One of the biggest concerns when taking CBD is its potential interaction with over-the-counter drugs, prescription medication, and other substances. Pills, alcohol, and certain food items produce different effects when taken at the same time.
Caffeine alone has 82 identified drug interactions, 25 of which produce moderately severe to severe side effects. Even seemingly harmless ingredients such as black pepper are known to interact with many prescription drugs. You probably have noticed that labels on some medicine bottles warn you not to consume grapefruit when taking medication because it can significantly alter the way the body metabolizes the drug. Herbs like watercress, St. John's Wort, and goldenseal produce similar effects.
Just like other chemical substances that you put in your body, CBD acts on certain receptors as it metabolizes and exits from your system. These interactions create the potential for CBD to interfere with current medications that you are taking.
Potential interactions between cannabis and drugs have been identified as relatively mild. In fact, some substances seem to work better when mixed with cannabinoids.
Interactions between chemical compounds can produce two types of effects: additive and synergistic.
When the interaction between two chemicals produces an effect that equals the sum of their parts (e.g. 1+1 = 2) it is called additive.
When the interaction between two chemicals produces an effect that is greater than the sum of their parts (e.g. 1+1 = 3) it is called synergistic.
Combining CBD with another substance can create a synergistic effect – leading to an exaggerated response in the body. When CBD interacts with a substance that is metabolized by the same receptors in the body, it can modify the potency and effectiveness of the other substance.
CBD can prevent your system from metabolizing certain compounds which slows down the elimination of a drug from your body. Drugs that stay too long in your system can be dangerous especially if you are taking powerful painkillers such as oxycodone and fentanyl.
Even if the interaction is potentially beneficial, you should work closely with your physician to closely monitor your CBD dose.
It is also important to note that THC/CBD ratios vary in each strain profile. Different amounts of cannabinoids and terpenes in your CBD oil can influence its effects.
While most of the available research indicates that CBD oil is safe for human consumption, it does pose a few risks when taken in combination with certain substances.
One of these risks is the inhibition of the Cytochrome P450 enzyme in the liver.
CBD interacts with drugs the same way grapefruit does – it inhibits the metabolizing function of the Cytochrome P450. And if you cannot take grapefruit juice with a particular drug, then you should not take CBD too.
Cytochrome P450 and prescription drugs
Cytochrome P450 is a class of enzymes in the liver that play a significant role in breaking down drugs and toxins that enter the body – including over 60% percent of drugs on the market. These include Valium, Xanax, Klonopin, antihistamines, antiretrovirals, and steroids.
According to the Davis Drug Guide, there are more than 50 enzymes that process and eliminate toxins from the body. The one responsible for the metabolism of most prescription drugs is the CYP3A4 enzyme.
When writing prescriptions, doctors have to consider the average amount of time it takes for a drug to be processed by the P450 system before determining an appropriate dosage.
If a patient is taking only one drug and the system is generally healthy, medical practitioners can easily come up with accurate dosage information. When you introduce another substance that has the ability to alter processing times, the drug could metabolize slower or faster. If the Cytochrome P450 system is unhealthy due to liver disease or other pre-existing conditions, it might not be able to metabolize the drug at all.
How CBD interacts with the Cytochrome P450 system
CBD can increase or decrease the effects of prescription drugs when it interacts with receptors in the human endocannabinoid system (ECS). [R]
CBD is known to inhibit the ability of Cytochrome P450 enzymes to metabolize certain drugs, leading to a much longer processing time.
When the CYP450 system stops or slows down its metabolizing function, higher levels of a drug you took stays in your system at one time. This can lead to adverse reactions and even overdose.
If CBD is preventing a drug from accessing the CYP3A4 enzyme, the drug stays in your body much longer. This makes it more potent and leaves you vulnerable to its actions and side effects. CBD could also keep certain drugs from having a timely effect. [R]
Another important role of CYP enzymes is activating certain substances. Medications called prodrugs remain inactive as it enters your body. They will not work until they are broken down by the CYP enzymes. If CBD is blocking these enzymes, it can render prodrugs totally useless.
The interaction between CBD and Cytochrome P450 is most prominent in anti-seizure medications designed for treating epilepsy.
One study in 2015 found that the anticonvulsant clobazam (CLB) and CBD both metabolized along the CYP pathway. During the 8-week trial, 13 children with refractory epilepsy took CLB and CBD together. The researchers found elevated blood concentrations of CLB, with 10 of the 13 subjects reporting side effects. The simple remedy was to reduce the dosage of CLB.
The good news is that 9 of the 13 epileptic kids experienced a reduction in seizures by more than 50 percent. The team then concluded that CBD in combination with CLB is a safe and effective treatment for refractory epilepsy.
