Oxycodone, morphine and the chemistry of addiction

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.