CBD and Tramadol - April 2024

Can CBD Oil Be Taken with Tramadol? 

Tramadol has been used as a pain reliever for years. However, because of its potential for abuse, it may not be for everyone. Veterinarians also use Tramadol for dogs in pain.

CBD and tramadol may be useful pain relievers. However, using them in combination brings about adverse effects and is, therefore, not recommended.

Many drug interaction reports between CBD oil and Tramadol do not state specific dosage interaction, except for the National Institutes of Health research which stated that CBD oil could lessen the analgesic efficacy of high dosage Tramadol⁽⁵⁾.

Tramadol is an analgesic that modulates moderate to severe pain by traveling within the central nervous system through metabolite binding to specific opioid receptors⁽⁶⁾.

The primary mu-opioid receptors (muORs) mediate the analgesic effects of opioids⁽⁷⁾. 

A prospective cohort study stated that the use of full-spectrum cannabidiol, which has psychoactive effects, could significantly lessen opioid use and improve chronic pain and sleep quality among patients who use opioids to manage pain⁽⁸⁾.

However, a study made by The American Society for Pharmacology and Experimental Therapeutics concluded that the use of CBD might inhibit the liver enzyme CYP2DC responsible for metabolizing Tramadol and other opioids, such as codeine which is commonly used as an alternative to Tramadol when pain is mild to moderate, in the body⁽⁹⁾. By inhibiting the drugs’ metabolisms, there would be higher levels of both tramadol and codeine in the system and so the analgesic effect of CBD could be from that mechanism alone, rather than from the direct effects of CBD.

Can another analgesic be a substitute for Tramadol so that CBD Oil can be taken? 

There is no established alternative to Tramadol so that CBD oil can be taken. 

Tramadol relieves acute and chronic pain with moderate to severe intensity. It is used in the pain management of osteoarthritis, acute myocardial infarction, acute myocardial infarction, and Brugada syndrome⁽¹⁰⁾.

It is also used for dental, post-operative, chronic cancer, back pain, and acute renal pain relief⁽¹¹⁾.

However, Tramadol can cause common side effects like headaches, constipation, and dry mouth⁽¹²⁾.

The more severe side effects are breathing difficulty or short, shallow breathing, hallucinations, urinary difficulty, seizures, confusion, and the low blood pressure symptoms of dizziness, exhaustion, and lack of energy⁽¹³⁾.

Severe allergic reaction (anaphylaxis) also happens, but rarely⁽¹⁴⁾.

Other analgesics can be used as a replacement for Tramadol that have fewer side effects when compared to Tramadol. 

A 2005 experimental study in rats concluded that metoclopramide is a viable low-cost alternative to Tramadol in treating post-operative pain because it offers fewer side effects commonly linked to Tramadol, such as nausea, tremor, and vomiting⁽¹⁵⁾.

Since there are no studies currently available about drug interactions between metoclopramide and CBD oil, consulting a doctor before use is highly recommended.

According to a February 2020 JAMA medical journal research, Tramadol had a higher mortality risk compared to the anti-inflammatory medications naproxen, diclofenac, and etoricoxib⁽¹⁶⁾.

More clinical trials are needed to confirm the research because it did not attribute the result to specific causes. Several external factors may have led to the conclusion⁽¹⁷⁾.

An NIH study stated that naproxen is not recommended to use with CBD products from the cannabis plant because naproxen’s CYP2C8/9 enzyme substrate interacts with CBD oil⁽¹⁸⁾.

The study has advised avoiding administering CBD oil with naproxen, decreasing the naproxen dose, or monitoring for adverse effects and toxicity to minimize side effects⁽¹⁹⁾.

It is also not recommended to take CBD oil while taking diclofenac because there are indications that CBD decreases its metabolization because CBD may inhibit the hepatic enzyme CYP2C9⁽²⁰⁾.

Take caution in using CBD products like cannabis oil with etoricoxib and corticosteroids because of possible drug interaction even if there is no published report⁽²¹⁾.

Drug interactions between ibuprofen, over-the-counter medications, and other NSAIDS with cannabinoids have not yet been demonstrated. 

Can CBD replace Tramadol?

