The forgetful marijuana user is a common comedy trope, but the memory-impairing effects of pot’s most psychoactive ingredient, Δ9-tetrahydrocannabinol (THC), are serious impediments to medical uses for cannabis. Those effects result from THC stimulating increased production of COX-2, the same enzyme that is inhibited by nonsteroidal anti-inflammatory drugs such as aspirin, say Chu Chen and colleagues at Louisiana State University (Cell 2013, DOI: 10.1016/j.cell.2013.10.042). The team observed that THC induced a dose- and time-dependent increase in COX-2 in mice, so they tested the behavioral effects of giving mice THC along with a COX-2 inhibitor. Mice given both substances did not suffer the impairment of working memory and fear conditioning that the THC-only mice experienced, nor did they display the same degree of lethargy. THC has been shown to help the mouse brain clear Alzheimer’s-associated amyloid-β plaques; the team showed that this ability is not reduced by COX-2 inhibition. The results could broaden medical applications of THC and inform future studies on the biochemical mechanisms of cannabinoid activity.