The Interactions Between Codeine and Weed

codeine and thc
By Nick Congleton Updated March 8th

Medically reviewed by Dr. Brian Kessler, MD

Severe and chronic pain are, unfortunately, common problems experienced by millions of American adults. Codeine is an opioid pain reliever prescribed to treat both moderate pains and, in some cases, chronic cough. 

Cannabis is also commonly used to treat pain. In fact, pain is one of the top reasons physicians recommend medical cannabis. A 2022 report found that 28% of patients in the Northeast and 31% in the Midwest were using medical cannabis to treat pain.

Since both medications treat pain, many patients wonder if they can use codeine and weed together.

The answer to that question is surprisingly more complex than most people might think. Like other opioids, codeine has potentially serious risks that must be considered, both independently and when used alongside cannabis.

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What Is Codeine?

Codeine is an opioid medication that’s commonly prescribed to treat moderate pain, chronic coughing, restless leg syndrome, and sometimes diarrhea. 

Opioids have been used for centuries to relieve pain. Historically, they were derived from the poppy flower. And while some modern opioids are synthetic or partially synthetic, codeine is still derived from the sap of the opium poppy.

Codeine is a prodrug of morphine, meaning it’s chemically similar to morphine but inactive until the body’s metabolic process converts it to morphine within the body. Codeine is also regularly used in conjunction with other medications

Opioids are a classification of drugs that bind to opioid receptors in the brain. When opioids bind to these receptors, they block pain signals. They also trigger the release of dopamine and endorphins, which manipulate the brain’s reward systems. This is why there’s such a high risk of addiction associated with these medications.1

Opioid abuse is an epidemic in the United States, responsible for thousands of overdose deaths yearly. In fact, in 2020, 75% of overdose deaths in the U.S. resulted from opioids, like codeine. In addition to developing a physiological dependence to opioids, people can develop a physical tolerance, meaning they’ll need more and more of the substance to get the desired effects. These increasing amounts lead to higher risks of complications and overdose, making extended use or misuse of opioids a serious public health threat.

Interactions Between Codeine and Weed

woman speaking with doctor about medication

If you’re considering using cannabis and codeine together, it’s best to understand the risks of each first. 

While cannabis is generally considered safe to use when dosed appropriately, codeine has many associated risks, including the ever-present risk of overdose and dependence.

Common side effects of cannabis, particularly at high doses, include:

  • Anxiety
  • Paranoia
  • Sleepiness
  • Changes in appetite
  • Dry mouth
  • Changes in perception of time
  • Short-term memory problems

Opioids, like codeine, have much more severe risks. The possibility of dependence is very high, and the danger of fatal overdose is real. Common side effects of codeine include:

  • Headaches
  • Problems passing urine
  • Pain in the stomach or abdomen

Codeine also has more serious side effects. These can be serious on their own or may indicate an underlying medical problem. If you experience any of these more severe side effects, speak to your doctor immediately. 

  • Short-temper or agitation
  • Hallucinations
  • Fever
  • Unusual or unexplained sweating
  • Confusion
  • Racing or fast heartbeat
  • Unexplained or unusual chills or shivering
  • Severe stiffness in the muscles
  • Muscle twitching
  • Loss of coordination
  • Vomiting
  • Nausea
  • Diarrhea
  • Dizziness
  • Changes or loss in appetite
  • Erectile dysfunction
  • Changes or irregularity in menstruation
  • Decreased sex drive
  • Shallow breathing
  • Loud or noisy breathing
  • Labored breathing
  • Difficulty swallowing
  • Irregular heartbeat
  • Rashes
  • Unexplained, unusual, or excessive itching
  • Hives
  • Vision blurriness or changes
  • Seizures

Both cannabis and opioids, like codeine, interact with receptors distributed throughout the brain and body. In animal studies, researchers found that cannabinoid receptors were clustered in areas with a high concentration of opioid receptors, like the spinal cord2 and the brain’s pain centers.3 Researchers found that the same was true for the brain’s reward centers.4

There’s also evidence that cannabinoid receptors can play a role in how effective opioids are. In a study conducted on genetically-modified mice, researchers found that mice lacking CB1 receptors did not receive the same reward effects of heroin, another opioid, as the unmodified mice did.5 However, researchers in another study found that removing cannabinoid receptors didn’t affect how well morphine, the opioid codeine is metabolized into, treated pain.6

A study going back to 1997 found that THC increased the amount of endogenous opioids found in the spinal cord of rats.7 Another study found that blocking the enzymes active in the opioid system also blocked the pain-relieving effects of THC.8

These findings further highlight the known danger of serotonin syndrome, a condition that occurs when the brain has too much of the neurotransmitter, serotonin. Serotonin syndrome can be serious, resulting in seizures, coma, and even death. Using codeine and cannabis together poses an increased risk of serotonin syndrome.

