Bradley E. Alger, PhD, professor in the Departments of Physiology and Psychiatry at the University of Maryland School of Medicine, has been studying natural brain chemicals called endogenous cannabinoids (“endocannabinoids”) for nine years. Endocannabinoids have been called the ‘brain’s own marijuana,’ because they activate the cannabinoid receptors that are also stimulated by THC, the main psychoactive ingredient of cannabis. The natural chemicals mimic marijuana’s effect on the brain and are therefore analogous to the brain chemical endorphin, another natural compound that attaches to opiate receptors and mimics opiates effects in our brains. However, the cannabinoid and opioid systems are quite distinct.
Endocannabinoids modulate neurons that have roles in appetite, phobias, anxiety and depression. According to Dr. Alger, “It was well-established that endogenous cannabinoids act on a fast time scale and control moment-to-moment communication among neurons, but the endogenous cannabinoid system also plays a role in medical conditions, such as chronic pain, anxiety and depression that act persistently over the long-term.
Dr. Alger and Jimok Kim, PhD, a research associate in the Department of Physiology, wondered how a system adapted for short-term signaling could produce such long-lasting effects. They developed a model to investigate how long-term changes in brain activity would affect endocannabinoids. The work revealed a new and unsuspected mode of control of this ubiquitous signaling system.
This study, entitled “Reduction in Endocannabinoid Tone is a Homeostatic Mechanism for Specific Inhibitory Synapses,” has just appeared online in Nature Neuroscience. What it shows is that the background level of neuronal activity influences a continuous, ongoing release of anandamide, an endocannabinoid whose function had been mysterious. Anandamide does not take part in short-term endocannabinoid effects, but drugs effective in treating chronic pain, anxiety and depression appeared to target the anandamide pathway.
Since these clinical states are thought to involve persistent changes in neuronal activity, discovery of anandamide’s role forms a critical link between the basic and clinical neuroscience involved. Dr. Kim says, “It brings light to the ways in which the endocannabinoid system might be targeted in future therapeutic drug design strategies.”
Adds Dr. Alger, “This work will help translate the bench side of endogenous cannabinoid research to the bedside of cannabinoid-based therapies for a host of clinical disorders.”
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