dc.contributor.author |
McPartland, JM |
en |
dc.contributor.author |
MacDonald, C |
en |
dc.contributor.author |
Young, Michelle |
en |
dc.contributor.author |
Grant, PS |
en |
dc.contributor.author |
Furkert, Daniel |
en |
dc.contributor.author |
Glass, Michelle |
en |
dc.date.accessioned |
2017-08-17T02:43:32Z |
en |
dc.date.issued |
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 |
http://hdl.handle.net/2292/35170 |
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 http://www.sherpa.ac.uk/romeo/issn/2378-8763/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
en |
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 |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
631868 |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Chemistry |
en |
pubs.record-created-at-source-date |
2017-06-22 |
en |
pubs.dimensions-id |
28861508 |
en |