Neuronal Kv7 (KCNQ) voltage-gated potassium channels contribute to various neurophysiological functions (such as hearing, learning, and pain modulation), and, when mutated, cause distinct pathologies (such as hearing loss, epilepsy, and intellectual disability). Cannabidiol (CBD) is a pan-Kv7 modulator, Kv7.2/3 M-channel activator and EMA-approved antiepileptic. Yet, the potential therapeutic efficacy of similar phytocannabinoids on Kv7 channels remains to be studied. Here, we aim to investigate the pharmacology of cannabinoids structurally related to CBD, such as Δ9‑Tetrahydrocannabinol (THC), Cannabinodiol (CBND) and Cannabinol (CBN), to ascertain their effects and putative underlying mechanisms. We express human Kv7.2/3 and Kv7.4 channels and mutants through RNA injections in Xenopus laevis oocytes. Channel characteristics before and after application of cannabinoids are recorded using the two-electrode voltage clamp (TEVC) technique from oocytes or via planar patch clamp technique from constitutively expressing CHO cells. We apply in-silico docking and molecular dynamics simulations together with mutagenesis to predict and validate cannabinoid binding sites. We determined that CBND is less efficacious than CBD in activating Kv7.2/3 and Kv7.4. THC shows small inhibitory effects in both channels, while CBN displays no modulation. Mutagenesis, docking, and simulations suggest CBND/CBD share a binding pose in Kv7.4. THC/CBN did not share this pose, possibly due to their greater geometric planarity and one fewer H-bond donor than CBD/CBND. CBD, but not CBND, preferentially adopts a specific rotamer conformation, potentially explaining efficacy differences. In conclusion, the effect of phytocannabinoids on Kv7.4 may depend on H-bond and molecular geometry characteristics, this provides clues for future drug development.