The fact that medications and supplements can interact inside your body if you take them at the same time is no news. It’s why your doctor pointedly asks what medications you are currently taking. (S)he is not just being nosey—the doctor needs to know if a medication (s)he might prescribe you will interact adversely with something you are already taking.
That’s why it is important to always be very clear with your doctor about everything you take! Even over-the-counter medications and supplements can produce unpredictable, harmful effects when mixed with the wrong drug in your system.
What is fairly new to the conversation is CBD, especially considering how new CBD oil and related supplements are to the market — or at least, the legal market.
While new to the modern medical discussion, the source of CBD, cannabis, has a long history in traditional medicine. Archeological finds in Japan have revealed preserved cannabis achenes dating back 10,000 years. The earliest known cultivation of cannabis dates back to Taiwan thousands of years ago, with Korea and China also heavy users. Cannabis was used to make hemp and paper, it was consumed, and possibly it was also appreciated for its psychoactive properties. The drug soma, mentioned in the vedas (Hindu scriptures), may have been cannabis.
CBD is short for cannabidiol, one of over 100 chemicals known as cannabinoids found in cannabis plants. It is found in all cannabis plants, including industrial hemp and the two strains of marijuana, cannabis sativa and cannabis indica. When people consume marijuana, they consume significant amounts of CBD. They also consume a significant amount of THC, a different cannabinoid known for its psychoactive properties that cause the marijuana “high”.
Unlike THC, CBD is not a psychoactive substance. It creates no “high.” However, CBD compounds remained Schedule 1 narcotics, in the same class as heroin, like all other cannabinoids. In 2018, however, CBD was made legal by a Federal agricultural bill, as long as it was made from industrial hemp rather than marijuana and as long as the final product contained no THC (or only trace amounts of it).
The checkered legal history of cannabis—including widespread criminalization throughout the 20th Century that is only just lifting in the 21st Century—belies the fact that the body actually produces many cannabinoids naturally. The body even has a system for these cannabinoids—the endocannabinoid system, a series of receptors that the body’s natural cannabinoids bind to and that help the body maintain homeostasis—internal balance.
When THC, the psychoactive cannabinoid, enters the bloodstream, it actually binds to the endocannabinoid receptors, CB1 and CB2. CBD, by contrast, does not bind to CB1 and CB2 receptors. However, it is suspected that CBD interacts with the endocannabinoid system by helping regulate the body’s production of its own natural cannabinoids.
Since legalization, CBD has enjoyed galloping popularity. The fad has vaulted CBD to near-mythical status in terms of its reputed health benefits. Early studies and anecdotes have posited CBD as:
This is just a partial list of the benefits CBD is reputed to confer. No fewer than 50 conditions have entered the conversation as possible indicators for therapeutic CBD consumption. These conditions include, but are not limited to:
This list is impressive enough to bolster CBD’s reputation as a “miracle cure.”
The problem is CBD has produced few actual miracles in the form of clinically significant results. Partially owing to its short history as a legal compound in the developed world, scientific studies of the effects of CBD are few and far between.
Since legalization, many studies have been conducted, but extracting medically-significant results from trials of any substance can be a long process. Some studies will take years to reach their conclusions. Others contain structural defects, like a small sample-size, lack of double-blind placebo control, or the use of animal trials to extrapolate encouraging results for the benefit of the human population.
CBD also suffers from the strength of its weakness—so many conditions are reputed to be susceptible to CBD that it would take decades and lots of money to test them all. Many of the conditions on the list of CBD indicators made the list on the strength of anecdotal evidence—somebody somewhere took CBD oil one time and experienced a miraculous remission of their cancer.
While heartwarming, this is not a scientific result. Many more people with the same condition must be studied to establish causation. Without it, trusting CBD as a “cure” for that condition is little better than superstition.
Another consequence of the limited scientific literature on CBD is that we don’t fully understand how it interacts with other substances. This makes the mixing of CBD with any other substances inherently risky.
It is worth noting that little evidence as to the dangers of CBD exists either. All the evidence available suggests that CBD is a remarkably benign substance. Unlike THC, it produces no psychoactive effect (i.e. no “high”). Additionally, documented side effects of CBD are rare and mild, typically limited to conditions like dizziness or an upset stomach.
