CBD and drugs: What are the interactions?

Do you have doubts about whether to use CBD can interact with the medications you are taking? You are not the only one. In this blog post, we will explain the main known interactions between cannabidiol or CBD and some medications.

We remind you that this article is informative and is not intended as a substitute for professional advice. Consult your physician if you have any doubts about the use of CBD.

What are CBD-drug interactions?

Drug-drug interactions occur when one drug alters the absorption, distribution, metabolism, elimination (pharmacokinetics) or effects (pharmacodynamics) of another drug, when administered simultaneously (1). In this post, we will focus on the interaction between the CBD oil or cannabidiol when used in conjunction with certain medications.

How CBD exerts its effects in the body: Alterations in pharmacokinetics

Pharmacokinetics is the study of how the compounds we ingest are absorbed, distributed, metabolized and eliminated in our body to produce desired effects. In general, for a substance to act, it has to cross different “compartments” of our body in order to reach the bloodstream. In this process, substances must reach the liver to be metabolized and converted into substances that can have an effect on our body, which are called active metabolites. These active metabolites are then transported through the blood and can thus exert their effect on the organism. In the case of cannabidiol (CBD), it is transported through the blood until it reaches the target cells, which are those that have cannabinoid receptors. cannabinoid receptors receptors, on which it will exert its effects.

Differences between cannabidiol by inhaled and oral routes

The more the body tissue is in contact with our blood vessels, the less barriers the substance we consume has to reach our blood and from there to its therapeutic target in the body. For this reason, intravenous drugs have an instantaneous effect. Likewise, inhaled substances or drugs have an almost immediate effect, since the lungs, being in charge of oxygenating our blood, have a large number of small blood vessels that carry oxygenated blood to our body.

In the case of cannabidiol pharmacokinetics , when we inhale vaporization products with CBDThese have a more rapid effectThe lung cells, being in direct contact with the bloodstream and having enzymes that can metabolize cannabis (2), do not represent any barrier between cannabis and the bloodstream. cannabinoids and our blood.

Orally, the effect of cannabidiol is more delayed, as there will be more barriers for the drugs to reach the bloodstream. For example, if CBD oil is ingested orally*, it has to cross the walls of our gastrointestinal tract to reach the liver, be metabolized and subsequently be transported through the blood.

Cannabidiol oil can also be partially absorbed by the sublingual membrane* (the area under the tongue) which is very thin and rich in blood vessels, but the rest of the unabsorbed dose will be ingested and will follow the same route as the oral route.

CBD and oral drug interactions (infographic).
CBD and oral drug interactions (infographic). * The oral use of CBD oil is not regulated in some countries such as Spain.

The highest incidence of CBD-drug interactions is related to the simultaneous consumption of drugs that are also metabolized by the liver. Both cannabinoids and the concomitant drug, by interacting with the liver enzymes that both need to be metabolized, can cause the accumulation of one of the two and give rise to adverse effects (3).

Vaped CBD is partially metabolized in the lung, thus decreasing the possibility of interactions with hepatically metabolized drugs. It is worth mentioning that one of the advantages of using cannabidiol via air, such as vaporization with CBD, is that hepatic metabolism will be partially reduced (because the lung cells themselves metabolize cannabidiol) and, therefore, the possibility of drug interactions may be reduced.

However, possible interactions that alter the pharmacodynamics of the drugs should be considered and will be explained below.

CBD vaporization and interactions with oral medications (infographic).
CBD vaporization and interactions with oral medications (infographic).

Interactions between CBD and other drugs: Alterations in pharmacodynamics.

Pharmacodynamics refers to the effects exerted by a substance in the body. Pharmacodynamic interactions are those that occur when substances with the same pharmacological targets are consumed, i.e., two substances that act on the same sites of action, same cell, receptor or enzyme, resulting in an additive, synergistic or antagonistic response to the effect of one of the two drugs.

Why it is important to follow medical indications

When using CBD along with other medications, it is crucial to be aware of pharmacodynamic interactions. These occur when substances act at the same sites in the body, such as receptors or enzymes, and may have additive, synergistic or antagonistic effects.

