Tramadol and Weed: Is It Safe to Take Both?

tramadol and marijuana
By Nick Congleton Updated March 8th

Fact-checked by Alexandra Arnett, MS

Medically reviewed by Dr. Brian Kessler, MD

Tramadol is an opioid medication commonly prescribed to treat moderate pain. As a synthetic opioid, tramadol does not occur in nature; instead, it was created in a lab, similar to fentanyl. 

Tramadol is used to treat both immediate moderate pain, like pain following surgery, and chronic pain, like arthritis pain. Since cannabis is also commonly used by patients experiencing acute and chronic pain, it’s natural to wonder if the combination of cannabis and tramadol would be more effective.

There are clear risks to using cannabis in combination with an opioid pain medication, and some unique properties of tramadol could make it especially risky under certain circumstances. And with many consumers using cannabis as an alternative to highly addictive opioid medications, it’s worth considering if cannabis might be a better replacement than supplement to the use of tramadol for pain relief.

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What is Tramadol?

Tramadol is a synthetic opioid commonly prescribed to treat moderate pain. It is available in both short-term and extended-release formulations, depending on the pain being treated.

Like other opioids, tramadol works by binding to opioid receptors in the body to suppress pain signals, leading to an overall reduction in pain. Opioids also trigger the release of endorphins and dopamine, leading to feelings of euphoria and triggering the brain’s reward system, which leads to addiction. This is why it’s vital that opioids, like tramadol, only be used according to a doctor’s recommendation.

Opioid abuse is an epidemic in the U.S., leading to thousands of overdose deaths every year. According to the CDC, 75% of overdose deaths in 2020 were caused by opioids. Not only does prolonged opioid use result in physical dependence and withdrawal symptoms, it builds tolerance. As someone requires and uses higher doses of an opioid, the risk of serious side effects, like respiratory depression and overdose, also increases.

While tramadol was initially thought to be safer than other opioids (and wasn’t even classified as one initially), recent research is painting a different picture. In one study, mortality rates of patients taking tramadol were higher than those taking other opioids. Even though this research is limited, it is concerning.

Like many medications, tramadol has a list of common side effects, which include:

  • Drowsiness
  • Anxiety and nervousness
  • Headaches
  • Mood changes
  • Dry mouth
  • Heartburn
  • Tightness in the muscles
  • Uncontrollable shaking in one or more body parts

Tramadol can also cause more serious side effects, including the risk of overdose and death. These side effects may indicate a more serious underlying reaction. They include:

  • Rashes, hives, or blisters
  • Difficulty swallowing
  • Difficulty breathing
  • Swelling, especially in the face, tongue, hands, feet, ankles, or legs
  • Mood swings or agitation
  • Unexplained sweating or fever
  • Fast or racing heartbeat
  • Muscle stiffness
  • Unexplained muscle twitching
  • Shivering
  • Nausea
  • Vomiting
  • Diarrhea
  • Loss of muscle coordination
  • Confusion
  • Hallucinations
  • Loss of consciousness
  • Difficulty thinking or concentrating
  • Excessive fatigue or drowsiness
  • Headaches
  • Seizures

Tramadol is also known under several brand names, which include:

  • Conzip
  • Qdolo
  • Rybix ODT
  • Ryzolt
  • Ultram
  • Ultram ER

Since tramadol is not a naturally-derived opioid, it doesn’t function exactly like most other opioids. As a result, the risk of overdose is higher because tramadol does not respond completely to the administration of naloxone.

Tramadol and Weed: Possible Risks and Side Effects

Tramadol and cannabis affect the body differently, but there is evidence that those systems may be interconnected. In animal studies, researchers found high concentrations of endocannabinoid receptors in the same areas where the body has high concentrations of opioid receptors, like the spinal cord, the brain’s pain centers,2 and even the brain’s reward circuit.1,2

There’s further evidence that these two systems interact. In a study on mice genetically modified to remove endocannabinoid receptors, the mice did not repeatedly self-administer heroin, suggesting that they did not receive the pleasurable or addictive effects.3 In an animal study from 1997, researchers found that THC increased the amount of opioid precursors found in the spinal cords of rats.4 On a similar note, research found that blocking the enzymes active in the opioid system of the body also blocked the pain-relieving properties of THC.5

While this doesn’t amount to concrete proof, it does suggest that the body’s endocannabinoid system and the opioid system are related and can affect each other. So, it’s entirely possible that cannabis can impact or amplify the effects of tramadol. 

There’s another clear concern about mixing cannabis and tramadol: serotonin levels.

Cannabis increases levels of serotonin, a neurotransmitter, in the brain. Generally, this is a good thing since serotonin plays a vital role in the body and makes people feel good. However, when combined with another substance that also increases serotonin levels, like cannabis, there’s a risk of developing serotonin syndrome, a potentially fatal condition caused by excess serotonin. The NIH warns against using tramadol along with other substances that cause an increase in serotonin levels because of the risk of serotonin syndrome. 

Tramadol is also associated with a higher risk of seizure.6 And while cannabis has a long history of treating seizures – and studies reviewing current literature back up those findings7 – further study is needed. And if using cannabis has the potential to amplify tramadol’s effects, it stands to reason that it could potentially increase the risk of seizure associated with tramadol. This is especially concerning because research indicates that the prevalence of seizures associated with tramadol was dose-dependent. 

Tramadol and Weed: Are There Any Benefits to Taking Both?

