THCA: The Cannabinoid That “Gets No Respect”

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!

References

  1. Baker PB, Taylor BJ, Gough TA. The tetrahydrocannabinol and tetrahydrocannabinolic acid content of cannabis products. J. Pharm & Pharmacol. 1981; 33:369-372.
  2. Ruhaak LR, Felth, J, Karlsson PC, Rafer JJ, et al. Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa Biologic and Pharmaceutical Bull; 2011 34:774-778
  3. Moldzio R, Pacher T, Krewenka C, Kranner B, et al. Effects of cannabinoids Δ(9)-tetrahydrocannabinol, Δ(9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures. Phytomed 2012: 19:819-824.
  4. 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

Several Major Universities To Offer Cannabis Courses and Even Grow Some on the Side!

In a previous blog post I wrote that several community colleges and lesser know universities were offering summer and/or continuing education classes about cannabis.  While these course offerings were impressive, most were community-based and specifically designed to support local cannabis growers and the emerging cannabis business in these locales.

More recently, however, several major universities including Ohio State University, the University of Washington, the University of Vermont and the University of California-Davis announced that they will offer courses designed to provide students and healthcare professionals with an understanding of the physiology, medical and legal implications of cannabis use.

And, quite surprisingly, Louisiana State University has entered into a private agreement with a Las Vegas-based biopharmaceutical pharmaceutical company GB Sciences to cultivate and supply cannabis for disease indications that the company plans to treat including chronic pain, arthritis, cardiovascular problems, asthma and inflammatory bowel disease. While LSU entered into this agreement, it is not clear whether or not it relationship with GB Sciences may affect its sources of federal funding because cannabis is still illegal at the federal level.

Nevertheless, it is becoming abundantly clear that academia sees an opportunity to get into the cannabis business one way or the other. Below is a sampling of the cannabis courses and seminars that are currently being offered.

The University of Vermont offers a medical marijuana and cannabis certification course for clinicians who want the latest information regarding medical cannabis and possible healthcare applications of the plant.

The Moritz College of Law at Ohio State University offers a seminar style course on the legalization of cannabis that will examine the social and historical backdrop of intoxicant prohibition, and assess the legal reforms and political debates now having an impact on the control and regulation of marijuana distribution and use.

The University of Washington offers a course for healthcare professionals on the use of medical cannabis to treat chronic pain.

The University of California-Davis will offer a course to biology majors that will cover the biology of cannabis and cannabinoids as well as their physiological effects in multiple systems, underlying mechanisms and therapeutic values. It also will survey the history of cannabis use, cover the endocannabinoid system and discuss potential medical targets for cannabis and their relative effectiveness.

Finally, there is a big push at University of California at Los Angeles to create a research center to study the medicinal effects of cannabis on a variety of disease indications.

References

  1. http://cannabisscienceblog.com/2017/06/15/69/ accessed September 25, 017
  2. https://www.businessreport.com/article/lsu-finalizes-medical-marijuana-agreement-gb-sciences/ accessed September 25, 2017
  3. http://learn.uvm.edu/com/program/cannabis-science-and-medicine/ accessed September 25, 2017
  4. http://moritzlaw.osu.edu/academics/course-explorer/category/criminal-law/ accessed September 25, 207
  5. http://adai.uw.edu/mcacp/ accessed September 25, 2017
  6. http://www.ucdmc.ucdavis.edu/physiology/ accessed September 25, 2017
  7. http://dailybruin.com/2017/05/23/editorial-ucla-must-build-marijuana-research-center-study-effects-of-legalization/ accessed September 25, 2017

Cannabis Extracts, Cannabinoids and Cancer Treatment

There is a growing body of evidence that cannabinoids may have anti-tumor and cancer–fighting effects (1, 2).

Numerous studies have demonstrated inhibition of tumor growth in vitro and in animal models of disease for a variety of cancers including glioblastoma, breast, prostate, thyroid, colon, skin, pancreatic, leukemia and lymphoma (3).

The exact mechanism by which cannabinoids exert their anti-tumor effects is thought to occur via suppression of proliferative cell signaling pathways, inhibition of angiogenesis (blood vessel formation) and cell migration, stimulation of apoptosis (programmed cell death) and induction of autophagy (intracellular degradation) [3, 4].  Interestingly, cannabinoid receptors CB1 and CB2 have been found in higher concentrations on tumor cells than on surrounding normal tissue for a variety of cancers (5, 6).  Also, several studies suggest that cannabinoids may selectively inhibit tumor cell growth and proliferation while sparing normal tissue (3, 7).

Although cannabinoids exhibit possible anti-tumor effects, only a single Phase 1  clinical trial that assessed the safety and efficacy of THC in 9 patients with treatment refractory glioblastoma multiforme has been published (8).

However, at present, there are only two Phase 2 clinical trials underway or completed to assess the effect of cannabis extracts on solid tumor growth (NCT02255292) and glioblastoma (NCT01812603).  Clearly, more clinical studies are necessary to determine whether or not Cannabis extracts or different cannabinoids (singly or in combination) can be used as safe and effective cancer treatments for solid tumors.

References

  1. 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.
  2. Lynch ME, Campbell F. (2011) Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. British Journal of Clinical Pharmacology 72(5):735-744.
  3. Pisanti S, Malfitano AM, Grimaldi C, et al. (2009) Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents. Best Practice & Research. Clinical Endocrinology & Metabolism 23(1):117-131.
  4. Salazar M, Carracedo A, Salanueva IJ, et al. (2009) Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. The Journal of Clinical Investigation 119(5):1359-1372.
  5. Caffarel MM, Andradas C, Mira E, et al. (2010) Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition. Molecular Cancer 9:196.
  6. Qamri Z, Preet A, Nasser MW, et al. (2009) Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer. Molecular Cancer Therapeutics 8(11):3117-3129.
  7. Flygare J, Sander B. (2008) The endocannabinoid system in cancer-potential therapeutic target? Seminars in cancer biology 18(3):176-189.
  8. Guzman M, Duarte MJ, Blazquez C, et al. (2006) A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. British Journal of Cancer 95(2):197-203.