Could these common medications help curb addiction?

When Anna Rose Childress considers the opioid epidemic, she is struck by what she calls “a life-threatening disconnect.”

On the one hand, “we have FDA-approved medications that are proven effective for battling opioid problems,” she says. “But most patients are not taking them, or are missing doses, losing the overdose protection that is especially critical in the age of fentanyl.”

Childress, a research professor in psychiatry at University of Pennsylvania’s Perelman School of Medicine, has dedicated the bulk of her career to understanding how drug “reminder” cues can lead to addiction relapse.

In new clinical trials, Childress and her Penn colleague Kyle Kampman are testing whether “add-on” medications — drugs already approved by the FDA for treating bipolar disorder and schizophrenia — may help patients being treated for opioid-use disorder counter problems that get in the way of taking their life-saving opioid medications.

“This overuse cycle can begin even when an individual is initially prescribed opioids for pain.”

We talked to Childress about why addiction can be so hard to break and what new options are available for people who struggle with opioid use disorder despite efforts to get help.

The good news is that we have three types of FDA-approved medications. Two of these, methadone and buprenorphine-naloxone, act somewhat like opioids — they help to blunt the flu-like opioid withdrawal symptoms. The third, naltrexone, is protective because it prevents opioids like heroin and fentanyl from activating the places (“receptors”) in the brain and body where opioids usually act. All three of these medications have been shown to reduce illicit opioid use, and thus to prevent overdose deaths.

Still, overdose deaths have spiraled upward. Philadelphia is on pace to exceed last year’s high of more than 1,200 deaths, due to the highly potent synthetic opioid fentanyl that is now present in the vast majority of opioids sold on the street. You don’t know how much you’re getting, and it takes very little to kill you.

» READ MORE: You can now get an injectable form of naloxone without a prescription in Pennsylvania

All drugs that are misused activate our brain’s powerful motivational/reward circuits. These are circuits that encourage us to “go!” — ideally to survival-driven rewards such as food and sex. Drugs activate these “go!” circuits in a way that is stronger than the natural rewards, tricking the brain into rearranging its priorities. Also, cues such as drug-related sights, sounds, or smells can trigger strong desire for the drug, and this vulnerability is present long after the last use of the drug.

In addition, some individuals have a harder time with putting on the brakes, being able to “stop!” the pull of drugs. To make things more challenging, these vulnerabilities are aggravated by stress and adversity, which can lead to drug use as a coping strategy.

» READ MORE: Struggling with an addiction, or know someone who is? Here are ways to get help.

All rewarding drugs have the potential for compulsive use in vulnerable individuals. For example, cigarette smoking is very difficult to stop. And in terms of illness and mortality, it has a far greater overall impact on public health than all the other drugs combined. But the health effects of cigarette smoking are slow to accrue, with lots of opportunities in a lifetime to reduce or stop smoking.

In contrast, the high lethality of the opioids — especially in the age of fentanyl, where a lethal dose is visually equivalent to a few grains of salt — means that many individuals will die without an opportunity to recover.

It’s also worth noting that over-use of opioids can develop quite quickly, as the body rapidly adapts to the euphoric and analgesic effects — meaning larger and larger doses are required to achieve the same effects. And when opioids are stopped abruptly, an uncomfortable, flu-like syndrome (withdrawal) emerges. Using more opioids to alleviate it sets up a vicious cycle. This overuse cycle can begin even when an individual is initially prescribed opioids for pain.

» READ MORE: Philadelphians who died of a drug overdose often had sought help for addiction, report finds

We are testing “add on” treatments to see whether these medications can help individuals stay on their opioid medications, helping to prevent overdose and improving their quality of life.

One of the medications, cariprazine, interacts with a special brain receptor — dopamine D3 — that is strongly implicated in cue-triggered “GO!” states. Cariprazine has been shown to reduce cocaine-seeking in animals, and in our own pilot research in human cocaine users, cariprazine seemed to blunt the brain’s response to cues for cocaine.

The fact that cariprazine is also FDA-approved for bipolar swings and schizophrenia is a potential bonus. For some individuals, cariprazine might help both with their drug use and their psychiatric symptoms.

» READ MORE: Philadelphia is creating a pop-up garden to memorialize thousands of overdose victims

The second medication, olanzapine, is being tested because analyses of clinical data gathered across two decades showed that opioid use disorder patients who also took olanzapine for their mental health issues were more likely to be in remission than those taking other anti-psychotics.

The fact that these drugs are already FDA-approved for other conditions is important. The development pipeline for new medications, from early animal work through human safety trials to eventual efficacy trials, is sometimes two decades. Since these drugs have already been proven to be safe and effective, it means we can confidently study them right now in human addiction.

People differ, sometimes dramatically, in their response to medications and other treatments. For these studies — as for most clinical trials — the next steps will be to understand why some people benefited more than others.

We will use both genetics and imaging information to help understand the “who benefits” question. And, of course, we have a short list of other FDA-approved medications that look very encouraging.

It is a promising time for addiction research. In the opioid arena, researchers are edging closer to finding safer, non-addictive analgesics — medications that would provide good pain reduction, but without the risk of overdose and compulsive use.

» READ MORE: Overdose prevention should be a part of each college’s core curriculum | Opinion

We and others are also particularly interested in having treatments that might be able to reduce craving and drug use for more than one drug category, as many individuals have problems with more than one drug. Treatments that provide a general calming of the brain’s “go!” response, or a general boost to the “stop!” circuitry (or both) should take us closer.

There is also exciting research using brain stimulation techniques to reach some of the critical brain circuits. Other studies are using brain feedback to help train your brain to be better at stopping impulses and urges.

Most of these techniques are still in their early stages, but we greatly look forward to bringing these tools to our patients who struggle with substance use and are in great need.

Anyone interested in learning more about whether they would be a good candidate for a clinical trial on opioid use disorder should talk to their doctor or visit www.med.upenn.edu/csa/trc_clinical_trials.html

» READ MORE: I overdosed in Delaware. The state bears some blame for its high rate of deaths. | Opinion