Video length: 3:20
Dr. Sergi Ferre speaking: The therapeutic and side effects of opioids are largely mediated by their ability to bind and activate the so-called mu opioid receptors. Mu opioid receptors are localized on the spinal cord to mediate the analgesic effects, while mu opioid receptors localized in the brain stem in an area called the VTA seem to be mainly responsible for the rewarding and euphoric effects. This is because the VTA is the localization of the cell bodies of neurons that synthesize dopamine which is a key neurotransmitter in the processing of natural rewards. We previously demonstrated that only the VTA mu opioid receptors form complexes with receptors for the neurotransmitter galanin. We call these complexes mu opioid galanin receptor heteromers.
And now by using artificial cell systems, we’ve been able to demonstrate that only in these complexes, mu opioid receptors acquire specific properties --such as a selective insensitivity to methadone as compared to fentanyl or morphine. We then predicted that methadone would be a much weaker activator of the VTA dopamine system than fentanyl and morphine --- which we have been able to demonstrate using two experimental rat models.
Dr. Mimi Belcher speaking: The result from the clinical trials that Sergi just described made a powerful prediction that unlike other opioids like heroin or fentanyl, methadone rarely is associated with euphoric effects or a feeling of a "high," and so we had the unique opportunity to study the effects of different opioids in patients with addiction to opioids and patients with restless leg syndrome. We were able to demonstrate that methadone was the only opioid that showed a clear dissociation of the therapeutic effects in terms of alleviation of opioid withdrawal symptoms, or alleviation of restless leg syndrome symptoms. versus euphoric symptoms, so a therapeutic dose of methadone was associated with significantly lower instances of self-report of high as compared to other opioids. and or findings are really in accord with the classic literature demonstrating that although opioid-addicted individuals use methadone illicitly they do not for the purpose of really trying to achieve the feeling of euphoria or high, but more for purposes of self-medicating.
Dr. Eric Weintraub speaking: Well, the findings of the study are quite exciting, as it may help diffuse some of the stigma attached to medication-based therapies for opioid use disorder. it is indeed true that individuals taking methadone are not having rewarding effects from it. They will no longer be viewed as being addicted to another drug, which will decrease a major societal stigma barrier to this life-saving treatment. I think it will also stimulate further research into finding other medication-based therapies for opioid disorder that are not rewarding to the individual but will help prevent overdose and death.