Preliminary pharmacology, promising properties

Within the genealogy of cannabinoid chemical synthesis, tetrahydrocannabinolic acid, or THCA, acts as the “parent” to tetrahydrocannabinol (THC). THCA, found in raw, unprocessed cannabis, is the precursor to THC. The synthesis process occurs through decarboxylation, where carbon dioxide is released from the compound. This chemical reaction can occur quickly under high heat (over 200 degrees) [1]. Thus, consuming THCA will not produce any psychoactive effects – but, inhaling the smoke from the cannabis plant, will facilitate the synthesis to THC and therefore produce the typical THC “high.”

A few in vivo studies have attempted to elucidate the affinity of THCA toward cannabinoid (CB) 1 and 2 receptors. Although results from these experiments are a bit contradictory, it does appear that THCA binds to, and activates, CB1 receptors [2]. However, additional studies must be conducted to confirm the role of THCA as a CB1 receptor agonist and to determine its distribution in the central nervous system.

Outside of the cannabinoid system, THCA appears to affect phospholipid and prostaglandin metabolism and TRP channel signaling [2]. Thus, THCA may indeed exert its effects on a multitude of systems via endocannabinoid and non-endocannaboid signaling mechanisms throughout the body.

While THC has been very well studied, less is known about its precursor, since smoking is a very popular method of consumption – which degrades the compound. However, initial research has indicated that THCA has several potential medicinal properties as an anti-inflammatory, antiemetic, and neuroprotective agent.

Inflammation. A preclinical study showed that THCA reduces inflammation in colon epithelial cells [3]. Although cannabidiol (CBD) also exhibited anti-inflammatory properties, the effect was dose dependent. While preliminary, these results indicate that THCA may be used to treat inflammatory bowel disease.

Antiemetic. A preclinical study evaluated the effects of THCA on nausea-induced behavior. While THCA was successful in reducing nausea, a CB1 antagonist blocked its effects [4]. These results indicate that the antiemetic actions of THCA occur through its action on CB1 receptors and that THCA may be effective in treating nausea.

Neuroprotective. A study using cell lines investigated the affinity of six cannabinoids on PPARγ, a receptor implicated in inflammatory processes and neurodegenerative diseases, such as Huntington’s disease [5]. Researchers found that THCA is a potent PPARγ agonist; additionally, THCA exerted neuroprotective activity through its action on this receptor. Although a Phase II trial of THC/CBD failed to improve symptoms in Huntington’s disease, it is possible that a THCA-only formulation could in fact be beneficial for this condition, as well as other neurological disorders.

Significant challenges exist for further study of THCA. As with all other cannabinoids, THCA remains a Schedule I substance in the US. This designation creates funding barriers between this agent and the researchers who wish to study its pharmacological and systemic properties. Additionally, its low profile (compared to THC) and rapid conversion to THC (under the right conditions) makes it an elusive agent.

Despite these complications, THCA has many favorable characteristics. Like CBD, it is non psychoactive. It also is available in raw cannabis, requiring less processing than other cannabinoids.

Perhaps, in the near future, greater focus will fall on THCA and we will learn more about its pharmacology and wide array of medicinal properties and clinical applications.

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References

  1. Iffland, K., Carus, M., Grotenhermen, F., “Decarboxylation of Tetrahydrocannabinolic acid (THCA) to Active THC”, European Industrial Hemp Association, 2014, pg. 1-3.
  2. Moreno-Sanz, G, “Can You Pass the Acid Test? Critical Review and Novel Therapeutic Perspectives of Δ9-Tetrahydrocannabinolic Acid A”, Cannabis Cannabinoid Res,2016, Volume 1, pg. 124-130.
  3. 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, Volume 2,
    pg. 167-182.
  4. Rock, E.M., Kopstick, R.L., Limebeer, C.L., Parker, L.A., “Tetrahydrocannabinolic Acid Reduces Nausea-induced Conditioned Gaping in Rats and Vomiting in Suncus murinus”, Br J Pharmacol,2013, Volume 170, pg. 641-648.
  5. Nadal, X., Del Río, C., Casano S., et al., “Tetrahydrocannabinolic Acid is a Potent PPARγ Agonist with Neuroprotective Activity”, Br J Pharmacol,2017, Volume 174, pg. 4263-4276.