Intraocular Pressure, Ocular Toxicity and Neurotoxicity in Response to 11-Hydroxy-Δ9-Tetrahydrocannabinol and 1-Nantradol

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Abstract
Both acute and chronic effects on intraocular pressure of 11-hydroxy- Δ9-tetrahydrocannabinol (11-OH-Δ9-THC; a metabolite of Δ9-THC) and 1-nantradol (a synthetic cannabinoid) have been examined in the cat. Acute effects of these cannabinoids on ocular tension have also been determined in the monkey. Single dose effects of several other hydroxylated Δ9-THC metabolites have been evaluated in either the cat or the monkey. Results indicated that 11-OH-Δ9-THC and 1-nantradol produced similar acute effects in both species, with 1-nantradol significantly lowering intraocular pressure and 11-OH- Δ9-THC producing no change. Neither 11-OH- Δ9-THC nor 1-nantradol lowered ocular tension chronically when delivered for nine days to cat eyes via osmotic minipumps and connecting extraocular cannulas. Neither cannabinoid likewise produced ocular toxicity, although both produced neurotoxicity, as assessed by evaluation of electroencephalograms recorded from rats. Both 8-β-OH- Δ9-THC and 8-β-11-diOH- Δ9-THC were inactive with regard to acute effects on ocular tension. These results support previous findings suggesting that hydroxylation of the terpene portion of the Δ9-THC molecule significantly reduces intraocular pressure lowering activity. In addition, results from these and earlier studies suggest that structural requirements for tension lowering effects, ocular toxicity, and neurotoxicity, may well be distinctively different.