Oxycodone and Weed Interaction: Benefits and Risks

weed and Oxycodone
By Nick Congleton Updated March 8th

Medically reviewed by Dr. Brian Kessler, MD

Semi-synthetic opioids, like oxycodone, are commonly-prescribed medications used to treat moderate to severe pain. In 2017, doctors wrote 191 million prescriptions for opioids, and although in 2020 these numbers decreased, doctors still wrote 43.3 opioid prescriptions per every 100 people in the U.S. Despite the wide use of these drugs, they can carry severe risks, and the chance of dependence and overdose with opioids is extremely high.

Both oxycodone and cannabis are popular choices for managing pain, leading many people to wonder if they can safely combine them. Other people look to cannabis as a potential replacement for dangerous and addictive opioids. The relationship between these pain treatments can be complicated. Below, we list some clear answers to help you understand how the two may interact, and whether it’s safe to combine oxycodone and cannabis.

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What Is Oxycodone?

Opioids are a broad classification of medications that bind to opioid receptors in the body. These medications are derived from the poppy flower. Naturally-derived opioids like opium, morphine, and codeine, are called opiates. 

However, synthetically-derived opioids, like fentanyl, are created in a lab by modifying natural opioids. Sometimes referred to as semi-synthetic opioids, oxycodone falls into this category.

Oxycodone is often labeled under different pharmaceutical brand names. These include:

  • Dazidox
  • Endocodone
  • ETH-Oxydose
  • Oxaydo
  • Oxecta
  • Oxycontin
  • Oxyfast
  • OxyIR
  • Percolone
  • Roxicodone

Oxycodone is also prescribed in combination pills that contain other pain relievers as well. Those include:

  • Combunox
  • Endocet
  • Endodan
  • Lynox
  • Magnacet
  • Narvox
  • Oxycet
  • Percocet
  • Percodan
  • Perloxx
  • Primlev
  • Roxicet
  • Roxiprin
  • Taxadone
  • Tylox
  • Xolox

Opioids have historically been used to treat pain. That’s because when opioids bind to receptors in the brain and body, they block pain signals. These medications also trigger the release of endorphins and dopamine, two chemicals that cause feelings of pleasure and trigger the brain’s reward system.1 Essentially, whenever someone uses opiates, they’re programming their brain to do it again.

This relationship with the brain is why there’s a high risk of addiction with opioids, including oxycodone. Not only is oxycodone habit-forming, but it also carries a high-risk of overdose. In 2020, 75% of all overdose deaths in the U.S. involved opiates. As the body develops a tolerance to opiates it will require an increase in dosage to produce the same effects. Higher doses increase the risk of complications and overdose.

Interactions Between Oxycodone and Weed

Oxycodone and Weed interaction

Before considering combining oxycodone and cannabis, it’s important to look at the potential risks and side effects of each one independently. Generally, combining two medications doesn’t alleviate the risk of their individual side effects and can potentially make them worse.

The possible side effects of cannabis are well-known and comparatively quite mild. They’re also less likely to occur if consumers stick to smaller doses. Still, they’re worth keeping in mind:

The side effects of oxycodone have the potential to be much more serious. Common side effects of oxycodone include:

  • Chills
  • Cold sweats
  • Confusion
  • Difficulty breathing
  • Dizziness, lightheadedness, and faintness
  • Fever
  • Tightness in the chest
  • Twitching

Less common but severe side effects of oxycodone include:

  • Unexplained swelling or bloating in the extremities
  • Blood in the urine
  • Burning sensation when urinating
  • Itching, tingling, numbness, burning, and “pins and needles” sensations
  • Chest pain
  • Coughing
  • Decreased frequency of urination and decreased amount of urine
  • Difficulty or pain when urinating
  • Difficulty swallowing
  • Dizziness
  • Dry mouth
  • Fainting
  • Irregular or fast heartbeat
  • Unusual feeling of warmth
  • Redness or flushing, especially in the face and neck
  • Frequent urination
  • Headaches
  • Skin rashes, including hives and itching
  • Increased thirst
  • Increased urination, including clear, pale, or diluted urine
  • Lightheadedness
  • Cramping and muscle pain
  • Nausea
  • Swelling in the face, especially around the eyes and the eyelids, face, lips, and tongue
  • Rapid breathing
  • Speedy weight loss in a short period of time
  • Seizures
  • Constipation, which may be severe
  • Vomiting, which may be severe
  • Stomach pain
  • Sunken eyes
  • Unusual or unexplained sweating
  • Painful or swollen lymph nodes
  • Excessive thirst
  • Shaking feet and/or hands
  • Excessive or unexplained tiredness or weakness
  • Excessive or unexplained weight gain
  • Wrinkled skin

In extreme cases, oxycodone can impact vital functions, like breathing, leading to serious medical consequences and even death.

