Chronic treatment with Delta(9)-tetrahydrocannabinol enhances the locomotor response to amphetamine and heroin. Implications for vulnerability to drug addiction.

Cannabis sativa preparations are some of the most widely used illicit recreational drugs. In addition to their direct addictive potential, cannabinoids may influence the sensitivity to other drugs. The aim of the present study was to determine if a cross-sensitization between Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and other drugs (amphetamine and heroin) could be demonstrated. We examined the effects of a chronic treatment with Delta(9)-THC (0.6, 3 and 15mg/kg, ip) on the locomotor response to amphetamine (1mg/kg, ip) and heroin (1mg/kg, ip). Chronic treatment with Delta(9)-THC resulted in tolerance to the initial hypothermic and anorexic effects. Pre-treatment with Delta(9)-THC increased the locomotor responses to amphetamine and heroin. This cross-sensitization was time-dependent as it was observed three days after the last injection of Delta(9)-THC for amphetamine, and a relatively long time after the end of chronic treatment (41 days) for heroin. Moreover, the enhanced response to amphetamine or heroin was noted in some individuals only: the high-responder rats (HR). These animals have previously been shown to be vulnerable to drug taking behaviors. It is hypothesised that repeated use of Cannabis derivates may facilitate progression to the consumption of other illicit drugs in vulnerable individuals.