Buprenorphine’s Effect on Other Opioids

Buprenorphine is an opioid that acts as an agonist of the mu opioid receptor (MOR), which causes pain relief, just like class II opioids. It also has side effects similar to other opioids, including tolerance, dependence, abuse potential, constipation, sedation and potentially fatal respiratory depression.

What distinguishes buprenorphine from other opioids is that it is only a partial MOR agonist (50%). Thus the effects of buprenorphine -- both pain relief and the undesirable side effects – don’t exceed half that of other, full agonist opioids.

Buprenorphine also has a ceiling of maximum effectiveness that reaches a plateau as the dosage is increased. That ceiling is well below what can be obtained with morphine and other opioids, but the side effects can still lead to death in opioid-naïve patients. Buprenorphine has a long plasma half life, binds very strongly to MOR, and remains bound for extended periods of time. Its usefulness in treating OUD is believed to lie in these properties, because it activates MOR sufficiently to curb drug craving, but not enough to elicit the euphoric effects that can lead to addiction.

When an opioid that has higher analgesic potency, but lower MOR affinity, such as morphine or heroin, is also administered, buprenorphine wins the battle to bind and remains bound to MOR. It can displace both heroin and naloxone from MOR, but neither can displace buprenorphine. Naloxone can be effective when co-administered with buprenorphine -- as it is in combination drugs such as Suboxone -- but not after the administration of buprenorphine.

Buprenorphine is also a kappa opioid receptor antagonist, which is thought to further reduce euphoria and addictive reinforcement. That’s great for patients with OUD, because it helps them resist the temptation to abuse opioids, and dampens or eliminates the euphoric effect of heroin or other opioids should they relapse.

Increasingly, buprenorphine is being advocated for chronic pain patients. With no more "proof" of efficacy for treating chronic pain than any other opioid, it has emerged as a less objectionable opioid because it appears safer in the eyes of addiction treatment specialists, such as Dr. Andrew Kolodny, who object to full MOR agonists for chronic pain.

Yet safety is in the eyes of the beholder. Despite its decreased abuse potential, buprenorphine can still be abused and cause overdoses because the ceiling effect for respiratory depression does not apply universally, particularly to opioid-naïve patients and children. Buprenorphine has caused the death of at least one child from unintentional exposure.

Buprenorphine should not be used as the first opioid prescribed for chronic pain. Because it cannot achieve the full analgesic effects that other opioids can, there is significant risk of buprenorphine leaving pain undertreated or even untreated. A chronic pain patient on long-term buprenorphine therapy who experiences acute or breakthrough pain may not be able to get relief by taking another opioid. Even more disturbing is the lack of pain control in patients who need surgery, have an acute injury from trauma or an acute painful medical emergency.

Buprenorphine Injection

Recently Indivior, a spin-off of Reckitt Benckiser Pharmaceuticals (which makes Suboxone), submitted a New Drug Application to the Food and Drug Administration on a subcutaneous injection formulation of buprenorphine.