Given the potentially severe side effects, it’s important to understand how cannabis and oxycodone may interact. While there is little research tackling the subject directly, there are some indicators that the two do interact based on how each influences the body.

Both cannabis and opioids interact with receptors that are responsible for regulating and maintaining various processes in the body. In several animal studies, researchers found that cannabinoid and opioid receptors were clustered in the same regions of the body, including the spinal cord2 and areas of the brain associated with pain.3 Research has also found the same to be true in part of the brain associated with reward.4 

Interestingly, there’s also evidence that cannabinoid receptors play a role in the effects that opioids produce. In one animal study, researchers genetically modified mice to not have CB1 receptors (the receptors that THC interacts with in the body). They found that mice did not receive the same reward effects from heroin, a semi-synthetic opioid, that unmodified mice did.5 However, in a similar study, researchers examined the effects of removing cannabinoid receptors on morphine’s ability to treat pain, and found that morphine seemed to work just as well in most situations.6

The evidence that the systems that process opioids and cannabinoids may be interconnected doesn’t stop there. In fact, it may be that they depend on one another for their effects. One study found that THC increased the amount of endogenous opioids produced in the spinal cord of rats.7 In another study, enzymes blocking the opioid system were found to also block the pain-relieving effects of THC.8

The endocannabinoid system and the endogenous opioid system in the body appear to be closely related. And while further study is required to understand precisely how, the interaction between them raises questions about the potential benefits and risks of using both cannabis and opioids.

Is It Safe to Combine Oxycodone and Weed?

Oxycodone and Weed risks

The safety of combining oxycodone and cannabis is unclear, especially with the lack of studies explicitly addressing their interaction. While there are efforts underway to change that, the answer remains unclear. 

There’s still genuine risk involved in using both cannabis and oxycodone simultaneously. Scientific evidence indicates that cannabis can enhance the effects of opioids, meaning there’s a high probability that using cannabis with a higher dose of oxycodone – even a prescribed dose – could increase the risk of adverse effects from the opioid, including overdose and death. 

However, that isn’t necessarily the case in all instances. A 2018 study found that the combination has the potential to decrease opioid use.9 And a 2023 study looked at whether cannabis enhanced the respiratory depression caused by oxycodone and concluded that cannabis didn’t affect it.10

Given the lack of direct evidence on how cannabis and oxycodone interact, the decision on whether to combine the two is best made with the support of a qualified medical professional

Oxycodone or Medical Marijuana: Which is Better for Moderate Pain Relief?

Oxycodone vs Weed for pain

It’s difficult to say for certain whether cannabis or oxycodone provides better pain relief. As of 2023, there isn’t much research directly comparing the two, though there are trials underway. That said, both cannabis and oxycodone are well-documented to alleviate pain.

Cannabis can potentially be used to reduce opioid use and there have been case studies where patients have done just that.11

Some evidence suggests that cannabis legalization reduces opioid-related deaths. One study found that the presence of recreational cannabis dispensaries was linked to a 17%-21% decrease in opioid overdoses.12 Reviews of the existing body of research have drawn similar conclusions.13

There are studies that cite the opioid crisis as a clear reason to transition away from opioids and towards cannabis.14 Other studies suggest cannabis is a means to treat opioid use disorder (opioid addiction).15 And opioid addiction is a qualifying condition for medical cannabis in some states.

Pain is very subjective, with multiple factors influencing how patients report the intensity of their pain symptoms. As a result, it’s difficult to say whether cannabis or oxycodone is the better pain treatment, but there’s growing evidence that cannabis may be a viable alternative. 

Before transitioning from an opioid prescription to cannabis, consult with your doctor to discuss the potential benefits, risks, and a safe way to transition if you choose to do so.

Can Opioid Use Disqualify You from Getting a Medical Marijuana Card?

