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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).

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

There 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

. 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.”

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

Case Study: CBD Targets Multiple Symptoms

By Janice Newell Bissex, MS, RDN, FAND
CRx Magazine
Vol. 2, No. 1, P. 6

Patients suffering from pain, anxiety, depression, insomnia, migraines, autoimmune and inflammatory disorders, and other conditions are increasingly turning to medical cannabis and CBD for relief.1 Many are dissatisfied with the side effects of traditional pharmaceuticals for these conditions and are searching for a more holistic approach to managing their health.

Case Presentation
A 48-year-old woman presented with a history of anxiety and depression, pain, insomnia, constipation, and focal nodular hyperplasia (benign tumors of the liver). She was looking to reduce her medications for these conditions and to improve her overall health. She had been prescribed the following medications: venlafaxine (Effexor), progestin (Norethindrone), Tylenol PM for sleep, plus Advil and Tylenol, as needed for pain.

The patient was diagnosed with focal nodular hyperplasia at age 35. She had two surgeries to remove tumors in her liver at ages 36 and 43, and an ablation procedure at age 47 to cut off the blood supply to a large tumor. Semiannual MRIs to check on the growth of her tumors have consistently shown an increase in tumor size and number.

Plan of Care
The patient was considering but was skeptical of using cannabis, since it had historically made her uncomfortable and paranoid. I explained that THC could have that effect, but, when combined with adequate CBD, these adverse effects could be ameliorated.2 In the meantime, I recommended an organically grown, broad spectrum (containing additional cannabinoids, terpenes, and flavonoids found in the plant), hemp-based CBD.

After discussing options, we chose a water-soluble CBD tincture for its fast onset and enhanced absorption. I advised a starting dose of three to four drops three times a day for a total daily dose of 9 to 12 mg. While this is a low dose, my goal in practice is always to start low and go slow with dosing in order to find the minimum effective dose.

One advantage of a tincture is that the patient can self-titrate depending on the severity of symptoms. For many of my clients, this particular nano-enhanced water-soluble tincture has proven to be effective at lower doses than those required with other tinctures or soft gels. I encouraged the patient to keep a journal of her symptoms and the dosage used and to increase the number of drops slowly until she found relief. This journaling helps clients find their optimal doses.

Some clients prefer the ease of taking a daily soft gel, but oral CBD (edibles and soft gels) has a greater likelihood of interacting with some pharmaceutical medications. Ingested CBD undergoes first-pass metabolism by the liver, utilizing the Cytochrome P-450 (CYP450) enzyme system.3 If another medication requiring this enzyme system for metabolism is taken at the same time as the CBD, it could affect the blood levels of that medication. For some drugs this may not be an issue, but for medications with a narrow therapeutic window, it’s necessary to proceed with caution. Some blood thinners and antiarryhthmics utilize the CYP450 enzyme system and fall into this category. A general rule is that medications contraindicated with grapefruit could potentially be affected by ingested CBD.4

In cases in which there could be an interaction, I typically steer clients away from oral CBD and toward a tincture, or make sure the CBD and medication are taken at least eight hours apart. Even though the risk of interaction between CBD and my patient’s venlafaxine is low, I still advised that an ingestible CBD should not be taken at the same time as this medication.

Outcome
After three weeks, the patient e-mailed to say “I have been taking the CBD oil—Hydro PCR Hemp Oil—and have seen a big improvement in my sleep. I haven’t taken a Tylenol PM since I started, and I seem to have more energy. I take six drops in the morning and six drops at night. Just for convenience I don’t carry it around for an afternoon dose.”

It’s important to consider clients’ lifestyles and work with them to determine regimens that are easy to follow. For this client, carrying a bottle of tincture to work was not convenient, and she found relief with twice-a-day dosing.

After three months, the patient reported that she was still sleeping well and that her anxiety was markedly decreased. She shared one example of a situation that historically had caused a fair amount of stress. At a recent annual family gathering, she was very calm and did not feel the need, as in the past, to “bite someone’s head off!”

