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Does CBD Interact With Fentanyl?

CBD & fentanyl are both used to combat pain — but are they safe to use together? Learn why you should avoid using CBD with fentanyl.

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Daily CBD , last updated on December 17, 2021

Although the degree of this interaction is mild within the normal dose ranges of both compounds, the coadministration of CBD with fentanyl should be avoided. 

Fentanyl has a narrow therapeutic range, which means doses even slightly too high could result in overdose. 

While the effects of CBD are distinct from fentanyl, and the chances of experiencing side effects are low, the severity of these side effects makes this combination worth avoiding entirely. 

Does CBD Interact With Fentanyl?

Yes, CBD may interact with fentanyl by inhibiting its breakdown and enhancing some of its analgesic and sedative activity. 

CBD and fentanyl are both metabolized in the liver by the enzymes CYP3A4 and CYP3A5 [1,2].

When CBD and fentanyl are taken together, both compounds may experience a delay in elimination, leading to a longer duration of effects. If fentanyl isn’t eliminated entirely before a second, third, or fourth dose is given, it could result in a gradual increase in serum levels. If serum concentrations get too high, it can result in an overdose. 

With that said, the risk of this combination is considered low. 

A recent study evaluated the safety of coadministration of CBD (400 mg, 800 mg) and fentanyl (0.5 mcg, 1 mcg). The study concluded that CBD did not exacerbate the side effects associated with IV fentanyl and coadministration of CBD with fentanyl is relatively safe and well-tolerated [3].

A pre-clinical study conducted on rats suggested that CBD can have a significant effect on inhibiting heroin-seeking behavior [5]. This data provides an insight to conduct further studies to evaluate the importance of CBD in reducing opioid addiction and relapse.

Other Names For Fentanyl

Fentanyl is sold under many names, all of which share the same risks and potential interactions.

  • Actiq
  • Duragesic
  • Sublimaze 
  • Abstral 
  • Fentral 

Similar Medications to Fentanyl

Fentanyl is an opioid analgesic. CBD will interact with all opioid analgesics similarly — increasing the painkilling effects, prolonging elimination from the body, and increasing the chances of side effects.

Theoretically, CBD could increase the chances of overdosing on these medications — however, there are no reports to back this up, and studies have confirmed this combination is generally considered safe. 

Here’s a list of medications that share a similar level of risk when combined with CBD:

  • Buprenorphine (Cizdol & Brixadi)
  • Codeine
  • Pethidine (Meperidine & Demerol)
  • Hydrocodone (Hysingla ER, Zohydro ER & Hycodan)
  • Hydromorphone (Dilaudid)
  • Methadone (Methadose & Dolophine)
  • Morphine (Kadian & Roxanol)
  • Oxycodone (Percodan, Endodan, Roxiprin, Percocet, Endocet, & OxyContin)
  • Tramadol (Ultram, Ryzolt & ConZip)

Is It Safe To Take CBD & Fentanyl Together?

CBD and fentanyl have a low risk of interaction and are considered safe when used within the recommended doses. 

However, because of the severity of fentanyl overdose and the potential antagonistic effects of CBD, it’s wise to avoid this combination unless under direct medical oversight. 

With that said, studies have shown the interaction of CBD and fentanyl when coadministered is proven to be of mild severity and well-tolerated [6].

It is always advised to consult your doctor before using CBD and fentanyl together or with any other medication to avoid potential risks. 

Is CBD A Viable Alternative To Fentanyl?

CBD may be a viable alternative to fentanyl for mild to moderate pain or for managing long-term (chronic) pain. However, fentanyl is significantly stronger than CBD and is much more suitable for immediate, powerful pain inhibition.

While both substances are used for pain, the difference in potency makes them useful for different situations entirely.

There are no specific studies on the combined use of CBD and fentanyl to evaluate their effect together in pain management. It is, however, proven that CBD can be used to reduce pain in patients who have a refractory response to fentanyl or other failed treatments [4]. 

CBD, through various studies, has been proven to reduce chronic pain in patients with multiple sclerosis [7], intractable chronic pain in cancer patients [8,9], refractory neuropathic pain following failed spinal surgery [10], and pain due to fibromyalgia. It’s not useful in all kinds of pain. 

But it can serve as an alternative for pain management in patients who do not respond to fentanyl or opioid analgesics.

CBD is not FDA approved and is mostly used as an over-the-counter product for pain management.

What Is Fentanyl?

Fentanyl is classified as an opioid analgesic. It is a synthetic compound. It acts through the μ opioid receptor and, to a lesser extent, through delta and kappa receptors that are present throughout the central and peripheral nervous system to increase the pain threshold. 

It is a highly lipid-soluble substance and easily penetrates the central nervous system.

It is available in different forms like intravenous injection, transdermal patch, buccal and sublingual tablets, oral lozenge, and sublingual and nasal spray.

Fentanyl Specs:

Drug Name Fentanyl
Trade Names Actiq, Sublimaze, Duragesic
Classification Synthetic Opioid
CYP Metabolism Enzyme CYP3A4 & CYP3A5
Interaction With CBD Metabolic Competition & Agonistic 
Risk Of Interaction Mild

What Does Fentanyl Do?

