Licit and illicit drugs
Jason Payne-James, Richard Jones in Simpson's Forensic Medicine, 2019
Multiple new drugs are increasingly becoming available as governments limit the availability and legality of so-called ‘legal highs’. For example, ‘Spice’ has recently become popular. It is sold mostly over the Internet and at ‘head shops’. Spice is the popular name for a molecule named JWH-018 (1-pentyl-3-[1-napthoyl]indole). It exerts many of the same effects as the cannabinoids but has a completely different structure. Although the structure of Spice is very different from THC, it nonetheless avidly binds at the same C1 and C2 receptor, at exactly the same sites where THC is active. The effects produced are said to be the same as smoking marijuana, but are believed to last much longer. The potential use of this compound as a transdermal pain reliever is under investigation, but if it ever does come to market there will, no doubt, be a thriving black-market trade.
Taser—Conducted Electrical Weapons
Darrell L. Ross, Gary M. Vilke in Guidelines for Investigating Officer-Involved Shootings, Arrest-Related Deaths, and Deaths in Custody, 2018
□ Test for the classical drugs (heroin, methamphetamine, MDMA, LSD, and cocaine). Also, test for THC as this is being increasingly linked to unexpected death (Bachs & Morland, 2001; Sattout & Nicol, 2009). Also, request testing for newer dangerous synthetics, such as K2/Spice, bath salts and JWH-018 (found in fake marijuana) (Angoa-Perez et al., 2011; Murray, Murphy, & Beuhler, 2012; Prosser & Nelson, 2011; Rosenbaum, Carreiro, & Babu, 2012; Ross, Watson, & Goldberger, 2011; Spiller, Ryan, Weston, & Jansen, 2011). (See Chronic Medical Information section.)
NPS
Ornella Corazza, Andres Roman-Urrestarazu in Handbook of Novel Psychoactive Substances, 2018
The growing number of online drug shops, the new trend of home production, the temporary legal status, and the relatively cheap price of these substances increased the availability of NPS. Therefore, the popularity of these substances is principally explained by practical or even economical aspects of their use, such as the temporary absence of legal risks; the low cost; their easy availability via the Internet (Cottencin, Rolland, & Karila, 2014); their attractive, multicoloured packaging and exotic brand names; or the fact that they are often not easily detectable in urine and blood samples (Fattore & Fratta, 2011). Presumed purity of NPS can also be mentioned as one of their main benefits for users. As an example, despite different physical characteristics of various synthetic cannabinoid products, definitely high purities (ranging between 75% and 100%) of JWH-018 and JWH-073 were found (Ginsburg, McMahon, Sanchez, & Javors, 2012), although it is also addressed that the more severe withdrawal syndrome of synthetic cannabinoids in comparison to cannabis could be due to the fact that these synthetic products may contain heterogeneous compounds, such as amphetamine-like substances (Nacca et al., 2013) or even synthetic opioids, like O-desmethyltramadol (Dresen et al., 2010). Pharmacokinetical characteristics of NPS also increase their reputation among the users. For instance, in case of cathinones, the high blood-brain barrier permeability of especially mephedrone and MDPV was proven in an in vitro model (Simmler, Rickli, Hoener, & Liechti, 2014), whereas increased reinforcer efficacy and abuse liability of methylone was found by employing intravenous self-administration and intracranial self-stimulation in rats (Watterson et al., 2012). Yet, research regarding NPS pharmacokinetics in humans is lacking.
