As newer research is endorsing the use of CBD oil, its use is becoming more trendy and widespread, and many different questions start to sprout. Whether the product is safe? Does it cause side effects? What are the long term effects? Can CBD oil interact with medications?
You want to try CBD oil, but you are unsure if it goes well with the prescription drugs you are taking. Is it going to fine or a recipe for disaster?
You are right to think about such questions because CBD oil can interact with several prescription drugs.
This article will walk you through the way CBD gets metabolized inside your body.
We will also discuss some possible mechanisms as to how it might interact with other drugs.
Finally, we will explore an exhaustive list of medication that can potentially interact with CBD oil.
CBD oil and Drug Interactions
We have some idea as to how CBD oil interacts with drugs and medication.
However, no one has systemically looked into the effects CBD oil might have on different prescription drugs and medication.
The clearest evidence comes from a study on Epidiolex, which is an approved treatment for rare forms of epilepsy.
These studies found that taking high doses of CBD oil could increase the levels of other antiepileptic drugs. Some common side effects included toxic liver effects and increased sedation [1, 2].
A recent study found that CBD led the patient to have thinner blood than expected [1, 2].
But how can CBD oil lead to such interactions?
We are going to explore these things in detail in the coming section.
CBD Oil Drug Interactions – The CYP450 Pathway
Before getting into the detail of knowing how CBD interacts with other medication and drugs, it is important that you understand the mechanism of CBD metabolism.
When CBD or any other chemical enters the body, they are quickly metabolized.
This process is quite complicated.
Metabolizing CBD includes many pathways involving different enzymes and molecules working together to get rid of the compound.
Metabolism also involves breaking the molecule into simpler molecules, which the body can use.
The different products of a drug’s metabolism are called metabolites. They will have different properties than the original drug.
Most of the drugs and chemicals are metabolized inside your liver.
Inside the liver, these chemicals are changed into simpler versions that can be easily excreted out of the body.
The major enzyme system responsible for metabolizing drugs and substances inside the liver is the cytochrome P450 system.
Cytochrome P450 is a cluster of liver enzymes, which control and break down the drugs.
CBD oil can inhibit the activity of this enzyme, which in turn affects how different compounds get metabolized [1, 2].
Metabolizing THC- How is THC Metabolized?
Cytochrome P450 enzyme has a big role in metabolizing THC.
It adds an oxygen atom to the structure of THC. This process is called oxidation.
Due to oxidation, a compound becomes more soluble, which makes it easier for kidneys to filter it out.
Most of the metabolized THC gets excreted through your feces (around 65%). Another 25% is excreted through your urine [1, 2].
One thing is important to mention here, and it is that the different routes of taking THC will have different effects.
When you inhale THC, it passes through the lungs into the general circulation including the brain.
From there, it enters the liver where it gets metabolized [1, 2].
After inhalation, the levels of THC reach a peak within 8 minutes and decrease rapidly within 3-4 hours [1, 2].
Oral ingestion of THC takes it into the small intestine and finally to the liver.
From there, the P450 enzymes (CYP2C and CYP3A enzymes) metabolize it.
Metabolizing CBD- How is CBD Metabolized?
The interaction between P450 and CBD is strange; both of them cancel each other’s effect.
Research has shown that CBD is metabolized by cytochrome P450 enzyme while functioning as an “inhibitor” of the same enzyme.
CBD thus takes the center position of enzyme interactions and stops P450 from interacting with other compounds.
The main extent to which CBD acts as an inhibitor P450 depends mainly on how tightly CBD attaches itself to the enzyme site.
This, in turn, depends on how you take CBD oil and the quantity you choose to intake.
Low doses of CBD won’t have any major effect on cytochrome activity.
However, no one knows the exact dosage at which CBD stops interacting with other drugs.
In general, the oral consumption of CBD is slower than inhalation. Let us look at these methods in more detail [1, 2]:
During smoking cannabinoid, more than 2000 chemicals are formed and oxidized.
