The CSP generated energy landscape of cocaine is shown in Figure (a). The predicted structure with the lowest energy matches the experimental structure (CSD refcode COCAIN10) with a RMSD25 of 0.07 Å. Its energy is around 0.8 kcal/mol lower than the second lowest energy predicted structure using PBE-D3, which is in agreement with previously reported energy landscapes using the PBE-D functional. However, the energy gap between the known experimental structure and second lowest energy candidate structures reduces to 0.3 kcal/mol using r 2 SCAN-D3, indicating possible limitations in PBE-D3 for the purpose of high accuracy ranking. A few benchmark studies have shown that r 2 SCAN-D3 describes the energy and structure in a variety of chemical environments more accurately than PBE-D3, in particular, for hydrogen bonding and dispersion interactions that are typically present in organic molecular crystals. The top 7 predicted structures, which are within the lowest 1.8 kcal/mol energy window from our calculations, match those from a previous study within a RMSD25 of 0.2 Å. The energy gap between the known experimental structure and other top candidate structures is further increased when using the PBE0-MBD functional (Figure (e)), often considered as a more reliable method for calculating crystal lattice energies according to prior studies. The relative stabilities of the top predicted structures vary slightly as a function of temperature, but the experimental form remains the most stable at all temperatures (Figure (a) in SI). This further indicates the low likelihood of observing any additional more stable Z'=1 polymorph of cocaine. Such a CSP landscape, with the global minimum separated by about 1.0 kcal/mol from all other candidate structures, is uncommon in our experience. Most drug-like molecules we have studied have many predicted structures within 1.0 kcal/mol of the global minimum using accurate periodic DFT.