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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1901-1910
Number of pages10
JournalPsychopharmacology
Volume233
Issue number10
DOIs
StatePublished - 1 May 2016

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Dronabinol
Cannabinoids
Cannabinoid Receptor CB1
Locomotion
Methamphetamine
Cannabis

Keywords

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

Cite this

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title = "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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Δ9-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids in mice and rats. / Gatch, Michael B.; Forster, Michael J.

In: Psychopharmacology, Vol. 233, No. 10, 01.05.2016, p. 1901-1910.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Forster, Michael J.

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