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

Summary & key facts

This lab study tested how the cannabis compound THCA-A binds to the two main cannabinoid receptors (CB1 and CB2). The THCA-A sample was found to contain 2% THC, and THCA-A showed only very weak binding and little or no effect at these receptors. The authors say some of the small binding and activity they saw was likely caused by THC contamination or by THCA-A turning into THC, so the true receptor activity of pure THCA-A is probably even weaker.

Key facts:

• The THCA-A reference sample contained 2% THC as measured by high-performance liquid chromatography (HPLC).
• In competition binding tests, THCA-A had approximate Ki values of 3.1 μM at human CB1 and 12.5 μM at human CB2.
• THC showed much stronger binding: about 62-fold greater affinity at CB1 and 125-fold greater affinity at CB2 compared with the measured THCA-A values.
• In a cAMP efficacy assay, 10 μM THCA-A produced a slight inhibition of forskolin-stimulated cAMP at CB1 (suggesting weak agonist activity) and showed no measurable efficacy at CB2.
• The authors report that THCA-A binding at 10 μM roughly matched THC binding at 200 nM, which supports the idea that THC contamination or THCA-A decarboxylation to THC contributed to the observed activity.
• The paper notes THCA-A is thermally unstable and readily decarboxylates into THC during heating or storage, making THC contamination difficult to avoid and complicating interpretation of THCA-A pharmacology.
• The authors conclude that THCA-A has little affinity or efficacy at CB1 or CB2 and that some or all of the small effects measured may be artifacts from THC contamination or conversion.

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 ...

Topics

Cannabis and Cannabinoid Research GABA and Rice Research Neurotransmitter Receptor Influence on Behavior

Categories

Health Sciences Medicine Pharmacology

Tags

Agonist Binding site Biochemistry Cannabinoid Cannabinoid receptor Chemistry Ligand binding assay Radioligand Assay Receptor Stereochemistry