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How can CBD interact with medications?

How can CBD interact with medications?

As medicinal cannabis has gained significant attention in recent years, it is important to understand: 

CBD also affects the metabolization of drugs, varying their effects on our body.

Pharmacokinetics

To understand how and why CBD can interact with medications, it is necessary to know what are the different processes to which a drug is subjected during its passage through our body, something known as pharmacokinetics and consists of the following steps: 

  1. Absorption or the process by which a drug passes into the bloodstream.
  2. Distribution of the drug to the places where it will produce its action 
  3. Metabolism 
  4. Elimination

This can vary the bioavailability of the medication, that is, the amount of drug that remains in our body, thus causing an effect different from that expected.[1]

It all depends on the form of administration

The way in which CBD is administered will also influence whether or not drug interactions occur, since the mode of administration affects the amount of CBD that can be present in the liver and how quickly it reaches it. [2]

  • Topical route. Although topical cannabinoids can be absorbed through the skin and into the joints, they do not enter the bloodstream in this case. There is no potential for drug interactions to occur using this route. [2]

To learn more about the administration routes you can read the article, reviewed by the Neuropsychologist and Phytotherapist, Tommaso Bruscolini. 

We'll go into more detail later!

Inhibitory effect

It may increase its toxicity and the risk of adverse effects.[3][4] Adjust the dose. This fact can also be used to our advantage. 

The same therapeutic effects can be achieved with lower doses of medication and thus we will have fewer side effects related to said drug and a higher quality of life.

Inducing effect

If CBD exerts an inducing effect on the enzyme responsible for the metabolism of a drug, the activity of the enzyme is enhanced. [3] [4]. This causes our medication to be metabolized faster. If the amount of drug is less than expected, its effects decrease.

Therefore, the desired therapeutic effects may not be achieved. [3] [4] If you are taking a medication that interacts with CBD in this way you would have to seek medical advice to readjust the dose. Appropriate administration routes can also be used to avoid these interactions, such as the correct use of the sublingual route or the inhaled route. [5]

Synergistic effect

Synergistic effect CBD can also act synergistically with some drugs such as opioids. As a result, additive effects are obtained, greater than those achieved if only the drug is administered [3] [4]. In this case, the effects of the drug are enhanced, so the same effect can be achieved with a lower dose

The exact mechanism by which this happens is still unknown. However, it is believed that it may be because both substances achieve the same effect in our body, despite activating different processes, hence the synergy. [3] [4]. If a synergistic effect occurs, the same effect can be achieved with a smaller amount of medication, so it is recommended to seek medical advice to readjust the dosage.

Non-steroidal, such as:

  • Ibuprofen 
  • Diclofenac 
  • Naproxen
  • Some drugs for arthritis

The enzymes CYP2C9 and CYP2C19 mainly metabolize them. [3] This cannabinoid has a slight inhibitory effect on them, that is, it inhibits the metabolism of these drugs through CYP450. The drugs remain circulating in the bloodstream and could lead to overdose or toxicity. [3] If you are going to consume any of these drugs together with CBD, it is recommended seek medical advice  to reduce the dose and monitor adverse effects and toxicity.

 Alternative routes of administration may also be considered, such as correct use of sublingual or inhalation.

CBD and pain relievers (Opioids)

Many of the pain relievers we commonly take for pain relief are opioids. Some examples are the following:

  • Morphine 
  • Methadone 
  • Oxycodone 
  • Codeine 
  • Tramadol (Studies are lacking to understand the interaction) 
  • Fentanyl (Studies are lacking to understand the interaction)

Some of them, such as codeine or oxycodone, have to be converted into other molecules to exert their effect on the body. Enzymes of the UGTs family carry out this conversion. [5] CBD is an inhibitor of UGT enzymes, so the analgesic effects of codeine or oxycodone will be less if consumed together with CBD.

However, many studies show that cannabis increases the effect of opiates. However, why?