Additionally, adverse side effects don’t seem to be age-specific. CBD seems to have no negative effects specific to the elderly, children, or even infants. Pregnant mothers may have extra concerns to consider, and CBD may transfer to breast milk, but early results show promise for CBD to cross generations in its beneficial effects.
Interactions with drugs are another story. Again, the research is still in its infancy, but CBD does have some documented effects on the body that raise concerns about the way CBD might interact with other medications—even a great many medications. Here’s an in-depth look at how CBD may interact with other substances, including over-the-counter medications and prescription drugs.
The most important thing is to always be clear with your doctor about what substances you ingest. If you take a regimen of CBD, or if you plan to start a regimen of CBD at any time in the near future, make sure to bring it up with your doctor when they ask you what substances you currently take, especially when the doctor prescribes you medication.
The key to understanding how CBD and medications could adversely interact is to understand how the body metabolizes the various substances.
Metabolism is the chemical process by which the body breaks down and uses substances you put into it, including both food and drugs. Metabolism consists of two distinct processes: anabolism, the buildup of substances, and catabolism, the breakdown of substances.
Both processes are based on biochemical reactions. The key catalysts inside our bodies that cause biochemical reactions are called enzymes. These chemicals mix with the substances we ingest and cause the chemical reactions that allow metabolism to happen.
There is a specific enzyme that metabolizes between 50% and 60% of all clinically-prescribed medications. It is somewhat unimaginatively called CYP3A4, and it’s a subclass of enzymes with the equally unimaginative name CYP450.
Medications that depend on CYP3A4 for their catabolism include such staples as acetaminophen (Tylenol), codeine, ciclosporin (cyclosporin), diazepam (Valium), and erythromycin
CYP3A4 is found in the liver. When a medication enters the bloodstream, it passes through the liver where it interacts with CYP3A4 enzymes and causes catabolism, allowing the body to use the medication for whatever purpose it is intended for. CYP3A4 is also responsible for the metabolism of cannabinoids like CBD.
One documented effect of taking CBD is the inhibition of CYP3A4 production. When you take CBD oil, your body may have less CYP3A4 in it, and as such become an inefficient metabolic machine for more than half of the prescribed drugs on the market.
Without enough CYP3A4, the body may not metabolize medications as quickly as they are designed to be. This might cause higher-than-expected levels of the medication to linger in the bloodstream, failing to deliver the full beneficial effect while also prolonging any negative side effects. Without efficient metabolism of a medication, the doctor’s prescribed dose could result in toxic levels of the drug building up.
Interestingly, CBD isn’t the only substance that inhibits the production of CYP3A4. Examples include clarithromycin, diltiazem, erythromycin, itraconazole, ketoconazole, ritonavir, and verapamil.
If you take a strong CYP3A4 inhibitor before taking CBD, your body might not be able to process the CBD efficiently, depriving you of fast access to its effects while maintaining your blood-CBD levels for longer.
Other medications actually induce the production of CYP450. Examples include rifampin, phenytoin, and phenobarbital. If you take one of these medications in conjunction with CBD, the CBD might metabolize faster, due to the higher concentrations of the metabolic enzymes in the liver.
CBD is widely considered to be a fairly benign substance. However, the body of clinical and scientifically significant study data on CBD is very limited. This is partially due to the longstanding illegal status of cannabinoids. CBD has a relatively short history of legal use and a rising level of public acceptance.
With the hype around CBD at an all-time high, we can expect many more studies to yield a wealth of new data, but it will take years for the studies to be completed, the papers published, and the data fully understood so that scientific conclusions can be drawn. Until then, experiments with CBD will always be conducted at the user’s own risk.
Generally speaking, mixing CBD with any other medication that depends on CYP450 enzymes, inhibits the production of CYP450, or induces the production of CYP450 enzymes is asking for trouble. Medical science can’t quite tell us exactly what kind of trouble and how much of it, but do you really want to find out?
Since more than half of all medications depend on CYP450 enzymes to be metabolized, check carefully which of your prescribed and over-the-counter medications fit this criterion and look for delayed or suppressed effectiveness, as well as extended side effects and possible signs of drug toxicity.
Examples of drugs with CYP450 effects that represent cause for concern include:
One class of drugs to be particularly wary of are called prodrugs. These drugs must be metabolized to become active, therapeutic compounds. The version of the drug you ingest is actually inert and depends on the biochemical reaction with CYP3A4 to become active at all. If CBD suppresses your CYP3A4 levels, a prodrug might not even work at all.
