The data presented herein demonstrate that the combination of THC and a carbonic anhydrase inhibitor, e.g., acetazolamide, unexpectedly synergize to treat OSA. The co-administration of two different doses of both THC and a carbonic anhydrase inhibitor is sufficient to reduce AHI, which is an accepted clinical measure for the treatment and/or amelioration of symptoms associated with OSA. Taken together, these data are enabling for method for the treatment of OSA, and compositions for simultaneous administration of THC and a carbonic anhydrase inhibitor whether in a single composition or dosage form, or co-administration of two separate compositions or dosage forms.