Oxycodone and Weed

Opioid use won’t disqualify most patients from medical cannabis and can actually be a reason physicians recommend cannabis, depending on the state.

In Pennsylvania, opioid use disorder can qualify someone for cannabis treatment if conventional treatments have failed. In other states, like New Jersey, opioid use disorder qualifies a person for medical cannabis outright, with the hope that cannabis can help get the individual away from opioids, like oxycodone.

If you’re using an opioid, like oxycodone, you may still qualify to purchase medical cannabis, but it is best to discuss with a physician before adjusting your dosage or supplementing an opioid prescription with cannabis.

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Science indicates that the body’s endocannabinoid system and its endogenous opioid system are closely interlinked. While it’s unclear exactly how they interact, there is evidence that they can influence one another. 

This emerging understanding brings promise for new medical treatments, but is also cause for caution. Some cannabis consumers have used it as an alternative that helped them lower the required doses of oxycodone. At the same time, cannabis may potentially intensify the effects of opioids, like oxycodone, making them more dangerous at higher doses.

If you’re considering using cannabis and oxycodone simultaneously, have a discussion with your physician. Following your doctor’s recommendations is the safest way to treat pain.


1 “Prescription Opioids DrugFacts.” National Institute on Drug Abuse, 2021, nida.nih.gov/publications/drugfacts/prescription-opioids.

2 Salio C, Fischer J, Franzoni MF, Mackie K, Kaneko T, Conrath M. CB1-cannabinoid and μ-opioid receptor co-localization on postsynaptic target in the rat dorsal horn. Neuroreport. 2001;12(17):3689-3692. doi:https://doi.org/10.1097/00001756-200112040-00017

3 Wilson-Poe AR, Morgan MM, Aicher SA, Hegarty DM. Distribution of CB1 cannabinoid receptors and their relationship with mu-opioid receptors in the rat periaqueductal gray. Neuroscience. 2012;213:191-200. doi:https://doi.org/10.1016/j.neuroscience.2012.03.038

4 Pickel VM, Chan J, Kash TL, Rodríguez JJ, MacKie K. Compartment-specific localization of cannabinoid 1 (CB1) and μ-opioid receptors in rat nucleus accumbens. Neuroscience. 2004;127(1):101-112. doi:https://doi.org/10.1016/j.neuroscience.2004.05.015

5 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:https://doi.org/10.1016/S0166-4328(00)00311-9

6 Miller LL, Picker MJ, Schmidt KT, Dykstra LA. Effects of morphine on pain-elicited and pain-suppressed behavior in CB1 knockout and wildtype mice. Psychopharmacology. 2011;215(3):455-465. doi:https://doi.org/10.1007/s00213-011-2232-5

7 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:https://doi.org/10.1016/S0024-3205(97)00405-0

8 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:https://doi.org/10.1016/S0028-3908(98)00005-7

9 Cooper ZD, Bedi G, Ramesh D, Balter R, Comer SD, Haney M. Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability. Neuropsychopharmacology. 2018;43(10):2046-2055. doi:https://doi.org/10.1038/s41386-018-0011-2

10 van Dam CJ, van der Schrier R, van Velzen M, et al. Inhaled Δ9-tetrahydrocannabinol does not enhance oxycodone-induced respiratory depression: randomised controlled trial in healthy volunteers. British Journal of Anaesthesia. Published online January 31, 2023. doi:https://doi.org/10.1016/j.bja.2022.12.018

11 Lynch ME, Clark AJ. Cannabis Reduces Opioid Dose in the Treatment of Chronic Non-Cancer Pain. Journal of Pain and Symptom Management. 2003;25(6):496-498. doi:https://doi.org/10.1016/s0885-3924(03)00142-8

12 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:https://doi.org/10.1136/bmj.m4957

13 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:https://doi.org/10.1016/j.outlook.2017.08.012

14 Lucas P. Rationale for cannabis-based interventions in the opioid overdose crisis. Harm Reduction Journal. 2017;14(1). doi:https://doi.org/10.1186/s12954-017-0183-9

15  Wiese B, Wilson-Poe AR. Emerging Evidence for Cannabis’ Role in Opioid Use Disorder. Cannabis and Cannabinoid Research. 2018;3(1):179-189. doi:https://doi.org/10.1089/can.2018.0022

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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