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CBD Drug Interactions Explained: What Drugs Should Not Be Taken With CBD

cbd and drug interaction

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Recent years have seen CBD’s popularity rise as it is proving to have wide-ranging therapeutic effects as well as being able to relieve a host of symptoms safely and effectively as well as do so in a manner that is not harmful to the body. The other most abundant phytocannabinoid in the cannabis plant, Tetrahydrocannabinol (THC), is intoxicating and psychoactive and CBD is not – these are unwanted yet inevitable parts of the experience of consuming high THC cannabis extracts.

In addition to seizure disorders, CBD has also been found to help relieve symptoms of other conditions. These include anxiety, depression, schizophrenia, inflammatory and neuropathic pain, Parkinson’s disease, Crohn’s and other forms of inflammatory bowel disease, as well as certain types of cancer.

However, even though most of the science indicates CBD oil can be safely used on its own, it is a highly potent compound that interacts with many different body systems. Therefore, CBD is shown to be an effective therapeutic agent, but it can also be rendered dangerous when combined with other substances, such as pharmaceutical drugs.

Let’s find out why.

Understanding Metabolism

As a prelude to understanding CBD’s interaction with medications, we absolutely must first understand the functioning of the body’s metabolism, the aspects involved in CBD metabolism, the way in which CBD is metabolized and how CBD affects something in the body called the Cytochrome P-450 system.

What Is Metabolism?

Metabolic rate is often referred to as a factor that affects how easily or rapidly one gains or loses weight. Scientifically speaking, this is what is known as basal metabolic rate, or how many calories an individual needs in order to function normally at rest.

The basal metabolic rate, on the other hand, is not the same as metabolic rate, as metabolic rate is the process by which foods are broken down and absorbed by the body, largely taking place in the gut and liver through the first-pass effect.

Simply stated, the liver breaks down food into its component compounds so that it can be utilized by the body. A carbohydrate is broken down into sugar, a fat into triglycerides, and a protein into amino acids. The body’s metabolism converts these compounds into metabolites under the control of enzymes, which then serve as fuel for cellular processes and building blocks for tissues and organs.

Metabolism of CBD

Just as food has to undergo this process, so does CBD, but in a very specialized form referred to as drug metabolism. In the case of a medication, the rate at which it breaks down into metabolites and how long those metabolites remain within the body is known as drug metabolism.

Consequently, CBD ingested through the mouth, whether in the form of an oil, tincture, capsule, or edible, passes through the digestive system before it enters the bloodstream through the intestines. CBD then travels to the liver via the blood and enters the liver through the hepatic portal. As CBD enters the liver, enzymes break it down into metabolites. After metabolizing, CBD can then be circulated throughout the body in the bloodstream.

The Cytochrome P450 System

Furthermore, it plays an important role in detoxifying and excreting foreign drugs (so-called xenobiotics) as well as other types of toxic substances, in addition to breaking down compounds into metabolites.

It does this via a system called the cytochrome P450 system (CYP). This system is composed of several enzymes which incorporate heme as a cofactor to process fat-soluble compounds into more water-soluble ones, aiding in their absorption and utilization.

Over 60% percent of any drug consumed is metabolized by the CYP system.

 The cytochrome P450 system is also used by pharmaceutical researchers and doctors to determine, calculate, and predict drug dosage effects as well as potential side effects.

Scientists can calculate accurate dose information using the average time it takes the drug or medication to process through the CYP if only one therapeutic compound is being processed by the liver and the system is generally healthy.

It is important to note, however, that there are certain compounds which can have an impact on the CYP system, like CBD, causing certain drugs to metabolize faster or slower than they normally would have.

CBD And The Cytochrome P450 System

Also, CBD is able to directly interact with the liver’s CYP system. Preclinical research indicates that CBD inhibits CYP enzyme activity by binding to the enzymatic site and replacing competing chemical compounds, thus inhibiting other chemical compounds from being metabolized.

The amount of CBD that you consume, how you metabolize it and the type of CBD product you use will all influence how CBD inhibits the binding of the cytochrome P450 binding proteins. The reason for this is that these factors determine how tightly the CBD molecules are bound to the enzyme’s active site, with stronger bonds resulting in greater competitive inhibition.

It means that CBD is on top when it comes to getting metabolized by CYP enzymes when compared with other medications. Therefore, CBD works to deactivate all other treatments that pass through the enzyme system.

A few factors determine how effective it is in its competition with other medicines, but mostly how much of the CBD reaches the bloodstream. There will be little or no effect on CYP activity if it is not very large, and the majority of the medication will be metabolized. Moreover, taking large amounts of CBD will bind to more of the sites of enzyme activity, which will inhibit the breakdown of more of the other medicine.