If you are taking medication together with CBD, you should consult your doctor to make sure you are consuming both products safely and effectively.
Drugs that interact with CBD
CBD can potentially interact with any drug that is metabolized by CYP enzymes. According to the Indiana University Department of Medicine, drugs that are known to pass the CYP450 pathway include:
- Angiotension II blockers
- Beta blockers
- Calcium channel blockers
- HMG CoA reductase inhibitors
- HIV antivirals
- Immune modulators
- Oral hypoglycemic agents
Not all medication within these categories will cause an interaction with CBD. It is also possible that medications outside the list can have an impact when taken with CBD. Always consult your doctor before supplementing with CBD oil.
As mentioned earlier, prodrugs will only have a therapeutic effect after they are metabolized. Codeine is a popular drug that is metabolized into morphine. Vyvanse and Concerta are ADHD medications that also fall into this category. If these drugs are not processed by the CYP3A4 enzyme, there will be very little active compound to achieve the desired therapeutic effect.
If you have liver issues and are worried that your CYP450 pathway may not be functioning properly, your doctor can test the system to ensure that the drugs you are taking can provide you with the expected relief.
CBD and drugs that control blood sugar levels
According to Murray Mittleman, associate professor of medicine at Harvard Medical School, cannabis smokers have better carbohydrate metabolism than non-users. As lead author of a study in 2013, Mittleman observed that fasting insulin levels were lower and the patients appeared to be less resistant to the insulin produced by their body to maintain a normal blood-sugar level.
Several studies have also shown that cannabis can help lower rates of obesity and diabetes.
However, there are very few studies that have looked specifically at how CBD, THC, and other cannabinoids interact with drugs that impact blood sugar levels. If you have diabetes or are taking medication to control glucose levels, inform your doctor if you notice any side effects from CBD so they can make appropriate adjustments.
CBD and drugs that lower blood pressure
There is insufficient information on how CBD interacts with medication designed to lower blood pressure.
THC, on the other hand, is known to simultaneously activate CB1 and CB2 cannabinoid receptors. This can trigger a cardiovascular stress response and elevate cardiac oxygen consumption while reducing blood flow to the arteries. While reports of adverse side effects are rare, patients who are taking blood pressure medication must exercise caution when consuming THC.
CBD and blood thinning drugs
CBD may possibly slow down the metabolism of blood thinners (warfarin, heparin) as well as drugs with a risk of blood thinning (ibuprofen, naproxen). [R]
Studies have shown that CBD can also increase the effects of these drugs. The longer a drug stays in the body, the higher the risk of bleeding. Taking CBD with blood thinners should be closely monitored by a medical professional. [R]
CBD and opioids
The analgesic properties of cannabis are well-established. More and more medical professionals are coming forward to suggest cannabis as alternative pain medication and possibly provide a solution to the current opioid crisis. [R]
From a toxicity perspective, cannabis as a substitute to narcotic medications would be a far better first-line treatment for chronic pain. [R]
But what if cannabis is mixed with opioid therapy? Could cannabis reduce dependency on opioids or increase the risk of abuse?
Dr. Donald Abrams, chief of hematology-oncology at San Francisco General Hospital, examined the effects of combining vaporized cannabis with opioids in a small study in 2011. The findings showed no significant change in opioid concentrations in the blood after exposure to cannabis. The subjects also reported a 27% decrease in pain following cannabis administration.
Dr. Abrams concluded that cannabis can safely augment the analgesic effects of opioids while reducing opioid doses, lowering the risk of dependency, and presenting fewer side effects.
CBD and Adderall
Adderall is commonly prescribed for patients who have attention deficit disorder (ADD) and attention deficit hyperactivity disorder (ADHD). It is the drug of choice of many college students as Adderall is known to improve the ability to concentrate and boost academic performance.
Adderall is also known for its side effects which include fatigue, depression, and anxiety which are felt most when the drug begins to wear off.
CBD has calming properties which could possibly weaken Adderall. This can create a more balanced feeling if the effects of Adderall are too strong. It must be noted that taking CBD during the comedown may cause excessive fatigue or feelings of relaxation.
CBD and antidepressants
The most popular antidepressants are SSRIs, SNRIs, and tricyclic. These medications are designed to relieve symptoms of anxiety and depression although they do not work for everyone. Some people are unable to feel relief from antidepressant medications alone.
When CBD interacts with the endocannabinoid system, it works on receptors that are responsible for regulating mood and emotions. Studies have suggested that CBD may relieve symptoms of depression through these interactions in the brain. Patients who have added CBD to their SSRI medications have reported improved symptoms.
Combining CBD and antidepressants is not without risk. CBD has the potential to inhibit the metabolism of many antidepressants leading to adverse events.
