07 Jun MCAM has the Potential to Transform the Future of Opioid Use Disorder Treatment
MedicalResearch.com Interview with:
Colleen G. Jordan, MBS
Department of Medical Education
Geisinger Commonwealth School of Medicine
MedicalResearch.com: What is the background for this study?
Response: Opioid addiction and misuse remain a prevalent issue in the United States (U.S.). There have been more than one-million drug overdoses in the U.S. since 1999 , largely driven by opioids, which exacerbate the strain on resources in hospitals, treatment centers, first responders, patients, and their families. The existing pharmacotherapies for opioid use disorder (OUD) are not working.
Naloxone is a competitive mu opioid receptor antagonist used to reverse respiratory and CNS depression in those experiencing an opioid overdose but requires further dosing to prevent subsequent overdose. Naltrexone is a competitive mu opioid receptor antagonist, and has extended-release formulations intended to reduce relapse and promote adherence, yet patient noncompliance and retention continue to be limiting factors. Methadone is commonly used to treat opioid addiction as a replacement for illicit opiates but is itself an addictive substance which can result in overdoses  and can lead to withdrawal if not closely monitored by a licensed professional. Buprenorphine is currently used to treat opioid use disorder (OUD), and while it reduces illicit drug use, it is less effective than methadone for retaining patients in treatment. For these reasons, there is an urgent need for new opioid misuse interventions.
The objectives of this study  were to understand the implications of OUD and overdose treatments and determine the strengths and shortcomings of current treatments in comparison with the novel drug candidate methocinnamox (MCAM). These were completed through an extensive literature review into the history of the opioid epidemic in the United States, opioid receptors in the brain, current pharmacological treatments, and the pharmacological properties of MCAM.
MedicalResearch.com: What are the main findings?
Response: The first major finding relates to currently available OUD and overdose treatments. Naloxone is the currently used overdose treatment but is also used to treat OUD concomitantly with buprenorphine. Naloxone is a competitive mu, kappa, and delta, opioid receptor antagonist which is effective for reversing deadly effects of opioids but has a short duration of action and is easily surmountable. Naltrexone is used to treat OUD and is a competitive mu, kappa, and delta, opioid receptor antagonist. The extended-release formulation provides a longer duration of action but exhibits poor patient compliance and is surmountable. Methadone is a mu and delta opioid receptor agonist which reduces illicit drug use but retains the issues of dependence, misuse, diversion, patient noncompliance and extensive adverse effects and drug reactions. Buprenorphine is a partial mu and kappa opioid receptor agonist and full delta opioid receptor antagonist which reduces the euphoria and some safety concerns with opioid agonists. Buprenorphone, however, is equal to or less effective than methadone in treatment and retains many issues seen with methadone, including the potential for respiratory depression when combined with benzodiazepines.
Second, MCAM is novel drug that is a pseudo-irreversible mu opioid receptor antagonist which prevents opioid agonists from binding for a two-week period. Preclinical research has found that a single subcutaneous dose of MCAM prevents both acute opioid overdose and subsequent overdose for up to two weeks with minimal adverse effects. Some studies predict no potential adverse drug reactions when combined with benzodiazepines and alcohol. Currently, MCAM’s pharmacokinetic properties are not fully understood, but its pharmacodynamic properties are believed to play a prominent role in its long-lasting effects. The insurmountable extended duration of action overcomes the shortcomings of naloxone and naltrexone. The extended duration of action could avoid the noncompliance challenges of naltrexone, methadone, and buprenorphine. MCAM also has reversible competitive antagonism of the delta and kappa opioid receptors, but these interactions are of short duration. The known adverse drug reactions and drug-drug interactions of MCAM are less than those of methadone and buprenorphine.
MedicalResearch.com: What should readers take away from your report?
Response: While opioid antagonists, naltrexone and naloxone, are essential drugs for treating OUD and reverse the effects of an overdose, respectively, they have risks that pose considerable limitations to their efficacy. Methadone and buprenorphine have significant limitations for use in OUD treatment and present safety issues by being opioid agonists themselves . Using pain management pharmacotherapies such as kappa or delta opioid receptor agonists concomitantly with MCAM also presents antinociceptive therapy during the withdrawal process and OUD treatment. MCAM has the potential to transform the future of OUD treatment, thereby reducing the tremendous healthcare and societal consequences of the opioid epidemic .
MedicalResearch.com: Is there anything else you would like to add?
Response: It is important to note that there is no current testing of MCAM in humans. Comparisons were made using currently available research with animal models. As more is learned about MCAM, its potential in combating the opioid crisis may change. Although MCAM could be an excellent addition to OUD and opioid overdose treatments, addiction is a complex biopsychosocial disorder. Pharmacotherapies are just one part of an evidence-based multimodal treatment for OUD.
- Mann B. More than a million Americans have died from overdoses during the opioid epidemic. NPR, December 30, 2021. https://www.npr.org/2021/12/30/1069062738/more-than-a-million-americans-have-died-from-overdoses-during-the-opioid-epidemi
- Kaufman DE, et al. Methadone overdoses increased 48% during the COVID-19 epidemic. MedRxiv: https://www.medrxiv.org/content/10.1101/2022.04.14.22273870v1
- Jordan CG, et al. The potential of methocinnamox as a future treatment for opioid use disorder: A narrative review. Pharmacy 2022; 10:48. https://www.mdpi.com/2226-4787/10/3/48
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