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Speakers share latest research on cannabinoids
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Three presenters here at the academy plenary session discussed the dangers of recreational use of cannabinoids and the potential benefits of medicinal use.
The session was partially sponsored by Primary Care Optometry News.
Prakash Nagarkatti, PhD, vice president for research at the University of South Carolina, explained that there are two types of cannabinoids: exogenous, which are found in marijuana plants, and endogenous, which we produce ourselves in small amounts. The endocannabinoids are responsible for regulating memory, appetite, sleep and the immune system – a wide array of metabolical functions. The introduction of a large number of exogenous cannabinoids will upset the function of the endogenous cannabinoids.
Prakash Nagarkatti
While it is normal for our immune system to trigger inflammation when attacked, it is not normal for that inflammation to exist chronically. Alzheimer’s disease, cancer, cardiovascular disease, obesity and diabetes are conditions related to chronic inflammation, he said.
Most of the drugs used to treat inflammation have side effects, including increasing susceptibility to infection and cancer, Nagarkatti said.
“We need to have more efficient and less toxic drugs to treat inflammatory conditions,” he said.
“When normal cells are under attack, they have mechanisms to commit suicide so they will not cause additional infection, through a process called apoptosis, or programmed cell death,” Nagarkatti said. “We’ve shown that we can induce 90% to 95% apoptosis in immune cells with the use of cannabinoids, specifically, CB2 receptors.
Cannabinoids are also important inducers of regulatory T cells, which have a role in suppressing inflammation, he said, and those deficient in these cells have autoimmune disease.
While no human clinical trials have been conducted, in mice, cannabinoids have been found to suppress hepatitis C and multiple sclerosis, block colitis and not only prevent but eradicate cancer, Nagarkatti said.
“Our research is based on highly purified compounds of select CB1 and CB2 agonists,” he said. “We have not done research on the entire marijuana plant or someone smoking marijuana. Because it has over 400 chemicals, there may be something toxic in there.”
Allan Flach, MD, PharmD, professor of ophthalmology at the University of California San Francisco, discussed the direct ocular effects of marijuana.
He said that marijuana makes the pupils smaller, not larger, and decreases tear production.
“If we have a drug that lowers IOP and simultaneously dries the tear film, especially in an older population, that won’t work well,” he said.
Marijuana also induces conjunctival hyperemia, photophobia, blepharospasm, accommodative changes, prominent corneal nerves and horizontal phorias (reduced control), he said. Areas of vision not affected include visual acuity, visual field, refractive error, degrees of phoria and stereoscopic perception.
“The range of color vision is increased, but subtle,” he noted.
“Central nervous system effects are a potential problem, as well as tachycardia, hypotension, negative inotropic effects, hypothermia, hyperglycemia, urinary frequency and diarrhea,” he said.
Flach allowed 12 patients with end-stage glaucoma who did not respond to any other therapeutic means compassionate access to cannabinoids.
“IOP was lowered in all, but not sustained,” he said.
Numerous side effects included dizziness, sleepiness, confusion, light-headedness, sedation, distorted perception, anxiety, mild euphoria, depression and dry mouth.
“No patient had a happy high,” he added.
Flach urged caution when evaluating early clinical findings, citing the need for human studies.
“We don’t understand the mechanism of action, we don’t know the best cannabinoid to use and we don’t know the best mode of administration,” he said.
Staci Gruber, PhD, director of the cognitive and clinical neuroimaging core at the McLean Hospital Brain Imaging Center and an associate professor of psychiatry at Harvard Medical School, has conducted extensive research on the recreational use of marijuana.
She said that 23 states and Washington, D.C., have medical marijuana laws, and four have recreational marijuana laws.
In 2012, more than 5 million Americans reported daily marijuana use; 18.9 million reported use in the past month; 36.4% of U.S. high school seniors report use, she said.
“It remains the most widely used illicit substance in the nation,” Gruber said.
“People say if it’s legalized, usage rates will go up,” she said. “However, in Colorado, the usage rates are 20% vs. 37% across the nation.”
The brain develops from the back to the front and from the bottom to the top, into the third decade of life, Gruber said, and the last part of the brain to become fully developed is the frontal cortex. This area is responsible for decision-making, problem-solving and the ability to inhibit appropriate responses.
“Your frontal cortex is your brain’s filter; it stops you from saying things you know you shouldn’t,” she said.
Gruber has used a number of tests to compare early onset smokers (those who began smoking regularly prior to age 16) to late onset smokers and controls. All smokers were considered to be chronic, heavy marijuana smokers who self-reported marijuana use in 5 of the last 7 days and tested positive for urinary cannabinoids.
“Smokers are worse at measures of frontal function than controls, and those who started using before age 16 score worse than nonsmokers and late-onset smokers,” she said.
One type of test showed that smokers are significantly more impulsive than controls.
Brain scans show a structural difference in those who are exposed to marijuana early vs. those exposed later, Gruber continued.
“Earlier age of onset is associated with lower white matter integrity, suggesting brain changes resulting from early exposure,” she said, “and lower white matter organization is related to higher behavioral impulsivity.”
Gruber’s take-home message was that “adolescents are at a loss to make the best decisions without marijuana,” and early onset of use further impairs their neurodevelopmental ability. – Nancy Hemphill, ELS, FAAO