Intentional Misuse and Abuse of Loperamide: A New Look at a Drug with “Low Abuse Potential”

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 .…”

“…In the last few years (particularly from 2014), an increasing trend in intentional misuse and abuse of loperamide has been reported. [16][17][18][19] Consequently, morbidity and mortality have increased in parallel, mainly due to previously underrecognized cardiac toxicity, potentially fatal. 39 However, typical opioid CNS effects, including miosis, CNS depression, and respiratory depression may also occur.…”

“…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.…”

“…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. In fact, the increasing occurrence of neurological and, particularly worrying, cardiovascular toxic effects (potentially fatal 20 ) has prompted many authors to claim for increased control over the availability of loperamide, and research on this drug and its effects is being renewed.…”

Novel opioid detoxification using loperamide and P‐glycoprotein inhibitor

“…Current literature confirms that only excessively high doses can cause serious cardiac side-effects and potential death. [24][25][26][27][28][29][30][31] This study addressed the safety of loperamide over a short period of time and during the study development no serious adverse events were reported. Despite differences in study design, this finding is comparable with other treatment approaches used for opioid detoxification 17,18,32,33 and, when considered together with the finding that no instances were reported of additional requests for either medication, suggests that this protocol is not only safe, but also well-tolerated.…”