Cannabis: Its Functions and Interactions| How Does it Affect Your Body?

Cannabis: Its Functions and Interactions| How Does it Affect Your Body?

  December 08, 2020    AVisenMD

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What is the difference between Marijuana and Hemp? 

Both Marijuana and Hemp belong to the Cannabis Sativa (L.) herbaceous plant. The terms used are based on the content of delta-9-tetrahydrocannabinol (THC) content found in each. Marijuana contains more than 0.3mg/gm of THC in the dry weight of the plant, where Hemp has less than 0.3mg/gm of THC content. While Marijuana is a schedule 1 drug, that is it has no significant medicinal value and is highly addictive, Hemp has been legalized in the states that have approved USDA programs. 

Our Endocannabinoid System: 

The endocannabinoid system (ECS) is an integral system that plays an important role in the development of the central nervous system (CNS) via a process called synaptic plasticity, whereby neurons change their interconnections based on the response to inner and environmental aspects. The ECS contains three parts: the endogenous cannabinoids, the cannabinoid receptors and the various proteins that function as enzymes for the synthesis and breakdown of these molecules. Two best studied endogenous cannabinoids are called 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (anandamide). Exogenous cannabinoids, such as THC, exert their biological effects by interacting with the cannabinoid receptors present in the CNS. Because of the common use of cannabis socially and the role of endocannabinoids in multiple biological processes, a lot of research has been done on the ECS. It regulates both physiological and cognitive processes and maintains overall health and homeostasis. The ECS is responsible for fertility, pregnancy, prenatal and postnatal development, mood, memory, appetite, sensation of pain and inflammation. Endocannabinoids play major roles in immunomodulation; they also possess anti-cancer and anti-inflammatory effects. Phytocannabinoids are cannabinoids extracted from the cannabis plant and agricultural hemp, called cannabidiol (CBD). 

Functions of THC vs. CBD: 

The exogenous cannabinoids, THC and CBD, that are extracted from the cannabis flower are originally in the form of weak acids. They undergo a chemical process called decarboxylation to finally become a more potent version of themselves. Possible medical roles of THC include neuroprotection, anti-convulsion, muscle relaxation. Whereas, CBD primarily functions as antioxidant, anti-neoplastic (anti-cancer), anti-anxiety, anti-acne. 

Drug-Drug Interactions: 

Drug interactions occur pharmacokinetically, that is by affecting the metabolism of drugs by altering their enzymes, such as the cytochrome P450 (CYP450). CYP450 is manipulated by interacting components through either induction or inhibition. Induction of CYP450, which may take a longer period of time (several days), causes reduced levels of drugs in blood as their metabolism is increased, which further reduces their effects on the body. On the other hand, the CYP450 inhibition takes little time and leads to an increase in drug concentration in the blood via slowed metabolism, which exaggerates the drug effects, resulting in adverse effects and related toxicities. All phytocannabinoids inhibit CYP40 enzymes, CBD being the strong inhibitor. 

• Warfarin and cannabis: Cases have been reported where the International Normalized Ratio (INR) was found to be increased in patients who were previously taking warfarin due to certain heart conditions and were co-administered with cannabis. The strongest risk factor is increased bleeding/hemorrhage and therefore, patients must be warned against it. 
• Clobazam and cannabis: Several studies have established the use of Clobazam and CBD adjuvently for the treatment of refractory epilepsy in children as they both inhibit the CYP450 enzymes. It has been found that when CBD is co-administered in such cases, the blood levels of Clobazam are increased many fold, which reduces the occurrence of epilepsy by almost 50%. 
• Rifampicin, Ketoconazole, Omeprazole and cannabis: Ketoconazole and Omeprazole (CYP450 inhibitors) were shown to increase while Rifampicin (a CYP450 inducer) was shown to reduce THC and CBD concentrations. 

 

References:

1. Alsherbiny, M. A., & Li, C. G. (2018). Medicinal Cannabis-Potential Drug Interactions. Medicines (Basel, Switzerland), 6(1), 3. https://doi.org/10.3390/medicines6010003

2. Namdar, D., Anis, O., Poulin, P., & Koltai, H. (2020). Chronological Review and Rational and Future Prospects of Cannabis-Based Drug Development. Molecules (Basel, Switzerland), 25(20), 4821. https://doi.org/10.3390/molecules25204821 

3. Cox, E. J., Maharao, N., Patilea-Vrana, G., Unadkat, J. D., Rettie, A. E., McCune, J. S., & Paine, M. F. (2019). A marijuana-drug interaction primer: Precipitants, pharmacology, and pharmacokinetics. Pharmacology & therapeutics, 201, 25–38. https://doi.org/10.1016/j.pharmthera.2019.05.001 

4. Lu, H. C., & Mackie, K. (2016). An Introduction to the Endogenous Cannabinoid System. Biological psychiatry, 79(7), 516–525. https://doi.org/10.1016/j.biopsych.2015.07.028