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Unchartered Waters: CBD & its Drug Interactions

Madds A.

February 8, 2021

Since the day Hemp farming was legalized in U.S, the range of the different roles CBD is playing in recent times is wide and often confusing or even overwhelming. Despite the spectacular rise in the use of CBD in many unique ways in recent times, some of which would perhaps raise a few eyebrows (only in a good way though), there is a cloud of ignorance around it to some degree.

CBD is short for cannabidiol, which is a chemical compound from the Cannabis sativa plant, namely marijuana or hemp, according to the US National Library of Medicine. Delta-9-tetrahydrocannabinol (THC) is the major active ingredient in marijuana, while Cannabidiol (CBD) is also obtained from hemp, which contains only very small amounts of THC. Out of the many cannabinoids compound in existence, THC and CBD are the most renowned members of the cannabinoid family.

THC is the main psychoactive compound in marijuana that produces the high-relaxing sensation or psychotropic effects. On the other hand, CBD is known to moderate the psychotropic effects produced by THC and therefore provides less of a psychotropic effect and more of an effect which is moderated and therefore the combined effect is mentally therapeutic. Both THC and CBD react with the endocannabinoid system of the brain in order to produce their effects. While THC stimulates the receptor (namely CB1) present in the endocannabinoid system and produces the high effect, on the other hand CBD alters the shape of the receptor, making it difficult for the THC to produce its effects, and therefore moderates or balances the effects associated with THC such as paranoia and anxiety.

There is a huge push for the production of CBD only medicines and products. This is due to the phenomenon that a drug with a single active ingredient is easier to develop, test, produce, prescribe and regulate as well as due to a wide range of health-related benefits CBD has to offer of its own. These range from anxiety, depression, schizophrenia, inflammatory and neuropathic pain, Parkinson’s disease, and different forms of inflammatory bowel disease, as well as certain types of cancer. It is also being used in the form of inhalers to quit smoking as per the 2013 study by Addictive Behaviors to a stress and anxiety buster.

However, before putting any chemical compound inside your body, you must be familiar with the chemical as well as with the working mechanisms of your own body. A large number of people aren’t familiar with either of them. Despite the effective and multi-purpose utilities of any chemical compound in the world, there are facts about CBD that one must be aware of before having a go at it. One such ‘not-so-talked-about’ fact is CBD’s interactions with other drugs and medications.

Although it’s a fact that CBD’s healing effects outnumber its side-effects by a huge margin, however just like any other compound, once in contact with other compounds, CBD is bound have a different set of interactions. These interactions tend to alter its original effect and make it not so effective at the end of the day. The interaction CBD has with these drugs is closely related to the interactions our body has with these drugs.

So out of all things, first let’s divert our attention to human body’s metabolic mechanisms and its interactions with different compounds.

Metabolic and CBD Drug Interactions

Whatever you consume, it will be broken down by your body in order to sustain life. Even when you take a drug or medication, it is broken down by the body in order to derive its effects. This process largely takes place inside the gut or the intestines and even the liver. When you consume food for example, it is broken down by the liver into its individual compounds in order for it to be used by the body.

Therefore, carbohydrates are broken down into sugars, fats into triglycerides, and proteins into amino acids. Subsequently, these individual compounds interact with enzymes which are proteins produced by the body to act as catalysts in these reactions and transform the compounds into metabolites (simpler molecules) that can then be used by the body, for the sustenance of the body and biological processes.

Similarly, when a particular drug or chemical compound is consumed by the body, it is broken down through similar process and the foreign substances that are harmful to the body are eliminated in their simplest forms.

The Showstopper

Cytochrome P450 (CYP450) is a group of enzymes that break down complex drugs/medications, into water-soluble compounds and extract the inutile substances from the body. The same CYP450 enzyme group interacts with the cannabinoids such CBD and breaks it down into simpler compounds.

Drugs such as ketoconazol, itraconazol, ritonavir, and clarithromycin inhibit CYP450 on interacting with it. This means that the interaction between the enzyme and these drugs slows down the enzyme’s effect and hence slows down the process of breaking down of these drugs. For the same reason, the administration of these drugs is strictly regulated. The delayed process would result in the medication being present in the body for a longer period of time than what is needed and hence, exaggerating its effect adversely. Interestingly, some drugs on interaction may also exaggerate the effect of CYP450 and hence, hastening the metabolic rate, resulting in the substances getting flushed out of the body sooner than expected. A table of the inhibitors and inducers of each CYP450 enzyme:

Now the question arises, how does CBD react with your body with such drugs being already present within? The answer is varying for different medications, since each reacts in a different way to CYP450 and hence causing an effect which may vary on coming in contact with CBD. For starters, it must be understood that CBD inhibits the activity of CYP450 enzymes by binding itself to the site where the enzymes show their effects and therefore, blocking the enzymes’ activity.

The effect is also known as Competitive Inhibitory Effect since the CBD competes with other drugs and medications to be metabolized on priority. The longer it takes to metabolize CBD, the longer the metabolic breakdown of the competing drugs is delayed and the longer they stay within the body. The resultant effect are adverse such as suppressed immune system, internal bleeding, nausea and in extreme cases even overdose of the drug.

Any drug compound which is metabolized by the CYP450 group can be potentially affected by the action of CBD either increasing its concentration in the body (which can be relatively more harmful) or decreasing it. Some of the compounds metabolized by the CYP450 enzymes; also known as substrates are:

• Caffeine, clozapine (Clozaril), theophylline – CYP1A2
• Carvedilol (Coreg), celecoxib (Celebrex), glipizide (Glucotrol), ibuprofen (Motrin), irbesartan (Avapro), losartan (Cozaar) – CYP2C9
• Omeprazole (Prilosec), phenobarbital, phenytoin – CYP2C19
• Amitriptyline, carvedilol, codeine, donepezil (Aricept), haloperidol (Haldol), metoprolol (Lopressor), paroxetine, risperidone (Risperdal), tramadol (Ultram) – CYP2D6
• Alprazolam (Xanax), amlodipine (Norvasc), atorvastatin (Lipitor), cyclosporine (Sandimmune), diazepam (Valium), estradiol (Estrace), simvastatin (Zocor), sildenafil (Viagra), verapamil, zolpidem (Ambien) – CYP3A5

Grapefruit juice is often held at par with CBD when it comes to its interactions with the CYP450 enzymes as both of them are inhibitors of the enzyme group. A majority of drugs and medications come with grapefruit juice warning on them.

Some of them are antibiotics, antihistamines, painkillers, cancer medication, blood thinners and also anti-depressants. CBD must not be consumed without any regulation or monitoring while one is on these medications. Adverse effects of CBD upon interaction with these drugs can be:

• Nausea
• Drowsiness
• Lethargy
• Vomiting
• Fatigue
• Diarrhea in some cases
• Loss of appetite
• In extreme cases internal bleeding and overdose

What Must Be Done?

CBD is more than often consumed as a pain reliever for many ailments such as cancer and arthritis. Keeping in mind CBD’s interaction with such medications, it is necessary that expert medical guidance is sought for in order to avoid any potential dangers which these interactions might pose to the body. In case of prior warnings that come along with the drugs, check the bottle for such warnings which declare these potential threats.

Seeking a doctor’s prescription would be the best thing to do if one is planning to take CBD as a supplementary medication. Keeping a strict check on CBD intake under monitoring is a must in case one is consuming CBD along with a drug indulges in interaction with it. A safe way forward after all, is the best way to reap the full benefits of CBD.