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William R. Marrs of the University of Washington Neurobiology and Behavior Program studies cell signals that are analogs of marijuana-derived chemicals.  (Source: University of Washington)

A visualization shows high levels of the endocannabinoid receptor ABHD6 in nerve cells. The receptor breaks down endocannaboids, reducing their efficacy.  (Source: University of Washington via Nature Neuroscience)
Inhibition of receptor could lead to more effective pain control and other therapeutic effects

Even as marijuana is on the verge of legalization for recreational and medical uses on a state-level across the U.S., its advocates are struggling with the substance's health effects.  After all, on a base level, smoking marijuana is inhaling a smoky mixture of organochemicals, many of which are carcinogenic (such as certain phenolic compounds, i.e. benzo[a]pyrene).  While water pipes or oral consumption are sometimes used, they reportedly give weaker effects.

Thus it is interesting that researchers at the Neurobiology and Behavior program at the University of Washington (UW) have discovered the latest in a long string of chemicals your body produces that resemble those found in marijuana -- chemicals that could eventually be turned into a smokeless replacement that offers the full efficacy of marijuana's most useful effects.

The class of compounds is known as "endocannabinoids" -- an amalgamation of "endo", Latin for inside, and cannabis, the scientific name for the genus of the marijuana plant.  The latest endocannabinoid they discovered is named 2-AG and binds to receptors on nerve cells and microglia.  Microglia are a specialist cell that cleans up debris like dead cells and plaque.

Together the signal is thought to trigger brain cell relocation and the reduction of inflammation.  This could explain why similar compounds released from smoking 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.

In their most recent work they discovered that 2-AG binds to a enzyme called ABHD6.  They say that the enzyme, whose purpose was previously a mystery, "is a bona fide member of the endocannabinoid signaling system."  

Further, they discovered that the enzyme uses water to break down 2-AG, degrading the signal and reducing its effectiveness.

With this discovery researchers can now devise ways to inhibit the enzyme, increasing the potency of cannabis chemicals or their synthetic analogs.  They could also try to devise new compounds resistant to hydrolysis (water-driven splitting).  Either way the net impact would be that the beneficial effects of the pharmochemicals would be accentuated.

The new study is published in the journal 
Nature Neuroscience.  The lead author is William R. Marrs, while the senior author is Dr. Nephi Stella, UW professor of pharmacology and psychiatry.  The study was funded by the National Institute on Drug Abuse and the National Institute of General Medical Sciences, both part of the National Institutes of Health.  In total 19 other researchers contributed from the study, including some at the Scripps Research Institute and Indiana University.





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