Semi-synthetic opioids, like oxycodone, are prescription 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 100 people in the United States. 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 commonly associated with pain relief, which has led some people to explore whether they can be used together. Others are curious whether cannabis might offer an alternative approach to pain relief under appropriate medical guidance. In this guide, we examine the current research on how these two may interact and the potential risks associated with combining them.
What Is Oxycodone?
Opioids are a broad classification of medications that bind to opioid receptors in the body. These medications are derived from the opium 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 also 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. These two chemicals 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.
Combining Cannabis and Oxycodone: What the Latest Research Says

Combining cannabis and oxycodone may influence how each substance affects the body. However, this interaction is not fully understood. The risks involved shouldn't be overlooked.
Cannabis and oxycodone both carry potential side effects. Cannabis effects are typically milder and may include:
- Anxiety
- Paranoia
- Drowsiness
- Dry mouth
- Appetite changes
- Altered perception of time
- Short-term memory issues
Oxycodone, by contrast, can cause more serious adverse effects. These can include confusion, dizziness, breathing difficulties, and in some cases, life-threatening respiratory depression. Less common but severe reactions may include swelling, hives, chest pain, seizures, or extreme fatigue.
Research suggests these substances interact at a biological level. Both cannabis and opioids act on systems that regulate pain and other physiological processes. Animal studies show that cannabinoid and opioid receptors often appear in the same areas of the brain and spinal cord.2,3 Research has also found the same to be true in part of the brain associated with reward.4
In some trials, blocking one system impacted the effectiveness of the other. For example, THC appeared to increase natural opioid levels. Meanwhile, opioid blockers reduced THC’s pain-relieving effects.5 This overlap has led researchers to explore whether cannabis might influence the body’s response to opioids. They may do so by either intensifying effects or potentially reducing the required dose.6
Other studies, including one from 2018, have explored whether cannabis might help reduce opioid use. Findings remain mixed and largely preliminary. Some population-level data have linked cannabis legalization to a reduction in opioid-related deaths. However, this correlation doesn't confirm causation.9
Ultimately, more research is needed. There is no clear clinical guidance yet on combining cannabis and oxycodone. The safest course is to speak with a qualified healthcare provider to assess your personal risk and discuss treatment goals.
Can Opioid Use Disqualify You from Getting a Medical Marijuana Card?

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.
Are You Considering Using Cannabis and Oxycodone?
Combining cannabis with any substance or medication carries its own risks. Cannabis research is still in its earliest stages, and there is a lot that researchers still don't know. That leaves the door open for unexpected interactions with other substances. If you are considering combining cannabis with any other substance or medication, speak to your doctor for proper medical guidance.
Likewise, stopping the use of a prescribed medication can lead to unintended consequences. Many medications take time to build up in the body. Stopping suddenly can cause unpleasant and potentially serious or even fatal side effects. If you'd like to stop using or replace a medication, you need to follow the guidance of your medical provider to make any approved adjustments safely.
References
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
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