Why CBD’s Competitive Inhibitory Effect On The Cytochrome P450 System Is Important

A medication such as CBD, when metabolized in this way, both changes and prevents the metabolism of certain other drugs. As a result, a higher concentration of other drug compounds remains in the body at a single time.

Nonetheless, these elevated concentrations should be considered as potentially detrimental to health, including the risk of bleeding and the suppression of the immune system. But what is more troubling is the possibility of overdose.

CBD and Drug Interactions

A lot of people believe CBD is a biologically inert compound, but that’s not true. In contrast, CBD is similar to any other medication in that its pharmacokinetics and pharmacodynamics are complex, and its potential for interaction with other medications and medical conditions is significant.

CYP metabolizes therapeutic compounds, so CBD can interact with any compound metabolized by this pathway. When you are told by your pharmacist not to eat grapefruit, watercress, take St. John’s Wort, or take goldenseal, that may be an indication that your medicine is metabolized by the CYP system. The results of this test are not conclusive, so please always consult your pharmacist or doctor first (more about that later).

Researchers are also beginning to explore drug interactions with CBD more directly, along with the rise in popularity of CBD for medical and complementary purposes.

A list of prescribed drugs that interact with cannabinoids was created by two professors at Pennsylvania State Medical University. In their study, researchers looked for compounds in CBD products that interfere with or compete with the breakdown of other drugs.

They used products containing CBD alone and products that contained delta 9 tetrahydrocannabinol (THC). Researchers examined enzymes within the body that break down THC and CBD and compared these findings with prescribing information for similar medicines to look for overlap between the two.

The Pennsylvania State website provides a list of 57 medications that cause drug interactions. Medications that are used for thyroid hormones, oral contraception, and opioid pain relievers are included in this category. CBD can increase the levels of blood thinners, coumadin, and other medicines in blood by following the same mechanism that grapefruit juice uses. 

Medicines that fall under this list have a narrow therapeutic index, which means that there isn’t much difference between a therapeutic and toxic dose.

 By increasing drug action, this small margin makes these interactions medically problematic. Moreover, 139 other medicines were also listed that may interact with cannabidiol but do so with low risk, as well. 

 CBD and prescription drugs are the subject of many studies. The following are a few things to consider if you are thinking about using CBD. 

CBD should not be used if your medication contains grapefruit warning; look for the grapefruit warning on the label. People should avoid taking these medicines while eating grapefruit because of a grapefruit warning on the label.

In accordance with the FDA, grapefruit consumption can cause an increased level of medicine in our bloodstream, leading to overdoses and side effects. Now that we know both CBD and grapefruit juice inhibit drug metabolism, it stands to reason that any medicine that prohibits grapefruit juice also causes adverse effects when consumed with CBD.

Medications That Come With A Grapefruit Warning.

There are many medications that come with grapefruit warnings, but not all of them require that grapefruit be avoided. Before thinking about where to purchase CBD oil or grapefruit medicines, patients, who are taking these medications, should consult with their doctor before taking CBD.

  • Blood thinners and betablockers
  • Anticancer medications
  • Antibiotics and antimicrobials
  • Antihistamines
  • Antiepileptic drugs, valproic acid
  • Antihypertensive medicines
  • Cholesterol medications
  • Corticosteroids
  • Medications for erectile dysfunction
  • Gastrointestinal medications used to treat GERD, nausea
  • Heart rhythm medications
  • Immunosuppressants
  • Antidepressants, anxiety medications, and mood-stabilizing drugs
  • Prostate medicines

List of drugs and medications which could be contraindicated for use with CBD

Indiana University Department of Medicine lists the following medications and pharmaceuticals that could be contraindicated for use with CBD:

