Previous preclinical research suggests that L-methamphetamine (L -MA) has potential therapeutic utility to treat psychostimulant abuse. This study examined potential abuse-related and adverse physiological effects of D -MA and L -MA alone and in combination in rats, as these effects had not been previously characterized. Potential abuse-related effects were examined in locomotor sensitization and conditioned place preference paradigms. Body temperature was monitored to assess the physiological effects of these drugs or drug combinations. In the locomotor study, D-MA induced locomotor sensitization to both D-MA and L -MA. L -MA induced locomotor sensitization only to D-MA. Responses to a combination of L-MA and D -MA were not differentially affected by L-MA or D-MA conditioning. In the conditioned place preference study, D-MA and L -MA each induced significant place preference. L -MA did not attenuate D-MA-induced place preference. In the body temperature study, D-MA induced hyperthermia and L -MA induced hypothermia. In combination, L -MA did not affect D-MA-induced hyperthermia. These data suggest that L -MA alone produces less abuse-related and adverse physiological effects than D-MA, but modulates and is modulated by concurrent and subsequent D-MA exposure, which may enhance the abuse liability of both drugs. These findings should be considered when L -MA is proposed for replacement therapy.

Conflicts of interest

The authors declare that they have no competing interests.

• R01 DA034806/DA/NIDA NIH HHS/United States
• R21 DA040777/DA/NIDA NIH HHS/United States