Inhalation exposure to smoke from synthetic “marijuana” produces potent cannabimimetic effects in mice

Abstract

BACKGROUND Use of synthetic “marijuana” has increased in recent years, produced adverse effects and prompted the temporary DEA ban of five specific cannabinoid analogs, including JWH-018. The objectives of the current study include determining the chemical content of the herbal product, Buzz, assessing its behavioral effects upon inhalation exposure to mice, determining whether CB1 receptors mediate its pharmacological activity, and ascertaining its biodisposition in blood and various organs. METHODS Using a nose-only exposure system, mice were exposed to smoke produced from combustion of an herbal incense product, Buzz, which contained 5.4% JWH-018. Cannabimimetic effects following smoke exposure were evaluated using the tetrad procedure, consisting of the following indices: hypomotility, antinociception, catalepsy, and hypothermia. Additionally, blood and tissues were collected for JWH-018 quantification. RESULTS Inhalation exposure to Buzz produced dose-related tetrad effects similar to marijuana as well as dose-related increased levels of JWH-018 in the blood, brain, heart, kidney, liver, lung, and spleen. The behavioral effects were blocked by rimonabant, a CB1 receptor antagonist. Effects produced by Buzz were similar in magnitude and time-course to those produced by marijuana, though equipotent doses of Buzz and marijuana yielded considerably lower brain levels of JWH-018 than THC for the respective materials. CONCLUSIONS Inhalation exposure to a product containing JWH-018 penetrates into the brain and other organs and produces CB1 receptor-mediated behavioral pharmacological effects in mice. The increased potency of JWH-018 compared to THC, the variable amount of drug added to various herbal products, and unknown toxicity, undoubtedly contribute to public health risks of synthetic cannabinoids.

JWH-018 impairs sensorimotor functions in mice

“…* p < 0.05, ** p < 0.01, *** p < 0.001 vs. vehicle. Brents et al, 2011;De Luca et al, 2012;Wiebelhaus et al, 2012;Macri et al, 2013a.b;Vigolo et al, 2015) leaving the effects caused by JWH-018 on sensorimotor functions undiscovered. Therefore, this preclinical study could be relevant for understanding potential sensorimotor alterations caused by JWH-018 in mice and could be also useful to better understand the effect caused by synthetic cannabinoids on sensorimotor responses in humans.…”

“…Although it is known that JWH-018 reproduces the typical cannabinoid tetrad (Wiley et al, 1998(Wiley et al, . 2012Brents et al, 2011;Wiebelhaus et al, 2012) impairs memory (Marti et al, 2013a) and cardio-respiratory function (Marti, 2014) in rodents, its effects on sensorimotor responses are still unknown. Sensorimotor responses in rodents can be studied by means of the startle reflex test (Koch, 1999) which can be elicited by visual, acoustic and tactile stimuli in a variety of animal species and in humans (Landis and Hunt, 1939).…”

“Legal Highs” – An Emerging Epidemic of Novel Psychoactive Substances

“…Of note, some of them, such as JWH-015, JWH-365, JWH-372, and (+)WIN 55,212-2, exhibit higher affinity for CB 2 than CB 1 receptors (Aung et al, 2000;Wiley et al, 2014). Studies on animals have revealed that SCs elicit a characteristic cannabinoid tetrad of effects: hypothermia, analgesia, catalepsy, and suppression of locomotor activity (Brents et al, 2012;Wiebelhaus et al, 2012;Zawilska & Wojcieszak, 2014). In a drug discrimination stimulus test, JWH-015, JWH-073, and (+)WIN 55,212-2 substituted for Δ 9 -THC (Ginsburg, Schulze, Hruba, & McMahon, 2012;Vann et al, 2009).…”

New Synthetic Drugs in Addictovigilance

“…Psychotic disturbances of the paranoid type, and signs such as anxiety, agitation, irritability, convulsions, fainting, nausea and vomiting and hypokalaemia can also be observed. Finally, alongside neuropsychiatric effects, [84][85][86][87] cardiovascular effects have more recently been described, [84,88,89] including tachycardia, palpitations, hypertension, chest pain, myocardial infarct, and one case of heart arrest in a patient with coronary disease.…”