Fatal intoxication with new synthetic cannabinoids AMB-FUBINACA and EMB-FUBINACA
Published in Clinical Toxicology, 2019
Piotr Adamowicz, Ewa Meissner, Marta Maślanka
Synthetic cannabinoids are currently the largest group of new psychoactive substances monitored by both the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) and United Nations Office on Drugs and Crime (UNODC) [1–3]. Seizures of these types of substances have dominated the global amount of new psychoactive substances seised [2]. The popularity of this group of compounds is supported by the number of many serious poisonings, including fatalities [1]. Synthetic cannabinoids represent a wide group of compounds with different chemical structures that all share the ability to affect the cannabinoid receptors (CB1 and CB2) in the body, mimicking the effects of tetrahydrocannabinol (THC), the main psychoactive component of cannabis [1]. JWH-018 was the first synthetic cannabinoid detected in smoking mixtures, in 2008 [1]. Since then, over 251 different synthetic cannabinoids have been reported to UNODC while almost 179 compounds from this group were notified to the EMCDDA by 2017 [2,3]. This upward trend is maintained because synthetic cannabinoids that become subjected to legal control are replaced by new uncontrolled substances.
Old and new synthetic cannabinoids: lessons from animal models
Published in Drug Metabolism Reviews, 2018
Mary Tresa Zanda, Liana Fattore
Two compounds of the naphthoylindoles family, JWH-018 and JHW-073, fully substitute and generalize for THC in trained mice (Brents et al. 2013; Gatch and Forster 2014; Marshell et al. 2014), rats (Järbe et al. 2011; Wiley et al. 2014) and rhesus monkeys (Ginsburg et al. 2012). A synergistic substitution effect of JWH-018 and JHW-073 for THC has also been reported when the two synthetic cannabinoid agonists are administered jointly (Brents et al. 2013). Other compounds of the JWH series, such as JWH-122, JWH-200, JWH-201, JWH-203, JWH-210, and JWH-250, fully substitute for THC (Gatch and Forster 2014, 2016; Wiley et al. 2014). However, the JWH-320 compound fails to substitute for THC, probably due to its low affinity for the CB1 cannabinoid receptor (Wiley et al. 2014). When the JWH-018 compound is used as training drug in drug discrimination procedures, it readily establishes a discriminative stimulus effect in rats (Wiley et al. 2014) and rhesus monkeys (Rodriguez and McMahon 2014) and is fully substituted by THC, WIN 55,212-2, and CP 55,940 (Rodriguez and McMahon 2014; Wiley et al. 2014). Other synthetic cannabinoid agonists of more recent generation, the indole-derivative compounds UR-144 and XLR-11, fully substitute for THC in a dose-dependent manner (Wiley et al. 2013). Likewise, compounds of the aminoalkylindole family, such as AM678, AM2201, AM2233, and AM5983, exhibit full substitution and generalization to THC and show higher potency when compared to THC (Järbe et al. 2011, 2016).
Acute side effects after consumption of the new synthetic cannabinoids AB-CHMINACA and MDMB-CHMICA
Published in Clinical Toxicology, 2018
Maren Hermanns-Clausen, Dieter Müller, Josephine Kithinji, Verena Angerer, Florian Franz, Florian Eyer, Hartmud Neurath, Gesine Liebetrau, Volker Auwärter
AB-CHMINACA is a full agonist with a high affinity (Ki = 0.519 nM) and potency (EC50 = 2.55 nM) at the CB1 receptor [7]. Most recently, the intrinsic activities of AB-CHMINACA and MDMB-CHMICA at the CB1 receptor were determined using a cAMP accumulation assay (CB1 receptor, DiscoverX). The results revealed that both substances also act as full agonists at the CB1 receptor. The half-maximal effective concentration (potency) of MDMB-CHMICA (EC50 = 0.142 nM) is not only higher compared to JWH-018 (EC50 = 1.132 nM), but even higher than that of AB-CHMINACA (EC50 = 0.278 nM) [8]. The natural cannabinoid THC was not measured in this assay. However, another author reported a 10-fold greater potency of JWH-018 (EC50 = 1.22 ± 0.29 nM) compared to THC (EC50=15.29 ± 4.52 nM) [9].
Related Knowledge Centers
- Anandamide
- Cannabinoid Receptor
- Endocannabinoid System
- Tetrahydrocannabinol
- Analgesic
- Agonist
- Binding Selectivity
- Synthetic Cannabinoids
- 2-Arachidonoylglycerol
- Jwh-073