Pharmacokinetics and pharmacodynamics of THCA
Tetrahydrocannabinolic acid (THCA) is a cannabinoid produced by the cannabis flower. It is a relatively unstable compound that is easily decarboxylated by heat. While it does not have any psychoactive properties itself, when decarboxylated, it forms into tetrahydrocannabinol (THC), the psychoactive component of cannabis. THCA may play an important role in the treatment of neurological issues such as neurodegenerative and neuroinflammatory disease.1
THCA in the precursor to THC. THCA is found in the raw flowers of the cannabis plant but can be easily converted into THC by heating or baking the flower. Heat, however, is not the only method of decarboxylation. Age and light cause decarboxylation as well.2 Because of this, THCA is notoriously unstable and hard to research. With mice, THCA in an oil carrier shows a very short half-life time of 67 minutes.3 In humans, the half-life after an oral dose is closer to 3.4 hours.1 THCA cannot be vaporized or smoked, as the heat causes its transformation into THC. In a study of mice, researchers injected an oil and THCA mixture to several subjects. They found that THCA peaks quickly in the plasma and slowly tapers off over about 2 hours.3 The Cmax from a 10 mg/kg solution was approximately 2.8 µm/ml.2 The presence of the THCA in plasma as well as the brain shows that while difficult, THCA can be isolated and given in a manner where it does not carboxylate.
The rapid decarboxylation of THCA into THC makes it extremely difficult to see the mechanisms of THCA inside the body. Research has shown that THCA has little affinity for the CB1 and CB2 receptors.1 Upon initial consumption of THCA and THC by a heat source, it appears as though their concentrations are similar but then rapidly diverge. The THCA is almost all converted to THC3. THC has a partial affinity for CB1 and CB2 receptors and causes the psychoactive effect of cannabis. While THCA does not bind readily to the endocannabinoid system receptors, it does have an affinity for PPARƴ receptors.1 PPARƴ receptors involve insulin sensitivity as well as glucose metabolism. In general, PPARƴ play a major role in homeostasis of energy and metabolic function.4 Because of the affinity for these particular receptors, THCA may play an important role in several different bodily functions. In fact, THCA has shown to high neuroprotective activity.1 This means that THCA can have a positive effect on neurodegenerative diseases like Parkinson’s or Alzheimer’s. It may also have a positive effect of neuroinflammatory diseases such as Multiple Sclerosis. THCA has also been seen to have anti-inflammatory properties to treat arthritis and lupus as well as anti-emetic properties to combat nausea and appetite loss.5
THCA is a precursor to the psychoactive cannabinoid THC. It is hard to isolate THCA as it decarboxylates into THC by heat, age, and light. If isolated and taken, THCA has a similar Cmax curve as THC – it starts with high concentration in the plasma and slowly tapers off. THCA, unlike THC, has little affinity for CB1 and CB2. It does, however, has affinity for PPARƴ receptors that help regulate homeostasis of the body. Because of this, THCA may have positive effects on neurological diseases as well as anti-inflammatory effects on arthritis and anti-emetic properties.
- Eddington N. Metabolism of active and non-active agents of the cannabis plant. MCST608 Lecture Slides. University of Maryland School of Pharmacy.
- McPartland JM, MacDonald C, Young M, Grant PS, Furkert DP, Glass M. Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two. Cannabis Cannabinoid Res. 2017;2(1):87-95.
- Lyndsey L, Anderson IK, Low SD. Banister IS, McGregor, Jonathon CA. Pharmacokinetics of Phytocannabinoid Acids and Anticonvulsant Effect of Cannabidiolic Acid in a Mouse Model of Dravet Syndrome. Journal of Natural Products. 2019;82(11):3047-3055.
- Tyagi S, Gupta P, Saini AS, Kaushal C, Sharma S. The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J Adv Pharm Technol Res. 2011;2(4):236-240.
- What is THCA and what are the benefits of this cannabinoid? Leafly.com website. Accessed on July 12, 2020.