It has been reported that some hydrophobic ligands of G-protein-coupled receptors access the receptor's binding site from the membrane rather than from bulk water. In order to identify the most probable ligand entrance pathway into the CB1 receptor, we performed several steered molecular dynamics (SMD) simulations of two CB1 agonists, THC and anandamide, pulling them from the receptor's binding site with constant velocity. The four main directions of ligand pulling were probed: between helices TM4 and TM5, between TM5 and TM6, between TM7 and TM1/TM2, and toward the bulk water. The smallest forces were measured during pulling between TM7 and TM1/TM2. We also performed supervised molecular dynamics (SuMD) simulations for both anandamide and THC entering the CB1 receptor's binding site and found the same pathway as in the pulling simulations. The residues F1742.61 and F1772.64 (both on the TM2 helix) are involved in the gating mechanism and, by forming π-π interactions with ligand molecules, facilitated the ligand orientation required for passage. Using SuMD we also found an alternative binding site for THC. The results of mutagenesis studies evidencing that residues F1742.61 and F1772.64 are important for CB1 ligand binding are in agreement with our observations.