Amphetamine-type stimulants (ATSs) are a large family of substances of abuse, characterized by well-known mood-and performance-enhancing properties. This class encompasses several high-potency stimulants and entactogens, such as the precursor compound d-amphetamine (AMPH), its synthetic N-methylated derivatives methamphetamine (METH) and 3, 4-methylenedioxy-N-methylamphetamine (MDMA, or "ecstasy"), as well as novel designer drugs, based on substituted forms of the natural alkaloid cathinone. ATSs (and in particular METH) are among the most commonly abused substances worldwide, second only to Cannabis sativa; indeed, the rate of concurrent consumption of METH and cannabis has been increasing over the last decade, particularly among adolescents. Anecdotal evidence suggests that marijuana may offset some unpleasant subjective effects of ATSs, such as anxiety and paranoia. Both drugs have been shown to increase schizophrenia vulnerability in young vulnerable individuals, raising the possibility that their concurrent intake may have synergistic effects with respect to the development of psychotic manifestations. In addition, the combination of these two substances may affect their subjective effects and exacerbate their abuse liability. Although current evidence on the neurobiological interactions of cannabis and ATSs remains mostly elusive, initial studies in animal models suggest that the cannabinoid system may play a relevant role in the motivational and addictive properties of ATSs; furthermore, cannabinoids may modify the behavioral effects and even attenuate some untoward long-term consequences of ATSs. In this chapter we review the available evidence on these potential interactions and outline some key mechanisms that may account for the mutual modulatory influence of these substances.