Treating opioid abuse: costly research is well worth it

We like every catastrophe to have a single cause because a villain, especially one that had been identified, is a satisfying thing. In the case of opioid use disorder, one villain is Purdue Pharma, makers of OxyContin, a powerful pain reliever and euphoric that the company claimed was not addictive. It is addictive, but so are   enormous profits. Purdue is getting its slow-drip punishment, in the form of massive lawsuits, and it faces insolvency.

Opioids, whether from Purdue or heroin pushers, fall on receptive ground. Millions of people have been treated with OxyContin and were not addicted. Others, seeking pain relief, or who were stressed or traumatized, became addicted, particularly in West Virginia, Ohio and New Hampshire. Others were thrill-seekers and got trapped. If we lay the map of overdose deaths by region onto maps of poverty and despair, they overlap. This is as much a disease of social disruption, family trauma, boredom and the effects of war as of over-prescription. Picking a single villain narrows the targets. Purdue’s practices have been curtailed, but the epidemic continues. 

The second failure is that we have not applied what we know. Some people can stop taking opioids and remain drug-free. Leaving dependence behind in one step is preferable for many reasons, not least convenience, employability and expense.  Unfortunately, quitting without Medically Assisted Treatment (MAT) often fails. As an earlier column explained, most deaths from opioids come soon after detox, because opioid receptors on neurons that control breathing have been reactivated during abstinence. This makes them very sensitive to heroin or fentanyl. A single miscalculated first dose is enough to stop breathing.  

Buprenorphine (Suboxone), methadone, and extended release naltrexone (Vivitrol) all prevent craving for heroin of similar drugs. They activate the opioid receptor, but less (or perhaps differently) than heroin and fentanyl do. Patients do not experience euphoria or have cravings for heroin. Clinical trial results from The National Institutes on Drug Abuse indicate that MAT using these drugs reduces relapse and overdose deaths, curbs criminal activity and reduces infections from contaminated needles (see: www.drugabuse.gov). MAT is now established therapy, and with long acting formulations has become more convenient (see below). Strangely, its use is not universal and some reports suggest that treatment with these substances after acute detox has been decreasing. 

Why is this? Buprenorphine, methadone and extended release naltrexone are all opioids and some therapists object that one addiction is being exchanged for another. The 12-step programs and their social support often successfully treat alcoholism, but demand complete abstinence. Such programs are usually not sufficient for severe opioid dependence. Switching one addiction for another, as opponents put it, allowing patients to become functional with buprenorphine and not die of overdoses seems vastly preferable to following programs that demand complete abstinence. It is sobering that 72,000 people died of overdoses in 2017, at least 50,000 of them from opioids, the rest from other drugs like meth or mixtures of different drugs. Millions more are chronic users.

Despite the current political paralysis in Washington, The National Institutes of Health (NIH) has received extra funding (billions) to study opioid addiction. They, of course, have come up with an acronym for their program: HEAL, for Helping to End Addiction Long Term. Many projects are being supported, including a new drug (ANS-6637) to limit opioid cravings, which has entered formal clinical trials. Clinicaltrials.gov lists 307 trials involving opioids. The website of The National Institute of Drug Abuse (NIDA), part of the NIH, is also a good source of information. 

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Opioid users lead complicated lives and it is challenging to do clinical trials because patients often drop out, but Drs. Ismene Petrakis and Sandra Springer, both physicians at the Yale School of Medicine and attending physicians at the VA Connecticut Healthcare System, have received a grant to test the effectiveness of two forms of long-acting buprenorphine (one injectable and one in pill form). 

The VA is experienced with the many needs of traumatized veterans and the regulatory rules that come with clinical trials, as is Yale, which runs a residency program in addiction medicine. This study will last a year and enroll hundreds of patients in 20 VA hospitals. Addicted veterans, possibly already patients of the VA, will be followed for adherence to the protocols and their physical conditions, including the infectious diseases that are associated with intravenous drug use.  

The study will cost $40 million. If it yields actionable results it will be worth it. We are not looking to “end addiction long term” as the HEAL acronym suggests. A few score people restored to a useful life and a better way to accomplish that for veterans would be sufficient.

I am grateful to Ziba Kashef of YaleNews (ziba.kashef@Yale.edu) for alerting me to this study. Richard Kessin is Professor of Pathology and Cell Biology Emeritus at the Columbia University Irving Medical Center.  He can be reached at Richard.Kessin@gmail.com.