Can we target opioid abuse with another opioid drug? (Archive)

Originally posted February 9, 2018.

Katie Reichard studies how stress changes a population of brain cells involved in processing rewards and making decisions: dopamine neurons. This research helps us develop treatments for mental health disorders associated with chronic stress, including depression, anxiety, and addiction.

Imagine a treatment for opioid addiction that reduces risk of relapse and overdose that was just a pill you placed under your tongue daily? That treatment already exists but is currently only available to 10-30% of individuals in recovery from heroin or other opioids[i]. So what is the catch?

This treatment, buprenorphine (\ ˌbyü-prə-ˈnȯr-ˌfēn , -fən \) , is also an opioid. It activates the same system in the brain that heroin activates but works in a different way. The small differences between buprenorphine and heroin make one a life-saving treatment and the other a highly addictive, lethal drug. Let’s get our facts straight about these opioid drugs.

A dose of buprenorphine activates a smaller response than heroin, but is still considered “stronger”. The type of biologists who study the actions of drugs, pharmacologists, describe the strength of a drug using multiple measures. We look at how much drug is needed to produce its maximum response and how large a response the drug can produce. Buprenorphine takes less drug to produce its maximum response, but the maximum response of buprenorphine is much smaller than that of heroin.

Let’s look to a drawing to dive a bit deeper. The blue ovals represent a simple unit of life, or cell, in your body. The opioid receptor (yellow) straddles the inside and outside of the cell. When molecules flow past the cell, they can be caught by a receptor, like a ball in a glove. This causes the receptor to change shape and stimulates a response inside the cell. On the left, you can see the triangular blue drug fits into the opioid receptor, like a pitcher’s glove loosely holding a ball. It stimulates a large change in the shape of the receptor and a large response. We call this a full agonist (drug) with a low affinity, or fit, for the receptor. On the right, the purple triangle fits snugly into the opioid receptor, like a ball tightly gripped by a catcher’s glove. However, this time, the receptor barely changes shape, and the response is smaller. This makes it a partial agonist[ii]with high affinity, or fit.

Because buprenorphine fits into the opioid receptor, it stimulates a response. For someone who has never taken an opioid, this produces a small high, but this high is barely noticeable to an opioid user. People taking buprenorphine can live more productive, fulfilling lives than those who take drugs that produce disruptive highs and lows, but this is not the only benefit of the drug. The opioid receptors have a much higher preference for buprenorphine than heroin[iii]. As a result, if a person taking buprenorphine relapses to a drug like heroin, heroin has a hard time knocking the buprenorphine out of its spot. It blocks heroin from producing a full effect, preventing the high, but also preventing effects like reduced breathing rates which are the cause of overdose death.

Due to its properties as a partial agonist, buprenorphine alleviates craving, and due to its properties as a high-affinity drug, it blocks overdose. In 2015, opioid overdose took more lives than American troops lost in the Vietnam War[iv], and the pharmacology speaks for itself. Why aren’t we doing more to get this treatment to those who need it most? This article is a great place to learn more about the benefits and barriers of medically assisted opioid treatment.

[i] 2016 National Survey of Substance Abuse Treatment Services, SAMHSA https://www.samhsa.gov/data/sites/default/files/2016_NSSATS.pdf

[ii] For further explanation of partial agonists: https://en.wikipedia.org/wiki/Partial_agonist, https://www.ncbi.nlm.nih.gov/pubmed/11356949

[iii] [iii]Australian National Clinical Guidelines and procedures for the use of buprenorphine in the Maintenance Treatment of Opioid Dependence

[iv] https://www.vox.com/policy-and-politics/2017/6/6/15743986/opioid-epidemic-overdose-deaths-2016