Marijuana May Grow Neurons in the Brain

Advocates for medical marijuana can take heart over the findings of two Canadian research teams.

A synthetic cannabinoid—similar to the compounds found in marijuana, but substantially stronger—causes the growth of new neurons and reduces anxiety and depression, investigators at the University of Saskatchewan here reported.

And researchers at the University of Calgary said they’ve found evidence that the brain contains so-called CB2 cannabinoid receptors, previously seen in immune tissue but thought not to exist in brain tissue. The discovery, they added, could lead to new drugs to treat nausea associated with cancer or AIDS.

Most so-called drugs of abuse—such as alcohol or cocaine—inhibit the growth of new neurons, according to Xia Zhang, M.D., Ph.D., of the University of Saskatchewan.

“Only marijuana promotes neurogenesis,” Dr. Zhang said.

The finding—reported in the current issue of the Journal of Clinical Investigation—does not involve smoked or ingested marijuana, but rather a synthetic compound dubbed HU-210, which Dr. Zhang said is 100 times as powerful as tetrahydrocannabinol (THC), the compound responsible for the highs experienced by recreational users.

Dr. Zhang and colleagues showed that administration of HU-210 in high but not low doses, not acutely but over a period of several weeks, promotes new neurons in the hippocampus of rats by causing neuronal progenitor cells to proliferate.

The new neurons were associated with a reduction in behaviour typical of anxiety and depression, such as unwillingness to eat in a novel situation.

When neuronal progenitor cells in the hippocampus were destroyed by x-rays, however, the HU-210 had no effect, Dr. Zhang said.

The finding is “exciting” because it offers the possibility of new ways to treat anxiety and depression, said Lisa Kalynchuk, Ph.D., also of the University of Saskatchewan. Dr. Kalynchuk, like Dr. Zhang a member of the university’s neural systems and plasticity research group, was not part of the research team.

“It certainly shows that drugs that act on these cannabinoid receptors—and that would include marijuana—can have beneficial effects on brain and behaviour,” she said.

At the University of Calgary, Keith Sharkey, Ph.D., and colleagues have for the first time showed that the cannabinoid receptor CB2 can be found in the brain stem of rats. What’s more, they reported in the Oct. 14 issue of Science, manipulating the two cannabinoid receptors—CB1 and CB2—blocked emesis in ferrets.

If it can be translated to humans, the finding has direct implications for several aspects of clinical care, Dr. Sharkey said, including:

Nausea and vomiting associated with diseases such as HIV/AIDS
Common physiological reactions, such as morning sickness
Better pain management

“We would be thinking of the implications of our finding (as) being able to develop novel anti-emetic therapeutics that would target this system and block emesis without having very many side effects,” he said.

THC is known to be effective in the treatment of nausea and vomiting, and acts on neurons in the brainstem, Dr. Sharkey said. The researchers hypothesized that endocannabinoids—endogenous compounds that resemble the active ingredient in marijuana—might act at the CB2 receptor in the brainstem to reduce emesis.

Using morphine to stimulate vomiting in ferrets—since rats do not vomit—Dr. Sharkey and colleagues showed that endocannabinoids that preferentially target the CB2 receptor blocked vomiting better than compounds that prefer the CB1 receptor.

Dr. Sharkey said the well-known use of marijuana to treat nausea and vomiting probably relies at least partly on this newly discovered mechanism, although others may be involved.

In the long run, he said, the hazards associated with marijuana make it unattractive as a therapy. “This is a way to use the body’s own systems that can perhaps enhance the benefits and reduce the costs a bit,” he said.

The finding “gives us important and unexpected insights,” said Raphael Mechoulam, Ph.D., of the Hebrew University of Jerusalem, who was the first to isolate THC and later discovered the first endocannabinoid.

It “has changed the way we think about the flow of information within the brain, and how the brain communicates with other parts of the body,” Dr. Mechoulam said in a statement.

Primary source: Journal of Clinical Investigation

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