CBD quickly absorbs in the lungs and reaches to high concentrations quickly.
Then, it spreads quickly into the whole body through blood.
CBD can be detected in the blood easily, and it reaches peak levels within 5 to 10 minutes.
During the oral intake, CBD travels through the digestive system, where the small intestine absorbs it.
From there, it travels into the lymph and deposits into the bloodstream so that it can be processed further.
Therefore, oral ingestion takes more steps, and each step takes more time.
The Grapefruit Comparison
You might be surprised to discover that the Grapefruit juice interacts with drugs in a fashion similar to CBD.
Grapefruit juice is perhaps one of the substances that most commonly interact with the liver enzymes and other drugs.
The reason it interacts with other drugs is due to its action on the P450 system.
Grapefruit juice is an inhibitor of the P450 system.
So if you are taking a drug that is metabolized by the P450 system together with the grapefruit juice, the drug won’t get metabolized quite effectively.
As a result, the levels of that drug in your blood will rise quite significantly.
Let’s add CBD into this picture as well.
CBD is an inhibitor of the P450 system like grapefruit juice.
So if you are taking a drug metabolized by the P450 system together with CBD and grapefruit juice, the P450 enzyme will get even more strongly inhibited.
As a result, the levels of that drug in your blood will go even higher.
Basically, if any medicine isn’t advised with grapefruit, it shouldn’t also be taken with CBD as well.
Also, you should avoid taking a drug metabolized by the P450 system together with CBD and grapefruit juice.
CBD Drug Interactions- Exploring the List of Drugs and Medications
Here is an exhaustive list of drugs, medications, and substances that are shown to interact with CBD oil.
You should observe caution while using these drugs together with the CBD oil.
Let’s get to it.
1. Interaction between CBD oil and Sedatives
CBD has a CNS calming effect of its own, so you might speculate that it might potentiate the effects of other sedatives.
In reality, it does not.
Researchers have not noticed any significant changes in the levels of effects of different sedatives (like barbiturates and sedatives) when used concurrently with CBD.
Researchers have looked into the combined use of CBD and sedatives like clonazepam.
But, they have not noticed any significant interactions or potentiation of the effects of these sedatives .
2. Interaction between CBD and Seizure Medication
In general, CBD oil is quite effective for seizures.
In one publication, researchers studied the effects of CBD oil on the blood levels of 19 different anti-epileptic medication .
They noticed that CBD increased the serum levels of certain medication but kept the levels of the rest unchanged.
CBD increased the blood levels of zonisamide, topiramate, eslicarbazepine, rufinamide, and N‐desmethylclobazam.
However, the blood levels of the remaining anti-epileptic medications did not change with the use of CBD.
These include valproate, levetiracetam, phenobarbital, clonazepam, phenytoin, carbamazepine, lamotrigine, oxcarbazepine, ethosuximide, vigabatrin, ezogabine, perampanel, and lacosamide.
However, as a rule of thumb, you should always observe caution while using CBD oil together with anti-epileptic medication.
3. Interaction with Chemotherapy Drugs
There is an absolute lack of human studies that could explain the link between using CBD and the metabolism of different anti-cancer medication.
The information available so far comes from laboratory studies.
The effects of CBD on different anticancer medication seems to occur through two main mechanisms.
Cancer cells contain a variety of proteins that make them resistant to the action of chemotherapy drugs.
These proteins either prevent the drug from attaching to the cell or entering the cell or they throw the drug out once inside.
This way, the chemotherapy drug never gets to act on the cancer cells.
In a review carried out, researchers were able to identify that CBD causes a significant decline in the metabolism of different chemotherapy drugs through the P450 system.
Also, CBD seems to inhibit different proteins on the cancer cells and potentiates the action of chemo drugs .
In simpler terms, CBD oil might help potentiate the effects of different chemotherapy drugs.