CBD can help relieve pain similarly addressed by prescribing Tramadol. 

Pain associated with cancer, neuropathy, and central pain such as multiple sclerosis can be suitably managed with CBD⁽²²⁾.

A study proves that CBD subdues inflammatory and neuropathic pain⁽²³⁾.

CBD’s anti-inflammatory properties are expounded in the Journal of Pharmacology and Experimental Allergic Contact Dermatitis⁽²⁴⁾.

CBD may also relieve muscle weakness, which is a significant symptom of neuropathy⁽²⁵⁾.

CBD can also be used to manage pain that does not respond well to other treatments like optimized opioid therapy in conditions such as intractable cancer pain and chronic musculoskeletal pain⁽²⁶⁾.

The University of Michigan Health Lab published an article declaring that the benefits of opioids like Tramadol and cannabinoids are similar, but that opioids are not as useful for chronic pain even though physicians prefer to use opioids over the use of cannabis, primarily due to its Schedule 1 status. ⁽²⁷⁾

Opioids are more useful for pain associated with peripheral damage or inflammation resulting in nerve pain. Symptoms of this condition include⁽²⁸⁾:

• numbness, prickling, and tingling in hands and feet
• sharp, burning, or throbbing pain 
• touch sensitivity
• muscle weakness
• paralysis (rare)

The endocannabinoid system plays an important role in the central nervous system. 

Cannabinoids are preferred for neuropathic and centralized pain conditions like fibromyalgia⁽²⁹⁾.

Other conditions with neuropathic and centralized pain conditions are allodynia, where the pain is experienced with ordinary touch, chronic pain syndrome, and neurological injuries such as stroke and spinal cord injury⁽³⁰⁾.

Although their benefits are comparable, the article expressed that both opioids and cannabinoids should not be used as primary therapies for chronic pain because the benefits are minimal⁽³¹⁾.

The article suggested that physicians are reluctant to prescribe cannabis because the appropriate formulation and dose has not been determined ⁽³²⁾.

It also advised pharmaceutical companies to stop marketing opioids for a broad range of conditions until studies confirm opioids’ extensive scope of efficacy⁽³³⁾.

Tramadol vs. CBD

Tramadol was not yet classified as an opiate in 1995. However, the FDA identified Tramadol as a controlled substance in 2014 due to widespread abuse and addiction to it. It is Schedule IV, lower risk of abuse than OxyContin, a Schedule II drug ⁽³⁴⁾.

Contrary to Tramadol and some similar prescription medications, CBD is non-addictive according to a 2015 research conducted by Nora Volkow⁽³⁵⁾.

However, Wayne Hall of the Society for the Study of Addiction stated in 2018 that it was premature to expand access to medical cannabis to solve the U.S. opioid crisis of addiction (e.g., to Xanax) and overdose⁽³⁶⁾.

What To Look for in a CBD Oil When You Are Taking Tramadol

Obtain medical advice before taking CBD products in the form of oils or tinctures. 

It is best to follow these steps before purchasing:

1. Although CBD products with hemp oil are legal in the U.S. federal system, verify the laws regarding the sale, possession, and use of CBD products in the state of purchase.
2. Read online reviews before buying in the website store. Confirm whether the clinics and brick-and-mortar and stores you buy from are authorized to sell CBD products. Buy only from reliable and legitimate brands.
3. Select pure CBD oils falling under the crystalline isolate category over full-spectrum oils that retain tetrahydrocannabinol (THC) and other cannabinoids that cause a high sensation.
4. Check for additional ingredients. MCT oils and melatonin are safe and beneficial. Beware of high-risk ingredients like vegetable glycerin and propylene.
5. Determine appropriate dosing by corresponding the dose for the condition it is used for.

Trust the advice of an experienced medical professional specializing in CBD from hemp plants instead of searching online in Google to avoid risks and side effects like withdrawal symptoms. Proper medical guidance is needed in corresponding use, dosage, and administration concerning a patient’s health condition and maintenance medications. 

CBD can interact with other compounds that are metabolized in the body by cytochrome P450 or CYP3A4 enzymes⁽³⁷⁾.