In some cells, there is a protein called P-gp, which is responsible for expelling some substances to the outside. Morphine and methadone are some examples. This causes the amount of opioids that enter our brain to be lower. It has been observed that CBD inhibits this protein, allowing greater amounts of morphine to enter the cells. This fact could be the explanation for the synergistic effect, which would explain the greater effect of opioids with lower doses if they were consumed together with CBD. [6]

Opioids such as fentanyl or tramadol are not substrates of the P-gp protein. The effects of CBD on these drugs are still unknown. Therefore, more studies are necessary. [6] Consumption of CBD together with some opioid analgesics does not increase the risk of suffering adverse effects. In fact, the same effect can be achieved with lower doses of the drug. [7] 

You can seek medical advice to readjust the dosage. 

In the case of opioids such as fentanyl or tramadol, whose interactions with CBD are not yet fully understood, consult your doctor or use alternative routes to ingestion to avoid any possible effects.

CBD and pain relievers (Non-opioids)

Paracetamol (acetaminophen) is another commonly used pain reliever*, but it is not an opioid. Enzymes known as UGTs metabolize it. [6] 

*Fun fact: The analgesic effect of paracetamol is due to an indirect activation of cannabinoid receptors (CB1). [8] CBD is an inhibitor of UGT enzymes, so the concentration of paracetamol in our body will be higher. This causes an increased risk of side effects, such as liver damage. [6] It is recommended to reduce the dose of the drug to reduce this risk, always seeking medical advice. Other routes of administration other than ingestion may also be considered.

CBD and flu

Some flu medications commonly used to relieve cold symptoms use doxylamine as the main ingredient, an antihistamine that is also frequently found in allergy medications. CBD has an inhibitory effect on the enzymes that break down these medications. 

Consuming them simultaneously can produce an increase for drug, thus causing an increase in adverse effects such as drowsiness, confusion and, in more severe cases, deterioration of motor function. [11] The best option is to adjust the dose to reduce the risk of adverse effects. Seek medical advice and consider other routes of administration than ingestion.

CBD and hormonal contraceptives

There are different opinions about the result of consuming CBD together with hormonal contraceptives, so further study is still required.

Currently, various clinical trials are being carried out to evaluate the possible interactions of birth control pills with CBD. However, so far, the literature only offers us information on how these preparations can affect the entire Cannabis plant (including CBD and THC, and not separately). 

If you want to know more about how THC interacts with medications, you can read the article on drug interactions or watch Dr. Sarah Chinelo's  training video

Bibliography:

  1. Bornheim ML, Almira M. Effect of cannabidiol on cytochrome P-150 isozymes. Biochem Pharmacol. 1989.
  2. Project CBD. Canabinoid-drug interactions. 2018.
  3. Brown JD, Winterstein AG. Potential adverse drug events and drug-drug interactions with medical and consumer cannabidiol (CBD) use. J Clin Med. 2019.
  4. Alsherbiny MA, Li CG. Medicinal cannabis - Potential drug interactions. Medicines (Basel). 2018.
  5. Kim J, De Jesus O. Medication Routes of Administration. [Updated 2021 Feb 25].
  6. Vázquez M, Guevera N, Maldonado C, et al. Potential pharmacokinetic drug-drug interactions between cannabinoids and drugs used for chronic pain. BioMed Research International. 2020.
  7. Nielsen, S. et al.   Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis. Neuropsychopharmacology. 2017.
  8. Bertolini A, Ferrari A, Ottani A, Guerzoni S, Tacchi R, Leone S. Paracetamol: new vistas of an old drug. CNS Drug Rev. 2006.

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Author information

Biotechnologist : Specialised in science communication

Nuria Chamorro Dia

Graduated in Biotechnology with a mention in Health from the Polytechnic University of Madrid, after a one-year stay at the University of Helsinki, where she took several subjects in the Masters in Neuroscience and Advanced Immunology. After a six-month stay at the University of Helsinki studying metabolic regulation in prokaryotes, she returned to Madrid to do a master's degree in Journalism and Science Communication at the Carlos III University.

She has worked in different projects as a science communicator, generating content for the general public and professionals on different areas of science (health, ecology, nanotechnology, synthetic biology, etc.).

Currently, she works as a science writer in a communication company, HealthCare, elaborating and revising medical and pharmaceutical information content. The therapeutic areas she works with are: vaccines, oncology, immunology and HIV.

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