"It is reasonable to conclude that there is a therapeutic potential of cannabinoids for the treatment of Alzheimer's disease," wrote David Schubert, senior researcher and a professor at Salk Institute for Biological Studies.
Keith Fargo, director of scientific programs and outreach for the Alzheimer's Association, refers to marijuana as a "legitimate avenue of research." The association funded some of Schubert's early research and Fargo sees therapeutic potential in components (or chemical derivatives) of cannabis to alleviate brain inflammation.
Not everyone is as optimistic as Fargo.
While Schubert's study may be "interesting," the results are not yet ready for prime time -- treating actual patients, said Dr. Donovan Maust, an assistant professor of psychiatry at the University of Michigan. Maust, who is not affiliated with the study, examined dementia as a qualifying condition for medical marijuana in his own separate study
"It is difficult to say what, if any, effect this might have in humans, even if it would successfully promote clearance of [plaque]," said Maust.
Meanwhile, Dr. David Casarett, chief of palliative care services at Duke University, remains open to the possibility that medical marijuana is beneficial.
"I spoke to many family members of people with mild or moderate dementia who believed that THC or whole-plant marijuana was effective in alleviating the confusion and agitation that sometimes occurs," said Casarett, author of the book
This idea is supported by a 2014 review
of the existing research on marijuana; Dutch scientists found two studies showing THC is useful in treating the behavioral symptoms of dementia. Similarly, a very small 2016 study
of 11 participants found THC helped decrease symptoms of delusions, agitation or aggression, irritability, apathy and sleep in patients with Alzheimer's disease.
While easing the complaints of patients is helpful, scientists hope for something much more out of marijuana and all other avenues of research --- namely, a preventative treatment or even a cure for Alzheimer's.
Unfortunately, there are still no effective therapies for stopping Alzheimer's and other neurodegenerative conditions.
The pros and cons of targeting plaque
One reason for the lack of treatments is these diseases cause very complex damage to the brain -- it's a thorny knot to untangle.
Schubert believes pharmacological scientists share in the blame as well. Contemporary researchers take a "reductionist" approach, according to Schubert. They focus on very small drug targets, such as a single protein found in neurons in the brain. The research is too narrowly focused, said Schubert.
Another reason experimental drugs for Alzheimer's have failed is they've all been targeting the toxic amyloid plaque that clogs the brain and kills brain cells, noted Schubert. "The hooker in this whole thing is you can have individuals loaded with plaques that are cognitively normal," he said. "And you can have the opposite -- no plaques but dementia."
A long and winding road
Schubert's current study of THC got started about 10 years with a drug candidate he derived from curcumin, the main ingredient of the Indian curry spice turmeric.
"The Indian population doesn't get much Alzheimer's," noted Schubert. The existing molecular structure of curcumin was "lousy," so he and his colleagues refined and strengthened it, creating a drug they refer to as "J147."
Experimenting on a large number of animal models with different diseases (including stroke and dementia), Schubert's team discovered J147 reduces inflammation and decreases damage to nerve system cells in the rodents modeling Alzheimer's disease.
To raise money from funders, though, he had to explain exactly what made J147 effective. Conducting more experiments with the drug, he and his colleagues discovered it worked through a pathway of cannabinoid receptors. The endocannabinoid system, which was named after the marijuana plant Cannabis sativa, helps diverse cells communicate and coordinate.
"And that's what got us into this marijuana thing," said Schubert, explaining that once they knew the drug had a cannabinoid-like effect, they went to the source, marijuana, to see if its own cannabinoid, THC, did the same thing as J147.
Sure enough, THC activated cannabinoid receptors and, in turn, this prevented accumulation of plaque and the death of nerve cells and stopped brain inflammation. Lab data supports this, noted Casarett: Other experiments have shown cannabinoids playing a role in reducing inflammation in the central nervous system.
According to Fargo, the really important thing about Schubert's study is "it gives us a better understanding of the cannabinoid system" and how it's possible to tilt the balance in the brain away from cell death and toward cell survival. Dying neurons in the brains of Alzheimer's patients contribute to their loss of memories and mental abilities -- if you could stop the many individual cell deaths, you might stall the progress of Alzheimer's, he suggested, and Schubert's study points in this direction.
Though Schubert would be interested in learning more about cannabinoids, regulations surrounding marijuana research make such a task daunting.
In fact, "relatively few" researchers are currently exploring medical marijuana, said Fargo, who explained there are just a small number of ongoing clinical trials and most of these consist of very few people -- less than a hundred.
"It's much harder than it should be to do research on medical marijuana and the cannabinoids it contains," said Casarett, who believes the single most important thing the government could do to improve medical marijuana research would be to reclassify marijuana as Schedule II or III.
"The bottom line is I'm absolutely convinced that medical marijuana has real medical use," said Schubert. Clearly, he's not alone.