Kratom as an opioid alternative: harm, or harm reduction? A systematic review of literature.

Background: Kratom (Mitragyna speciosa Korth.) products are increasingly endorsed for self-management of multiple ailments, including as opioid substitution. The FDA has expressed that there is no evidence to indicate that this botanical is safe or effective for any medical use.Objective: We systematically review the current state of the literature concerning the impact of kratom and its alkaloids in all paradigms that involve opioids.Methods: A keyword search of online literature databases identified 16 preclinical studies, 25 case reports, and 10 observational studies meeting our pre-selected criteria.Results: All rodent models support alkaloids' action on opioid receptors, translating in their ability to mitigate opioid withdrawal. Some studies found mitragynine (MG) to have less reinforcing properties than morphine, and possessing tolerance-sparing properties when coadministered with morphine. Two studies that assessed 7-hydroxymitragynine (7OHMG) found it to substitute for morphine with potential for tolerance and dependence. Aside from addiction development, case reports outline a variety of confounding toxicities. Ten surveys of users, some conducted with assistance from pro-kratom lobbying organizations, find a high self-reported efficacy as an opioid substitute, with minimal reported adverse effects.Conclusion: With no reported controlled human clinical trials, in the light of rising concerns surrounding kratom's liabilities, there is insufficient evidence to allow any conclusions to be drawn. Case reports and observational studies carry significant bias toward harm and efficacy, respectively. Existing animal studies are heterogeneous in methodology and ultimately findings, with concern for interspecies variability and human translatability. Further research should investigate the safety and efficacy of using kratom alkaloids as opioid substitutes.

Naltrexone and Its Noroxymorphone Minor Metabolite - A Case Report.

As part of substance use maintenance programs, individuals are monitored for sobriety through urine drug screens. A positive screen, and its confirmation and interpretation, can have devastating consequences, sometimes even leading to termination from the program and relapse. Naltrexone metabolism involves several steps and metabolites - one minor metabolite with very little mention in medical literature being noroxymorphone. This is also the final intermediate in the metabolic pathway of oxycodone; hence, detection is naturally presumed by clinicians to be attributed to oxycodone use. Through this case report, we alert clinicians that, depending on individual pharmacogenomics, it is possible to obtain a positive confirmation of this component alone (without any oxycodone pathway intermediates) with naltrexone administration.

Kratom Withdrawal: A Systematic Review with Case Series.

Recent years have seen a widespread increase in kratom use, not just for the purpose of easing opioid withdrawal, but also for management of emotional and mental health concerns by individuals without histories of opioid use. Chronic use can lead to dependence, tolerance, and withdrawal on cessation, and clinicians are seeing an increasing number of presentations involving the latter. Although there is literature discussing the use of kratom to assist in opioid withdrawal, this article comprehensively examines independent withdrawal from kratom. We systematically review existing evidence and provide our own clinical cases. Clinicians need to be aware of the withdrawal symptomatology and implement a similar approach as for opioid withdrawal with long-term maintenance to prevent relapse.

Loperamide, the "Poor Man's Methadone": Brief Review.

Loperamide is widely available as an inexpensive, over-the-counter remedy commonly used for management of diarrhea. Although an opioid, at therapeutic doses it acts primarily on the gastrointestinal tissues; however, larger than recommended amounts facilitate central nervous system (CNS) penetration. Such high doses of loperamide have recently gained popularity among users of opioids to manage withdrawal symptomatology and, less frequently, to achieve psychoactive effects. Chronic loperamide use can result in development of tolerance and, upon abrupt cessation of use, withdrawal. With increasing prevalence of use, side-effects are noted, one particularly being life-threatening cardiac arrhythmias. Users are often not forthcoming and routine drug screens do not detect loperamide, so providers need to be alert to such practices in order to recognize intoxication, be able to screen for use, and facilitate entry into treatment.

Withdrawn: The Behavioral Profile of methylenedioxypyrovalerone (MDPV) and α-pyrrolidinopentiophenone (PVP) - A Systematic Review.

The article entitled, "The Behavioral Profile of Methylenedioxypyrovalerone (MDPV) and α­ pyrrolidinopentiophenone (PVP) - A Systematic Review", submitted in Current Drug Abuse Reviews (CDAR) by Dr. Cornel N Stanciu has been withdrawn from the journal in accordance with BSP Editorial Policies.