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THC Vs. CBD: Structural and Functional Comparison

Out of the hundreds of known cannabinoids, two have garnered the most scientific interest. Cannabidiol (CBD) and delta-9 tetrahydrocannabinol (THC) occur naturally in the cannabis plant and interact with the body’s endocannabinoid system. The compounds influence the activity of two main receptors of the Endocannabinoid system, affecting numerous physiological pathways. 

At the most fundamental level, CBD and THC differ in one single aspect: chemical action. THC is psychoactive, thus induces euphoric effects in the individuals. On the other hand, CBD is non-psychoactive and, therefore, does not cause a high.

The Structures of THC and CBD

Both CBD and THC have the exact same molecular formula: C21H30O2. The molecular mass of the two compounds is almost the same as well. THC has a mass of 314.469 g/mol 314.464 g/mol, whereas CBD has a mass of 314.464 g/mol. 

THC and CBD also share a very identical biosynthesis pathway. The process starts with Cannabigerolic acid, the “Mother Compound” from which all cannabinoids are produced. CBGA undergoes a string of chemical reactions to convert CBD and THC’s precursor acids — cannabinolic acid (CBDA) and tetrahydrocannabinol acid (THCA). These precursor acids are then transformed into their ultimate forms — CBD and THC — via decarboxylation, which involves the removal of CO2 groups from their structures.

However, this happens with one noticeable difference. CBD has a hydroxyl group where THC has a cyclic ring. This trifling difference imparts in the two compounds their characteristic physiological effects. 

The Chemical Properties of THC and CBD

Both THC and CBD have the following chemical properties:

  • Low solubility in water because of their predominantly hydrophobic structures. 
  • Excellent solubility in organic mediums, such as ethanol and acetone. 
  • Both exist in cannabis as acids, which easily undergo decarboxylation, and chemical alteration via heating. This is obvious, considering smoking is one of the most popular methods of taking CBD and THC. 
  • THC can bind to glass and plastic surfaces. This makes the compound’s storage and preservation easy in organic solvents. 

The physiological effects of CBD and THC

THC acts on both CB1 and CB2 receptors of the endocannabinoid system. Its physiological action on CB1 is partially agonistic. This means it stimulates the activity of CB1 receptors instead of inhibiting it and is also one of the main reasons why it produces psychotropic effects. 

CBD counteracts the effects of THC on the CB1 receptor. Acting as an antagonist molecule, it alters the structure of CB1 to make THC’s binding ineffective. 

CB1’s preponderance is in the central and peripheral nervous systems. It is equipped with G-protein, which triggers its activity. The endocannabinoid system activates CB1’s endogenous cannabinoids or endocannabinoids. These include 2- arachidonoylglycerol (2AG) and anandamide. 

Exogenous cannabinoids or phytocannabinoids found in the cannabis plant, including THC and CBD, can also influence these receptors. As already mentioned above, THC stimulates CB2 receptor activity to produce psychoactive effects. On the other hand, CBD falls into the category of negative allosteric modulators, and as a negative allosteric modulator, it changes the structure of the CB1 receptor. 

CBD’s ability to alter receptor change makes it possible to resist the influence of agonist molecules that activate CB1 receptors. However, one thing noteworthy here is that CBD doesn’t directly interact with CB1 receptors. Meaning, it doesn’t bind to the receptor’s constituent compounds, and therefore, plays no role in producing psychotropic effects reminiscent of THC.

How This Combo Produces the Entourage Effect?

CBD and THC interact with each other through the Entourage effect. The entourage effect is a synergistic relation between two cannabinoid compounds. With regards to THC and CBD, THC induces a high in users, whereas CBD stands to combat this high. This is why most experts recommend full or Broad Spectrum CBD products over CBD isolates. These products contain a healthy mix of cannabinoids, which complement and balance each other’s properties. 

CBD may also alleviate some negative effects of THC. These include dementia, anxiety, hallucinations, delirium, and loss of motor skills. 

Even though CBD and THC work great together, the market for CBD and THC only products is booming. This is mainly because of the misconception spread by pharmaceutical companies that a single-action drug is easier to research, test, produce, and regulate. However, as more research about “holistic” medicinal drugs continue, this mindset may change. The notion of whole plant medicines, in particular, may prove pivotal in driving this perspective. 

The Future of CBD and THC

Cannabis was used as a potent medicine in ancient China thousands of years ago. Since then, its potential has remained rather underutilized due to certain legalities and regulations. There was a vandalizing stereotype surrounding cannabis in the past century and the better part of this decade that hindered the progress of Cannabis science.

 Though researchers conducted experiments to unravel the therapeutic profile of cannabis and its derivative compounds, their efforts were largely limited to animal models. The results of animal studies are not translatable into humans, and therefore, the mystery hovering over cannabis has remained intact. 

In 2018, the FDA approved the first CBD based pharmaceutical grade drug known as Epidiolex. Children who had two severe forms of epileptic disorders used Epidiolex to control seizures. Epidiolex proved highly effective. To date, it is the only drug that has undergone extensive human clinical trials. GWS pharmaceuticals introduced Sativex, another CBD-based drug, in 2015, but it didn’t yield any favorable results. 

 Like CBD, THC may also have vast medicinal potential. Hitherto, the FDA has greenlit only two THC-based drugs. One is called Dronabinol, which is a gelatinous capsule used to treat symptoms of patients undergoing chemotherapy, such as vomiting, nausea, and weight loss, and appetite suppression.

The other is Nabilone. Nabilone is a synthetic cannabinoid containing THC, which may help chemotherapy patients control vomiting and nausea. It has proved highly effective in managing these symptoms as compared to other drugs that have largely failed. 

Both CBD and THC have enormous potential as viable medicines. Scientists suggest both have various therapeutic properties, including anti-anxiety, anti-inflammatory, and neuropathic and neuroprotective properties. 

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