These CYP450 and CYP3A4 enzymes break down substances such as drug medications and toxins that are formed within the cells. 

Since CBD competes for these enzymes, CBD products limit the metabolism of drugs, heightening the concentration levels of drugs in the bloodstream.

CBD can increase the blood levels when taken with the blood thinner Coumadin, and it can raise levels of certain other medications in your blood by the same mechanism that grapefruit juice does.

Important Facts About Tramadol

The pain medication Tramadol was discovered and synthesized in 1962 by the German company Grunenthal GmbH. It was introduced in the market under the name Tramadol in 1977. It became available in the U.S. after 1995⁽³⁸⁾.

Tramadol has severe drug interactions with alvimopan, procarbazine, rasagiline, and selegiline. It has severe interactions with approximately 49 drugs and moderate interactions with around 269 drugs⁽³⁹⁾.

Mild drug interactions with Tramadol include the following⁽⁴⁰⁾:

• marijuana 
• sage 
• asenapine 
• brimonidine
• darifenacin
• eucalyptus 
• naloxone
• nilotinib
• dextroamphetamine
• maraviroc
• ziconotide 
• paroxetine
• lidocaine 

As a prescription drug, oral doses of Tramadol come in tablets, reconstituted suspension, and extended-release capsules⁽⁴¹⁾.

Veterinarians are in consensus that Tramadol is the most common painkiller for dogs because of the minimal risk of side effects and addiction⁽⁴²⁾.

Conclusion

CBD could significantly lessen opioid use and improve chronic pain and sleep quality among patients who use opioids such as oxycodone to manage pain.

Using CBD with high doses of Tramadol can lessen its analgesic effects. The effect when Taking Tramadol in lower doses is unknown.

Using CBD with Tramadol may slow the drug’s metabolism in the body and increase the high levels of Tramadol in the bloodstream, which appears to contradict the statement above. If the metabolism of tramadol is slower, then higher levels of tramadol (in the face of CBD) would mean a higher analgesic effect. Thus, the end result is that we do not have all the answers, yet.

It is, therefore, best to seek medical advice before using CBD oil when taking Tramadol.

