Release date: October 12, 1999
Contact: D.W. Pate PhD MSc HortaPharm B.V. Schinkelhavenkade 6,
1075 VS Amsterdam, The Netherlands
TEL: 31-20-618-5591 / FAX: 31-20-6185726

In the human population over 50 years of age, 1-3% will suffer the effects of glaucoma, a disease that is usually characterized by an increased eye pressure. If not treated, this abnormal pressure damages the optic nerve, causing a gradual deterioration of vision, and ultimately leads to blindness. In 1971, it was discovered that the use of marijuana decreases eye pressure, due to the action of its major psychoactive ingredient, THC. As a consequence, the medical use of marijuana has become the last hope for a minority of patients unresponsive to conventional glaucoma therapy. Interest in pharmaceutical development of marijuana-type medicines (cannabinoids) increased after the discovery of a brain receptor for these compounds in 1988, which enabled researchers to begin the design and development of novel drugs that fit this site. Research was further accelerated in 1992, by the discovery of a brain chemical that is equivalent to THC, named "anandamide", which also fits into the receptor. 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, also called arachidonyl ethanolamide (AEA). It was thought that AEA might act at an undiscovered "THC receptor" in the eye, and regulate eye pressure in the same way as does smoking marijuana, but without providing psychoactive effects. Evaluation of chemical modifications to the AEA molecule were also made in the hope that one of the resulting compounds might have potential as a glaucoma drug. 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 by the brain.

A synthetically-modified AEA compound 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 blocking agent prevented the latter eyedrop application from working, which implies an interaction between the synthetically-modified AEA compound and a cannabinoid receptor. This study suggests that the body's AEA may have a local effect on the regulation of eye pressure. Some synthetic analogs of the AEA molecule 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.

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Dale Gieringer (415) 563-5858 // canorml@igc.apc.org
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