Ephenidine, diphenidine, and methoxphenidine complications reported to the French Addictovigilance Network

Abstract

Ephenidine, diphenidine, and methoxphenidine belong to the family of diarylethylamines that are psychoactive substances derived from lefetamine (N, N-di-methyl-1,2-diphenylethylamine, also called L-SPA). These dissociative anesthetic compounds act as potent and selective N-methyl-d-aspartate receptor antagonists and were recently classified as narcotic drugs in France. The available data suggest a significant risk of psychic and somatic complications. To obtain more information, this retrospective study analyzed all spontaneous notifications of serious cases of ephenidine, diphenidine, and methoxphenidine abuse collected by the French Addictovigilance Network from 2012 to 2016 and classified them as proven, probable, and possible. For each case, age, sex, concomitantly ingested substances, pattern of abuse of psychoactive drugs, and related complications (scored using the poisoning severity score) were collected. Eighteen cases were identified (one in 2013, five in 2015, and 12 in 2016) in 16 men (median age: 31.5 years [IQR 25-75% 27-34]). Ephenidine, diphenidine, and methoxphenidine were involved in four, seven, and 11 cases, respectively. No case was considered proven, 16 cases were considered possible, and two probable due to polysubstance abuse (co-ingestion of other new psychoactive substances). The reported clinical complications were minor in five cases, moderate in six cases, and serious in four cases, and included psychiatric, neurologic, and cardiovascular problems. This analysis indicates that the number of reported cases progressively increased from 2012 to 2016 and mainly concerned methoxphenidine. The addictive potential of these substances seems highly probable; but further investigations are needed to limit their harmful effects.

A structural spectroscopic study of dissociative anaesthetic methoxphenidine

“…10,11 According to unofficial user experiences, MXP is less active than common arylcyclohexylamines like methoxetamine, deschloroketamine or ketamine, 12,13 yet it may be quite addictive. 9,[14][15][16] Despite the lower potency, several intoxications were associated with this substance to date. 12,13 Symptoms like rhabdomyolysis, ischemic cerebral disease, acute kidney failure or other serious psychic and somatic complications can also occur during the intoxications.…”

“…12,13 Symptoms like rhabdomyolysis, ischemic cerebral disease, acute kidney failure or other serious psychic and somatic complications can also occur during the intoxications. 14,17,18 Some symptoms may be even indistinguishable from those of major psychoses and thus it could be misdiagnosed. 19 Moreover, MXP is sometimes used in combination with other NPS, 20 which further complicates attributing particular effects to the substances.…”

Ephenidine, diphenidine and methoxphenidine complications reported to the French Addictovigilance Network: another brick in the wall!

“…In this issue, Eiden et al. provided an interesting case series describing the harms attributed to the abuse of these molecules. They reported 18 cases of ephenidine, diphenidine and methoxphenidine abuse including 16 possible and two probable cases, confirmed by blood/urine detection.…”

“…These NPS, easy to obtain, have been abused as alternatives to ketamine, sharing their pharmacological antagonist activity on the N-methyl-Daspartate (NMDA) receptor [7]. In this issue, Eiden et al [8] provided an interesting case series describing the harms attributed to the abuse of these molecules. They reported 18 cases of ephenidine, diphenidine and methoxphenidine abuse including 16 possible and two probable cases, confirmed by blood/urine detection.…”