Examples of prodrugs include codeine, which gets synthesized into morphine in the liver. ADHD drugs Concerta and Vyvanse are two others.
Vicodin is the most commonly-prescribed pain killer. An opioid, it is habit-forming and can produce side effects including dizziness, nausea, impaired breathing, and cognitive impairment.
Opioids are not known to interact adversely with CBD. The exception is codeine, a prodrug that only activates as a painkiller when it is metabolized, a process that CBD can inhibit. Vicodin does not share this property with codeine.
Simvastatin is the first of a class of drugs known as “statins,” a type of drug prescribed to persons suffering from high cholesterol. It remains the most popularly-prescribed statin.
Simvastatin is metabolized by CYP3A4. Taking CBD in conjunction with simvastatin may decrease the drug’s effectiveness, prolong its side effects, and possibly lead to medication toxicity due to the drug’s prolonged presence in the bloodstream.
Linisopril is prescribed to patients suffering from high blood pressure, a precursor to kidney failure. It is also indicated for people suffering from diabetes and congestive heart failure.
Lisinopril is classified as angiotensin converting enzyme (ACE) inhibitor. While its function is to inhibit the production of enzymes, it is not known to inhibit CYP3A4, meaning it is unlikely to inhibit the function of CBD. It is also not a prodrug, unlike some of its analogs, meaning it is less likely to be affected by an inhibition of CYP3A4 that may result from ingestion of CBD.
Lovothyroxine is the generic form of the thyroid medication Synthroid. It is a synthetic thyroid hormone used to treat hypothyroidism (an underactive thyroid). An excess of this hormone can produce chest pain, rapid heart rate, headache, sweating, anxiety, and weight loss.
Lovothyroxine is known to inhibit CYP450 enzymes, meaning it could inhibit the effects of CBD oil.
The antibiotic azithromycin is usually prescribed to treat throat, sinus, and ear infections. It can also be prescribed to treat bronchitis, pneumonia, and certain bacterial sexually transmitted infections. It may produce the side effects of vomiting, gas, bloating, and diarrhea.
Unlike its relative erythromycin, azithromycin only metabolizes weakly with CYP450 enzymes and is not known to either stimulate or inhibit the production of CYP450 enzymes. There is little or no indication that azithromycin will interact adversely with CBD.
The generic version of the drug Glucophage, metformin is used to treat type 2 diabetes. Common side effects include gas, nausea, bloating, reduced appetite, and diarrhea.
Metformin is not metabolized in the way most other drugs are, meaning changes in CYP3A4 due to CBD ingestion will most likely not affect it. However, metformin is known to be a strong CYP3A4 inhibitor in its own right, meaning it could inhibit the effectiveness of CBD metabolism.
Lipitor is another statin, commonly prescribed to patients suffering from high cholesterol. It is also prescribed to patients suffering from coronary artery diseases as a safeguard against stroke, heart attack, and chest pain. It may also cause diarrhea, constipation, muscle pain, fatigue, gas, heartburn, and headaches.
Lipitor is metabolized by CYP3A4. Taking CBD in conjunction with simvastatin may decrease the drug’s effectiveness, prolong its side effects, and possibly lead to medication toxicity due to the drug’s prolonged presence in the bloodstream.
The generic form of the drug Norvasc, amlodipine is a calcium channel blocker. It is prescribed to prevent chest pain and treat high blood pressure. It can cause headaches, dizziness, chest pain, and swollen extremities.
Amlodipine is metabolized by CYP3A4. Taking CBD in conjunction with simvastatin may decrease the drug’s effectiveness, prolong its side effects, and possibly lead to medication toxicity due to the drug’s prolonged presence in the bloodstream.
Amoxicillin, a relative of the revolutionary antibiotic penicillin, is used to treat many kinds of bacterial infections, including skin, throat, ear, tonsil, and urinary tract infections. Possible side effects include heartburn, nausea, rash, diarrhea, itching, and abdominal pain. Some people are also allergic to amoxicillin.
Studies have not demonstrated the propensity for amoxicillin to inhibit the production of CYP3A4, meaning it is unlikely to produce an adverse reaction with CBD.
Hydrochlorothiazide is a diuretic. It is prescribed to patients suffering from high blood pressure. It is known to produce side effects like electrolyte imbalance, rash, fatigue, light sensitivity, and low blood pressure.
