THCA is generally referred to as an inactive precursor of THC, but research has demonstrated that this chemical compound may have potential therapeutic properties.
Δ9‐THCA is produced naturally in the cannabis plant. It is a non‐psychotropic cannabinoid and its potential to bind to CB1 receptors is still debated.
A more recent study by McPartland et.al. showed that freshly prepared and highly pure Δ9‐THCA (98%) has a low binding affinity for CB1 and CB2 receptors1.
THCA-A has shown to inhibit the release of TNFα in a dose-dependent manner and, weakly inhibit cyclooxygenase enzymes (COX-1 and COX-2) in a high concentration range (mM), compared with nonsteroidal anti-inflammatory medications (NSAIDs)2.
The anti-inflammatory activity of Cannabis extracts on colon epithelial cells of an IBD model is suggested to be derived from THCA3. This study suggested that the anti-inflammatory activity of THCA was at least partially mediated by GPR55 receptor agonism.
It is suggested that Δ9‐THCA enters the CNS and PPARγ is the major target responsible for its neuroprotective and anti‐inflammatory activity4&5. THCA-A binds and activates PPARγ with higher potency than THC5.
Δ9-THCA-A is a partial and selective PPARγ modulator, empowered with lower adipogenic activity than the full PPARγ agonist rosiglitazone (RGZ) and enhanced osteoclastogenic effects in hMSC4. It is proposed that Δ9-THCA-A as a low adipogenic PPARγ agonist, may be capable of improving the symptoms of obesity-associated metabolic syndrome and inflammation4.
Δ9‐THCA has been shown to be neuroprotective in mice treated with 3‐NPA, improving motor deficits and preventing striatal degeneration. It attenuates microgliosis, astrogliosis, and up‐regulation of pro-inflammatory markers induced by 3‐NPA in mice5.
Δ9‐THCA shows potent neuroprotective activity, which warrants its consideration for the investigation of treatments of Huntington’s disease and other neurodegenerative and neuroinflammatory conditions.
- McPartland JM, McDonald C, Young M, Grant Phillip S, Furkert DP, Glass M (2017). Affinity and efficacy studies of tetrahydrocannabinolic acid A at cannabinoid receptor types one and two. Cannabis Cannabinoid Res 2: 87–95.
- Ruhaak LR, Felth J, Karlsson PC, et al. Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa. Biol Pharm Bull. 2011;34:774–778.
- Nallathambi R, Mazuz M, Ion A, et al. Anti-Inflammatory Activity in Colon Models Is Derived from Δ9-Tetrahydrocannabinolic Acid That Interacts with Additional Compounds in Cannabis Extracts. Cannabis Cannabinoid Res. 2017;2(1):167–182. Published 2017 Jul 1. doi:10.1089/can.2017.0027.
- Palomares B, Ruiz-Pino F, Garrido-Rodriguez M, et al. Tetrahydrocannabinolic acid A (THCA-A) reduces adiposity and prevents metabolic disease caused by diet-induced obesity. Biochem Pharmacol. 2020;171:113693. doi:10.1016/j.bcp.2019.113693.
- Nadal X, Del Río C, Casano S, et al. Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity. Br J Pharmacol. 2017;174(23):4263–4276. doi:10.1111/bph.14019.