A coherent representation of the external world requires the integration of sensory (bottom-up) input with contextual (top-down) information. Contextual signals reach primary cortical sensory areas through layer 1 (L1), the outermost layer of the neocortex. L1 harbors somas of GABAergic interneurons (INs), positioned among dendritic tufts of pyramidal neurons (PNs) and projections originating from cortical and subcortical areas. Neuron-derived neurotrophic factor (NDNF) is expressed by ~70% of the L1 IN population, which was shown to be activated by incoming top-down information. However, how L1 INs contribute to integrate contextual information is currently poorly understood. Using mouse genetics and FISH approaches, we found a large fraction (~70%) of L1 INs of the mouse primary visual cortex (V1) expressing the cannabinoid receptor type 1 (CB1) and a high colocalization with NDNF. We performed whole-cell patch clamp recordings from acute brain slices of V1. Using a mouse line, in which CB1+ neurons express tdTomato, we characterized the intrinsic excitability and the morphology CB1+ and CB1- L1 INs. We found that CB1+ L1 INs do not identify a specific morpho-functional IN subtype, as they exhibit a wide range of properties. CB1 receptors mediate suppression of presynaptic GABA-release through retrograde endocannabinoid signaling. We expressed Channelrhodopsin2 in NDNF+ INs and recorded from L2/3 PNs, where we show that CB1-mediated plasticity is present at L1-NDNF and L2/3 PN synapses. Therefore, we found functional CB1-mediated plasticity at an unexpected cortical GABAergic synapse. This may serve as a pivotal mechanism to gate top-down inputs onto PNs during sensory processing.