Pharmacological characterization of emerging synthetic cannabinoids in HEK293T cells and hippocampal neurons

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DOIResolve DOI: http://doi.org/10.1016/j.ejphar.2016.05.040
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TypeArticle
Journal titleEuropean Journal of Pharmacology
ISSN0014-2999
Volume786
Pages234245
Subjectsynthetic cannabinoid; cannabinoid receptor; HEK293; neurons; cAMP; calcium
AbstractThere has been a worldwide proliferation of synthetic cannabinoids that have become marketed as legal alternatives to cannabis (marijuana). Unfortunately, there is a dearth of information about the pharmacological effects of many of these emerging synthetic cannabinoids (ESCs), which presents a challenge for regulatory authorities that need to take such scientific evidence into consideration in order to regulate ECSs as controlled substances. We aimed to characterize the pharmacological properties of ten ESCs using two cell based assays that enabled the determination of potency and efficacy relative to a panel of well-characterized cannabinoids. Agonist-mediated inhibition of forskolin-stimulated cyclic adenosine monophosphate (cAMP) levels was monitored in live HEK293T cells transfected with human cannabinoid receptor 1 gene (CNR1) and pGloSensor-22F. Pharmacological analysis of this data indicated that all of the ESCs tested were full agonists, with the following rank order of potency: Win 55212–2≈5F-PB-22≈AB-PINACA≈EAM-2201≈MAM-2201>JWH-250≈ PB-22>AKB48 N-(5FP)>AKB-48≈STS-135>XLR-11. Assessment of agonist-stimulated depression of Ca2+ transients was also used to confirm the efficacy of five ESCs (XLR-11, JWH-250, AB-PINACA, 5F-PB-22, and MAM-2201) in cultured primary hippocampal neurons. This work aims to help inform decisions made by regulatory agencies concerned with the profusion of these poorly characterized recreational drugs.
Publication date
PublisherElsevier
LanguageEnglish
AffiliationNational Research Council Canada; Human Health Therapeutics
Peer reviewedYes
NPARC number23001796
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Record identifierfb1aeefc-df6d-4fc2-9c68-80aa3dbd1dfa
Record created2017-04-07
Record modified2017-04-07
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