MOLECULE

Delta-9-tetrahydrocannabinolic acid A

Delta-9-Tetrahydrocannabinolic acid A or THC acid A is classified as a delta-9-tetrahydrocannabinol, one of the major non-psychoactive cannabinoid compounds that are found only in the cannabis plant. THC acid A, and to a much lesser extent THC acid B, are biosynthetic precursors to delta-9-tetrahydrocannabinol (delta-9-THC), the principal psychoactive constituent of the cannabis plant. The difference between THC acid A and B is the position of the carboxyl functional group. In THC acid A, it is on the C-2 whereas in THC acid B, it is on the C-4 (PMID: 6991645). THC acid is produced via the following pathway: Geranyl pyrophosphate and olivetolic acid react, catalyzed by an enzyme Geranyl-pyrophosphate—olivetolic acid geranyltransferase to produce cannabigerolic acid which is then cyclized by the enzyme THC acid synthase to give THC acid. Over time, or when heated (via vaping or smoking), THC acid is decarboxylated, producing THC. While smoking a joint or baking cookies, THC acid A is partially converted into the psychoactive delta-9-THC via decarboxylation. Therefore, THC acid A is incorporated to a certain extent by cannabis consumers and is a promising candidate for use as an additional consumption marker (PMID: 22921834). While some studies showed that delta-9-THC acid binds cannabinoid type one (CB1) receptors with a Ki value of 23.5 nM (PMID: 25311884), others had found negligible activity (PMID: 18303850). Decarboxylation of THC acid A to THC during storage or under certain experimental conditions may contribute to these contrasting results. A recent study using freshly prepared and highly pure delta-9-THC acid (98%) showed that it yet had a low binding affinity for CB1 and CB2 receptors (PMID: 28861508), strongly suggesting that delta-9-THC acid biological activities are not mediated by interaction with these receptors. However, in another study, Delta-9-THC acid exhibited anti-emetic and immune-modulatory activities through CB1-dependent and CB1-in- dependent mechanisms, respectively (PMID: 16504929; PMID: 23889598). Delta-9-THC acid showed potent neuroprotective activity and may aid in the treatment of Huntington's disease and possibly other neurodegenerative and neuroinflammatory diseases (PMID: 28853159).