Novel adjunct therapy to eliminate opioid tolerance and mitigate side effects

Researchers at the University of Dundee have identified an adjunct to opioid therapy that suppresses the development of tolerance and may mitigate other severe side effects associated with opioid use.

→ Novel target in the pain pathway identified
→ Adjunct to opioid therapy discovered
→ Tolerance of opioid analgesia suppressed
→ Negative side effects of opioids potentially mitigated
→ Reversal of analgesic tolerance


Opioids have been used for thousands of years as analgesics. Morphine is still one of the most effective drugs for treating severe pain. Unfortunately, prolonged use of opioids leads to tolerance where increased doses are required to maintain the same level of pain relief. In addition to growing tolerance, increased opioid use results in a series of debilitating side effects, including psychological addiction, nausea, vomiting, constipation and respiratory depression; the latter is the likely cause of death during opioid overdose. Tolerance is arguably the most problematic aspect of opioid analgesia, particularly during palliative care. Sensitivity can be restored by rotation to an alternative opioid, but this is a risky strategy increasing vulnerability to overdose and mortality. Despite significant clinical concerns surrounding the appropriate prescribing and potential misuse of opioids, they are still the drugs of choice for treating severe and chronic pain. There are currently no alternative analgesics to replace opioids and so an innovative approach is required to develop new drugs or adjunct therapies to mitigate the multiple negative side effects and transform the treatment of severe pain.

The Opportunity

Researchers at the University of Dundee have established a method of altering the consequences of opioid receptor activation, potentially eliminating the adverse side effects associated with opioid use. They have shown that mice genetically engineered to lack a protein that regulates receptors in the pain pathway have a negligible tolerance to opioid analgesia. In turn, the researchers have identified a target protein that is recruited to the receptor by the regulatory protein; by inhibiting this target with a drug currently approved for use in patients for a different purpose, the researchers show that opioid analgesic tolerance is eliminated. Ongoing research will determine whether inhibitors of the target protein suppress opioid induced respiratory depression and constipation. The researchers have shown for the first time that inhibition of the target after prolonged morphine treatment can actually reverse established analgesic tolerance. With negligible tolerance and reduced effects of respiratory depression, a regular dose of opioid could be administered, substantially decreasing the potential for misuse and overdose. The successful application of this drug alongside standard opioids as an adjunct therapy may enable pain relief without debilitating side effects, transforming the management of severe and chronic pain.

Commercial Opportunity

The University is seeking a commercial partner for this technology and contact is welcomed from organisations interested in developing, licensing or exploiting this opportunity.

Download PDF: Novel adjunct therapy to eliminate opioid tolerance and mitigate side effects

IP Status: This technology is protected by patent (US 9050374) and three patent applications (EP 2744821, CN 103814046 and IN 1822DEN2014).

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