Loperamide, the “Poor Man’s Methadone”: Brief Review

Abstract

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.

Ventricular fibrillation due to overdose of loperamide, the “poor man’s methadone”

“…Loperamide has been reported to cause QTc prolongation and recalcitrant ventricular arrhythmias with symptoms ranging from palpitations to sudden cardiac death (SCD). At therapeutic doses, loperamide has a poor oral bioavailability of only 10–20%; it is metabolized by the cytochrome P450 (3A4 and 2C8) system with biliary excretion, resulting in minimal systemic absorption [4]. Of note, other medications with effects on the 3A4 system have been linked to ventricular arrhythmias, though causation has not been proven [8].…”

“…Since dissemination of its opioid properties in online recreational drug use forums, poison control centers have noticed a doubling in referrals for loperamide overdose since 2014 [3,4]. Loperamide has peripheral mu receptor agonistic properties in the gastrointestinal tract, and accidental and deliberate overdosage has been associated with opioid-like euphoria [5,6].…”

“…Loperamide has peripheral mu receptor agonistic properties in the gastrointestinal tract, and accidental and deliberate overdosage has been associated with opioid-like euphoria [5,6]. In fact, loperamide was, at one time, a schedule V drug due to its opioid properties, and has been described as the ‘poor man’s methadone’ [4]. In the absence of studies indicating any tolerance developing, even at supra-therapeutic dosages, it was removed from scheduling [7].…”

Radiographic dose‐dependency study of loperamide effects on gastrointestinal motor function in the rat. Temporal relationship with nausea‐like behavior

“…However, intense systemic and central actions may occur at sufficiently high doses or by use of inhibitors of loperamide metabolism and/or P‐glycoprotein. In the last few years (particularly from 2014), an increasing trend in intentional misuse and abuse of loperamide has been reported . Consequently, morbidity and mortality have increased in parallel, mainly due to previously underrecognized cardiac toxicity, potentially fatal .…”

“…15 Thirdly, the combined use with other drugs which inhibit metabolic enzymes (CYP3A4 and CYP2C8) may increase plasma concentrations of loperamide and inhibitors of P-glycoprotein may allow more loperamide to cross the blood-brain barrier and cause central opioid effects. 2,6 Although loperamide-induced central effects reached by overdose or drug-drug interactions can happen accidentally, in recent years many reports [16][17][18][19] have warned about the rising trend in its intentional misuse and abuse, facilitated or not by co-administration with drugs that increase bioavailability and central access of loperamide. Low cost, lack of detection in routine drug screen tests, and the high number of prodrug websites offering advice on how to best achieve central effects have favored loperamide abuse, and new terms like "the lope dope", 18 "the poor man's heroin", 17 or "the poors' methadone" 19 have even been coined.…”