JWH-018

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JWH-018

JWH-018 is an analytical reference material categorized as a synthetic cannabinoid.1 It has been found in Spice/K2-type herbal blends and may have neurotoxic properties. JWH-018 is regulated as a Schedule I compound in the United States. This product is intended for research and forensic applications.
JWH-018
WARNING This product is not for human or veterinary use.

JWH-018 is a synthetic cannabinoid which has been increasingly used by adolescents and adults, and is known to cause severe multi-organ failure. However, little is known about the complications and toxicological effects of JWH-018 on reproduction system. Therefore, the aim of the present study is to investigate the effects of JWH-018 on testis and spermatogenesis. Thirty CD-1 male rats were distributed into six groups, control group (C1 and C2), ethanol group (E1 and E2), and JWH-018 group (JWH1 and JWH2), which were administered 0.9% NaCl, %100 ethanol, and JWH-018 (0.3 mg/kg) respectively for 9 d. We euthanized C1, E1, and JWH1 group mice at day 2 and C2, E2, and JWH2 group mice at 45 d after the last injection to evaluate the acute testis damage and potential recovery of spermatogenesis. The histopathology of seminiferous epithelium was evaluated and organ weight, sperm concentration and motility, membrane integrity, and serum testosterone levels were statistically analyzed. In JWH1, seminiferous tubule degeneration, partial germ cell depletion disorganized seminiferous epitheliums were seen. We also observed significantly decreased sperm concentration, sperm motility, intact membrane, and testosterone levels in JWH1 group compared to other groups. Forty-five days after the JWH-018 treatment, sperm concentration, motility, and testosterone level were increased, suggesting that testis and spermatogenesis can recover. We concluded that the use of JWH-018 may adversely affect male reproductive potential and testis histopathology.

JWH-018 is a synthetic cannabinoid found in several versions of the herbal mixture “Spice.” Illicit use of this Spice cannabinoid centers on its psychoactive effects which mimic those of Δ9-THC in cannabis. While considerably more potent than similar amounts of cannabis, JWH-018 also presents significant challenges for detection by typical Δ9-THC testing assays.
In July, 2009, the US Drug Enforcement Agency (DEA) listed JWH-018 on its Drugs and Chemicals of Concern list. In addition to reported seizures of Spice in Ohio and Florida, several states have passed legislative action restricting the sale or possession of JWH-018 including Alabama, Arkansas, Georgia, Kansas, Kentucky, North Dakota, and Tennessee.

Natural cannabinoids and their synthetic substitutes are the most widely used recreational drugs. Numerous clinical cases describe acute toxic symptoms and neurological consequences following inhalation of the mixture of synthetic cannabinoids known as “Spice.” Here we report that an intraperitoneal administration of the natural cannabinoid Δ9-tetrahydrocannabinol (10 mg/kg), one of the main constituent of marijuana, or the synthetic cannabinoid JWH-018 (2.5 mg/kg) triggered electrographic seizures in mice, recorded by electroencephalography and videography. Administration of JWH-018 (1.5, 2.5 and 5 mg/kg) increased seizure spikes dose-dependently. Pretreatment of mice with AM-251 (5 mg/kg), a cannabinoid receptor 1-selective antagonist, completely prevented cannabinoid-induced seizures. These data imply that abuse of cannabinoids can be dangerous and represents an emerging public health threat. Additionally, our data strongly suggest that AM-251 could be used as a crucial prophylactic therapy for cannabinoid-induced seizures or similar life-threatening conditions.

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