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Evaluation of first generation synthetic cannabinoids on binding at non-cannabinoid receptors and in a battery of in vivo assays in mice
- Source :
- Neuropharmacology. 110:143-153
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Anecdotal reports suggest that abused synthetic cannabinoids produce cannabis-like “highs,” but some of their effects may also differ from traditional cannabinoids such as Δ9-tetrahydrocannabinol (THC). This study examined the binding affinities of first-generation indole-derived synthetic cannabinoids at cannabinoid and noncannabinoid receptors and their effects in a functional observational battery (FOB) and drug discrimination in mice. All seven compounds, except JWH-391, had favorable affinity (≤159 nM) for both cannabinoid receptors. In contrast, binding at noncannabinoid receptors was absent or weak. In the FOB, THC and the six active compounds disrupted behaviors in CNS activation and muscle tone/equilibrium domains. Unlike THC, however, synthetic cannabinoids impaired behavior across a wider dose and domain range, producing autonomic effects and signs of CNS excitability and sensorimotor reactivity. In addition, mice acquired JWH-018 discrimination, and THC and JWH-073 produced full substitution whereas the 5-HT2B antagonist mianserin did not substitute in mice trained to discriminate JWH-018 or THC. Urinary metabolite analysis showed that the compounds were extensively metabolized, with metabolites that could contribute to their in vivo effects. Together, these results show that, while first-generation synthetic cannabinoids shared some effects that were similar to those of THC, they also possessed effects that differed from traditional cannabinoids. The high nanomolar (or absent) affinities of these compounds at receptors for most major neurotransmitters suggests that these divergent effects may be related to the greater potencies and/or efficacies at CB1 receptors; however, action(s) at noncannabinoid receptors yet to be assessed or via different signaling pathways cannot be ruled out.
- Subjects :
- Male
0301 basic medicine
Indoles
Cannabinoid receptor
medicine.medical_treatment
Mianserin
Naphthalenes
Pharmacology
Article
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Receptor, Cannabinoid, CB1
In vivo
Receptor, Serotonin, 5-HT2B
Synthetic cannabinoids
medicine
Animals
Dronabinol
Receptor
Mice, Inbred ICR
Dose-Response Relationship, Drug
Cannabinoids
Illicit Drugs
Chemistry
Antagonist
JWH-018
Mice, Inbred C57BL
030104 developmental biology
Cannabinoid
Signal transduction
030217 neurology & neurosurgery
Protein Binding
medicine.drug
Subjects
Details
- ISSN :
- 00283908
- Volume :
- 110
- Database :
- OpenAIRE
- Journal :
- Neuropharmacology
- Accession number :
- edsair.doi.dedup.....1296deeaee94b61e5b75f86a71e0a0a9