well as schizophrenia, bipolar disorder, and obsessive-compulsive disorder. These need to be confirmed in human clinical trials. Current studies support an association of disorders such as these with chronic inflammation, which appears to decrease with the use of COX-2 inhibitors. Other targets The inhibition of COX-2 is paramount for the anti-inflammatory and analgesic function of the selective COX-2 inhibitor celecoxib. However, with regard to this drug's promise for the therapy of advanced cancers, it is unclear whether the inhibition of COX-2 plays a dominant role, and this has become a controversial and intensely researched issue. In recent years, several additional intracellular components (besides COX-2) were discovered that appear to be important for mediating the anticancer effects of celecoxib in the absence of COX-2. Moreover, a recent study with various malignant tumor cells showed that celecoxib could inhibit the growth of these cells, even though some of these cancer cells didn't even contain COX-2. Additional support for the idea that other targets besides COX-2 are important for celecoxib's anticancer effects has come from studies with chemically modified versions of celecoxib. Several dozen analogs of celecoxib were generated with small alterations in their chemical structures. Some of these analogs retained COX-2 inhibitory activity, whereas many others didn't. However, when the ability of all these compounds to kill tumor cells in cell culture was investigated, it turned out that the antitumor potency did not at all depend on whether or not the respective compound could inhibit COX-2, showing that inhibition of COX-2 was not required for the anticancer effects. One of these compounds, 2,5-dimethyl-celecoxib, which entirely lacks the ability to inhibit COX-2, actually turned out to display stronger anticancer activity than celecoxib itself and this anticancer effect could also be verified in highly drug-resistant tumor cells and in various animal tumor models. Adverse effects Analysis of clinical trial data revealed that there was a significant increase in the rate of vascular events with COX-2 inhibitors compared with placebo; "vascular events" are non-fatal myocardial infarction (MI) or heart attack, non-fatal stroke, and death from a vascular event such as MI or stroke. These results led Merck to voluntarily withdraw (rofecoxib) from the market in September 2004 and to regulatory authorities imposing a boxed warning on the label of celecoxib. Traditional NSAIDs were also found to have cardiovascular risks, leading to similar boxed warnings. The cause of the cardiovascular problems became, and remains, a subject