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  • Writer's pictureDr. Dan Jin

Novel Therapeutic Perspectives of THCA

THCA is the acidic precursor of Δ9-THC produced in glandular trichomes condensed on the surface of cannabis flowers and leaves. THCA is non-psychoactive with a wide range of therapeutic benefits, including anti-inflammatory, immunomodulatory, neuroprotective, and antineoplastic properties. 


(1) Does THCA bind to cannabinoid receptors?  


There are four studies investigated this question so far by testing the affinity of THCA to CB1 and CB2 receptors in vitro and the results were contradictory. The most recent study was conducted in 2017 and concluded that THCA effectively binds to both cannabinoid receptors, which agrees with the results obtained in an in vivo preclinical study performed in 2013 and another in vitro study in 2014. However, this result seems counterintuitive as THCA activates CB1 receptor, which is responsible for the psychoactive activities, yet lacks psychoactive activities. A plausible explanation could be that THCA could not pass the brain barrier into the central nervous system to perform psychoactive activities but could still be able to activate peripheral CB1 receptors, for example, for CB1-mediated antiemetic actions. 


(2) Pharmacological actions of THCA 


Cell-based experiments suggest that THCA have the following therapeutic potentials: 


  • Immunomodulatory effects 

THCA can inhibit the release of tumor necrosis factor alpha (TNF-α) from macrophages in a dose-dependent manner. TNF-α is an inflammatory cytokine promotes the inflammatory response, which, in turn, causes many of the clinical problems associated with autoimmune disorders, such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa, and refractory asthma. These disorders are sometimes treated by using a TNF inhibitor.  


  • Anti-inflammatory effects 

THCA weakly inhibit cyclooxygenase enzymes (COX-1 and COX-2), which are enzymes producing prostaglandins that promote inflammation, pain, and fever, compared with nonsteroidal anti-inflammatory drugs (NSAIDs). 


  • Neuroprotective effects 

In an in vitro model of Parkinson disease, THCA was neuroprotective against 1-methyl-4-phenyl pyridinium (MPP+) toxicity, increased cell survival and markedly improved the morphology of altered neurite. 


  • Anti-cancer effects 

THCA reduced cell viability in different prostate carcinoma cell (PCC) lines. THCA was also effective in inhibiting proliferation of two different human breast carcinoma (HBC) cells.

 

(3) THCA in Humans 


It is usually impossible to completely convert THCA to THC by making cannabis tea or by smoking. THCA is still the most abundant cannabinoid presents in the cannabis tea, and THCA converts to THC with 30% - 70% rate. THCA can be detected in serum, urine, and oral fluid of cannabis consumers up to 8h after smoking. For this reason, THCA may be used as a potential biomarker to differentiate between the intake of cannabis products and THC-based medication (i.e. Marinol with pure THC).  


Reference: 

  1. McPartland, J. M. et al. Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two. Cannabis Cannabinoid Res 2, 87–95 (2017). 

  2. Moreno-Sanz, G. Can you pass the acid test? Critical review And novel therapeutic perspectives of tetrahydrocannabinolic acid A (THCA-A). in ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY vol. 252 (AMER CHEMICAL SOC 1155 16TH ST, NW, WASHINGTON, DC 20036 USA, 2016). 

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