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1. Monte, Andrew A., et al. (2014 August). The effect of CYP2D6 drug-drug interactions on hydrocodone effectiveness. Acad Emerg Med, 21(8): 879–885. doi:10.1111/acem.12431. https://accurateclinic.com/wp-content/uploads/2018/07/The-Effect-of-CYP2D6-Drug-Drug-Interactions-on-Hydrocodone-Effectiveness-2014.pdf
2. ibid.
3. Capano, A., Weaver, R., and Burkman, E. (2020 Jan). Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: a prospective cohort study. Postgrad Med, 132(1):56-61. doi: 10.1080/00325481.2019.1685298. https://www.ncbi.nlm.nih.gov/pubmed/31711352
4. Yamaori, Satoshi, et al. (2011 August 5). Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6”. The American Society for Pharmacology and Experimental Therapeutics. DMD, 39:2049–2056, 2011. https://accurateclinic.com/wp-content/uploads/2018/07/Cannabidiol-a-Major-Phytocannabinoid-As-a-Potent-Atypical-Inhibitor-for-CYP2D6-2011.pdf
5. Monte, Andrew A., 2016, op. cit.
6. National Library of Medicine, National Center for Biotechnology Information. https://pubchem.ncbi.nlm.nih.gov/compound/Tramadol#section=Pharmacology-and-Biochemistry
7. Ibid.
8. Capano, et al., 2020
9. Yamaori, et al., 2011
10. National Health Service UK. (2018 November 26). https://www.nhs.uk/medicines/tramadol/
11. ibid.
12. ibid.
13. ibid.
14. ibid.
15. Ceyhan, A., et al. (2005 June). US National Library of Medicine, National Institutes of Health. Is metoclopramide an alternative to tramadol in management of post-operative pain? An experimental study. J Vet Med A Physiol Pathol Clin Med, 52(5): 249-53. https://www.ncbi.nlm.nih.gov/pubmed/15943610
16. Zeng, C., et al. (2019 March 12). Association of tramadol with all-cause mortality among patients with osteoarthritis. JAMA, 321(10): 969-982. doi: 10.1001/jama.2019.1347. https://www.ncbi.nlm.nih.gov/pubmed/30860559 
17. ibid. 
18. Brown, Joshua D. and Winterstein, Almut G. (2019 July). Potential Adverse Drug Events and Drug–Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. J Clin Med, 8(7): 989. doi: 10.3390/jcm8070989 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678684/
19. ibid.
20. Iffland, Kirstin and Grotenhermen, Franjo. (2017 June 1). An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies. Cannabis Cannabinoid Res, 2(1); 139-154. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569602/
21. Wilson-Morkeh, H., Al-Abdulla, A., Sien, L., Mohamed, H., and Youngstein, T. (2020 January). Important drug interactions exist between cannabidiol oil and commonly prescribed drugs in rheumatology practice. Rheumatology (Oxford), 59(1):249-251. https://www.ncbi.nlm.nih.gov/pubmed/31359066
22. Russo, E. (2008 February). Cannabinoids in the Management of Difficult to Treat Pain. Therapeutics and Clinical Risk Management, 4(1): 245-259. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2503660/
23. Xiong W., et al. (2012). Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors. J Exp Med, 209(6): 1121–1134. DOI:10.1084/jem.20120242.
24. Petrosino S., et al. (2018 June). Anti-inflammatory Properties of Cannabidiol, a Nonpsychotropic Cannabinoid, in Experimental Allergic Contact Dermatitis. Journal of Pharmacology and Experimental Therapeutics, 365 (3) 652-663; DOI: https://doi.org/10.1124/jpet.117.244368.
25. National Institute of Neurological Disorders and Stroke. (2018 August). Peripheral Neuropathy Fact Sheet. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Peripheral-Neuropathy-Fact-Sheet.
26. Russo, E. (2008 February). op. cit.
27. Clauw, Daniel. (2016  June 23). Why U.S. doctors love opioids and hate marijuana for chronic pain. M Health Lab. https://labblog.uofmhealth.org/rounds/why-us-doctors-love-opioids-and-hate-marijuana-for-chronic-pain
28. ibid.
29. Ibid.
30. Dydyk, Alexander M. and Givler, Amy. (2020 April 12). Central Pain Syndrome. https://www.ncbi.nlm.nih.gov/books/NBK553027/
31. Clauw, Daniel, 2016. op. cit.
32. ibid.
33. ibid.
34. Shmerling, Robert H. (2019 June 14).  Is tramadol a risky pain medication? Harvard Health Publishing. https://www.health.harvard.edu/blog/is-tramadol-a-risky-pain-medication-2019061416844
35. Volkow, Nora. (2015 July 20). Researching marijuana for therapeutic purposes: The potential promise of cannabidiol (CBD). National Institute of Drug Abuse. https://www.drugabuse.gov/about-nida/noras-blog/2015/07/researching-marijuana-therapeutic-purposes-potential-promise-cannabidiol–cbd.
36. Hall, Wayne, et al. (2018). It is premature to expand access to medicinal cannabis in hopes of solving the US opioid crisis. Addiction, 113, 987–988. doi:10.1111/add.14139. https://accurateclinic.com/wp-content/uploads/2018/06/It-is-premature-to-expand-access-to-medicinal-cannabis-in-hopes-of-solving-the-US-opioid-crisis-2018.pdf
37. “Cytochrome p450”. (2020, March 17). NIH Genetics Home Reference. Retrieved from https://ghr.nlm.nih.gov/primer/genefamily/cytochromep450.
38. Subedi, Muna, et al. (2019 March). An overview of tramadol and its usage in pain management and future perspective. Biomedicine & Pharmacotherapy, 111, 443-451. https://www.sciencedirect.com/science/article/pii/S0753332218373694
39. RxList. Cunha, John P., ed. (n.d).) Tramadol [Fact sheet]. https://www.rxlist.com/consumer_tramadol/drugs-condition.htm
40. Ibid.
41. Ibid.
42. All about Tramadol for dogs including alternatives. Innovet. https://www.innovetpet.com/blogs/recent-articles/tramadol-for-dogs

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