jwh-018 and Marijuana-Abuse

Synthetic cannabinoid-induced toxicity is increasing in frequency across the US, with more than 1057 reported cases as of August 2010. There is a paucity of literature on synthetic cannabinoid toxicity; however, there are various reports of adverse effects including tachycardia, hypertension, tachypnea, chest pain, heart palpitations, hallucinations, racing thoughts, and seizures. While reports suggest that toxic symptoms last no longer than 3-4 hours, with no residual adverse effects in many cases, there is concern about serious acute and long-term toxicities. This article reviews the development, abuse, toxicity, treatment, and legal status of synthetic cannabinoids. It is important for health-care professionals to recognize and appropriately treat synthetic cannabinoid-induced toxicity.

Topics: Cannabinoids; Humans; Illicit Drugs; Indoles; Marijuana Abuse; Naphthalenes

A subset of cannabis users develop some degree of Cannabis Use Disorder (CUD). Although behavioral therapy has some success in treating CUD, many users relapse, often citing altered sleep, mood, and irritability. Preclinical animal tests of cannabinoid withdrawal focus primarily on somatic-related behaviors precipitated by a cannabinoid receptor antagonist. The goal of the present study was to develop novel cannabinoid withdrawal assays that are either antagonist-precipitated or spontaneously induced by abstinence.. Precipitated THC withdrawal significantly increased plasma corticosterone. Precipitated withdrawal from either THC or JWH-018 suppressed marble burying, increased struggling in the tail suspension test, and elicited somatic withdrawal behaviors. The monoacylglycerol lipase inhibitor JZL184 attenuated somatic precipitated withdrawal but had no effect on marble burying or struggling. Spontaneous THC or JWH-018 withdrawal-induced paw tremors, head twitches, and struggled in the tail suspension test after 24-48 h abstinence. JZL184 or THC attenuated these spontaneous withdrawal-induced behaviors.. Outcomes from tail suspension and marble burying tests reveal that THC withdrawal is multifaceted, eliciting and suppressing behaviors in these tests, in addition to inducing well-documented somatic signs of withdrawal.

Topics: Animals; Behavior, Animal; Benzodioxoles; Cannabinoid Receptor Agonists; Dronabinol; Indoles; Male; Marijuana Abuse; Mice; Mice, Inbred C57BL; Naphthalenes; Piperidines; Pyrazoles; Rimonabant; Substance Withdrawal Syndrome

Products containing naphthalen-1-yl-(1-pentylindol-3-yl) methanone (JWH-018) and naphthalen-1-yl-(1-butylindol-3-yl) methanone (JWH-073) are emerging drugs of abuse. Here, the behavioral effects of JWH-018 and JWH-073 were examined in one behavioral assay selective for cannabinoid agonism, rhesus monkeys (n = 4) discriminating Δ⁹-tetrahydrocannabinol (Δ⁹-THC; 0.1 mg/kg i.v.), and another assay sensitive to cannabinoid withdrawal, i.e., monkeys (n = 3) discriminating the cannabinoid antagonist rimonabant (1 mg/kg i.v.) during chronic Δ⁹-THC (1 mg/kg s.c. 12 h) treatment. Δ⁹-THC, JWH-018, and JWH-073 increased drug-lever responding in monkeys discriminating Δ⁹-THC; the ED₅₀ values were 0.044, 0.013, and 0.058 mg/kg, respectively and the duration of action was 4, 2, and 1 h, respectively. Rimonabant (0.32-3.2 mg/kg) produced surmountable antagonism of Δ⁹-THC, JWH-018, and JWH-073. Schild analyses and single-dose apparent affinity estimates yielded apparent pA₂/pK(B) values of 6.65, 6.68, and 6.79 in the presence of Δ⁹-THC, JWH-018, and JWH-073, respectively. In Δ⁹-THC-treated monkeys discriminating rimonabant, the training drug increased responding on the rimonabant lever; the ED₅₀ value of rimonabant was 0.20 mg/kg. Δ⁹-THC (1-10 mg/kg), JWH-018 (0.32-3.2 mg/kg), and JWH-073 (3.2-32 mg/kg) dose-dependently attenuated the rimonabant-discriminative stimulus (i.e., withdrawal). These results suggest that Δ⁹-THC, JWH-018, and JWH-073 act through the same receptors to produce Δ⁹-THC-like subjective effects and attenuate Δ⁹-THC withdrawal. The relatively short duration of action of JWH-018 and JWH-073 might lead to more frequent use, which could strengthen habitual use by increasing the frequency of stimulus-outcome pairings. This coupled with the possible greater efficacy of JWH-018 at cannabinoid 1 receptors could be associated with greater dependence liability than Δ⁹-THC.

