Ocular hypotension, ocular toxicity, and neurotoxicity in response to marihuana extract and cannabidiol

Marihuana extract containing 21.3% delta-9-tetrahydrocannabinol (100 micrograms/hr), delta-9-tetrahydrocannabinol (20 micrograms/hr), cannabidiol (20 micrograms/hr), or the polyethylene glycol vehicle (1 microliter/hr) was delivered topically to cat eyes via osmotic minipumps over a 9-day period. Intraocular pressure differences between treated and untreated eyes of cats receiving marihuana extract remained 3-4 mmHg lower than those for vehicle controls, while differential values for the delta 9-THC-treated group remained reduced by 3-5 mmHg; data for these two groups did not differ statistically. Pressure differences between treated and untreated eyes of cats receiving cannabidiol were likewise 3-4 mmHg lower than values for controls. Ocular toxicity after delta 9-THC, consisting of conjunctival erythema and chemosis as well as corneal opacification, was quite severe. Although these changes also occurred after marihuana extract, their intensity was much reduced. In contrast, no ocular toxicity became apparent during administration of cannabidiol. While marihuana extract and delta 9-THC produced a dose-related increase in the appearance of 8-13 Hz polyspike discharges in the electrocorticograms of rats, both polyethylene glycol and cannabidiol lacked this effect. These results indicate that the ocular and central effects of marihuana extract and delta 9-THC are qualitatively similar. In addition, it appears that the ocular hypotensive effect produced by cannabidiol is relatively dissociable from both the ocular toxicity and the neurotoxicity associated with marihuana extract.