The discovery of the endocannabinoid system has lead to great strides in research development. At present, two cannabinoid receptors, CB1R and CB2R, are known. They belong to Class A rhodopsin-like GPCRs, and possess a different tissue distribution. Many synthetic compounds have been synthesized and tested for their cannabinoid activity. A particular class among them, the aminoalkylindole derivatives (typified by WIN55212-2) are hypothesized to interact in a binding site different from the main cannabinoid agonists. In this review we report the main aminoalkylindole derivatives, and other compounds which are hypothesized to interact in the same binding site. Furthermore we analyze the pharmacological profiles, the mutagenesis data and the computational models that describe their interaction in the cannabinoid receptors, evaluating the most important aspects for their activity and selectivity.