While further study is needed to understand exactly how these two systems interact, there’s evidence that they can affect one another. And that means that using both substances together has the potential to result in more profound or unexpected effects. So until further research is conducted, it is advisable to speak with a qualified doctor before combining codeine and cannabis.

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Can I Combine Codeine and Weed?

Since codeine has the potential for overdose, dependence, and potentially serious side effects, it’s never a good idea to combine it with another substance that could increase its effects unexpectedly. 

If you use cannabis and are prescribed codeine, or if you use codeine to treat pain and are thinking about medical cannabis, it’s best to speak with your doctor. Using both without medical supervision is dangerous and could result in hospitalization or death.

That said, using cannabis on its own or as a method of transitioning away from codeine may be beneficial when done safely and with the support of a qualified medical practitioner. Cannabis is generally considered a safer substance with minimal potential for dependence, and opioid dependence can even be a qualifying condition for medical cannabis in some states. 

Codeine or Medical Marijuana: Which is Better for Pain Relief?

person feeling relief from pain

Codeine and cannabis have both demonstrated their potential as effective pain relievers, though each one works through different mechanisms and has different potential risks and side effects. As such, selecting the proper method of pain management is a personal choice between you and your physician. 

Codeine is an opioid with a well-proven track record for moderate pain relief. It’s a treatment that’s been used for a long time, and that’s trusted by most doctors.

Meanwhile, a growing body of both research and anecdotal evidence has demonstrated the potential for cannabis to serve as an effective pain reliever. However, it doesn’t have the same type of well-established medical track record, leading some doctors to avoid prescribing it, despite the risks of overdose and dependency that alternative treatments like codeine can carry. 

Like other opioids, codeine has a range of potential side effects, including a high potential for abuse, dependence, and overdose. Opioids are responsible for the vast majority of overdose deaths in the United States.

Cannabis has comparatively mild side effects, all of which are temporary. Cannabis only has minimal potential for dependence, and there is no verified case of a cannabis overdose fatality. 

The opioid crisis is still killing thousands of Americans. And multiple studies have determined that cannabis legalization reduces the demand for opioids, including codeine. In a 2021 study, the presence of legal recreational cannabis dispensaries was linked to a 17% - 21% decrease in opioid overdose deaths.9 A scientific review of the existing body of evidence found a similar pattern.10 Some studies suggest that cannabis can be a valuable tool in reducing or replacing opioid use altogether.11 Others suggest that cannabis can even be used to treat opioid use disorder.12

While codeine is a well-established method for treating pain, there’s an ever-growing body of evidence that cannabis may be an effective alternative. Consult with your doctor if you are considering cannabis as a replacement for codeine.

Can Opioid Use Disqualify You from MMJ Card Eligibility?

mmj card

Opioid use will not disqualify someone from medical cannabis. In fact, in many cases, it’s just the opposite. 

Some states recognize cannabis as a potential alternative for opioids, and some even acknowledge it as a possible treatment for opioid use disorder. Both New York and New Jersey treat opioid use disorder as a qualifying medical condition for cannabis. Pennsylvania acknowledges opioid use disorder as a qualifying condition when conventional treatments have proven ineffective. 

Conclusion

Patients have praised both cannabis and codeine for their ability to offer effective pain relief. Codeine has been linked to much more severe side effects and an increased risk of overdose and dependency. This has led many patients to consider if cannabis may be a viable alternative to codeine for treating pain.

That said, using cannabis and codeine together can lead to amplified effects, increasing the risk of complications and opioid overdose. 

Speak to your doctor before combining cannabis and codeine (or any two medications). Your doctor can help you understand how the drugs may interact and may be able to provide an alternative option or a way to use cannabis to transition away from codeine. 

References

1. Abuse, National Institute on Drug. “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. 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

10. 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

11. 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

12. 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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