An Endogenous High

Apr 01, 2015 at 10:30 am by Staff


Sachin Patel, MD, PhD, agrees with the American Society of Addiction Medicine’s stance that there is no proven medical value to the marijuana plant as a whole. Yet, he notes, there is also no denying that many of those who smoke say it helps alleviate anxiety.

As director of the Patel Lab at Vanderbilt, he hopes to discover new ways to positively impact the endocannabinoid system – which is involved in a number of physiological processes including anxiety modulation, mood, pain sensation and appetite – without triggering the long-term side effects associated with regular or heavy marijuana use.

“There is substantial evidence with animal models that there might be components of marijuana that, for example, are shown to reduce anxiety,” noted Patel, an associate professor of Psychiatry and Molecular Physiology & Biophysics for Vanderbilt University Medical Center. The question he and colleagues hope to address, he continued, is “how to develop other drugs that could theoretically utilize those same mechanisms without having to smoke marijuana.”

While marijuana can temporarily produce euphoria, a reduction in stress and mild sedation, the drug can also result in impaired memory, judgment, motor function, and … in some cases … cause paranoia and hallucinations. Patel said barriers to understanding the efficacy (or lack thereof) of marijuana components on a variety of conditions range from variability of the components and strength among plants to being classified as a Schedule 1 narcotic by the Drug Enforcement Agency.

What is known is that tetrahydrocannabinol (THC) is the chemical responsible for many of the psychoactive effects of marijuana. While trying to mimic some of those effects in terms of reducing anxiety or dampening the ‘fight or flight’ response, Patel said the research team is taking an alternative approach that has so far shown to be quite a bit safer than THC in mouse models. “If we can find different mechanisms to activate the cannabinoid receptors, maybe that would be a better way to develop therapeutics without relying on THC,” he said.

The compounds being used by the research team to replenish the supply of molecules activating cannabinoid receptors don’t look like THC in terms of structure, although both achieve that result.

Instead, Patel said, “One of the mechanisms that we’re using is drugs that are able to inhibit COX-2 or cyclooxygenase 2, which is the target of Celebrex and other anti-inflammatory drugs.” He added, “We have found this enzyme actually breaks down endogenously produced marijuana molecules in the brain.” Patel continued, “When we develop drugs that inhibit the cyclooxygenase 2 enzyme, then … in theory … you stop the breakdown of endogenously produced cannabinoids and levels go up.”

Patel noted the drugs, given as injections in animal models, have shown effects of reducing anxiety and the stress response. In addition to measuring the levels of endogenous cannabinoids in the brain, Patel said you could also observe behavior that is clearly less anxious in the mice even a few hours later.

Despite this early success, Patel said moving from animal to human trials is still probably five to eight years away. “We’re working closely with other investigators at Vanderbilt to 1) develop better drugs that are more stable and better able to get into the brain, and 2) continue to try this in as many models as possible to make sure it’s a real effect.”

Once additional questions – like how much is too much – are answered, Patel said the potential use for such a therapeutic would be in those with generalized anxiety disorders, social anxiety disorder, and depression. “There is some evidence this also may be effective with specifically trigger-based anxiety that occurs in people with Post Traumatic Stress Disorder. That type of anxiety seems to be dampened by these drugs that are able to enhance endogenous cannabinoids,” Patel said.

The research team is also looking at the amygdala, a specific part of the brain known to be important in behaviors like anxiety and depression. “We’re trying to understand the role of the cannabinoid receptor on neuronal function in the amygdala,” Patel said. “If we understand the role of that receptor, we might understand how marijuana or these new drugs we’re trying to develop actually work in the brain.”

Ultimately, the target audience would be those not being helped by current treatments such as paroxetine hydrochloride, which typically alter serotonin levels. “And maybe people who are self-medicating with marijuana … maybe get them off of it,” Patel said. He added that there haven’t been any fundamentally new treatments in decades for this patient population.

With this new research, he concluded, “The hope would be that we now have a completely new approach to treating people with anxiety disorders and depression.”


More Information:

Patel Lab

Discovery Sheds New Light on Marijuana’s Anxiety Relief Effects 

Vanderbilt Study Finds Natural ‘High’ Could Avoid Chronic Marijuana Use

Vanderbilt Scientists Discover Potential New Way to Treat Anxiety


 

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