She also stated that since starting CBD, she has more energy and clarity and can focus better at work. Three coworkers have asked her why she is so productive lately. She’s also been able to exercise because of a reduction in pain and now plans to work with her physician to slowly decrease her dose of Effexor. Even though constipation was not a primary complaint, she’s seen a significant improvement in bowel function since starting CBD. Ten drops twice daily was determined to be her optimal dose, which is about 20 mg per day.

Finally, the patient recently had a liver MRI, which has always provoked anxiety. She reported a sense of calm before and during the procedure. Furthermore, she e-mailed to say that her MRI showed no tumors for the first time in 13 years.

“I don’t need to go back for a year. I have also found relief from most of the discomfort in my stomach/digestion from all my surgeries, and improvement with sleep and depression,” she said.

Discussion
CBD can be an effective treatment for anxiety, depression, insomnia, and pain, which can certainly improve quality of life.5,6 This patient is a good example of these benefits. Being more focused and productive at work, being able to exercise, and not getting upset with disagreeable people are a few of the positive effects she’s seen. The improvement in her constipation is not surprising, as there are cannabinoid receptors in the gut, and cannabis has been used effectively for digestive issues for centuries.7,8

It can’t be determined whether CBD played a role in the disappearance of her liver tumors, though there is research on the antitumoral action of cannabinoids. A study by Vara and colleagues, reported in Cell Death & Differentiation, showed a proautophagic and antiproliferative effect induced by cannabinoids on hepatic cancer cells.9

The fact that we don’t have decades of empirical data (randomized, double-blind, placebo-controlled clinical studies) proving the medical benefits of CBD and cannabis presents a challenge for many in the medical community. However, given the long history of the therapeutic use of cannabis, it’s incumbent on medical professionals to keep an open mind.10

New and ongoing studies would be much easier to accomplish if cannabis were removed from the Schedule of Controlled Substances. Its 1970 Schedule I status, reserved for drugs with high potential for abuse and no medical value, makes it federally prohibited, thereby limiting research.11,12 This outdated classification stands in the way of relief for people who are suffering.

Because I’ve seen dramatic results in hundreds of clients in my practice—in particular for anxiety, pain, and insomnia—with little to no side effects, I urge health care professionals to consider CBD and cannabis as viable adjuncts to treatment.

— Janice Newell Bissex, MS, RDN, FAND, is a certified holistic cannabis practitioner at JannabisWellness.com.

References

1. Han B, Palamar J. Marijuana use by middle-aged and older adults in the United States, 2015-2016. Drug Alc Dep. 2018;191:374-381.

2. Niesink R, van Laar M. Does cannabidiol protect against adverse psychological effects of THC? Front Psychiatry. 2013;4:130.

3. Pond SM. Tozer TN. First-pass elimination. Basic concepts and clinical consequences. Clin Pharmacokinet. 1984;9(1):1-25.

4. CBD-drug interactions: the role of cytochrome P-450. Project CBD website. https://www.projectcbd.org/medicine/cbd-drug-interactions/p450. Accessed November 7, 2019.

5. de Mello Schier AR, de Oliveira Ribeiro NP, Coutinho DS, et al. Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of cannabis sativa. CNS Neurol Disord Drug Targets. 2014;13(6):953-960.

6. Russo E. Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag. 2008;4(1):245-259.

7. DiPatrizio NV. Endocannabinoids in the gut. Cannabis Cannabinoid Res. 2016;1(1):67-77.

8. Ahmed W, Katz S. Therapeutic use of cannabis in inflammatory bowel disease. Gastroenterol Hepatol (NY). 2016;12(11):668-679.

9. Vara D, Salazar M, Olea-herrero N, Guzman M, Velasco G, Diaz-Laviada I. Anti-tumoral action of cannabinoids on hepatocellular carcinoma: role of AMPK-dependent activation of autophagy. Cell Death Differ. 2011;18(7):1099-1111.

10. Barna Bridgeman M, Abazia DT. Medicinal cannabis: history, pharmacology, and implications for the acute care setting. P T. 2017;42(3):180-188.

Case Study: CBD Targets Multiple Symptoms By Janice Newell Bissex, MS, RDN, FAND CRx Magazine Vol. 2, No. 1, P. 6 Patients suffering from pain, anxiety, depression, insomnia, migraines,