Hydrochlorothiazide is not metabolized by CYP3A4, nor is it known to inhibit or stimulate the production of the enzyme. This means it is not likely to produce an adverse reaction with CBD.
Since it became legal and took the wellness-products marketplace by storm, CBD has become available for ingestion in a variety of methods. Some of the most popular and readily available formulations include:
Most of what we think of as orally-ingested “CBD oil” is actually a tincture. This is a pure extract of CBD in liquid form, suspended in water and/or alcohol. CBD tinctures can be dropped under the tongue (“sublingually”) and absorbed through the lining of the lower mouth, or they can be mixed into a beverage and drunk for absorption in the gut.
CBD tinctures typically include a precise numerical formulation of the CBD content in milligrams. This is useful because you can accurately gauge the dose you are taking. Tinctures are beginner-friendly, but even seasoned CBD users tend to prefer them.
CBD tinctures only take about 20 minutes to take effect when applied sublingually and last several hours.
CBD oils, creams, and moisturizers are meant to be applied directly to the skin, usually directly to the area experiencing pain or inflammation. The CBD in the cream absorbs through the skin and enters the bloodstream.
CBD creams and moisturizers may be mixed with soothing agents like menthol. They absorb more slowly through the skin and in smaller amounts, taking about 90 minutes for peak effectiveness.
CBD can also be ingested through the gut by swallowing a capsule or eating a CBD-infused edible, which could take the form of a baked good, gummy, or other form.
Gut absorption is slower than sublingual absorption. Edibles and capsules take between 30 and 60 minutes to begin to take effect.
CBD is available in beverage form for an additional method of gut absorption.
“Vaping” is one of the most popular ways to ingest CBD. Short for vaporization, vaping involves heating up a viscous CBD mixture into vapor, and then inhaling it using a specialized, electrical powered vaporizer, like a battery-powered “e-cigarette” or “vape pen,” or a desktop vaporizer.
Vaping has become a cultural touchstone, especially with younger generations. A key to its popularity, however, is how fast substances are absorbed when inhaled. Like oxygen, vaporized CBD enters the bloodstream rapidly through the lungs, reaching its peak effect in mere minutes.
One thing all methods of CBD consumption have in common is that they all introduce CBD into the bloodstream. This is true whether it is dropped under the tongue, absorbed through the gut, absorbed through the skin, or inhaled. Ultimately, CBD will enter the bloodstream, where it makes its way to the liver for metabolism by CYP3A4 enzymes.
This means that regardless of the method of consumption, CBD is likely to interact with other medications in the same way.
Different consumption methods will produce different onset times. However, the method of consumption may affect the timing of your CBD dosage such that the drugs don’t interact. For example, if you want to take CBD after taking codeine and don’t want the drugs to interact, you could take CBD as an edible a whole hour earlier than you could vape it, since your body will have an extra hour to process the codeine before the CBD makes it to your liver.
Despite the hype, CBD is still in its early phases as a subject of serious scientific study. This includes the ways in which it interacts with other substances in the body.
CBD has a reputation for being harmless, inasmuch as any substance is considered harmless. Studies to date don’t do a whole lot to disprove it. Even as trials are ongoing, CBD remains legal and widely available in outlets ranging from dispensaries to smoke shops to specialty stores to pharmacies to grocery stores. There are few reasons not to try it.
Still, it is worth familiarizing yourself with the known ways in which CBD affects the body, especially the metabolism, and how these effects could reduce, enhance, or even nullify the effect of other drugs you may depend on.
Most notably, CBD is sensitive to CYP3A4, the enzyme responsible for its metabolism. Drugs that stimulate the production of this enzyme may speed up the metabolism of CBD, while drugs that inhibit the enzyme may slow and/or reduce the effectiveness of CBD.
CBD itself has been shown in studies to be an effective inhibitor of the CYP3A4 enzyme, a chemical catalyst responsible for the effectiveness of more than half of all prescribed drugs. A patient who takes CBD in conjunction with a medication that depends on CYP3A4 for its metabolism risks reducing the effectiveness of the medication in question. It may negate the effect entirely or may even cause toxic levels of the drug to remain in the blood stream even if the patient takes the prescribed dose.
The most important step you can take is to tell your doctor about the CBD you ingest and the CBD you intend to ingest. With legality and social acceptance surging, there’s no reason not to.
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