The introduction of two concepts, “local module” and “receptor heteromer”, facilitates the understanding of the role of interactions between different neurotransmitters in the brain. In artificial cell systems, cannabinoid CB 1 receptors form receptor heteromers with dopamine D 2 , adenosine A 2A and μ opioid receptors. There is indirect but compelling evidence for the existence of the same CB 1 receptor heteromers in striatal local modules centered in the dendritic spines of striatal GABAergic efferent neurons, particularly at a postsynaptic location. Their analysis provides new clues for the role of endocannabinoids in striatal function, which cannot only be considered as retrograde signals that inhibit neurotransmitter release. Recent studies using a new method to detect heteromerization of more than two proteins, which consists of sequential BRET–FRET (SRET) analysis, has demonstrated that CB 1 , D 2 and A 2A receptors can form heterotrimers in transfected cells. It is likely that functional CB 1 –A 2A –D 2 receptor heteromers can be found where they are highly co-expressed, in the dendritic spines of GABAergic enkephalinergic neurons. The functional properties of these multiple receptor heteromers and their role in striatal function need to be determined.