Inhalation exposure to smoke from synthetic "marijuana" produces potent cannabimimetic effects in mice - PubMed (original) (raw)

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

Jason M Wiebelhaus et al. Drug Alcohol Depend. 2012.

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 CB(1) 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 CB(1) 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 CB(1) 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.

Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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Figures

Figure 1

Figure 1

Buzz dose-dependently produces cannabinoid behavioral tetrad responses including (a) decreases in spontaneous locomotor activity, (b) antinociception in the radiant heat tail-flick test, (c) hypothermia, and (d) catalepsy in the ring immobility test. Mice were exposed via a nose-only exposure system to smoke produced from the incineration of placebo (50 mg), 10, 20, or 50 mg Buzz plant material. Baseline body temperature and tail flick latencies are found in Table 2.*p<0.05; ***p<0.001 vs. mice treated with 50 mg placebo smoke; Dunnett’s post-hoc test. All data reflect mean ± SEM; n=6 mice/group.

Figure 2

Figure 2

JWH-018 concentrations collected from blood, brain, heart, kidney, liver, lung, and spleen 1 h after mice were exposed to smoke produced from incineration of Buzz (10, 20, or 50 mg). JWH-018 was not detected in blood or tissue of mice exposed to placebo (not shown). **p<0.01; ***p<0.001 vs. mice treated with 50 mg placebo smoke; Dunnett’s post-hoc test. All data reflect mean ± SEM; n=4-6 mice/group of JWH-018 concentrations (ng/ml).

Figure 3

Figure 3

Pharmacological effects produced by inhalation of smoke from incinerated Buzz (20 mg) are CB1 receptor mediated. Rimonabant (3 mg/kg) significantly blocked Buzz-induced (a) decreases in spontaneous locomotor activity, (b) hypothermia, and (c) catalepsy in the ring immobility test. Baseline body temperatures are found in Table 2. *p<0.05; **p<0.01; ***p<0.001. Bonferroni’s multiple comparisons post-hoc test. All data reflect mean ± SEM; n=6 mice/group.

Figure 4

Figure 4

Incinerated Buzz and marijuana smoke dose-dependently produced cannabinoid behavioral responses including (a) hypothermia and (b) antinociception in the hot water bath tail withdrawal test. Mice were tested before exposure (i.e. 0 h or pre-exposure) and 30, 60, 120, 240 and 480 min after nose-only exposure to air, placebo, Buzz (20 or 50 mg) and marijuana (200 mg). Pre-exposure mean (± SEM) baseline temperatures were 38.20±0.15, 38.62±0.14, 38.55±0.10, 38.60±0.10, and 38.57± 0.15 °C for mice exposed to air, 50 mg placebo, 20 mg Buzz, 50 mg Buzz, and 200 mg marijuana, respectively. After 480 min (i.e. 8 h) mean (± SEM) body temperatures were 36.97±0.17, 37.25±0.28, 37.18 ±0.11, 37.07±0.15, and 37.05±0.18 °C for mice exposed to air, 50 mg placebo, 20 mg Buzz, 50 mg Buzz, and 200 mg marijuana, respectively. Baseline tail withdrawal latencies are found in Table 2. All data reflect mean ± SEM; n=6 mice/group.

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References

    1. Aceto MD, Scates SM, Razdan RK, Martin BR. Anandamide, an endogenous cannabinoid, has a very low physical dependence potential. J. Pharmacol. Exp. Ther. 1998;287:598–605. - PubMed
    1. Atwood BK, Huffman J, Straiker A, Mackie K. JWH018, a common constituent of ‘Spice’ herbal blends, is a potent and efficacious cannabinoid CB receptor agonist. Br. J. Pharmacol. 2010;160:585–593. - PMC - PubMed
    1. Auwarter V, Dresen S, Weinmann W, Muller M, Putz M, Ferreiros N. ‘Spice’ and other herbal blends: harmless incense or cannabinoid designer drugs? JMS. 2009;44:832–837. - PubMed
    1. Brents LK, Reichard EE, Zimmerman SM, Moran JH, Fantegrossi WE, Prather PL. Phase I hydroxylated metabolites of the K2 synthetic cannabinoid JWH-018 retain in vitro and in vivo cannabinoid 1 receptor affinity and activity. PloS One. 2011;6:e21917. - PMC - PubMed
    1. Coulter C, Garnier M, Moore C. Synthetic cannabinoids in oral fluid. J. Anal. Toxicol. 2011;35:424–430. - PubMed

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