THC, CBN, and nabilone were active in lowering intraocular pressure (IOP) in rabbits, while CBD was inactive.235 Certain derivatives of THC were more active in lowering IOP than the parent cannabinoid236; some topically used soft analogs that have no systemic

effects were also active in IOP reduction.237 The effect on IOP of 2-AG was biphasic (ie, an initial increase in IOP followed by a reduction). In contrast, noladin Inhibitors,research,lifescience,medical ether decreased IOP immediately after topical administration, and no initial IOP increase was observed. AM251 blocked the effect on IOP of noladin ether, but did not affect the action of 2-AG.238 Topical administration of anandamide and arachidonyl propionitrileamide decreased IOP; rimonabant antagonized the IOP reduction, suggesting that cannabinoids lower IOP through CB1 receptors.239,240 Significantly, higher levels of CB1 mRNA levels

were found in the Inhibitors,research,lifescience,medical ciliary body than in the iris, retina, and choroid. CB2 mRNA was undetectable. This expression pattern supports a specific role for the CB1 receptor in controlling IOP.241 Inhibitors,research,lifescience,medical When delivered topically to cat eyes with osmotic minipumps, whole marijuana extract, THC and other plant cannabinoids reduced IOP, while cannabichromene was inactive. Ocular toxicity was seen after THC treatment, consisting of conjunctival erythema and chemosis as well as corneal opacification. Although these changes also occurred with marijuana extract, their intensity was much reduced. In contrast, no ocular toxicity was apparent during administration of plant cannabinoids other than THC.242-244 Marijuana smoking was shown to reduce IOP as early as 1971; the effect was later confirmed.245-248 The peak effect Inhibitors,research,lifescience,medical of THC on the central nervous system coincided well with the BIBW2992 concentration reduction in intraocular

pressure induced by the drug; However, hypotonia outlasted euphoria. The results indicate that THC may have value as a hypotonizing ocular drug.249 The functional responses after THC inhalation in sitting normotensive Inhibitors,research,lifescience,medical and hypertensive patients included invariable increases in heart rate followed by substantial decreases in systolic pressure, diastolic pressure, and intraocular pressure. The intensity and duration of the arterial and ocular pressure responses to THC were greater in hypertensives than in normotensive CYTH4 patients; the changes in ocular pressure paralleled the changes in blood pressure in glaucoma patients.250 A single sublingual dose of THC, but not cannabidiol, reduced the IOP temporarily and was well tolerated by most patients.251 Cancer The antiproliferative action of cannabinoids on cancer cells was first noticed in the 1970s. Since then cannabinoids were found to act on various cancer cell lines, through various mechanisms.252,253 Cannabinoids were also found to be suppressors of angiogenesis and tumor invasion.