Smoking of cannabinoid-enhanced """"""""spices"""""""" is an emerging substance abuse problem. Although JWH-018 and other indole-derived cannabinoids that have been identified in Spice products produce marijuana-like intoxication, they are structurally distinct from cannabinoids contained in the cannabis plant;hence, in many states, they are not currently illegal and are readily available over the internet and in headshops. Indole-derived cannabinoids were originally developed as research tools to investigate the nature of cannabinoid receptors;however, very little is known about their pharmacology, particularly their behavioral effects, as only a small sample of the over 200 compounds in the JWH series have been tested in preclinical in vivo models. The proposed research will synthesize and evaluate JWH-018 and related indole-derived cannabinoids in rodent models that have been used to investigate the abuse properties of cannabinoids. Emphasis will be placed on determination of the extent to which the in vivo pharmacological profile of this class of cannabinoids differs from that of ?9-tetrahydrocannabinol, the primary psychoactive substituent of the marijuana plant. Further, use of male and female rodents will allow examination of possible sex differences in the effects of these cannabinoids. Results of the studies proposed here will increase knowledge of the behavioral effects of these abused cannabinoids in both sexes, thereby providing a scientific basis for evaluation of potential health concerns associated with acute and repeated use of the compounds, including their physical dependence liability.

Public Health Relevance

Herbal blends (""""""""Spice"""""""") containing synthetic cannabinoids, marketed over the internet as """"""""incense,"""""""" are being smoked as """"""""legal marijuana"""""""" by drug abusers wanting to become intoxicated. Although most users report that these compounds produce marijuana-like effects, results of the handful of preclinical in vivo studies that have been completed with this class of cannabinoids have revealed differences, as well as similarities, with ?9-tetrahydrocannabinol, the primary psychoactive ingredient of marijuana. To determine the extent to which the behavioral effects of these synthetic indole-derived cannabinoids are distinct from those of ?9-tetrahydrocannabinol, the proposed research will examine the effects of selected synthetic cannabinoids that have been identified in """"""""Spice"""""""" in rodent models of cannabinoid dependence.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Small Research Grants (R03)
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Molecular Neuropharmacology and Signaling Study Section (MNPS)
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Rapaka, Rao
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Research Triangle Institute
Research Triangle
United States
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Wiley, Jenny L; Lefever, Timothy W; Marusich, Julie A et al. (2016) Evaluation of first generation synthetic cannabinoids on binding at non-cannabinoid receptors and in a battery of in vivo assays in mice. Neuropharmacology 110:143-153
Wiley, Jenny L; Marusich, Julie A; Huffman, John W (2014) Moving around the molecule: relationship between chemical structure and in vivo activity of synthetic cannabinoids. Life Sci 97:55-63
Wiley, Jenny L; Lefever, Timothy W; Cortes, Ricardo A et al. (2014) Cross-substitution of ?9-tetrahydrocannabinol and JWH-018 in drug discrimination in rats. Pharmacol Biochem Behav 124:123-8
Lefever, Timothy W; Marusich, Julie A; Antonazzo, Kateland R et al. (2014) Evaluation of WIN 55,212-2 self-administration in rats as a potential cannabinoid abuse liability model. Pharmacol Biochem Behav 118:30-5
Wiley, Jenny L; Marusich, Julie A; Lefever, Timothy W et al. (2013) Cannabinoids in disguise: ?9-tetrahydrocannabinol-like effects of tetramethylcyclopropyl ketone indoles. Neuropharmacology 75:145-54
Marusich, Julie A; Lefever, Timothy W; Novak, Scott P et al. (2013) Prediction and Prevention of Prescription Drug Abuse: Role of Preclinical Assessment of Substance Abuse Liability. Methods Rep RTI Press :1-14
Wiley, Jenny L; Marusich, Julie A; Martin, Billy R et al. (2012) 1-Pentyl-3-phenylacetylindoles and JWH-018 share in vivo cannabinoid profiles in mice. Drug Alcohol Depend 123:148-53
Grabenauer, Megan; Krol, Wojciech L; Wiley, Jenny L et al. (2012) Analysis of synthetic cannabinoids using high-resolution mass spectrometry and mass defect filtering: implications for nontargeted screening of designer drugs. Anal Chem 84:5574-81
Wiley, Jenny L; Smith, Valerie J; Chen, Jianhong et al. (2012) Synthesis and pharmacology of 1-alkyl-3-(1-naphthoyl)indoles: steric and electronic effects of 4- and 8-halogenated naphthoyl substituents. Bioorg Med Chem 20:2067-81
Wiley, Jenny L; Marusich, Julie A; Huffman, John W et al. (2011) Hijacking of Basic Research: The Case of Synthetic Cannabinoids. Methods Rep RTI Press 2011: