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La Jolla scientists study cannabis components as treatments for Alzheimer’s disease and sports injury pain

Two La Jolla institutions are focusing studies on the potential of cannabis components to treat certain maladies.
Two La Jolla institutions are focusing studies on the potential of components of the cannabis plant to treat certain maladies.
(Associated Press)

Scientific studies by two La Jolla institutions are focusing on components of cannabis as treatments for ailments including Alzheimer’s disease and pain from sports injuries.

Salk Institute for Biological Studies

Decades of research on medical cannabis has focused on the compounds THC and CBD in clinical applications. But less is known about the therapeutic properties of cannabinol (CBN). But a new study by scientists at the Salk Institute for Biological Studies indicates that CBN can protect nerve cells from oxidative damage, a major pathway to cell death.

The findings, published online last month by the journal Free Radical Biology and Medicine, suggest CBN has the potential for treating age-related neurodegenerative diseases such as Alzheimer’s.

“We’ve found that cannabinol protects neurons from oxidative stress and cell death, two of the major contributors to Alzheimer’s,” said study senior author Pamela Maher, a research professor and head of Salk’s Cellular Neurobiology Laboratory. “This discovery could one day lead to the development of new therapeutics for treating this disease and
other neurodegenerative disorders, like Parkinson’s disease.”

Pamela Maher and Zhibin Liang
Pamela Maher and Zhibin Liang are authors of a Salk Institute for Biological Studies report on the potential for CBN to treat age-related neurodegenerative diseases such as Alzheimer’s.
(Courtesy of Salk Institute)

CBN is a compound of the cannabis plant that is molecularly similar to tetrahydrocannabinol (THC), but unlike THC, it is not psychoactive. It’s also less heavily regulated by the U.S. Food and Drug Administration.

Previous research by Maher’s lab determined that CBN had neuroprotective properties, but it wasn’t clear how it worked. The new study explains the mechanism through which CBN protects brain cells from damage and death.

Maher’s team looked at the process of oxytosis, which is thought to occur in the aging brain. Growing evidence suggests that oxytosis may be a cause of Alzheimer’s disease. In the study, the scientists treated nerve cells with CBN and then introduced an agent to stimulate oxidative damage.

They further found that the CBN worked by protecting mitochondria, the cell’s powerhouses, within the neurons. In damaged cells, oxidation caused the mitochondria to curl up — a change that also has been seen in aging cells taken from the brains of people with Alzheimer’s. Treating cells with CBN prevented the mitochondria from curling up and kept them functioning well, according to the study.

To confirm the interaction between CBN and mitochondria, researchers replicated the experiment in nerve cells that had the mitochondria removed. In those cells, CBN no longer demonstrated its protective effect.

“We were able to directly show that maintenance of mitochondrial function was specifically required for the protective
effects of the compound,” Maher said.

In another key finding, researchers reported that CBN did not activate cannabinoid receptors, which are required for cannabinoids (compounds found in cannabis) to produce a psychoactive response. Thus, CBN therapeutics would work without causing the person to become “high.”

“CBN is not a controlled substance like THC ... and evidence has shown that CBN is safe in animals and humans. And because CBN works independently of cannabinoid receptors, CBN could also work in a wide variety of cells with ample therapeutic potential,” said first author Zhibin Liang, a postdoctoral fellow in the Maher lab.

As a next step, Maher’s team is working to see if it can reproduce its results in a preclinical mouse model.

UC San Diego

The National Football League has awarded $1 million to two medical research teams — including one at UC San Diego — to study the impact of the non-intoxicating cannabis component cannabidiol (CBD) on pain management and recovery from sports-related injuries.

UCSD and the University of Regina in Canada were selected from among 106 submissions for research proposals executed by the NFL-NFLPA Joint Pain Management Committee, with UCSD’s team assessing the therapeutic potential of
cannabis for “relief of post-competition soft-tissue injury pain in elite athletes.”

According to an NFL statement, athletes outside the NFL will use vaporized treatments following game-related injuries, with the outcomes monitored via phone apps. Participating athletes will receive treatments of either 4 percent THC, 12 percent CBD, a combination of CBD and THC, or a placebo, according to UCSD. The university said that while no conclusions can be drawn until the study is completed, investigators believe the THC and THC/CBD combinations will prove to be the superior treatments.

According to a UC San Diego Health statement, professional rugby players were chosen for the initial trial, which not only will evaluate pain relief and recovery but also any effects on physical function, sleep, cognition and mood.

“An innovation of this research is using a real-world model of the NFL’s competitive injury burden with a group of elite athletes who experience similar injuries,” said Thomas Marcotte, a professor of psychiatry at the UCSD School of Medicine. “It’s a first-of-its-kind randomized trial to examine the possible practical efficacy of cannabinoids on post-competition pain.” ◆