Medication groupExamples
Steroids and corticosteroids hydrocortisone, cortisone, prednisone, triamcinolone and dexamethasone
HMG CoA reductase inhibitors (statins) atorvastatin, fluvastatin, lovastatin, pravastatin, pitavastatin, simvastatin and rosuvastatin
Calcium channel blockers amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nisoldipine and verapamil
Antihistaminesbrompheniramine. cetirizine, chlorpheniramine, clemastine, diphenhydramine, fexofenadine and loratadine
Prokinetics (motility drugs) domperidone, metoclopromide, levosulpiride, renzapride and pruclopride
HIV antiviralsabacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir alafenamide and disoproxil fumarate as well as zidovudine
Immune modulators immune globulins, immunosuppressive agents and immunostimulants, for example bacterial and viral vaccines
Benzodiazepines alprazolam, clobazam, clonazepam, clorazepate, chlordiazepoxide, diazepam, estazolam and lorazepam
Antiarrythmics amiodarone, flecainide, procainamide, propafenone, quinidine and tocainide
Antibiotics amoxicillin, doxycycline, cephalexin, ciprofloxacin, clindamycin, metronidazole, azithromycin, sulfamethoxazole-trimethoprim, amoxicillin-clavulanate and levofloxacin
Anestheticsbarbiturates, amobarbital, methohexital, thiamylal, etomidate., ketamine and propofol
Antipsychotics aripiprazole, asenapine, cariprazine, clozapine, lurasidone, olanzapine, quetiapine, risperidone and ziprasidone
Antidepressants citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vortioxetine and vilazodone
Anticonvulsants / Anti-Seizure Medications acetazolamide, carbamazepine, clobazam, clonazepam, ethosuximide, fosphenytoin, gabapentin, lacosamide, lamotrigine, levetiracetam, methsuximide, nitrazepam, oxcarbazepine, paraldehyde, phenobarbital, phenytoin, primidone, topiramate, valproic acid, vigabatrin, felbamate, tiagabine hydrochloride and zonisamide
Beta blockersacebutolol, atenolol, betaxolol, betaxolol, bisoprolol fumarate, carvedilol, esmolol, labetalol, metoprolol, nadolol, nebivolol, penbutolol, propranolol, sotalol and timolol
Proton-Pump Inhibitors (PPIs)omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole and dexlansoprazole
Angiotension II Blockersazilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan and valsartan
Oral Hypoglycemic Agents sulfonylureas, meglitinides, biguanides, thiazolidinediones, α-Glucosidase inhibitors, DPP-4 inhibitors, SGLT2 inhibitors and cycloset
Sulfonylureasglynase, micronase, amaryl, diabinese, glucotrol, tolinase and tolbutamide

Some medications are prodrugs since they need to be metabolized into their therapeutic compounds instead of being medically useful compounds by themselves (like most medications). The body processes the inactive compound into its active compound once it enters the body.

If the CYP system is involved in this process, inhibitors can mean that insufficient amounts of the active constituent of the drug compound are available in the body, which can result in some drugs failing to deliver the intended therapeutic effects.

Codeine, for example, is metabolized into morphine as a prodrug. Another popular medication in this category is lisdexamfetamine, marketed under the names Vyvanse and Concerta.

Why You Should Always Speak To Your Doctor First

There is no way to exhaustively list all the medications on which CBD could interact. Not all medications listed above cause an interaction (although it is wise to err on the side of caution if you are taking any of these medications).

It is therefore imperative that you seek medical advice before using any CBD product or oil. Additionally, your doctor can monitor both the therapeutic effects of CBD and the side effects of any medications you are currently taking, as well as any potential interactions between the CBD and the drugs. You can also talk to your doctor about what dosages of CBD and medication you should take simultaneously in order to ensure that you can do so safely.

Side Effects To Look For When You Take CBD And Medication

It is possible to experience some side effects if you increase the CBD or medication dose, such as drowsiness, nausea, sedation and decreased effects of medications such as breakthrough seizures. Fatigue, weight fluctuations, appetite changes, and diarrhea are some of the common side effects of CBD use. 

CBD use may increase the risk of cardiac disorder. Blood pressure fluctuations and heart rhythm disturbances may occur when both medication and CBD use have similar effects on the cardiovascular system.

Key Takeaways

CBD has been well studied and the World Health Organization cateforized it as a safe and well tolerated substance, while producing mild and few side effects. Furthermore, CBD acts as a real therapeutic agent for a number of conditions because it has a profound effect on a number of systems within the body. Yet, one should also remember that it is also this that makes it potentially dangerous when mixed with other drugs and should be treated with care.

If you are taking other medications, do not take CBD products without consulting your physician. You may be putting your life at risk by stopping your medicines to try CBD. Care must be taken when taking grapefruit warning medications. Before using CBD in conjunction with any other prescription drugs, you should seek professional advice.

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This article was written by an independent and third-party author specialising in CBD, hemp and cannabis research. Any opinion, advice or recommendation expressed in the article does not reflect the opinion of Kana Biosciences Ltd. or any of our employees. 

All information on this site is provided for informational purposes only and is not to be construed as medical advice or instruction nor meant to substitute for the advice provided by your own physician or other medical professional. Our products are not intended to diagnose, treat, cure or prevent any disease. We do not make any health claims about our products and recommend consulting with a qualified medical doctor or physician prior to consuming our products or preparing a treatment plan for any and all diseases or ailments. It is especially important for those who are pregnant, nursing, chronically ill, elderly or under the age of 18 years of age to discuss the use of these products with a physician prior to consuming. 

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