Tetrahydrocannabinol acid (THCA) and cannabidiol acid (CBDA), the two crucial organic components in cannabis and hemp, decarboxylate at different rates to their more active neutral forms. Theoretical calculations are used herein to analyze how the remote annulated ring or pendant substituent influences the rate determining steps of the decarboxylation processes. The uncatalyzed keto-enol tautomerization that precedes decarboxylation is found to be extremely slow in both cases albeit with a ten-fold preference for CBDA. A single molecule of methanol dramatically enhances the reaction rates by allowing for tautomerization through a more favorable six-membered ring transition state. Methanol-catalyzed tautomerization is found to be faster in THCA than in CBDA. This difference results from both the larger dipole moment of the THCA scaffold as well as its greater rigidity relative to CBDA. The greater dipole moment leads to a somewhat better binding of methanol. The lower entropic penalty in THCA towards tautomerization leads to faster decarboxylation.