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A recent analysis from Stanford University suggested that without any changes in currently available treatment, prevention, and public health approaches, we should expect to have 510,000 deaths from prescription opioids and street heroin from 2016 to 2025 in the US. In a recent review, Mayo Clinic Proceedings (October 2019), Gold and colleagues at Mayo Clinic reviewed the available medications used in opioid use disorders and concluded that in private and community practice adherence is more important as a limiting factor to retention, relapse, and repeat overdose. It is agreed that the primary utilization of known opioid agonists like methadone, buprenorphine and naloxone combinations, while useful as a way of reducing societal harm, is limited by 50% of more discontinuing treatment within 6 months, their diversion, and addiction liability. Opioid agonists may have other unintended consequences, like continuing the down regulation of dopamine systems. While naltrexone would be expected to have opposite effects, adherence is also low even after detoxification and long acting naltrexone injections. Recent studies have shown Naltrexone is beneficial by attenuation of craving via "psychological extinction" and reducing relapse. Buprenorphine is the MAT of choice currently but injectable Naltrexone plus an agent to improve dopaminergic function and tone may renew interest amongst addiction physicians and patients. Understanding this dilemma there is increasing movement to opt for the non-addicting narcotic antagonist Naltrexone. Even with extended injectable option there is still poor compliance. As such, we describe an open label investigation in humans showing improvement of naltrexone compliance and outcomes with dopamine augmentation with the pro- dopamine regulator KB220 (262 days) compared to naltrexone alone (37days). This well studied complex consists of amino-acid neurotransmitter precursors and enkephalinase inhibitor therapy compared to treatment as usual. Consideration of this novel paradigm shift may assist in not only addressing the current opioid epidemic but the broader question of reward deficiency in general.

Improving naltrexone compliance and outcomes with putative pro- dopamine regulator KB220, compared to treatment as usual