The Effects of THCA and CBDA on The Human Endocannabinoid System
The use of cannabis for medicinal purposes dates back thousands of years and spans a plethora of cultures. Its function as a medicine to treat both physical and mental ailments remained a mystery up until the 20th Century when scientific methodologies gave us the first glimpse into what we now understand as cannabinoids. Soon after the discovery of these hidden compounds, research yielded yet another breakthrough: the human endocannabinoid system, its receptor sites, CB-1 and CB-2 and endogenous cannabinoids (1).
Little did researchers know, but these discoveries triggered an unstoppable curiosity, which continues to compound on itself. As investigations into this plant continued, and more chemicals were revealed, the identification of two unique cannabinoids sparked an entirely new understanding of the role cannabis plays in modulating human health.
THCA (delta-9-tetrahydrocannabinolic acid) and CBDA (cannabidiolic acid) are, in the most fundamental definition, the molecular precursors to their infamous counterparts, THC (delta-9-tetrahydrocannabinol) and CBD (cannabidiol). Created and stored in the glandular trichomes secretory cavity of cannabis plants, THCA and CBDA are molecularly similar to THC and CBD; however, their acidic state renders them non-psychoactive (2).
When heated, or decarboxylated, the molecular structure shifts by adding one carbon molecule and two oxygen molecules (3). This conversion transforms these acidic cannabinoids into a more neutral state, which in the most simplistic definition, stimulates CB-1 and CB-2 receptor sites and ultimately results in psychoactive effects most commonly associated with ingesting cannabis (4). While THC and CBD are regarded as having potent medicinal benefits, recent research has discovered their acidic molecular states interact with the human endocannabinoid system in a much different, but equally powerful, way.
Healing Without Heat – THCA and CBDA Effects on Disease Modulation
THC and CBD modulate their therapeutic qualities by acting as a partial agonist (THC) or a high potency antagonist (CBD) for CB-1 and CB-2 cannabinoid receptor sites by working synergistically with human-made cannabinoids, or endocannabinoids (5)(6). This interaction with cannabinoid receptors, and endocannabinoids, yields a host of benefits. For example, THC causes psychotropic effects by activating brain CB-1 receptors. CBD works in conjunction with THC to stimulate CB-1 and CB-2 receptors, which provides physiopathological effects, such as regulating the perception of pain and supporting cardiovascular functionality (6).
However, current research is unable to definitely confirm whether THCA or CBDA bind with cannabinoid receptors. Although a study published in Neurotoxicology and Teratology found minor activity in CB-1 receptors (7), the majority of other studies dilute their ability to bind to receptors. If this is the case, then what therapeutic value do these cannabinoids hold, if any?
When dealing with such advanced-level physiopathological concepts, it’s best to look at how these compounds work in nature. As cannabis reaches maturity, THCA accumulates in high concentrations along the flowers and leaves. Its purpose is to induce cellular death, known as necrosis, by creating a pathway through the mitochondrial membrane of cells (8). This action keeps the mature plant healthy by force eliminating dead, dying or damaged cells. Humans feature a similar mechanism, referred as programmed cellular death. This term is common when discussing cancer as an error in programmed cell death allows diseased cells to remain active. Ultimately, the proliferation of these diseased cells can result in cancer. While this is an important finding, it still doesn’t fully answer how these cannabinoids support human health and longevity.
Instead of relying on cannabinoid receptor activation, THCA and CBDA engage with the human endocannabinoid system by altering the efficiency of four primary functions: COX-1 Release, COX-2 Inhibition, TNF-Alpha Inhibition, Interleukin-10 Release (9). Ultimately, this means these cannabinoids actively support your own body’s ability to reduce inflammation, boost immune system performance and significantly lower overall pain levels (8). While the true effectiveness of THCA and CBDA is still under investigation, the use of these acidic cannabinoids within the modern cannabis industry shows great promise and is worth investigation by researchers and cannabis processors, alike.