Topics: Animals; Behavior, Animal; Conditioning, Operant; Data Interpretation, Statistical; Discrimination Learning; Discrimination, Psychological; Dose-Response Relationship, Drug; Dronabinol; Female; Hallucinogens; Illicit Drugs; Indoles; Macaca mulatta; Male; Marijuana Abuse; Naphthalenes; Piperidines; Pyrazoles; Receptor, Cannabinoid, CB1; Rimonabant; Substance Withdrawal Syndrome

Synthetic cannabinoids have been detected in various herbal blends sold legally in convenience stores, smoke shops, and on the Internet. Many of these compounds have extreme forensic significance. We developed and validated a rapid ultra-performance liquid chromatography-tandem mass spectrometry method for the determination of trace concentrations of two of these compounds, JWH-018 and JWH-073, in human blood. Samples underwent liquid-liquid extraction at pH 10.2 into ethyl ether. Tandem mass spectrometry was performed in positive electrospray ionization mode with multiple reaction monitoring using two transitions and one calculated ion transition ratio for each analyte. Deuterated analogs were used as internal standards. Total run time was 2.6 min. The linear dynamic range was 0.05-50 ng/mL with a limit of detection of 0.01 ng/mL for each analyte. Intra-run imprecision (at two different concentration levels, 2 and 8 ng/mL) was 3.9-10.3% for JWH-018 and 3.5-6.2% for JWH-073. Inter-run imprecision was 6.5-7.2% for JWH-018 and 4.8-5.5% for JWH-073. Intra-run accuracy was 95.9-112.7% for JWH-018 and 92.6-104.7% for JWH-073. Inter-run accuracy was 99.1-107.0% for JWH-018 and 97.7-102.0% for JWH-073. Carryover, exogenous drug interferences, ion suppression and matrix selectivity were also assessed. The method has been applied to postmortem forensic casework received by the laboratory and has proven to be robust and reliable. Concentrations of authentic samples have ranged from 0.1-199 ng/mL for JWH-018 and 0.1-68.3 ng/mL for JWH-073.

Topics: Adult; Chromatography, High Pressure Liquid; Forensic Toxicology; Humans; Indoles; Male; Marijuana Abuse; Middle Aged; Naphthalenes; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Substance Abuse Detection; Tandem Mass Spectrometry

Since 2004, a new wave of synthetic cannabinoids (SCs) known as "Spice drugs" has come under scrutiny because of their suspected link to neurological and psychiatric sequelae. These "herbal incense" or "potpourri blends" have gained popularity as a result of being more potent than natural cannabinoids, are not detected with current screening tests, and are easily modified by manufacturers to bypass legal restrictions. Unfortunately, cases of withdrawal phenomena, nausea, hypertension, and psychosis are now being reported in the medical literature. In addition, after reports in lay media of seizures and coma attributed to the consumption of the drug, anecdotal reports have emerged of similar findings in the medical literature.. We report on a 48-year-old man who, after consuming the herbal blend, lost consciousness and suffered several episodes of seizures. Despite a complicated ICU stay, the patient recovered well with no subsequent neurological sequelae.. The authors interpreted the history and findings consistent with the consumption of a large amount of synthetic cannabinoids leading to new-onset seizures and coma. However, at the time of admission, the lack of routine laboratory testing and treatment options delayed the diagnosis and delivery of appropriate therapy.

Topics: Acidosis, Respiratory; Cannabinoids; Critical Care; Dronabinol; Electrocardiography; Epilepsy, Tonic-Clonic; Glasgow Coma Scale; Humans; Illicit Drugs; Indoles; Internet; Male; Marijuana Abuse; Middle Aged; Naphthalenes; Self Medication; Tachycardia, Supraventricular