Does CBD Interact With Trazodone Or Effexor?

In our latest question and answer, the pharmacist discusses whether or not CBD (cannabidiol) interacts with trazodone or Effexor (venlafaxine).

Does CBD Interact With Trazodone Or Effexor?
May 11, 2018

Anna asked

Hello, could you tell me if I can take CBD oil (the bottle contains 500mg pure CBD, one drop contains 1,25 mg) and vitamins/supplements (C,K,B6,B12,B3,magnesium) with these medications: - Effexor 150 mg prolonged release (in the morning)- Trittico (trazodone) 75 mg prolonged release (in the evening)I'm afraid of potential interactions. 

Answer

CBDThere are a few potential interactions between CBD (cannabidiol) and the two medications in your inquiry, trazodone and Effexor (venlafaxine). Unfortunately, there isn't a lot of data regarding CBD interactions with specific drugs so we often need to extrapolate what we know about how they are metabolized to determine whether or not there are potential drug interactions to be concerned about.

Even then, we don't know much about CBD in general. We do know that CBD can inhibit certain metabolizing enzymes, a common characteristic of many drug interactions. However, there are many studies that theorize that while CBD does inhibit metabolizing enzymes, it takes extraordinarily large doses to do so and the inhibition is not to a significant extent for most individuals.

Nevertheless, until more studies are completed, CBD should be used cautiously in those taking prescription medications. Below, we discuss CBD and potential drug interactions with trazodone and Effexor in more detail.

What Is CBD (Cannibidiol)?

Cannabidiol, also known as CBD, is a non-euphoric constituent of cannabis, also known as marijuana.

While THC (delta-9-tetrahydrocannabinol) is likely more well-known due to its psychoactive and euphoric effects, CBD makes up almost 40% of many cannabis extracts and has a wide range of potential benefits when used medicinally, although more studies are needed to better understand the compound.

The amounts of CBD used in studies range greatly (from 1 mg to over 600 mg), but there is preliminary positive evidence for a variety of indications, including:

  • Anxiety
  • Epilepsy
  • Chronic pain
  • Seizures
  • Multiple Sclerosis
  • Insomnia
  • Parkinson's Disease

Further adding to the potential benefit of CBD, is the fact that it is considered CBD is considered "non-euphoric", even at high doses. In fact, many studies have shown that when combined with THC, CBD can decrease some unwanted effects, such as cognitive impairment.

CBD has recently has exploded in popularity, with many different products available over the counter. With this, it is important to consider potential drug interactions with prescription medication, such as Effexor and trazodone.

CBD (Cannibidiol) Drug Interactions

The two main constituents of marijuana, THC and CBD, are known to be metabolized by the cytochrome P450 system, the major enzymes involved in drug metabolism. Specifically, studies have shown that CBD can inhibit:

  • CYP2C9
  • CYP2C19
  • CYP3A4
  • CYP2D6
  • CYP1A1
  • CYP1A2

Metabolizing enzyme inhibition often leads to increased concentrations of drugs that are typical substrates for a particular enzyme. The majority of prescription medications are metabolized by CYP enzymes, therefore potential interactions are plentiful.

Effexor - CBD (Cannibidiol) Interaction

Effexor (venlafaxine) is extensively metabolized by the CYP2D6 enzyme. Interestingly enough, Effexor is metabolized to O-desmethylvenlafaxine, which is equally potent in terms of effects to venlafaxine. Changes to CYP2D6 are not thought to have a significant effect on how well the medication works. In fact, the prescribing information says this about the drug:
...studies indicate that the formation of ODV (O-desmethylvenlafaxine) is catalyzed by CYP2D6; this has been confirmed in a clinical study showing that patients with low CYP2D6 levels (“poor metabolizers”) had increased levels of venlafaxine and reduced levels of ODV compared to people with normal CYP2D6 (“extensive metabolizers”). The differences between the CYP2D6 poor and extensive metabolizers, however, are not expected to be clinically important because... venlafaxine and ODV are pharmacologically approximately equiactive and equipotent."

Based on what we know about Effexor metabolism, we wouldn't expect CBD to significantly affect it. However, there have been a few studies that suggest that there may be an increased risk of side effects in those taking Effexor with low or impaired CYP2D6 levels. Therefore CBD may theoretically increase the risk of certain side effects such as:
  • Nausea
  • Vomiting
  • Diarrhea 

Trazodone - CBD Interaction

Trazodone is extensively metabolized by CYP3A4. CBD inhibition of the enzyme may lead to increased trazodone levels, however studies have not confirmed this. If using CBD and trazodone together, watch for potential additive sedation and drowsiness. Before using CBD, it is important to let your doctor know so they can monitor you for potential side effects.

Summary

  • CBD (cannibidiol) is a non-euphoric constituent of cannabis plant, widely used for a variety of health effects.
  • CBD may potentially increase the side effects of Effexor (e.g. nausea). However, this is based on the theoretical inhibition of CYP2D6 and studies haven't specifically evaluated the interaction.
  • CBD may inhibit the metabolism of trazodone via CYP3A4 inhibition. This could potentially increase the risk the side effects. Studies have not evaluated this interaction however. 

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