Newly discovered mechanism controls levels and efficacy of a marijuana-like substance in the brain

By | August 8, 2010

A newly discovered molecular mechanism helps control the amount and effectiveness of a substance that mimics an active ingredient in marijuana, but that is produced by the body’s own nerve cells.

The results were reported in the latest Nature Neuroscience. The lead author on the study is William R. Marrs of the Neurobiology and Behavior program at the University of Washington (UW). The senior author is Dr. Nephi Stella, UW professor of pharmacology and psychiatry.

In previous papers, Stella and other scientists have noted that the body manufactures several cell signals that mimic the actions of marijuana-derived chemicals These signals are called endocannabinoids, a Latin-derived name for marijuana-like (cannabis) constituents created by the body’s own cells (endo).

Marrs, Stella and their research team study endocannabinoids, their receptors on cells, and the cell functions controlled by these signals.

They hope their future work encourages the design of therapies to modulate these molecular communications. Specifically targeted treatments, for example, might give cancer and AIDS patients the same medicinal benefits as marijuana without its mind-altering properties.

Because cannabinoid signaling systems are common throughout the body and affect a variety of functions, therapies aimed at these systems might be more wide-ranging than simply a better substitute for medicinal marijuana. Stella is especially interest in the potential for helping people with conditions for which even symptomatic treatment is limited or non-existent, such as multiple sclerosis, brain tumors, Huntington’s disease and other autoimmune or neurological disorders.

Earlier Stella’s group discovered a key endocannabinoid, called 2-AG, that carries a type of messaging between brain cells. 2-AG is also implicated in brain cell migration and brain tissue inflammation. It does this by activating one type of cannabinoid receptor on neurons, and another type of cannabinoid receptor on microglia, the tiny cells that clean up debris, like damaged nerve cells and plaque, in the brain and spinal cord. As the brain’s first line of defense against infection, microglia are attune to the most subtle clues suggesting an attack. …

“The enzymatic steps that control the production and inactivation of endocannabinoids constitute promising molecular targets for indirectly modulating the activity of cannabinoid receptors,” the authors noted. Designing treatments that manage the production and inactivation of important enzymes like ABHD6 could thereby control such conditions as brain inflammation or overactive brain signals. Other enzymes are involved in controlling the accumulation of different endocannabinoids.

via Newly discovered mechanism controls levels and efficacy of a marijuana-like substance in the brain.

Does the fact that endocannabinoids control overactive brain signals explain why some people slip into a trap of regular marijuana use? While the wrong amount of pot can definitely make people anxious, even paranoid, Patsy K. Eagan writing for Elle has an experience that seems all too common:

Women experience generalized anxiety disorder at twice the rate of men. Every year, as many as 4.5 million American women are diagnosed with GAD–not including the several other permutations of anxiety disorders, namely social phobia, obsessive-compulsiveness, post-traumatic stress, and agoraphobia–for which, as with most mental illnesses, they are prescribed medications. …

… surges of elation or rage would seize me at work while I was doing mundane tasks, like shelving. Once, I almost threw a punch at one of the regular, but by no means normal, customers: a squat man who'd tell the female clerks not to touch the (typically women's) magazines he was buying. After a few of these episodes, it became clear that there was no peace for me in Paxil. Calm came, I found, only from pot.A hundred years ago, a doctor might have recommended marijuana for my condition–or "nervous inquietude" as the U.S. Dispensatory called it in 1854–and to anyone suffering from menstrual cramps, gout, cholera, or migraines. During the nineteenth century, American pharmaceutical companies freely produced cannabis for ailments. But in 1937, Congress criminalized "marihuana" with a tax act. …

As my antidepressants were failing me, though, I couldn't help but pay attention to the fact that whenever I smoked pot with friends (after a soccer game, before a hike), it relaxed me–and the calming effect lasted for days. I returned to marijuana in my mid-twenties as a way to level the emotional extremes Paxil induced, and to avoid talking to another listless doctor who would just give me a new pill.

Leave a Reply