CBD and anti-psychotic drugs
The Department of Health has stated that THC should not be used by people with acute psychosis or unstable psychiatric conditions. CBD oil that does not contain any THC can potentially reduce symptoms of psychosis.
As with antidepressants, CBD can interact with antipsychotic medications. It has been found to slow down the elimination of some antipsychotic medications from the body.
Talk to your healthcare provider before mixing CBD oil with antipsychotic drugs. [R]
CBD and sedatives
Benzodiazepines (ativan, valium), barbiturates (phenobarbital), and narcotics (codeine) are known to produce a calming effect by influencing GABA neurotransmitters in the central nervous system. CBD, THC, and terpenes (myrcene and linalool) can also produce sedative effects through this pathway.
Cannabis creates an additive effect when combined with sedatives. It does not seem to elevate blood levels or increase the power of sedatives as would be the case in synergistic effect.
While THC can induce drowsiness and lethargy, the sedative effects of CBD are calming and wake-inducing.
There has been no report of negative effects from the interaction between CBD and sedatives but the potential impact of this combination is not fully known. To be sure, avoid mixing CBD with sedatives.
CBD and mood stabilizers
Mood stabilizers are often prescribed for the treatment of bipolar disorder and other mental health issues. Popular medications include lithium, lamotrigine, and valproic acid.
Studies have shown that CBD may have the same effects as lithium in helping improve mood in bipolar disorder patients.
There is a higher risk for mood swings in people who are suffering from bipolar disorder, which is why patients should not take anxiety-inducing THC.
CBD also has the potential to interact with mood stabilizers through the CYP450 enzyme system, as it does with antidepressants and antipsychotic medications.
CBD and anti-anxiety medication
Cannabis has been known to reduce anxiety for decades. It helps people relax with its calming effects. Benzodiazepines such as Xanax, Valium, Klonopin, and Ativan are often prescribed to patients who are dealing with anxiety.
Combining CBD with benzodiazepines has the potential to increase sedation. Cannabis products that contain THC may also worsen anxiety symptoms. Be sure to monitor side effects to ensure the safe administration of CBD and benzodiazepines.
CBD and anti-seizure medication
CBD has been proven to be an effective anti-seizure therapy for epilepsy patients. But without medical supervision, CBD can create problems when combined with anti-seizure medication.
In 1992, a study by Lester Bornheim found that a low dosage of CBD can still inhibit the Cytochrome P450 enzyme system. Prolonged concentrations of clobazam and norclobazam in the body could lead to even more aggressive seizures.
Consult your doctor before you add CBD to your epilepsy medication regimen. Only a medical professional can determine the appropriate dosage of CBD to effectively control epileptic seizures.
CBD and chemotherapy drugs
In the treatment of cancer, it is extremely important to administer accurate and precise dosages of chemotherapy drugs. Just a slight deviation could result in ineffectiveness or over-toxicity. [R]
Many chemotherapy drugs are formulated based on their metabolic rate. If you introduce CBD into your regimen, the metabolism process of these chemo drugs may be altered and result in higher concentrations of the drug entering the bloodstream.
Studies suggest that CBD may have the capability to reduce cancer pain and slow the growth of cancer cells. But before adding CBD to your chemotherapy treatment schedule, your physician must take into account the presence of CBD when determining the amount and type of cancer medication to administer.
CBD and caffeine
Caffeine has been the most popular psychoactive drug for ages. CBD is quickly gaining ground and now people are combining the two as both substances seem to work well together.
Caffeine is molecularly similar to adenosine which activates the A2a receptor. When caffeine binds to the A2a receptor, it inhibits the reuptake of adenosine. This action results in vasodilation – which increases focus and alertness.
CBD is a partial agonist of the A2a receptor so in theory it can also block adenosine. By combining caffeine and CBD, adenosine is blocked across the board resulting in more stimulation and reduced anxiety.
These effects depend on the dosage of CBD – high levels are more likely to cause drowsiness and sedation.
Caffeine is metabolized by the CYP1A2 enzyme. As CBD inhibits the CYP450 enzyme system, the elimination rate of caffeine will slow down. This can prolong the effects of the caffeine in your body which can be both good and bad.
On the positive side, CBD and caffeine can provide you with energy that lasts all day instead of just a few hours. On the negative side, mixing CBD and caffeine may keep you wide awake when you are trying to sleep.
CBD and alcohol
Mixing alcohol with any drug is dangerous. In fact, consuming alcohol with opioids, antidepressants, and sleep medication can be fatal.
Alcohol is metabolized in the body through different pathways. The three primary enzymes involved are:
- Alcohol dehydrogenase (ADH)
- Aldehyde dehydrogenase (ALDH)
- CYP450 (specifically CYP2E1)
In social drinkers, ADH and ALDH carry the entire workload of metabolizing ethanol. In chronic and binge drinkers, CYP450 provides assistance to the overloaded ADH and ALDH pathways.
