Evidence for the use of Cannabis Sativa as a treatment for pain can be traced back to the beginnings of recorded history. To date, the main use of ‘medical marijuana’ is for treating the most debilitating chronic pain disorders, such as neuropathic and cancer pains. However, the molecular and cellular mechanisms by which cannabinoids reduce pain are not known. While two cannabinoid-specific receptors (CB1 and CB2) have been identified, their pharmacological or genetic blocking did not abolish the effect of cannabinoids. This points to other, yet unidentified, receptors that mediate cannabinoid-induced analgesia. Recently, a family of somatosensory TRP channels, specifically TRPV1 and TRPA1, was proposed to be the cannabinoids ionotropic receptors. These receptors are mainly expressed on nociceptive fibers (i.e. Ad- and C- fibers) and their short activation evokes nociceptive pain, while their prolonged activation results in neuronal ‘shut-down’ and analgesia. In this multidisciplinary collaborative project, we are using specific pharmacological tools together with ion imaging, electrophysiology and behavioural tests to establish the role of TRPV1 and TRPA1 channels in cannabinoids-induced analgesia. We believe that detailed comprehension of mechanisms of cannabinoids-induced analgesia could facilitate rational design of novel and specific analgesics.