Cannabinoids are a class of chemical substances that are uniquely produced by the cannabis plant. There are around 60 distinct cannabinoids found in nature, but only a few have been studied extensively. The major psychoactive component is delta-9 tetrahydrocannabinol (often known as “THC”).
Cannabidiol (CBD) and cannabinol are two more well-known cannabinoids (CBN). Cannabinoid profiles change depending on cannabis species, cultivation methods, and harvest locations.
Cannabis sativa, which has high levels of THC, and Cannabis indica, which contains high levels of cannabinol (CBN), are the two most common types of cannabis. The human body also makes its own cannabinoids (called “endocannabinoids”). Throughout the neurological system, cannabinoids bind to cannabinoid receptors (CB1 and CB2) to regulate neurotransmitter release.
Intraocular pressure was shown to be reduced due to cannabis use in the year 1971. Eleven healthy volunteers were examined by optometrists both before and after they smoked 2 grams of cannabis to see how much of an impact the drug had on the human visual system.
Intraocular pressure changes in the participants ranged from +4% to -45%, which was a surprising finding. Later research has shown that around 65% of glaucomatous eyes would have a 30% pressure decrease after inhaling cannabis. Dosage-dependent blood pressure reduction lasts for three to four hours.
Intraocular pressure may be lowered by many cannabinoids, however THC is most notable among them. It is believed that it decreases tear production and increases tear drainage via binding to cannabinoid 1 (CB1) receptors in the eye.
THC’s blood pressure-lowering impact is not centrally mediated but rather a direct action on the eyes. Given this, it’s reasonable to assume that eyedrops would be an effective delivery method. The optic nerve is also said to benefit from THC’s neuroprotective properties. However, there is little support for this function.
There is evidence that CBD mitigates some of THC’s blood-pressure lowering effects. Both THC and CBD are found in varying concentrations in cannabis plants, so this is crucial information to have.
The use of cannabis to treat glaucoma has a number of drawbacks. First, the blood pressure-lowering action only lasts for a short time (three to four hours), thus regular dosage is required. For an illness that must be managed constantly throughout one’s life, this is obviously not feasible.
According to estimates, eight to ten smokes of marijuana would be enough to manage IOP for a whole day. This dosage would be more costly than standard glaucoma treatments and would have serious adverse effects on mental and physical health.
Another constraining element is tachyphylaxis. Nine individuals with advanced glaucoma were given inhaled THC pills every four hours in one trial. Even while everyone saw an improvement in their intraocular pressure (IOP), seven out of nine individuals eventually stopped responding to the treatment. All of the patients decided to stop therapy between one and nine months in because of a lack of efficacy or systemic adverse effects.
Producing synthetic cannabinoids devoid of psychotropic qualities or giving cannabinoids through eye drop might lessen the drug’s systemic effects.
There are two avenues being explored. In order to reduce intraocular pressure, HU211, a synthetic counterpart of THC, has been developed. The hydrophobic nature of cannabinoids has hindered their intraocular penetration thus far, but this may be solved by employing a microemulsion or cyclodextrin to assist the drops pass through the tear film.
Cannabinoids show promise as a potential novel glaucoma medication. Since they target a separate class of receptors, they may complement preexisting glaucoma therapies rather than competing with them. Unfortunately, the systemic effects, short duration of action, and probability of tachyphylaxis associated with cannabis use make it a poor choice as a therapy for glaucoma, especially when inhaled or ingested.
Research in the future should zero down on specific compounds rather than using variable plant samples. If cannabinoids are to have a role in the treatment of glaucoma, I believe it will be via the topical use of a synthetic equivalent of THC.