In 1971, it was discovered that the use of marijuana decreases eye pressure, due to the action of its major psychoactive ingredient, THC. A recently completed study was begun by David Pate in 1993 at the Department of Pharmaceutical Chemistry, University of Kuopio, Finland, to investigate an eyedrop form of anandamide or AEA, an endogenous ligand of the cannabinoid receptor.

It was thought that anandamide might act at an undiscovered cannabinoid receptor in the eye, and regulate eye pressure in the same way as does smoking marijuana, but without providing psychoactive effects. However, AEA does not dissolve in water, and also decomposes very rapidly.

Both of these problems were solved by inserting AEA into a large hollow molecule called cyclodextrin, which carried the AEA into water and protected it from the environment. AEA caused eye pressure to increase and then decrease, which was due to the compound being metabolized by enzymes in the eye. The other undosed eye did not respond, suggesting that regulation of eye pressure by AEA is controlled in the eye itself, rather than centrally by the brain.

A synthetic derivative of the natural anandamide acted to decrease eye pressure directly, without first increasing it, which indicated that this type of molecule was not metabolized by the eye. In addition, pre-treatment by a cannabinoid receptor blocker prevented the latter eyedrop application from working.

This study suggests that anandamide may have a local effect on the regulation of eye pressure. Some synthetic analogs of anandamide are enzymatically stable and decrease eye pressure by their action upon a cannabinoid receptor. Such novel anandamide-type compounds provide clues to a new pharmacological strategy for glaucoma treatment and are the subject of granted and pending international patents that the Finnish research group shares with HortaPharm B.V., a Dutch medical marijuana research and development firm.

(Source: Press release by HortaPharm B.V., D.W. Pate, of 12 October 1999)