Discovery Can Increase Potency Of Cannabis Chemicals In Brain


The latest research points the way towards increasing the potency of cannabis chemicals or their synthetic analogues

Researchers at the University of Washington have discovered the latest in a long list of chemicals your body naturally produces that resemble those found in marijuana — chemicals they say could eventually be turned into a smokeless cannabis replacement that offers and increases the full efficacy of marijuana’s most useful effects.
In previous papers, scientists have noted that the body manufactures several cell signals that mimic the actions of marijuana-derived chemicals. This class of compounds known as endocannabinoids, from the Latin “endo,” for inside, and cannabis, the scientific name for marijuana, plays a vital role in the human body’s regulation of things like inflammation, reports Jason Mick at DailyTech.

Photo: University of Washington
Lead author William F. Marrs: Pointing the way towards the future of endocannabinoid therapy

‚ÄčThe latest endocannabinoid to be discovered is named 2-AG. It binds in a lock-and-key fashion to receptors on brain cells. In so doing, 2-AG stimulates microglia, whose function is to defend the brain by cleaning up debris like dead cells and plaque.
The newly discovered endocannabinoid is thought to trigger brain cell relocation and the reduction of inflammation, possibly explaining why similar compounds found in marijuana — likely binding to the same receptors — can offer relief to the symptoms of brain-related diseases such as multiple sclerosis, brain tumors, Huntington’s disease and other autoimmune or neurological disorders.
Because cannabinoid signaling systems are common throughout the body and affect a variety of functions, therapies aimed at these systems might be far more wide-ranging than simply a substitute for, or adjunct to, medical marijuana.
In their most recent work, the scientists at the Neurology and Behavior program at UW discovered that 2-AG binds to an enzyme called ABHD6. They say that the enzyme, whose purpose was previously a mystery, “is a bona fide member of the endocannabinoid signaling system.”

Photo: University of Washington
Dr. Nephi Stella and his research team are studying substances naturally produced in the brain that mimic the active ingredients of marijuana

‚ÄčThe further discovered that the enzyme uses water to break down 2-AG, degrading the signal and reducing its effectiveness.
With this discovery, scientists can now work on ways to inhibit the enzyme, increasing the potency of cannabis chemicals or their synthetic analogues.
They could also attempt to create new compounds resistant to hydrolysis, the water-driven splitting used by ABHD6 to break down endocannabinoids like 2-AG.
Either way, the net impact would be that the desirable effects of marijuana’s chemicals, as well as of the endocannabinoids already present in the body, would be enhanced.
“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 these enzymes could thereby control such conditions as brain inflammation or overactive brain signals, according to the researchers — possibly increasing the effectiveness of marijuana and the body’s natural endocannabinoids in dealing with the effects of conditions like attention deficit/hyperactivity disorder (ADHD).
Each of these enzymes, the researchers pointed out, provides a unique therapeutic opportunity. Inhibiting specific enzymes could actually allow the fine-tuned direction of endocannabinoid signaling.
For example, blocking a specific enzyme to heighten a certain signal might increase pain relief, and also act as an anti-anxiety and antidepressant therapy, researchers said.
Drugs that reduce the activity of the ABDH6 enzyme might prevent brain damage from inflammation or other overactive responses to a virus.
The new study is published in the journal Nature NeuroscienceThe lead author is William F. Marrs, and the senior author is Dr. Nephi Stella, UW professor of pharmacology and psychiatry.
The study was funded in part by the National Institute on Drug Abuse (how funny that those Drug War goons at the NIDA helped fund a study that can actually benefit marijuana patients!) and the National Institute of General Medical Sciences, both part of the National Institutes of Health.