To avoid this type of interactions with CBD, medical indications are paramount, since only the treating physician will be able to explain to you what each of the medications he prescribes is for.

What effects can be seen with drug interactions with CBD?

The possible effects of cannabidiol interaction with drugs are varied but generally mild. They range from nausea, diarrhea, fatigue, dizziness, headaches and anxiety (4) to mention a few. There are also effects that are not observable to the naked eye and can only be seen in blood chemistry tests, such as an increase in liver enzymes.

Although CBD may be a substance with few adverse effects, when used in conjunction with medications it can alter the effect or toxicity of medications, resulting in stronger adverse effects.

Interactions between CBD and most common medications

List of drugs with hepatic metabolism that can interact with cannabinoids

The drugs commonly used to treat diseases are so many and so varied that listing them all is a difficult task. However, the Department of Pharmacology of the University of Pennsylvania published in 2020, a list of active principles of hepatic metabolism with which special care should be taken when administered together with CBD.

The list includes drugs with a narrower therapeutic index, i.e., those drugs whose small variations in plasma levels may cause them to lose their therapeutic effect or cause adverse reactions, and therefore should be monitored if combined with other therapies, such as CBD. For example, some anticoagulant drugs (such as acenocoumarol), synthetic thyroid hormone (levothyroxine) and some birth control pills (ethinyl estradiol).

The list postulates the theory that certain drugs with hepatic metabolism will have a higher or lower blood concentration when used with cannabinoids and, therefore, have a higher probability of presenting toxic or undesirable effects in users.

More information: CBD oil and Sintrom: is it contraindicated?

What is the effect of CBD when administered with drugs that have the same therapeutic target?

Interactions between CBD and drugs (infographic)
Interactions between CBD and drugs (infographic). Guidance information. In case of taking medication, it is essential to consult a doctor for personalized advice!!!!

CBD and non-steroidal anti-inflammatory drugs (NSAID)

Mixtures of cannabinoids including cannabidiol, when administered with NSAIDs such as ibuprofen and diclofenac, increased anti-inflammatory activity in an in vitro study (5).

Such findings suggest that the dose of anti-inflammatory drugs could be decreased if administered concomitantly with cannabinoids such as CBD. Since most NSAIDs are metabolized in the liver as is CBD, reducing NSAIDs will also help avoid toxic effects. We remind you that, like all the indications in this post, they are indicative, and you should consult your doctor for individualized advice.

CBD and analgesic drugs

In the scientific literature, it has not been reported whether there is any risky interaction of CBD with acetylsalicylic acid, better known as aspirin.

Another common analgesic is paracetamol, which by itself can cause liver failure in case of overdose, a risk that increases when administered with another drug with hepatic metabolism such as CBD (6).

Although paracetamol is a safe drug as it has a wide therapeutic margin, it may be advisable to decrease its concentration when administered simultaneously with CBD, as the risk of interactions may increase due to the fact that both compounds are hepatically metabolized. We remind you that, like all the indications in this post, they are indicative, and you should consult your doctor for individualized advice.

CBD and anti-epileptic and anxiolytic drugs

Medications to treat anxiety or epilepsy with active ingredients such as Valproate, Levetiracetam, Phenobarbital, Clonazepam, Phenytoin, Carbamazepine and Pregabalin, showed no alterations in their blood concentration when administered orally with CBD (7).

It should be noted that CBD may have anxiolytic effects, which will most likely result in an additive effect when used in conjunction with medications prescribed for the treatment of anxiety and thus result in undesirable sedative effects. You will find more information in the article on CBD for anxiety .

On the other hand, drugs such as Topiramate, Rufinamide, Zonisamide and Eslicarbazepine had an increase in blood concentration when used with cannabidiol (7). The accumulation of such drugs may trigger toxic effects in the patient.

CBD and Parkinson’s medications

CBD demonstrated good tolerability when administered to patients with conventional treatments for Parkinson’s disease in a study conducted in 2020.

