From the munchies to the giggles to paranoia, smoking marijuana causes widespread changes in the brain. Now researchers at Stanford University School of Medicine are a step closer to understanding how the drug's active ingredients - tetrahydrocannabinol and related compounds, called cannabinoids - may exert their effects.
David Prince, MD, the Edward F. and Irene Thiele Pimley Professor of Neurology and Neurological Sciences, and his colleagues found that a group of neurons that act as information gatekeepers in the brain's major information processing center, called the cerebral cortex, release cannabinoids that quiet their own activity. This form of self-inhibition is a novel way for neurons to regulate their own ability to send messages to their neighbors. Tetrahydrocannabinol from marijuana may work its brain-altering magic by binding to these same cells.
"Marijuana is a major drug of abuse with actions in the brain that aren't entirely known. Now we understand one piece of the puzzle," Prince said. The work of Prince and his colleagues John R. Huguenard, PhD, associate professor of neurology and neurological sciences, and Alberto Bacci, PhD, staff research associate, is published in the Sept. 16 issue of Nature.
The cells under scrutiny lie in the cerebral cortex. This region processes information from the eyes, ears, skin and other sense organs, regulates movement and performs complex functions such as those involved in thinking, learning and emotions. The cortex contains two major types of nerve cells: pyramidal neurons that excite both local and more distant neighbors, and inhibitory interneurons that act as local dimming switches, shutting down the activity of nearby brain cells. The inhibitory interneurons prevent the brain from taking in and responding to every thought, sight or sound it encounters. They also protect against runaway excitation such as that seen in epilepsy.
In previous work, other researchers had found that pyramidal cells manufacture and release cannabinoids that bind to a receptor on the membrane of interneurons. In this process, called retrograde signaling, the pyramidal cell does the equivalent of slipping its guardian interneuron some sleeping pills. It frees itself from inhibition by releasing cannabinoids that briefly decrease the interneuron's ability to release inhibitory molecules.