Researchers have confirmed the existence of a receptor in the brain that serves as a target for marijuana, a discovery that could lead to new drugs that mimic marijuana's medicinal powers while avoiding some of its mind-altering effects.
The finding, reported today in the scientific journal Nature, implies that the body may produce a natural marijuana-like substance that acts on the brain. The existence of these natural cannabinoids, as they would be called, is still uncertain, but researchers suspect they must exist because a receptor for them exists in the brain. The discovery is expected to spark a race to find the substances.
The discovery should help researchers understand how marijuana affects the brain.
The research reported today by Lisa Matsuda and her colleagues at the National Institute of Mental Health deals with the cloning of the marijuana receptor, which sits on the outside of brain cells and is shaped specifically to grab molecules of the active ingredient in marijuana, delta-9-tetrahydrocannabinol or THC, and produce a specific reaction within the brain cell. Until now, the putative existence of a specific marijuana receptor was controversial and considered
by many researchers to be unproven.
"I'd say it's one of the most important discoveries in marijuana research," said Solomon Snyder of Johns Hopkins University, the neuroscientist who almost two decades ago helped discover that the brain harbors receptors for opiates such as heroin and morphine, as well as natural brain opioids such as the endorphins, which produce the oft-touted "runner's high."
Lewis Judd, director of the National Institute of Mental Health, where the research was accomplished, said, "Now scientists may be able to develop drugs that possess marijuana's positive medicinal effects without its negative effects, such as an intoxicated feeling, disorientation, and impaired preception and memory."
Marijuana is legendary among recreational users for its mood-altering effects, which can include feelings of calm and giddiness and can shift preceptions of time and space. But among physicians and researchers, marijuana is also known to prevent nausea, reduce blood pressure, stimulate appetite, kill pain and suppress convulsions. But efforts to create synthetic versions of the drug have been frustrated by a poor understanding of how marijuana works in the brain.
Traditionally, the study of marijuana has been limited to relatively few researchers. With the latest advance -- finding and cloning the gene for the marijuana receptor -- scientists say they now have a powerful tool for understanding how the drug operates in the brain and for designing more sophisticated versions of therapy.
"I bet the field will explode," Snyder said.
The work ends a long-running debate over marijuana's method of action in the brain. Ever since the active ingredient in marijuana was discovered by Raphael Mechoulam in 1965, most researchers have assumed marijuana affects brain cells by sticking to the surface of cells in an indiscriminate way and somehow disrupting cell function. The active ingredient THC is notoriously sticky stuff, a trait that has made laboratory work difficult and the results confusing.
A few years ago, researchers led by Allyn Howlett of St. Louis University School of Medicine first found evidence that a marijuana receptor existed. The work by Matsuda and her colleagues confirms this.
A receptor is a protein molecule embedded in the membrane of a cell so that part protrudes outside and part inside. The outer part is specifically shaped to bind to a molecule of complementary shape, much as a lock is shaped to fit a certain key. When the molecules bind, the inner part of the receptor changes, sending a signal that alters the cell's function.
In the brain, the marijuana receptor serves as a target for THC, which binds to the receptor but does not enter the cell. Instead, it activates a series of secondary messengers within the cell that cause the drug's effects.