However, an increase in liver enzymes indicating some toxicity was observed when doses greater than 20 mg/kg CBD were used in Parkinson’s patients (8). It is worth mentioning that such a study did not include patients who were taking medications that by themselves could cause liver failure. Therefore, the use of cannabidiol with antiparkinsonian drugs should be supervised by the medical specialist. For more information on the subject, see the post on CBD for Parkinson’s disease .

CBD and chemotherapy or anticancer drugs

Irinotecan and Docetaxel showed no alterations in their blood concentrations when in a study conducted in the Netherlands, patients consumed herbal medical cannabis tea (9). Therefore, it appears that the use of cannabis remedies does not represent a risk of toxicity with these drugs. You can expand this information in the post about CBD and cancer .

If you have further questions about CBD interactions with other medications, we invite you to consult with your medical specialist before using cannabidiol products. If you are a specialist or health professional, we recommend you to consult the references in this post. They are scientific articles that can help guide you on the use of drugs and CBD.

We remind you that this is an informative article that is not intended to prevent, diagnose or treat any disease. Its content can complement, but never replace, the diagnosis or treatment of any disease or symptom. Cannactiva products are not medicines. Consult your doctor before using CBD.

Referencias

M., & Campbell, A. (2021). Drug Prescribing: Drug-Drug Interactions. FP essentials, 508, 25-32.

2. Labiris, N. R., & Dolovich, M. B. (2003). Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. British Journal of Clinical Pharmacology, 56(6), 588-599.

3. Qian, Y., Gurley, B. J., & Markowitz, J. S. (2019). The Potential for Pharmacokinetic Interactions Between Cannabis Products and Conventional Medications. Journal of Clinical Psychopharmacology, 39(5), 462-471.

Kalaba, M., Eglit, G. M. L., Feldner, M. T., Washer, P. D., Ernenwein, T., Vickery, A. W., & Ware, M. A. (2022). Longitudinal Relationship between the Introduction of Medicinal Cannabis and Polypharmacy: An Australian Real-World Evidence Study. International Journal of Clinical Practice, 2022, 8535207.

5. Vinayaka, A. C., Shalev, N., Anil, S. M., Tiwari, S., Kumar, N., Belausov, E., Mani, K. A., Mechrez, G., & Koltai, H. (2022). Phytocannabinoids Act Synergistically with Non-Steroidal Anti-Inflammatory Drugs Reducing Inflammation in 2D and 3D In Vitro Models. Pharmaceuticals (Basel, Switzerland), 15(12), 1559.

6. Ewing, L. E., McGill, M. R., Yee, E. U., Quick, C. M., Skinner, C. M., Kennon-McGill, S., Clemens, M., Vazquez, J. H., McCullough, S. S., Williams, D. K., Kutanzi, K. R., Walker, L. A., ElSohly, M. A., James, L. P., Gurley, B. J., & Koturbash, I. (2019). Paradoxical Patterns of Sinusoidal Obstruction Syndrome-Like Liver Injury in Aged Female CD-1 Mice Triggered by Cannabidiol-Rich Cannabis Extract and Acetaminophen Co-Administration. Molecules (Basel, Switzerland), 24(12), 2256.

7. Gaston, T. E., Bebin, E. M., Cutter, G. R., Liu, Y., Szaflarski, J. P., & UAB CBD Program (2017). Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia, 58(9), 1586-1592.

8. Leehey, M. A., Liu, Y., Hart, F., Epstein, C., Cook, M., Sillau, S., Klawitter, J., Newman, H., Sempio, C., Forman, L., Seeberger, L., Klepitskaya, O., Baud, Z., & Bainbridge, J. (2020). Safety and Tolerability of Cannabidiol in Parkinson Disease: An Open Label, Dose-Escalation Study. Cannabis and cannabinoid research, 5(4), 326-336.

9. Engels, F. K., de Jong, F. A., Sparreboom, A., Mathot, R. A., Loos, W. J., Kitzen, J. J., de Bruijn, P., Verweij, J., & Mathijssen, R. H. (2007). Medicinal cannabis does not influence the clinical pharmacokinetics of irinotecan and docetaxel. The oncologist, 12(3), 291-300.

Masha Burelo
Investigadora en cannabinoides | Doctoranda en Neurociencia

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