Δ9-Tetrahydrocannabinoic acid or THCA, like the late great Rodney Dangerfield, simply “gets no respect” when compared with higher profile cannabinoids like CBD, CBG, or CBN that are highly touted in medical cannabis circles.
THCA is the carboxylated precursor of the psychoactive cannabinoid Δ9-tetrahydrocannabinol or THC. Unlike THC, THCA is not psychoactive and can be found in high concentrations (10%-20%) in certain cannabis strains (1). Interestingly, there is a growing body of evidence that suggest that THCA may possess a variety of medically-beneficial, therapeutic properties.
First, THCA has been reported to possess potent in vitro anti-inflammatory properties similar to those exhibited by COX-2 inhibitors like Celebrex (2). Second, THCA exhibited neuroprotective effects in various tissue culture and animal models of Parkinson’s disease (3). Finally, THCA may possess antiproliferative and anti-tumor effects against prostate cancer (4)
Unfortunately, like most other cannabinoid research, additional studies must be conducted to confirm or refute possible therapeutic benefits of THCA. That said, it is a cannabinoid that deserves more respect than it is currently getting!
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- De Pretrocellis L, Ligresti A, Moriello AS, Iappelli M, Verde R, et al. Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms. Br. J. Pharmacol 2013: 168:79-102
The anticancer effects of cannabis and individual cannabinoids are thought to be mediated via interaction of these compounds with their cognate receptors; cannabinoid receptor 1 (CB1) and CB2). CB1 receptors are widely distributed in the central nervous system (CNS) and brain whereas CB2 receptors are mainly found in the immune system with much lower and more restricted distribution in CNS (1,2)
Early in vitro studies using tumor cell lines and tumor xenograft mouse models suggest that cannabinoids can inhibit solid tumors and hematologic malignancies including gliomas (brain tumors), adenocarcinomas of the lung, breast, colon, pancreas and melanoma and also myeloma and lymphoma (3-5).
Although not completely elucidated, the mechanism of action of cannabinoids as anticancer agents has been attributed to induction of programmed cell death or apoptosis (via interaction with CB1 receptors), inhibition of angiogenesis or blood vessel growth (reduction in the expression of endothelial growth factor and its receptors) and a decrease in the activity of matrix metalloproteinase 2 which can lead to decreased tumor cell invasiveness and metastasis (6-8). In addition, cannabinoids possess potent anti-inflammatory and antioxidant properties that can also help to combat cancer (9). Finally, cannabinoids administered in combinations with conventional chemotherapy agents or radiation treatment have been observed to enhance antitumor activity (10-12).
While these preliminary findings are encouraging, much more basic research must be performed to identify the actual anticancer/anti-tumor action of cannabinoids and the individual cancer indications that would benefit most from their use. Once these things are established, large scale controlled human clinical trials will be necessary for regulatory approval of these agents as cancer treatments.
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- McAllister SD, Soroceanu L, Desprez PY. The antitumour activity of plant-derived non-psychoactive cannabinoids. J Neuroimmune Pharmacol 2015; 10:255–67.
- Massi P, Solinas M, Cinquina V, Parolaro D. Cannabidiol as potential anti cancer drug. Br J Clin Pharmacol 2013; 75:303–12.
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- Abrams DI, Guzman M. Cannabis in cancer care. Clin Pharmacol Ther 2015; 97:575–86.
- Abrams, DJ. Integrating cannabis into clinical cancer care. Curr Oncol. 2016; 23:S8-S14.
- Donadelli M, Dando I, Zaniboni T, et al. Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ros-mediated mechanism. Cell Death Dis 2011;2:e152.
- Torres S, Lorente M, Rodriguez-Fornes F, et al. A combined preclinical therapy of cannabinoids and temozolomide against glioma. Mol Cancer Ther 2011;10:90–103.
- Scott KA, Daigleish AG, Liu WM. The combination of cannabidiol and Δ9-tetrahydrocannabinol enhances the anticancer effects of radiation in an orthotopic murine glioma model. Mol Cancer Ther 2014;13:2955–67.
Δ-9-tetrahydrocannabinol or THC is the main active cannabinoid in Cannabis and it is primarily responsible for Cannabis’ psychoactive properties.
It was the first cannabinoid to be isolated and identified (1964) in Cannabis resin and flowers (1) The concentration of THC found in Cannabis and its extracts can vary based on plant variety, cultivation techniques and type of preparation.
Pure THC can be derived from natural sources (extraction from cannabis plants) or produced synthetically. (2) The molecule acts as a partial agonist of CB1 receptors found in the CNS and CB2 receptors found on immune cells. (2)
While THC exhibits potent anti-inflammatory and anti-emetic properties, its development as therapeutic drug treatment has been hindered by its accompanying psychotropic effects. Nevertheless, in the past, dronabinol (Marinol) a synthetic THC and nabilone (Cesamet) a synthetic THC-mimetic received FDA approval as appetite stimulants and treatments for chemotherapy induced nausea and vomiting (CINV) (3) However, neither drug is widely prescribed.
Finally, negative psychotropic reactions and possible development of tolerance to THC could limit the long term clinical and therapeutic uses of the molecule.
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- Hazenkamp A, Gortenhermen F (2010) Review on clinical studies with cannabis and cannabinoids 2005-2009. Cannabinoids 5(special issue):1-21.
- Bowles DW, O’Bryant CL, Camidge DR, Jimeno A. (2012) The intersection between cannabis and cancer in the United States. Critical Reviews in Oncology/Hematology 83(1):1-10.