Cannabis and tramadol have both shown the ability to relieve pain. This has led many people to question if combining the two would be more effective.

While there’s evidence to suggest that the combination may be effective in treating pain, the risks and side effects of combining cannabis and tramadol are too severe to recommend taking both simultaneously.

Tramadol has a fairly extensive list of side effects, some of which can be extremely severe, like seizures. Combining it with another substance that may amplify those effects isn’t worth the potential benefits.

Can Weed Be a Tramadol Replacement for Pain?

medical marijuana doctor

Tramadol is primarily prescribed to treat pain. There’s a mounting body of evidence that cannabis is also an effective pain reliever, albeit with less of an established track record than opioids.

While opioids, like tramadol, have an established medical history of treating pain, they’re also well known for their side effects and potential for addiction and overdose. 

In light of the opioid epidemic, researchers are constantly looking for alternatives. In a 2021 study, legal recreational cannabis dispensaries were linked with a 17% to 21% reduction in opioid overdose deaths.8 Further scientific review of existing evidence turned up a similar pattern.9

There’s even evidence that cannabis may be an effective treatment for opioid use disorder.10 In fact, some states are beginning to recognize that notion, allowing medical cannabis for the treatment of opioid use disorder or as an alternative to opioid-based pain treatments. 

Both New York and New Jersey list opioid use disorder as a qualifying medical condition for medical cannabis, allowing for the treatment of opioid addiction using cannabis. Pennsylvania lists opioid use disorder as a qualifying condition, but only when traditional therapies have proven ineffective. Plenty of other states have pain or chronic pain as qualifying conditions for medical cannabis, treating it as an alternative to opioids, while some states only allow medical cannabis for pain when opioid treatments have failed.

Opioid pain treatments, like tramadol, can be effective, but they carry a wide range of potentially serious side effects. And they have a high risk for dependence and overdose.

Meanwhile, many medical marijuana patients have reported that cannabis is an effective pain treatment that can be safely used over a long period of time with minimal risk of dependency and only mild side effects.

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What About Tramadol and CBD?

Cannabis is becoming more widely available as more states legalize the plant for both medical and recreational purposes, but some people still prefer CBD-rich or CBD-only products. CBD delivers many of the benefits of high-THC cannabis products, without the intoxication, making it ideal for daytime use.

While CBD may seem safer than high-THC cannabis, there’s still a risk of interaction with tramadol and other opioids. One of the main concerns is increased side effects from the tramadol, including excess drowsiness.

Interestingly, there are efforts underway to study CBD as a potential tool in treating opioid use disorder. While there aren’t results to report just yet, the fact that the NIH is willing to invest the time and resources to test CBD as a treatment means there’s reason to be optimistic.

If you’re considering using CBD and tramadol at the same time, consult with your doctor first to work out a plan that is both safe and effective for you.

Safety Tips When Using Tramadol and Weed

Though both tramadol and cannabis can each offer patients pain relief, using both together is not recommended. The combination presents a risk of amplified side effects, some of which can be severe or even life-threatening. If you’re looking for a long-term pain treatment without the risks and side effects associated with opioid pain relievers, consider speaking with a medical cannabis doctor about how you can safely incorporate cannabis into your treatment regimen.


1. Mansour A, Fox CA, Akil H, Watson SJ. Opioid-receptor mRNA expression in the rat CNS: anatomical and functional implications. Trends in Neurosciences. 1995;18(1):22-29. doi:

2. Katia B. Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies. Frontiers in Pharmacology. 2015;6. doi:

3. Cossu G, Ledent C, Fattore L, et al. Cannabinoid CB1 receptor knockout mice fail to self-administer morphine but not other drugs of abuse. Behavioural Brain Research. 2001;118(1):61-65. doi:

4. Corchero J, Avila MA, Fuentes JA, Manzanares J. Δ-9-Tetrahydrocannabinol increases prodynorphin and proenkephalin gene expression in the spinal cord of the rat. Life Sciences. 1997;61(4):PL39-PL43. doi:

5. Reche I, Ruiz-Gayo M, Fuentes JA. Inhibition of opioid-degrading enzymes potentiates Δ9-tetrahydrocannabinol-induced antinociception in mice. Neuropharmacology. 1998;37(2):215-222. doi:

6. Nakhaee S, Amirabadizadeh A, Brent J, et al. Tramadol and the occurrence of seizures: a systematic review and meta-analysis. Critical Reviews in Toxicology. 2019;49(8):710-723. doi:

7. Zaheer S, Kumar D, Khan MT, Giyanwani PR, Kiran F. Epilepsy and Cannabis: A Literature Review. Cureus. 2018;10(9). doi:

8. Hsu G, Kovács B. Association between county level cannabis dispensary counts and opioid related mortality rates in the United States: panel data study. BMJ. Published online January 27, 2021:m4957. doi:

9. Vyas MB, LeBaron VT, Gilson AM. The use of cannabis in response to the opioid crisis: A review of the literature. Nursing Outlook. 2018;66(1):56-65. doi:

10.  Wiese B, Wilson-Poe AR. Emerging Evidence for Cannabis’ Role in Opioid Use Disorder. Cannabis and Cannabinoid Research. 2018;3(1):179-189. doi:

The information in this article and any included images or charts are for educational purposes only. This information is neither a substitute for, nor does it replace, professional legal advice or medical advice, diagnosis, or treatment. If you have any concerns or questions about laws, regulations, or your health, you should always consult with an attorney, physician or other licensed professional.

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