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Researchers Discover New Marijuana-chemical Receptor

  1. Phungushead
    Inhibition of receptor could lead to more effective pain control and other therapeutic effects

    View attachment 16125 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.

    Photo captions:
    1. 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)

    2. 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)

    August 9, 2010 10:39 AM

    Here is the abstract for this study, found here:


  1. Balzafire
    Increasing the body's (but not brain's) cannabinoids dulls pain

    Just as the discovery of the opiate receptors hijacked by cocaine gave us insight into the presence and roles of endogenous opiates, the cannabinoid receptors acted upon by the THC in marijuana have helped identify endocannabinoids, the substances produced by our own body that normally trigger these receptors. Outside of the brain, peripheral cannabinoid receptors strongly inhibit pain initiation, but the chemical that signals through them was unknown. Finding it would help us understand pain initiation, and could thus help in the development of more effective and specific painkillers.

    Anandamide, from the Sanskrit word ananda, meaning bliss or delight, is an endocannabinoid that works in both the central nervous system and the periphery. It is degraded by the enzyme fatty acid amide hydrolase (FAAH). To home in on its effects in the periphery, a team of scientists in California and Italy made an inhibitor of FAAH that cannot cross the blood-brain barrier. Thus, upon its administration, anandamide levels stay stable in the brain but are elevated in the periphery.

    When standard FAAH inhibitors are given to mice, they “attenuate behavioral responses to noxious stimuli”—the mice writhe less after being injected with acetic acid. The new FAAH inhibitor had the same effect. This effect was blocked when inhibitors of the CB1 cannabinoid receptor were administered concurrently, indicating that anandamide achieves its pain modulation by acting through this receptor. CB1 receptors are found in peripheral nerve endings, where they are responsible for maintaining normal pain thresholds.

    In addition to tempering this acute pain, the peripheral FAAH inhibitor was also able to attenuate responses to persistent pain caused by nerve damage and inflammation. It is also able to modulate pain responses before they enter the spinal cord. And, in contrast to other cannaboid receptor agonists—like cannabis, for example—this one “did not alter daily food intake, feeding pattern (latency to feed, meal frequency and satiety ratio) or spontaneous locomotor activity in mice.” In other words, the mice didn't get the munchies.

    The authors note that analgesics that activate peripheral cannabinoid receptors often also have psychotropic effects. They hope that by enhancing the anandamide-based signaling system that functions outside of the brain, they can achieve a high level of analgesia without these sorts of side effects—as pleasant or desirable as some of them may be.

    By Diana Gitig
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