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

Cannabis and Its Effect on High Blood Pressure

According to recent estimates, about 75 million American adults have has high blood pressure (1), a condition commonly referred to as hypertension. If untreated, it can lead to cardiovascular disease, which is characterized by an increased risk of stroke, heart attack, and even heart failure. Hypertension was the cause of over 400,000 deaths in 2014 (1).

A number of factors, including poor diet, stress, physical inactivity, alcohol, and tobacco use increase the risk of developing hypertension (1). Hypertension can be managed by taking medications, reducing sodium in the diet, getting daily physical activity, and quitting smoking (2).

Previous reports suggest that consumption of cannabis and certain cannabinoids e.g, cannabidiol (CBD) may help to lower high blood pressure and represent a new treatment option for hypertension (3-5).   Further, results from a 15 year longitudinal study called the Coronary Risk Development in Young Adults (CARDIA) which followed 3,617 black and white young adults suggested that cannabis consumption was not independently associated with increased cardiovascular risk (6). However, study authors cautioned that it was associated with unhealthy behaviors including high caloric diet, tobacco smoking and other illegal drug use.

In a more recent retrospective analysis of 1213 young adults (20 years and older)—57% used cannabis—Yankey et al. (7) showed that cannabis use may increase the risk of death from hypertension. Study results suggested that cannabis users had more than three times the risk of death from hypertension-related causes. Moreover, increased duration of cannabis use was also associated with a greater risk of death from hypertension. However, it is important to note that the researchers acknowledged the difficulty of measuring frequency and quantities of marijuana used by study participants and the likelihood that illegal use was underreported (7). Put simply, there are confounding variables that call into question the conclusions of the study.

In summary, the positive or negative effects of cannabis consumption on cardiovascular health and disease still remain to be conclusively determined. New well designed and better controlled clinical studies will be necessary to verify or refute the effects of cannabis and cannabinoids on cardiovascular function and their ability to manage hypertension.

References

  1. https://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_bloodpressure.htm  Accessed August 23, 2017
  2. http://www.mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/high-blood-pressure/art-20046974  Accessed August 23, 2017
  3. Pacher P, Batkal S, Kunos G. Cardiovascular pharmacology of cannabinoids. Handb Exp Pharmacol 2005; 168:599-625
  4. Randall MD, Harris D, Kendall DA, Ralevic V. Cardiovascular effects of cannabinoids. Pharmacol Ther. 2002;95:191–202.
  5. Hiley CR, Ford WR. Cannabinoid pharmacology in the cardiovascular system: potential protective mechanisms through lipid signalling. Biol Rev Camb Philos Soc. 2004;79:187–205
  6. Rodondi N, Pletcher MJ, Liu K, Hulley SB, Sidney S  Marijuana use, diet, body mass index and cardiovascular risk factors (from the CARDIA study). Am J Cardiol 2006; 98:478-484
  7. Yankey B, Rothenberg R, Strasser S, Ramsey-White K, Okosun IS Effect of marijuana use on cardiovascular and cerebrovascular mortality: A new study using the National Health and Nutrition Survey linked mortality file. Eur J Preventive Cardiol 2017; DOI: 10.1177/2047487317723212 [Epub ahead of print]

THC: The Latest Buzz

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.

REFERENCES

  1. Mechoulam R, Gaoni Y. (1965) A Total Synthesis of Dl-Delta-1-Tetrahydrocannabinol, the Active Constituent of Hashish. Journal of the American Chemical Society 87:3273-3275.
  2. Hazenkamp A, Gortenhermen F (2010) Review on clinical studies with cannabis   and cannabinoids 2005-2009. Cannabinoids 5(special issue):1-21.
  3. 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.