By Dr. Minchul An, Co-Founder & CEO at Buzzn

CBD has been all the buzz lately in the health and wellness space; with evidence suggesting CBD oil may benefit those who suffer from anxiety or depression. However, many are wondering if supplementing CBD in addition to their antidepressant therapy is a safe and effective option. Here is what we know so far.

SSRIs are first-line medications used for the treatment of depression. They are well researched and provide relief to millions of people. Several have also reported that the use of CBD oil in combination with their SSRIs resulted in improved symptoms of depression without additional side effects. That being said, this combination may not be for everyone. CBD may have the potential to interact with SSRIs, and other antidepressants, resulting in increased amounts of antidepressant in the body and a higher risk of side effects.

Our liver enzymes, or cytochrome P450, are what allow us to metabolize drugs to be excreted from our system. They metabolize about a quarter of all drugs in our body. In fact, CBD works the same way in the liver as grapefruit. Therefore, CBD & drug interactions can mimic the interactions between grapefruit & drugs! Have a prescription bottle nearby? Check your bottle to see if there is a grapefruit warning label. It usually says, “avoid this medication with grapefruit.” If you see this auxiliary warning label, then this would essentially apply to CBD use also.

Cannabidiol (CBD), the most well researched cannabinoid, is a strong liver enzyme blocker —specifically CYP3A4. What that means is CBD inhibits this specific liver enzyme (CYP3A4) that’s used to metabolize other drugs in our body. As a result, CBD may increase serum concentrations of certain drugs (i.e. antidepressants) that are specifically metabolized by these very enzymes.

Other drug classes metabolized by CYP3A4:

  • Steroids.
  • HMG CoA reductase inhibitors.
  • Calcium channel blockers.
  • Antihistamines.
  • Prokinetics.
  • HIV antivirals.
  • Immune modulators.
  • Benzodiazepines.

Drugs that are potent inhibitors of (liver enzyme) cytochrome P450 — may decrease the metabolism of cannabinoids:

  • Potent CYP3A4 inhibitors may increase the bioavailability of CBD.
  • Potent CYP3A4 inhibitors include Clarithromycin, Diltiazem, Erythromycin, Grapefruit juice, Itraconazole, Ketoconazole, Nefazodone, Ritonavir, Telithromycin, and Verapamil.

Drugs that are inducers of (liver enzyme) cytochrome P450 — may accelerate the metabolism of cannabinoids:

  • Potent CYP3A4 inducers may decrease the bioavailability of CBD.
  • Potent CYP3A4 inducers include Carbamazepine, Hypericum Perforatum (St. John’s Wort), Phenobarbital, Phenytoin, and Rifampin.

CBD drug interactions may not always be bad though. CBD could make other drugs more effective, so much so that you can reduce the dosage of those other drugs and thus have less negative side effects to deal with. Keep in mind other cannabinoids like THC and CBN can interact with our cytochrome P450 system as well. CBD (along with THC and CBN) may interact with not only CYP3A4 aforementioned, but also other liver enzymes such as CYP2D6, CYP2C9 and CYP2C19. In regards to SSRI antidepressants, Fluoxetine and paroxetine are potent CYP2D6 inhibitors, whereas fluoxetine’s main metabolite, norfluoxetine, has a moderate inhibitory effect on CYP3A4. Sertraline is a moderate CYP2D6 inhibitor; citalopram appears to have little effect on the major CYP isoforms.

There is still so much we don’t know about the pharmacokinetics (PK) and pharmacodynamics (PD) of cannabinoids. CBD drug interactions could very much be dose-dependent, and may require higher doses to see any interference in drug serum concentrations. What we know is this: CBD is a drug with potential DDIs. The current prescription drug on the market is Epidiolex — a concentrated dose of pure CBD isolate derived from marijuana. It’s classified by the DEA as a Schedule 5 drug used for the treatment and prevention of seizure disorders. 

Big takeaway: If you have an extensive medication history or are taking medications to control any mood disorder(s), please consult with a healthcare professional before adding on any new CBD supplement / hemp extract. They will be better able to assist you in optimizing your regimen and ensuring there are no serious health implications. We’re also here to help, feel free to contact for a consultation.

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