Here's what you should know about alcohol and CBD:
- The CB1 receptor plays a significant role in reinforcing the attributes of alcohol [R]
- Combining alcohol and CBD results in significantly lower blood alcohol levels [R]
- CBD reduces alcohol consumption, motivation and relapse [R]
- CBD protects the liver from steatosis caused by binge drinking [R]
- CBD slows down neurodegeneration caused by binge drinking [R]
- CBD may help treat alcohol-induced liver diseases associated with inflammation, oxidative stress, metabolic dysregulation, and neutrophil-mediated injury [R]
- Combining alcohol and THC creates undesirable side effects while CBD helps reduce alcohol consumption significantly and mitigates alcohol withdrawal symptoms [R]
Although the pharmacokinetics of alcohol and CBD are not yet fully explored, it is well known that CBD inhibits the CYP450 enzyme system which plays a significant role in breaking down alcohol. CBD could also alter levels of ADH and ALDH.
Studies suggest that alcohol may increase THC levels in the blood. On the other hand, there is evidence that people are likely to consume less alcohol when they take cannabis. [R]
In one of the earliest studies back in 1985, published by the National Institute on Drug Abuse (NIDA) titled Alcohol and Marijuana: Concordance of Use by Men and Women, researchers looked into the consumption patterns of three different environments: only alcohol, only cannabis, and alcohol and cannabis combined.
Here are some of the findings:
- 14 out of 16 subjects drank significantly less alcohol when both alcohol and cannabis were available (compared to only alcohol)
- 12 out of the 16 subjects consumed slightly more cannabis when both alcohol and cannabis were available (compared to only cannabis)
Although it is a small and ancient study, the findings seem consistent with anecdotal evidence. When both alcohol and cannabis are available, people smoke a little more but drink a lot less.
That being said, we still do not recommend that you mix CBD and alcohol.
First of all, alcohol and cannabis increase your risk of impaired driving than when consuming either one independently.
Secondly, cannabis inhibits nausea and vomiting. If you had too much to drink and the CBD prevents you from vomiting, you could die from alcohol toxicity.
While CBD is known to inhibit the Cytochrome P450 enzyme system, its mere presence does not always affect the way drugs are metabolized in your body. No one knows exactly how much CBD would cause a clinically significant effect. Nor do we know how long the effects of CBD on these enzymes would last.
What we do know is that CBD could inhibit the breakdown and elimination of blood thinners, which could lead to excessive bleeding. Patients taking CBD should pay close attention to changes in their blood levels and strictly follow doctor's orders on appropriate dosage.
Cancer patients who are undergoing chemotherapy must also be aware that taking CBD may produce higher concentrations of chemo drugs in the blood. If CBD turns out to delay metabolism of chemotherapy drugs, that could be a problem.
For most people, CBD is relatively safe, well-tolerated, and causes far less drug interactions than common prescription medication. But like any substance, CBD does interact with other chemical compounds and it is extremely important to understand how it affects your current diet and therapeutic regimen. Generally, anyone taking a gram or more of CBD per day should expect some kind of interaction.
Also of note, the CBD oil you are taking probably does not only contain CBD. Numerous compounds from the cannabis plant such as terpenes and other cannabinoids present potential interactions and can vary from strain to strain.
Individuals metabolize drugs through the same CYP enzyme pathways at different rates so there is no way to know how much CBD can cause a drug interaction or tolerance in a particular person.
One of the most compelling arguments for prescribing CBD or medical cannabis is their therapeutic versatility. Cannabis reduces the need to combine multiple medications that could potentially create adverse interactions.
Dr. Donald Abrams, professor of clinical medicine at the University of California, San Francisco, echoes this point: "Why would I write six different prescriptions which may interact with each other when I could just recommend one medicine?"
Dr. Abrams cautions that highly concentrated CBD tinctures and oils may have potential interactions with pharmaceuticals. Given that the doses on the market today are highly concentrated and vendors are not exactly transparent on the actual CBD content of their products, it can be difficult to assess drug-drug interactions.
More human trials are needed to evaluate how CBD could affect the potency and effectiveness of other drugs. Doctors can easily spot symptoms of an adverse interaction and simply reduce dosage of one substance or another to find the level that provides relief while avoiding harm.
Epidiolex researchers applied the same process to resolve negative interactions between CBD and anti-epileptic drugs. In June 2018, the FDA eventually approved Epidiolex (cannabidiol) for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome.
Until there is significant evidence on the safe interaction of CBD with other drugs, please exercise extreme caution when mixing high doses of CBD with other substances. Always consult your physician or a certified health professional before adding CBD to any other prescribed medication.