hallucinogens; Humans; Indoles; Methamphetamine; Methylamines; Molecular Structure; Naphthalenes; Paper; Pentanones; Powders; Pyrrolidines; Substance-Related Disorders; Synthetic Cathinone; Tablets

Since 2008, herbal mixtures with synthetic cannabinoid compounds have been sold as incense throughout the world. Although these new drugs are labeled as not for human consumption, these products are smoked for their cannabis-like effects. This study reports the structural and spectral elucidation of four cannabimimetic compounds seized in Belgium: (4-methoxyphenyl)-1-(pentyl-1H-indol-3-yl)methanone (RCS-4), 1-(5-fluoropentyl)-3-(1-naphtoyl)indole (AM-2201), 2-(2-chlorophenyl)-1-(1-pentylindol-3-yl)ethanone (JWH-203) and 4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210). Laboratory investigations were conducted by liquid chromatography (LC)-ultraviolet spectroscopy, high-resolution accurate mass detection and nuclear magnetic resonance (NMR) analysis. This combined analytical approach allowed the detection of illicit compounds for which reference materials were not available. To facilitate identification and to complete existing databases, ultraviolet spectra and NMR data of all seized products are presented. Additionally, LC-quadrupole time-of-flight data were recorded to provide absolute identification.

Topics: Cannabinoids; Chromatography, High Pressure Liquid; Forensic Sciences; Humans; Illicit Drugs; Indoles; Magnetic Resonance Spectroscopy; Molecular Structure; Naphthalenes; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Ultraviolet; Substance Abuse Detection; Substance-Related Disorders