Medical marijuana has quickly gained acceptance as a viable treatment for a variety of health conditions, such as the side effects of chemotherapy, the neurodegenerative effects of Alzheimer’s disease, certain seizures and chronic pain without the addictive effects of opioids.
But in ophthalmology, medical marijuana has encountered the headwinds of controversy. The American Glaucoma Society in 2010 issued a statement against recommending medical marijuana for treatment of glaucoma, the most plausible use for medical marijuana, and even more recent literature advises against its use.
But AXIM Biotechnologies Inc., a company that specializes in cannabinoid research and development, has taken the plunge into developing therapies for glaucoma and dry eye by putting noted glaucoma specialist Robert Ritch, MD, in charge of its clinical programs in ophthalmology.
The Medical Marijuana Movement
Twenty-eight states and Washington, DC, have legalized medical marijuana, and seven states plus Washington, DC, have legalized recreational marijuana in some form. Dr. Ritch tells OIS that medical marijuana is more widely available for research today than it was when he started exploring its potential for glaucoma about 25 years ago.
Today’s medical marijuana is not street weed. It is specially grown to have fewer of the chemicals that make you high. Cannabinoids are the chemical compounds – tetrahydrocannabinol (THC), cannabidiol (CBD), and at least 113 others – that the cannabis flowers secrete. They are known to relieve a variety of symptoms, such as nausea, pain, inflammation, even anxiety. They mimic endocannabinoids, which Dr. Ritch describes as “marijuana-like compounds in the body” that are naturally produced to mediate cell activity.
Although the anti-inflammatory effects of marijuana seemingly make it well suited to reduce intraocular pressure (IOP) in glaucoma, its effect only lasts two to three hours, which means a user would have to take several doses during the day to get sustained IOP-lowering.
Dr. Ritch’s curiosity got piqued years ago when a 73-year-old patient who had IOPs usually in the 20s came into the office one day with IOPs of 13 mm Hg. “He said he’d been smoking grass,” Dr. Ritch says. “The problem is, who wants to get high at 7 o’clock in the morning? The patient said he had two tokes at bedtime and that carried him through the next day.”
The Mechanism of Action
Inhaling or ingesting marijuana has the effect of any herbal extract, Dr. Ritch says. “A single molecule has specific effects on specific pathways,” he explains. Using gingko biloba extract (GBE) as an example, he notes that it comprises 24% flavonoids, which are antioxidants, and also possesses gingkolides and bilobalides, which are neuroprotective, as well as compounds that improve ocular and peripheral blood flow and stabilize mitochondrial structure and function. “There are many different actions,” he says, “There are 60 different compounds in GBE, 30 of which are found nowhere else in nature.
“If you then extrapolate that information to cannabinoids, one must assume that there are many different compounds in addition to THC that are getting into your body and doing various things,” Dr. Ritch adds.
“If you take more than one compound and perhaps add them together, such as cannabidiol and cannabigerol added to THC, then are we going to get a greater activity? What is the side effect profile, etc.?” Dr. Ritch says. “That’s about as far as I can take it. With a plant, many different compounds will enter your body.” These are a couple of the questions Dr. Ritch hopes to answer in his research. The company partnered with Ora Inc. to conduct the trials.
Cannabinoids have the potential to attack glaucoma through multiple pathways, Dr. Ritch says. “There are drops currently available that have more than one mechanism of action, such as increasing aqueous humor outflow and reducing its inflow. With cannabinoids, there could be a drop or other formulation that not only lowers IOP – THC improves trabecular outflow and improves uveoscleral outflow – but also provides neuroprotection, providing a double mechanism of action, one in the front of the eye and one in the back of the eye.”
Home-based tonometers and devices such as Triggerfish, Sensimed’s FDA-approved contact lens sensor, would be important tools for clinical trials of the IOP-lowering effects of cannabinoids by gathering data that are not obtainable during office hours, Dr. Ritch says.
Adds Dr. Ritch, “Research in this whole area is just beginning. Ten or 15 years ago it was difficult to do research in this area because of legalities, but now the government is waking up.
“Once the ball starts rolling like that, you can’t stop it, and all medical uses must be investigated. It’s a matter of necessity.”
In ophthalmology, the medical marijuana ball is rolling.