THC and its therapeutic potential
Author: MVZ Kevin Antonio Cárdenas Noriega, Master's thesis student in Animal Science at the School of Veterinary Medicine and Animal Husbandry (UANL). Lines of research: Cannabis and the modulation of the Endocannabinoidoma (eCBoma).
CBD and THC are the two main phytocannabinoids in the cannabis plant. THC is mainly responsible for the high sensation of marijuana, however, it has great potential as a treatment for various diseases.
THC is the most studied cannabinoid of the plant and is the main responsible for the psychotropic effects of cannabis flower. [5] This phytocannabinoid is derived from Delta 9-tetrahydrocannabinolic acid (THCA). [16] When heat is applied or time is allowed to pass, THCA loses a carboxyl group (a process known as decarboxylation), forming THC.
THCA is not psychoactive, it is the decarboxylation that confers this effect to THC.
A bit of history: we did not always know about the existence of THC When was it first synthesized?
The first formal investigations into the psychoactive properties of cannabis were conducted by brothers T. and H. Smith in 1857. However, the chemical structure of THC was elucidated and partially synthesized more than a century later. In 1964, Gaoni and Mechoulam named it Δ1- 3,4-trans-tetrahydrocannabinol. [10]
Faced with the question "how does THC interact with the body?", further research was conducted and the cannabinoid receptors or CBRs were discovered, then the endocannabinoids and finally the endocannabinoid system or SEC. [9, 18]
CBD and THC are the most abundant and best known cannabinoids in the cannabis plant, but THC is often considered a 'drug' because of its psychoactive effects. However, it has a wide variety of medicinal applications.
THC can help with...
THC is an agonist of CB1 and CB2 receptors, and the interaction with CB1 is what gives it psychoactive effects. By activating the CBRs, THC can exert its effects on numerous physiological activities, regulating: [4,13,22]
the perception of pain
energy metabolism
neurological functions
the immune response
gastrointestinal function
cardiovascular function
the inflammatory response
liver function
anti-tumor response, among others.
CBD and THC may exert beneficial effects on the immune system. In vitro studies have reported the presence of CB1 receptors in human T lymphocytes.
In turn, THC treatment has been reported to induce changes in cytokines, which are compounds associated with inflammation.
THC reduces cytokines of the pro-inflammatory response (Th1 response) and increases anti-inflammatory cytokines of the Th2 response, such as IL-4. [14]
THC has been tested in different preclinical and clinical models of inflammation and pain with varying results. In a study using crude extracts of THC, CBD and CBN (cannabinol) on a rat model of acute inflammatory leg edema, THC was reported to be 80 times more potent than aspirin and twice as potent as hydrocortisone. [23]
But there are also disadvantages
The psychoactive properties of THC on the central nervous system are considered undesirable effects. Among these are: [3,5]
anxiogenic effects (e.g., paranoia),
short-term memory problems,
distortion of the perception of time,
accelerated heartbeat,
low blood pressure, etc.
Long-term administration of THC has been reported to produce tolerance, dependence and withdrawal syndrome. Dependence occurs in approximately 10% of cannabis users. It should be noted that this percentage is lower than that reported for tobacco, alcohol, cocaine and heroin use. In addition, to date, no deaths attributed solely to marijuana use have been reported. [1]
Some studies have shown that tolerance occurs when there is prolonged and repeated exposure to THC, and cells respond by decreasing the number of their CB1 receptors. Cells may also increase these receptors under other conditions. [15]
The good news is that other compounds produced by the plant can diminish the unwanted effects of THC. [7] These include terpenes, which interact with phytocannabinoids or even with other terpenes, [16] generating the so-called entourage effect. The entourage effect refers to the synergy or potentiation that is created between all the compounds in the plant that makes the pharmacological effects better and more potent. [24]
THC and pain
The medicinal use of cannabis has been widely reviewed, however, its clinical use has been partially limited due to the very narrow therapeutic index of THC. [21]
Weber et al (2009) used THC in chronic central neuropathic pain and reported a decrease in the use of other analgesics. Overall, patients reported decreased pain intensity, improved mood and quality of life, and a decrease in opioid medication.
However, not all individuals responded to THC treatment and 25% of the individuals withdrew from the experiment for different reasons.
Contrary to reports by some authors, in a placebo-controlled phase 2 study in patients with chronic abdominal pain, THC was not shown to significantly decrease pain when compared to placebo. The authors suggested that the analgesic effects of THC could be attributed mainly to an affective and cognitive modulatory effect leading to reduction of discomfort and pain. [8]
In conclusion
Numerous studies using medical cannabis have reported a better response when using full or broad spectrum extracts that in addition to CBD and/or THC include other cannabinoids and other molecules such as terpenes.
Based on studies conducted with THC alone, it is clear that research is still needed to determine whether THC is the therapy of choice in all cases of pain or inflammation. THC is a relatively safe substance when compared to analgesics and anti-inflammatory drugs. However, studies are still needed to elucidate the molecular mechanisms by which it exerts its effects.
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