Oxycodone, morphine and the chemistry of addiction

Both pain medications are often abused, but oxycodone may be more addictive

December 23, 2014
As overdoses from prescription medications spike nationwide, researchers are starting to investigate how commonly abused pain medicines affect reward systems in our brains. [Image credit: Flickr user Victor]

You’ve probably heard of dopamine, the chemical that gets released in our brains when we perform high-reward activities like eating, having sex and listening to music. As it turns out, many medicines tinker with our dopamine levels. But since dopamine reinforces our craving for pleasure and thrill, dopamine-altering drugs can be highly addictive.

Dopamine is connected to several neurological disorders, such as schizophrenia, Parkinson’s disease, attention deficit hyperactivity disorder (A.D.H.D.) and restless legs syndrome. The drugs used to treat these conditions are specifically designed to target our dopamine levels.

Yet we don’t understand how certain drugs affect our dopamine levels, even when those drugs have an extremely high potential for addiction. Among these are two of the most common prescription painkillers: oxycodone and morphine.

Both oxycodone and morphine are opioid painkillers, a class of drugs that also includes fentanyl, codeine and methadone. According to the Centers for Disease Control and Prevention, drug overdose is now the leading cause of injury death nationwide. Of those deaths, roughly 70 percent involve opioids. But despite the fact that opioids are among the most abused prescription medications, scientists know little about how they affect dopamine levels.

Now a recently published study has shed some light on the topic. In a paper published in October in the European Journal of Neuroscience, scientists reported that oxycodone could release much more dopamine than morphine does.

“Since we know little about how opiates modulate dopamine release, we chose two opiates that are abused and prescribed for pain: morphine and oxycodone,” one of the study’s primary investigators, Brandon J. Aragona, explained in a video interview.

The researchers tracked how oxycodone and morphine affected dopamine levels in rats’ brains. “We discovered that oxycodone evoked a robust and long-lasting increase in dopamine,” said Aragona, a professor of psychology and neuroscience at the University of Michigan. “In contrast, morphine evoked a very short increase in dopamine, lasting only about one minute.”

Despite oxycodone’s apparently higher risk of provoking addiction, pain doctors seem to prefer it over other medications, Aragona noted in the video. And addicts seem to prefer it, too. “It’s prescribed more, and therefore it’s out there more,” he said. “This is why it’s one of the fastest growing — if not the fastest — abused drug.”

Even for drugs that explicitly manipulate dopamine in one direction or another, predicting risks can be hard. Altering dopamine can trigger all sorts of disturbing effects, including hallucinations, pathological gambling, hypersexuality, separation anxiety and movement disorders. For instance, schizophrenia medications, which decrease dopamine, could trigger symptoms of Parkinson’s disease such as tremors and impaired movement. Meanwhile, Parkinson’s medications, which increase dopamine, could trigger schizophrenia-like psychosis. (This makes is particularly challenging to treat someone with both schizophrenia and Parkinson’s.)

Addiction can be a tragic side effect of these medications as well. You may have listened to this Radiolab episode about Ann Klinestiver, a woman who developed a severe gambling addiction as a result of her Parkinson’s medications. Or you may have heard about two class action lawsuits, filed in 2010 by more than 100 Australians with Parkinson’s who claimed their medications caused compulsive gambling and pornography addictions. (They reached a settlement for one of the drugs in December 2013, but the other suit is still ongoing.)

As a result of high-profile cases like Klinestiver’s and these class action lawsuits, researchers know to look out for freaky side effects from drugs that specifically target dopamine. But it’s crucial to also examine medications that unintentionally alter dopamine. Studies like Aragona’s can provide some insight into how these drugs affect patients in ways we haven’t yet begun to understand. In particular, disentangling how different painkillers affect dopamine levels could help bring down addiction rates and the number of deaths from accidental overdose.

About the Author

Steph Yin

Steph Yin is a science writer & illustrator based in New York City. She hails from dreamy Providence, where she spent a lot of time “doing science” (read: baking dirt in windowless basements), making animations and chopping vegetables. Though nowadays she spends her time doing journalism, she really dreams of creating a traveling puppet show about science. Everyone is invited to help paper mâché, play music and boogie. Most recently she has been a contributor to Tweet her at @Steph_Yin, learn more at



[…] Oxycodone, morphine and the chemistry of addiction – Yet we don’t understand how certain drugs affect our dopamine levels, even when those drugs have an extremely high potential for addiction. Among these are two of the most common prescription painkillers: oxycodone and morphine. Both oxycodone and … […]

Cristiane says:

Martha,I just want you to know that you can not go thru the rest of this journey wiuhtot some sort of pain meds. Do NOT let them make you feel like a drug addict.I had my bilateral mastectomy in June and am still undergoing my reconstruction. One of my dear friends had her mastectomy 3 weeks prior to mine, so she used my plastic surgeon and we do our fills together. Sonja has a much better time than myself with her fills. I have had pain everytime with everyone of them BAD PAIN. By the time I get to feeling human again, it was time to go for another one. SIGH .! Sonja started getting a lot of pain as she was nearing the end of her fills. The fuller she got, the more pain she had. I have about 2 more fills to go and just had one on Monday. I am still in my recliner because since my surgery I have not been able to sleeep comfortably in my bed. Michele and I have spoke about several things to try, but none of them have worked for me.I only take my pain meds ( one before I go for my fill ), than I have to take them for a few days after my fill.I am with Michele.. gravity sucks. Actually, the only thing that helps me is to be in a reclined position. I am BLESSED to work out of my home, so I do know that Sonja missed quite a bit of work during her fills etc. I think you need to have a heart to heart with your Plastic Surgeon and also print out some of this material from Michele’s site so he knows you are communicating with other women traveling the same journey as you. My Plastic Surgeon understands the pain level, but he also specializes in Reconstruction with cosmetic surgery as he secondary. Most Plastic Surgeons who perform more cosmetic surgery are a little more reserved than the ones who do more reconstruction. Maybe they need to do a little more research. I am not saying that you have to be on them the entire time you are going thru your reconstruction, but for the first few days after your fills, they are definately needed. Everyone has a different pain level, so don’t feel bad about insisting on them. This is a very hard, painful and emotional journey to travel. You are not alone. I have spoke with many women who all feel the same as you and I.I am on facebook under Tina Ferrizzi Pappy. Please feel free to add me and I am sending you huge hugs my friend.I am so thankful for Michele. She has been my rock and I so admire and adore her! I am so glad you have joined her site.Hang in there my Breast Friend Huge hugs again!Tina

Jon says:

“Despite oxycodone’s apparently higher risk of provoking addiction”….that’s odd, I read the same thing you did and came to the conclusion that morphine is the more likely to provoke addiction. I would expect the higher addiction rate to be the drug that gives you the initial rush followed by withdrawl and cravings, not the one that gives you what you need for a long time. That’s why people crush up oxycontin, to get a big, initial rush and not have it delivered over a long period of time. Opioid addiction rates have increased dramatically since time-released versions of them came out, why are scientists having so much trouble figuring out that time-released versions are having the opposite of their intended effect?

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