Synthetic psychoactive cathinones: hypothermia and reduced lethality compared to methamphetamine and methylenedioxymethamphetamine

Abstract

Rationale: Synthetic psychoactive cathinones (SPCs) are drugs with psychostimulant and entactogenic properties like methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA). Despite clinical reports of human overdose, it remains to be determined if SPCs have greater propensity for adverse effects than MA or MDMA.

Objectives: To determine whether the SPCs cathinone (CAT), methcathinone (MCAT), mephedrone (MMC), and methylenedioxypyrovalerone (MDPV) have lower LD50 values than MA or MDMA.

Methods: Male and female C57Bl/6J mice received single injections of one of 6 doses of a test drug (0-160 mg/kg IP). Temperature and behavioral observations were taken every 20 min for 2 h followed by euthanasia of surviving mice. Organs were weighed and evaluated for histopathological changes.

Results: LD50 values for MA and MDMA, 84.5 and 100.9 mg/kg respectively, were similar to previous observations. The LD50 for MMC was 118.8 mg/kg, but limited lethality was observed for other SPCs (CAT, MCAT, MDPV), so LD50 values could not be calculated. For all drugs, death was associated with seizure, when it was observed. Rather than hyperthermia, dose-dependent hypothermia was observed for MMC, MDPV, CAT, and MCAT. Contrary to initial expectations, none of the SPCs studied here had LD50 values lower than MA or MDMA.

Conclusions: These data indicate that, under the conditions studied here: (1) SPCs exhibit less lethality than MA and MDMA; (2) SPCs impair thermoregulation; (3) effects of SPCs on temperature appear to be independent of effects on lethality.

Keywords: Cathinone; Lethality; Mephedrone; Methamphetamine; Methcathinone; Methylenedioxymethamphetamine; Methylenedioxypyrovalerone; Synthetic psychoactive cathinones; Temperature regulation.