Activating cannabinoid brain receptors could replace marijuana for anxiety treatment

Marijuana is the most commonly used illicit drug in the US, and its prevalence among adolescents and young adults has been increasing in recent years. But in a new study published in the journal Cell Reports, researchers say they may have uncovered a potential way to help some individuals stop using marijuana.

In the brain, endocannabinoids usually activate cannabinoid receptors, which are involved in regulating appetite, pain, memory and mood, among other physiological processes.

However, past studies have indicated that individuals with mood and anxiety disorders have reduced levels of endocannabinoids. Since the active ingredient in marijuana – tetrahydrocannabinol (THC) – can also activate the cannabinoid receptors, many people may use the drug to relieve symptoms of such disorders.

But the research team – led by Dr. Sachin Patel, professor of psychiatry and molecular physiology and biophysics at Vanderbilt University in Nashville, TN – says they have found a way to replenish levels of an endocannabinoid called 2-Arachidonoylglycerol (2-AG) in the brain, which may reduce the reliance on marijuana to treat mood and anxiety disorders.

Replenishing 2-AG levels reduced anxiety- and depressive-like behaviors in mice

To reach their findings, Dr. Patel and his team deleted an enzyme in adult male and female mice – called diacylglycerol lipase α (DAGLα) – that usually breaks down 2-AG, creating 2-AG-deficient mouse models.

The researchers say all mice displayed anxiety-like behaviors, while female mice displayed behaviors related to depression. “We were expecting that endocannabinoid deficiency would produce anxiety and depressive-like behaviors, but the female-specific depressive behavior took us by surprise,” Dr. Patel told Medical News Today.

However, the team found that replenishing 2-AG levels in the brains of the mice appeared to reverse anxiety- and depressive-like behaviors. The researchers say their findings indicate that “normalizing 2-AG deficiency could represent a viable […] therapeutic strategy for the treatment of mood and anxiety disorders.”

What is more, Dr. Patel told MNT that, although the technique has not yet been tested in humans, it has the potential to wean some heavy marijuana users off the drug:

“It is very possible that a subset of heavy marijuana users are actually self-medicating symptoms of anxiety or mood disorders.

We think that manipulating the naturally produced cannabinoids, like 2-AG, is likely to have the same anxiety-reducing, mood-elevating capacity without producing as many side effects as synthetic cannabinoids, like marijuana. This approach, then, would eliminate the drive to self-medicate with marijuana.”

Next, Dr. Patel said the team wants to find out exactly how 2-AG deficiency impacts the brain’s ability to regulate mood and anxiety. This, he says, would improve efficiency when the endocannabinoid-replenishing technique reaches clinical testing.

Last month, MNT reported on a study by researchers from the University of California-San Francisco, which suggested that exposure to secondhand marijuana smoke could be just as harmful to health as exposure to secondhand cigarette smoke.

Written by Honor Whiteman

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