Different chemotherapy drugs that might get potentiated with the use of CBD oil include methotrexate, cyclophosphamide, taxanes (e.g., paclitaxel), tyrosine kinase inhibitors (e.g., dasatinib), vinca alkaloids (e.g., vincristine), hormonal therapies (e.g., anastrozole), intercalants (eg, doxorubicin), and topoisomerase inhibitors (e.g., irinotecan).
4. Interaction with Anti-depressants
The concurrent use of CBD with anti-depressants is a complicated matter. Here is why.
Most of the antidepressants, like SSRIs (Selective Serotonin Reuptake Inhibitors), are metabolized inside the liver.
In the liver, they are metabolized by the P450 system .
Since CBD is an inhibitor of the P450 system, the level of antidepressants in your blood may increase.
There is also evidence suggesting that a patient can misuse CBD during the depressive state, which can cause life-threatening problems.
Moreover, when patients who suffer from depression or bipolar disorder take CBD, they are less likely to go into their treatment with the doctor.
Another thing that makes the interaction between CBD and antidepressants complicated is the switch from antidepressants to CBD.
While CBD is natural but it is not a substitute for antidepressants. You should never give up antidepressants abruptly as it can cause major side effects.
You should always give up antidepressants slowly and after the recommendations of your doctor.
It is also advisable that you inform your doctor if you intend to use CBD oil so that he can assist you in titrating the dose of both.
This will help you avoid any unnecessary side effects.
5. Interaction with Antipsychotics
Unlike THC, CBD does not have psychotic properties. In fact, it is emerging as a potential treatment option for psychosis and schizophrenia.
Different antipsychotic drugs, including risperidone, are metabolized by the P450 system.
Risperidone, in particular, is metabolized by the CYP2D6 subset of the P450 system (5, 6).
CBD is a known inhibitor of the CYP2D6. Therefore, the combined use of CBD and antipsychotic drugs can potentiate the effects of antipsychotic drugs.
You should always consult with your doctor before starting CBD oil if you are already taking antipsychotic drugs.
6. Interaction with Mood Stabilizers
Different mood stabilizers are used for treating bipolar disorder.
One of the most commonly known and widely used mood stabilizers is Lithium.
Many other medications also act as mood stabilizers for treating seizure disorders, which include valproic acid and lamotrigine [5, 6].
CBD has proved to help against bipolar disorder. Some studies have also found that CBD may have the same effect as Lithium.
As mentioned before, CBD does not seem to have any interaction with lamotrigine and valproate.
There isn’t enough information to comment on the effects of CBD oil on other mood stabilizers like lithium.
7. Interaction with Benzodiazepines
People have used CBD and cannabinoids for centuries to reduce anxiety.
As described before, the use of CBD with benzodiazepine like clonazepam can increase the blood levels of this drug.
This can increase the risk of side effects like excessive sedation [3, 5, 6].
8. Interaction with Stimulants
Stimulants are drugs that increase psychological activity in the nervous system. They make a person more alert and active.
Caffeine is one such example.
We are still learning how CBD interacts with different stimulants. However, preliminary data suggest that at lower doses, CBD might act as a stimulant.
Also, coffee seems to activate the same neuronal pathways as CBD. As a result, taking CBD together with other stimulants can increase alertness .
9. Interaction with Blood Thinners
Blood thinners are prescribed to people who suffer from clotting disorders. These include drugs like warfarin, rivaroxaban, etc.
You should observe caution when mixing CBD with anticoagulants, especially warfarin.
The P450 system metabolizes warfarin. There have been some case reports where the users developed significant bleeding when using warfarin in combination with CBD [5, 6, 9].
Therefore, always inform your healthcare provider if you intend to use warfarin or any other anticoagulant in combination with CBD or similar products.
10. Interaction with Blood Pressure Medication
CBD is known to cause a reduction in blood pressure.
In one study, the participants experienced a 5 mmHg reduction in blood pressure after a single dose of CBD .
This means that your blood pressure might become more labile if you are using CBD oil in combination with other anti-hypertensive medication.
Always observe caution when mixing CBD oil with anti-hypertensive drugs.