Fentanyl is a synthetic opioid analgesic drug. It acts through opioid receptors that are present in the brain and spinal cord in the outer membrane of nerve cells. 

Fentanyl has 50-100 times more affinity for μ-receptors than morphine. It also acts through delta and kappa receptors. The opioid receptors are G-protein coupled receptors that are particularly involved in the control of emotions, pain, and addiction.

When introduced to the body, fentanyl binds to the opioid receptors, and downstream signaling leads to inhibitory effects like decreased cAMP production, decreased calcium influx, and an increase in potassium ion efflux. 

These events lead to inhibition of ascending pathways to the CNS that are responsible for propagating pain signals. This interference in pain signal transmission leads to an increase in pain threshold, which is how it exerts its analgesic effect.

The uses of fentanyl are:

  • To induce general anesthesia
  • Spinal anesthesia
  • Epidural anesthesia
  • Pain management
  • Palliative care

It is also used illegally for recreational purposes.

Side Effects Of Fentanyl

  • Nausea
  • Vomiting 
  • Dizziness
  • Drowsiness 
  • Constipation 
  • Dry mouth 
  • Confusion 
  • Headache 
  • Abdominal pain 
  • Fatigue 
  • Anorexia 
  • Shortness of breath 
  • Anxiety 
  • Nervousness 
  • Itching 
  • Urinary retention 

Some serious side effects include:

  • Respiratory depression
  • Bradycardia
  • Vasodilation 
  • Muscle rigidity
  • Substance abuse
  • Physical dependence

Who Should Avoid Fentanyl?

Fentanyl isn’t safe for everyone — this powerful medication comes with a long list of contraindications. 

This prescription medication requires professional oversight to rule out any red flags or major contraindications. 

List of fentanyl contraindications include:

  1. People with known hypersensitivity to fentanyl or any opioid drugs or any excipients.
  2. People suffering from any obstructive respiratory disease (asthma, COPD, obstructive sleep apnea)
  3. People suffering from any severe liver dysfunction
  4. People suffering from any severe kidney disease
  5. People who have had any recent biliary tract surgery
  6. People who have had any recent head injury or conditions with increased intracranial pressure.
  7. People suffering from any kind of muscular disease (myasthenia gravis) 

Key Takeaways: Is It Safe To Take CBD With Fentanyl?

Although the interaction between CBD and fentanyl is relatively mild, it’s best to avoid taking them together. 

Their use together may increase the adverse effects associated with fentanyl. A higher serum concentration of fentanyl may occur if administered together with CBD over long periods of time, which may result in an overdose or other serious side effects. 


  1. Yamaori, S., Ebisawa, J., Okushima, Y., Yamamoto, I., & Watanabe, K. (2011). Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life sciences, 88(15-16), 730-736.
  2. Feierman, D. E., & Lasker, J. M. (1996). Metabolism of fentanyl, a synthetic opioid analgesic, by human liver microsomes. Role of CYP3A4. Drug Metabolism and Disposition, 24(9), 932-939.
  3. Manini, A. F., Yiannoulos, G., Bergamaschi, M. M., Hernandez, S., Olmedo, R., Barnes, A. J., … & Hurd, Y. L. (2015). Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans. Journal of addiction medicine, 9(3), 204.
  4. Argueta, D. A., Ventura, C. M., Kiven, S., Sagi, V., & Gupta, K. (2020). A balanced approach for cannabidiol use in chronic pain. Frontiers in pharmacology, 11, 561.
  5. Ren, Y., Whittard, J., Higuera-Matas, A., Morris, C. V., & Hurd, Y. L. (2009). Cannabidiol, a non-psychotropic component of cannabis, inhibits cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbances. Journal of Neuroscience, 29(47), 14764-14769.
  6. Manini, A. F., Yiannoulos, G., Bergamaschi, M. M., Hernandez, S., Olmedo, R., Barnes, A. J., … & Hurd, Y. L. (2015). Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans. Journal of addiction medicine, 9(3), 204.
  7. Rog, D. J., Nurmikko, T. J., Friede, T., & Young, C. A. (2005). Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology, 65(6), 812-819.
  8. Johnson, J. R., Burnell-Nugent, M., Lossignol, D., Ganae-Motan, E. D., Potts, R., & Fallon, M. T. (2010). Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC: CBD extract and THC extract in patients with intractable cancer-related pain. Journal of Pain and symptom management, 39(2), 167-179.
  9. Portenoy, R. K., Ganae-Motan, E. D., Allende, S., Yanagihara, R., Shaiova, L., Weinstein, S., … & Fallon, M. T. (2012). Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. The Journal of Pain, 13(5), 438-449.
  10. Mondello¹, E., Quattrone, D., Cardia¹, L., Bova, G., Mallamace¹, R., Barbagallo, A. A., … & Calapai, G. (2018). Cannabinoids and spinal cord stimulation for the treatment of failed back surgery syndrome refractory pain. Journal of pain research, 11, 1761.

Learn More About CBD-Drug Interactions

Learn More About CBD-Drug Interactions

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