Medicinal uses for cannabis: Glaucoma

The human eyeball is filled with fluid which exerts pressure to keep the eyeball spherical. Glaucoma is a condition where the channels through which the fluid flows gradually become blocked, and the intraocular pressure (IOP) gradually increases causing increasing damage to the optic nerve and gradual deterioration of vision. Glaucoma is the second-largest cause of blindness, and affects 1.5% of 50-year olds and 5% of seventy-year olds.

Standard treatments have unpleasant or dangerous side effects, and have little effect on intraocular pressures in end-stage glaucoma. Cannabis however lowers intraocular pressures dramatically, with none of the serious side effects. Patients who find that standard medicines do not help their conditions report that smoking cannabis quickly restores their vision. Many long-term glaucoma patients have successfully maintained their sight using cannabis for 20 or 25 years, and avoided the gradual painful deterioration to blindness that is otherwise inevitable.

However older generations, who are most at risk of glaucoma do not appreciate the euphoric side effects of smoked or ingested cannabis. There is also concern about the effects on the cardio-vascular system. These disadvantages are especially significant when one takes into account that a dose of cannabis needs to be taken about every 4 hours for the full benefits to occur.

There is hope that a cannabis-containing eyedrop could be developed in the future which would have no side effects but this is made difficult since cannabinoids are not naturally water soluble. However, animal experiments have taken place using THC dissolved in oil to aid its solubility, which have shown benefits without any of the afore-mentioned side-effects.

Whilst cannabinoids are known to lower IOP it is not currently known how they achieve this. There have been no conclusive tests to determine the mechanism of action, or even if the effect is achieved by brain-receptor interaction (as is the psychoactivity of cannabis). If the effect is achieved through CB2 receptors, then more specific cannabis-based medications could be developed that do not have any unwanted effect on the Central Nervous System. It is also of course possible that the medical effects work through an entirely different route and are not receptor-based. The uncertainty of cannabis' course of action in lowering IOP implies that it is also unknown whether or not it works in the same way as current medications do. If the mechanism of action differs from existing therapies then it is likely to be able to be used with other medications to provide additional benefits that wouldn't be seen if either medication was taken separately.

Several synthetic cannabnioids, including Nabilone, have been tested for the treatment of glaucoma with differing results in terms of efficacy to the condition and side-effects. Synthesised and isolated cannabinoids seem worthy of further investigation. It is feasible that future research could lead to the development of a drug based on cannabis which has fewer side effects and doesn't require such frequent dosing than THC alone. In addition, reducing IOP is not necessarily the only way to help glaucoma sufferers. More direct action on blood flow and neural protection may be of benefit. Researchers have studied a synthetic cannabinoid which is thought to provide some degree of neural protection.

Despite the possible drawbacks, one should be reminded that using cannabis evidently does some glaucoma sufferers a lot of good. 2 out of the 8 patients who are legally permitted to use cannabis medicinally in the US have used government-supplied cannabis for over 10 years to maintain their sight. It seems cruel to prohibit and, indeed, punish the huge numbers of glaucoma sufferers that could be helped by cannabis. Following a review of existing research, the Australian National Task Force on Cannabis concluded that it would not be desirable to criminalise such users.

Ironically, the discovery that cannabis lowers intraocular pressure was made accidentally during a police experiment. They were trying to discover if cannabis caused pupil dilation in users so that they could detect and arrest them more easily!

Scientific evidence

The effect of cannabis on intraocular pressure (IOP) in normal subjects has been well studied, however, the effect on glaucoma patients is less well known, with only a handful of patients studied. Only one study used herbal cannabis, the rest have used cannabinoids.

The Hepler & Frank study (1971) found that oral or smoked cannabis reduced intraocular pressures in normal subjects for about 4 to 5 hours with "no indications of any deleterious effects ... on visual function or ocular structure". They concluded that cannabis may be more useful than conventional medications and probably works by a different mechanism.

Almost all of the studies using cannabinoids have been double-blind and placebo controlled. Two studies were of the effects of oral or smoked THC on IOP in normal subjects. Hepler et al. (1976) reported that the drop in IOP was dose-related. Jones et al. (1981) found that tolerance to the effects quickly built up, and there was a rebound in IOP to above baseline levels when treatment was stopped. Another two studies used intravenous infusions of various cannabinoids. Perez-Reyes et al. (1976) found that only the cannabinoids that had psychoactive effects produced a drop in IOP. Cooler & Gregg (1977) reported a drop in IOP but increased anxiety. The effects of cannabinoids on IOP were confirmed in numerous animal experiments, reviewed by Adler & Geller (1986).

Three orally-taken synthetic cannabinoids have been investigated by Newell et al (1979) and Tiedeman et al (1981). These were given to patients who already had a high IOP. The cannabinoid BW146Y and Nabilone had the same efficiacy as smoked cannabis (but still had a short duration). BW29Y however did not have any significantly beneficial effect.

The few studies on glaucoma patients all involve small numbers of patients. Hepler et al. (1976) found that when THC was smoked for months at a time by glaucoma patients, the effect on intraocular pressure stayed constant and there was no deterioration of vision. However only 7 of the 11 patients showed the effect. Merrit et al. (1980) carried out a double-blind and placebo controlled study on 18 patients and found a significant reduction in IOP but unwanted cardio-vascular and pyschoactive side-effects.

Applying cannabinoids directly to the eyes should remove the side-effects but is proving difficult since they are not water-soluble. Merrit et al (1981) applied THC to only one eye in 8 patients, but found an effect on IOP in both eyes suggesting that the THC had been adsorbed into the bloodstream, rather than acting topically. However his patients reported no pyschoactive side-effects. Two other studies applying THC directly to the eye (as an eye drop) by Green et al (1982) and Jay et al (1983) showed no reduction in IOP.

In one report (Green et al, 1978) the solubility issues were to some extent overcome by dissolving THC in mineral oil, and using the resultant mixture as an eyedrop. THC, cannabinol, 8-alpha- and 8-beta-11-dihydroxy-delta-9-THC all produce a lowering of IOP when topically adminstered to rabbits. They result in no psychoactive effects and appear to be as efficacious as the traditional eye-drops used to reduce IOP (e.g. Pilocarpine) and often work for longer periods of time.

A non-psychoactive extract of cannabis was tested in combination with Timolol eye-drops in patients with high IOP by West et al (1980). They found that the effects of the two medications were complementary and were even effective in some cases where other medications had failed.

As mentioned above, there are other approaches to aiding glaucoma sufferers, including attempting to provude some neural protection. More research on this approach (with or without cannabis) needs to be done, but Yoles et al (1996) used a synthetic cannabinoid HU-211 which is thought to have potential neuroprotective effects. More recent (animal-based) studies by Beilin et al and Naveh et al have shown that this particular cannabinoid also lowers IOP.

Despite the research already done, much more seems to be needed in order to determine the optimum way to help sufferers of glaucoma with cannabis-based medications, if indeed they prove to be beneficial to sufferers compared to existing medications. Amongst others, both the Australian National Task Force on Cannabis (Hall et al, 1994) and a National Institute of Health workshop have called for more research to be done on this topic.