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Historical overview
Published in G. Hussein Rassool, Alcohol and Drug Misuse, 2017
Synthetic drugs are created using man-made chemical compounds that mimic the effects of illicit drugs and are commonly divided into two categories: Cannabinoids such as “Spice” and “K2 (synthetic marijuana products); and stimulants such as bath salts. Most synthetic stimulants contain chemical compounds that mimic the effects of cocaine, LSD and methamphetamine. Similar drugs include MDMA (Ecstasy). Historically, Spice was first introduced for sale in London in 2004. Competitive brands of Spice entered the US market and became prevalent throughout the country by 2008 (www.drugfreeworld.org). However, the chemical compounds were created for experimental purposes decades ago. These chemical compounds include: CP 47,497, named after Charles Pfizer of Pfizer Pharmaceuticals, developed in the 1980’s for scientific research; HU-210 (100 to 800 times more potent than natural THC) from Hebrew University of Jerusalem (1988); and JWH-018 and others in the JWH series, created by Professor John W. Huffman of Clemson University (South Carolina) in 1995 (www.drugfreeworld.org). When the chemical compounds found in synthetic marijuana were banned in the US (2012), it is reported that “underground chemists then developed new experimental drugs, UR-144 and XLR11, that mimic the effects of marijuana, to replace those that had been banned. In 2013, UR-144 and XLR11 were made illegal, but by that time a new generation of synthetic marijuana had surfaced” (www.drugfreeworld.org). Bath salts (synthetic cathinones) as psychoactive substance refer to a white powder or crystalline substance that has no bathing or other cosmetic use. The substances were first synthesised in France in 1928 and 1929, researched for potential medical use and later used as antidepressants in the former Soviet Union in the 1930’s and 40’s (www.drugfreeworld.org). The khat-like cathinones substance which contains the active ingredients Cathinone, Methcathinone and Cathine, entered the Israeli drug scene as hagigat. The bath salts gained broader popularity among drug misusers and appeared on Internet drug forums. The bath salts were introduced in the US in the 1990’s. N-BOMe, also known as “N-Bomb” or “Smiles”, is a powerful synthetic hallucinogen, similar to LSD. N-bomb was discovered in 2003 by chemist Ralf Heim at the Free University of Berlin, Germany. It was derived from a group of drugs called the 2C family of phenethylamines (PEA) (www.drugfreeworld.org). It was in 2010 that the drug emerged as a common recreational drug.
Detection of altered methylation of MB-COMT promotor and DRD2 gene in cannabinoid or synthetic cannabinoid use disorder regarding gene variants and clinical parameters
Published in Journal of Addictive Diseases, 2021
Yasemin Oyaci, Hasan Mervan Aytac, Ozge Pasin, Pinar Cetinay Aydin, Sacide Pehlivan
The interview was started by collecting sociodemographic and clinical information. Afterward, based on the DSM-5 criteria, the patients’ diagnosis was confirmed with a positive urine test. In the toxicology laboratory of hospital for the determination of metabolites of various synthetic cannabinoids in urine; in-vitro pre-analytical tests; Immunalysis K2 Direct EIA Kit (JWH-018, JWH-073, AM-2201, UR-144 and their metabolites) and Immunalysis Synthetic Cannabinoids-3 Urine Enzyme Immunoassay Kit (AB-PINACA and its metabolites), and Immunalysis for the detection of cannabinoid metabolites THC Urine Enzyme Immunoassay Kit is used.
UR-144, synthetic cannabinoid receptor agonist, induced cardiomyoblast toxicity mechanism comprises cytoplasmic Ca2+ and DAPK1 related autophagy and necrosis
Published in Toxicology Mechanisms and Methods, 2023
Muzeyyen Akar, Merve Ercin, Tugce Boran, Selda Gezginci-Oktayoglu, Gül Özhan
The use of UR-144 [(1-pentyl-1H-indol-3-yl) (2,2,3,3-tetramethylcyclopropyl) methanone] (Figure 1), a cannabinoid receptor agonist, is becoming popular in drug-addiction all around the world (Wiley et al. 2013; Adamowicz et al. 2017). It is commonly smoked in combination with herbs or tobacco products and also used orally or inhaled after vapourizing. Although it is an agonist of both CB1 and CB2 receptors, UR-144 shows a higher affinity for CB2 receptors (Wiley et al. 2013). Like other synthetic cannabinoids (SCs), UR-144 exhibits activities that are similar to but less potent than Δ9-THC (delta-9-tetrahydro cannabinol). UR-144 has a potential for medicinal use as a pain killer because CB2 receptors play a role in pain perception (Mauler et al. 2002; Kaluke et al. 2014; WHO 2014). However, it has no approved therapeutic use (WHO 2014). Additionally, abusers of the drug may need to increase its dose due to their drug tolerance. The usage dose varies widely between 0.5 and 100 mg, depending on abuser’s experience (Adamowicz et al. 2013; WHO 2014; Adamowicz and Lechowicz 2015). UR-144, like other SCs, is metabolized rapidly and the parent compound is rarely found in the blood (Adamowicz et al. 2013; WHO 2014). In one study, blood concentrations were reported in the range of 1.6–54.6 nM in 39 cases in whom UR-144 was used alone or in combination with other SCs or herbs (Adamowicz et al. 2017). The exposure concentration of UR-144 may be higher than observed. The toxic effects induced by UR-144 are paranoia, anxiety, depression, hallucinations and attention disturbance, while symptoms of overdose include disorientation, nausea, blurry vision, loss of consciousness, etc. (Adamowicz et al. 2017). Abusers’ need to increase the dose may lead to toxic effects (Choi et al. 2013). Besides neurological symptoms, myocardial infarction, acute kidney injury and ischemic strokes have been reported after taking mixtures containing UR-144 and/or other SCs (AKI, XLR11) (Castaneto et al. 2014). Tachycardia, which is potentially life-threatening, was reported by Adamowicz et al. (2017) following the use of UR-144 alone or in combination with other SCs.