Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two

Show simple item record McPartland, JM en MacDonald, C en Young, Michelle en Grant, PS en Furkert, Daniel en Glass, Michelle en 2017-08-17T02:43:32Z en 2017-05-01 en
dc.identifier.citation Cannabis and Cannabinoid Research 2(1):87-95 01 May 2017 en
dc.identifier.issn 2378-8763 en
dc.identifier.uri en
dc.description.abstract Introduction: Cannabis biosynthesizes Δ9-tetrahydrocannabinolic acid (THCA-A), which decarboxylates into Δ9-tetrahydrocannabinol (THC). There is growing interest in the therapeutic use of THCA-A, but its clinical application may be hampered by instability. THCA-A lacks cannabimimetic effects; we hypothesize that it has little binding affinity at cannabinoid receptor 1 (CB1). Materials and Methods: Purity of certified reference standards were tested with high performance liquid chromatography (HPLC). Binding affinity of THCA-A and THC at human (h) CB1 and hCB2 was measured in competition binding assays, using transfected HEK cells and [3H]CP55,940. Efficacy at hCB1 and hCB2 was measured in a cyclic adenosine monophosphase (cAMP) assay, using a Bioluminescence Resonance Energy Transfer (BRET) biosensor. Results: The THCA-A reagent contained 2% THC. THCA-A displayed small but measurable binding at both hCB1 and hCB2, equating to approximate Ki values of 3.1μM and 12.5μM, respectively. THC showed 62-fold greater affinity at hCB1 and 125-fold greater affinity at hCB2. In efficacy tests, THCA-A (10μM) slightly inhibited forskolin-stimulated cAMP at hCB1, suggestive of weak agonist activity, and no measurable efficacy at hCB2. Discussion: The presence of THC in our THCA-A certified standard agrees with decarboxylation kinetics (literature reviewed herein), which indicate contamination with THC is nearly unavoidable. THCA-A binding at 10μM approximated THC binding at 200nM. We therefore suspect some of our THCA-A binding curve was artifact—from its inevitable decarboxylation into THC—and the binding affinity of THCA-A is even weaker than our estimated values. We conclude that THCA-A has little affinity or efficacy at CB1 or CB2. en
dc.relation.ispartofseries Cannabis and Cannabinoid Research en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
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dc.title Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two en
dc.type Journal Article en
dc.identifier.doi 10.1089/can.2016.0032 en
pubs.issue 1 en
pubs.begin-page 87 en
pubs.volume 2 en
dc.description.version VoR - Version of Record en
dc.rights.holder Copyright: The author en
dc.identifier.pmid 28861508 en
pubs.end-page 95 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 631868 en Science en Chemistry en
pubs.record-created-at-source-date 2017-06-22 en
pubs.dimensions-id 28861508 en

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