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Δ9-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids in mice and rats

Abstract

Rationale

Novel cannabinoid compounds continue to be marketed as “legal” marijuana substitutes, even though little is known about their molecular and behavioral effects.

Objectives

Six of these compounds (ADBICA, ADB-PINACA, THJ-2201, RCS-4, JWH-122, JWH-210) were tested for in vitro and in vivo cannabinoid-like effects to determine their abuse liability.

Methods

Binding to and functional activity at CB1 cannabinoid receptors was tested. Locomotor activity in mice was tested to screen for behavioral activity and to identify behaviorally active dose ranges and times of peak effect. Discriminative stimulus effects of the six compounds were tested in rats trained to discriminate Δ9-tetrahydrocannabinol (Δ9-THC).

Results

ADBICA, ADB-PINACA, THJ-2201, RCS-4, JWH-122, and JWH-210 showed high affinity binding at the CB1 receptor at nanomolar affinities (0.59 to 22.5 nM), and all acted as full agonists with nanomolar potencies (0.024 to 111 nM) when compared to the CB1 receptor full agonist CP 55940. All compounds depressed locomotor activity below 50 % of vehicle responding, with depressant effects lasting 1.5 to nearly 4 h. All compounds fully substituted (<80 % Δ9-THC-appropriate responding) for the discriminative stimulus effects of Δ9-THC. 3,4-Methylenedioxy-methamphetamine (MDMA) was tested as a negative control and did not substitute for Δ9-THC (11 % Δ9-THC-appropriate responding).

Conclusions

All six of the compounds acted at the CB1 receptor and produced behavioral effects common to abused cannabinoid compounds, which suggest that these compounds have substantial abuse liability common to controlled synthetic cannabinoid compounds.

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Acknowledgments

Funding was provided by the Addiction Treatment Discovery Program of the National Institute on Drug Abuse for the behavioral data (NIH N01DA-13-8908) and for the in vitro data (N01DA-13-9881). Program staff was involved in selection of compounds and test parameters. The ATDP had no further role in study design; the collection, analysis, and interpretation of data; or the writing of the report. They have granted permission for the submission of this data for publication.

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Correspondence to Michael B. Gatch.

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All housing and procedures were in accordance with Guidelines for the Care and Use of Laboratory Animals (National Research Council 2011) and were approved by the University of North Texas Health Science Center Animal Care and Use Committee.

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Gatch, M.B., Forster, M.J. Δ9-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids in mice and rats. Psychopharmacology 233, 1901–1910 (2016). https://doi.org/10.1007/s00213-016-4237-6

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  • DOI: https://doi.org/10.1007/s00213-016-4237-6

Keywords

  • Cannabinoids
  • Drug discrimination
  • Locomotor activity
  • Abuse liability
  • Mouse
  • Rat