11. Interaction with Antibiotics and Antifungals
Several antibiotics are either inhibitors or inducers of the P450 system. Another major group of antibiotics is metabolized by the P450 system [5, 6, 9].
For the antibiotics that inhibit the P450 system, taking CBD with such antibiotics can further potentiate the P450 inhibition.
As a result, it can impair the metabolism of the drugs through the P450 system and increase the risk of their toxicity.
Common P450 inhibitor antibiotics include erythromycin, clarithromycin, isoniazid, fluconazole, and ciprofloxacin.
With P450 inducer antibiotics, the use of CBD will nullify their effect.
Although it has not been looked into through research; but theoretically speaking, this should not result in any significant interaction.
Common P450 inducer antibiotics include doxycycline and rifampicin.
12. Interaction With Antiviral Drugs (Anti-HIV/Anti-Retroviral Drugs)
Like antibiotics, several antiviral drugs are also inhibitors of the P450 system [5, 6, 9].
Therefore, when taken with CBD, these medications can further inhibit the P450 system and can increase the risk of toxicity of drugs metabolized through this system.
Common inhibitor antiviral drugs include indinavir, nelfinavir, ritonavir, and saquinavir.
13. Interaction With Pain Medication
CBD can potentiate the effect of all the pain medication due to its ability to blunt pain response in the body.
Therefore, you can experience a reduction in pain if you combine CBD with other pain medication.
It complements the action of pain medication acting through opioid receptors, anti-inflammatory pathways, and through nerve calming pathways. CBD can act through all of these pathways and can help ease the pain.
Are there any interactions of CBD with Herbs and Supplements?
Currently, there are no studies which indicate CBD interaction with supplements.
However, nothing can be said for certain. Therefore, researchers need to do more research to reach a conclusive result.
Combining Alcohol and CBD
Alcohol depresses the central nervous system. CBD has a similar kind of reaction but in small doses.
A 1979 study showed the link between alcohol and CBD.
The researchers chose 10 volunteers and administered them a placebo, CBD and orange, CBD and alcohol or just alcohol.
The results of the study showed that the volunteers who drank alcohol and alcohol-CBD had the biggest impairment in tests.
The researchers also found that the participants who took alcohol and CBD together had lower alcohol levels .
Some other studies have found that CBD can help with the potential side effects of alcohol.
A 2013 study was done which tested the effects of alcohol and CBD on rodents.
Researchers mainly wanted to find out the effect which CBD had on alcohol-induced neurodegeneration .
Researchers gave the animals CBD injections before giving alcohol. The study found that giving CBD reduced alcohol-induced neurodegeneration by 50% .
Some studies have also indicated that CBD helps prevent cell damage, which accompanies alcohol consumption.
Therefore, these studies clearly show that CBD is quite effective in preventing alcohol side effects.
However, there is limited data on taking them together.
CBD also affects different people differently.
Therefore, it is difficult to assume whether mixing alcohol and CBD will have the same effect on all people.
So, there are many reasons not to mix CBD with alcohol.
However, if you decide to mix alcohol with CBD, mix it in small amounts. You should also consult the doctor if you have any further concerns.
Caffeine and CBD – Better than a PB&J?
Well, if you are thinking of eating peanut butter and jelly sandwich, how about mixing coffee with CBD for a drink.
Research has shown that caffeine and CBD have synergistic effects .
A study was conducted on zebrafish, which showed that long-term caffeine and CBD consumption could minimize memory loss.
Although human and zebrafish are very different, this study shows that CBD and caffeine complement each other, when mixed together.
There is still need to research on humans.
A major benefit of mixing CBD and caffeine is that CBD alleviates anxiety.
Excessive intake of caffeine can cause anxiety. Therefore, CBD helps with these anxiety attacks.
CBD oil is an emerging remedy for several troublesome conditions.
However, there is still quite a lot that we don’t know about CBD oil.
Therefore, it is always advisable to consult with your healthcare provider before starting CBD oil or any similar product.
This is especially important if you are taking other medication that might interact with CBD oil.
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