Morphine and fentanyl: a glimmer of hope to fight addiction

A glimmer of hope for people who are addicted to morphine and its derivatives, including the infamous Fentanyl, causing hundreds of overdose deaths across the country. A team of researchers not only discovered the mechanism behind the withdrawal syndrome, but also successfully tested two existing drugs in mice that would alleviate the syndrome.

Morphine and its derivatives are proven medicines to treat severe and chronic pain, Yves De Koninck, from the University Institute of Mental Health of Quebec (IUSMQ), said in an interview.

But these opiates have three undesirable effects: they induce tolerance, so that the dose must be increased continuously to achieve the same effect, they paradoxically cause a hypersensitivity to pain and finally they are associated with painful withdrawal symptoms (Anxiety, headache, shivering, flushing, spasms and muscle pain, vomiting, insomnia, hypertension, tachycardia, etc.)

“This general reaction of the body makes it very difficult for people who take morphine for a long time to stop using it,” says De Koninck.

“It had already been discovered that withdrawal symptoms were related to a body response distinct from analgesia per se. […] There, we identified a molecule responsible for an exaggerated response in the nervous system. By taking morphine, we stimulate the production of this protein that causes an abnormal activity in the nervous system, “explains the researcher, who teaches at the Faculty of Medicine at Laval University.

De Koninck’s team then checked whether any existing drugs were acting on this protein. She found two: probenecid, used to treat gout, and mefloquine, which is used to prevent malaria. An unheard of luck, the professor rejoices.

“Often, when you discover a mechanism, you have to develop new molecules that will serve as medicines, and that’s a very long process that can last between 5 and 10 years. Having already prescribed drugs in humans, saves several years of research. Researchers will be able to do the first clinical tests right away to see if they are effective in preventing morphine withdrawal syndrome, “explains Yves De Koninck, adding that the results of preclinical tests (in mice) are encouraging. “It’s very, very promising. We could have something in five years, “says the researcher.

Normally, patients or drug addicts use methadone to wean their addiction to morphine or its derivatives, he recalls. “The methadone withdrawal process, which is itself a derivative of morphine, is very slow. And it’s complicated, people have to be very framed. The medications we found could help people get out of their addiction sooner. They would reverse the symptoms of withdrawal, but they would not affect the analgesic [and euphoric] effect of morphine at all, “says De Koninck.

Psychological counseling

Obviously, these drugs would not be a panacea for drug addicts who take opiates for their euphoric effect. As the psychologist Lucie Richer, of the Direction des programs mental health and addictions of the CIUSSS of the Capitale-Nationale, points out, the attachment of addicts to the substance that causes their loss is often linked to a ritual of appeasement of their ill- be. “Psychological weaning is often the most difficult thing for our users,” she says.

“Of course, for these people, it takes a psychological accompaniment to get them to agree to get rid of their addiction. But medications [such as probenecid and mefloquine] would remove an enormous barrier, which is that of weaning. It would make things a lot easier, “believes Yves De Koninck.

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