Marijuana and the brain: scientists discover the brain's own THC

Science News, Feb 6, 1993 by Kathy A. Fackelmann

William A. Devane was poring over his favorite book, The Life Divine, by Indian philosopher Sri Aurobindo, when he came across the Sanskrit word ananda, which means bliss. For several years, Devane had been searching for a brain compound that resembles the active ingredient in marijuana. Then and there he decided that if his quest proved successful, he would name the elusive chemical after ananda. Of course, Devane still had to find the compound, a task that involved sorting through thousands of substances active in the brain.

But find it he did. Late in December 1992, Devane and a group of Israeli colleagues at Hebrew University in Jerusalem reported isolating a natural marijuana-like compound in pig brains. Now that he has the marijuana-mimicking, pig-produced chemical, Devane is searching for the same stuff in human brains while working in a cramped laboratory of the National Institute of Mental Health (NIMH) in Bethesda, Md.

The notion that the brain makes its own marijuana fits in with a previous discovery: During the 1970s, neuroscientists found that nerve cells manufacture compounds that resemble opium, an addictive drug obtained from the juice of the seeds of the poppy plant.

This finding spurred an intensive effort to understand the brains natural opiate. Also in December 1992, two separate teams reported that they had mapped the structure of one of the opiate receptors, a protein on the nerve cell surface that recognizes and binds opiates, thus allowing these drugs to produce their mind-altering effects.

Taken together, the reports raise many questions about why the healthy brain produces chemicals that resemble marijuana and opium. Many scientists speculate that such internal compounds help humans cope with stress and pain. The findings may help neuroscientists figure out how these brain-made substances work at the molecular level. Ultimately that knowledge will help drug designers develop better painkillers and stress busters.

Marijuana-also known as grass, pot, Mary Jane, and a host of other names -- refers to the dried leaves and flowers of Cannabis sativa, a plant widely - and illegally - used in the United States as a recreational drug. Users typically roll the leaves into a paper wrapper and smoke the resulting marijuana cigarette. In small to moderate doses, delta-9-tetrahydrocannabinol (THC), the plant's active ingredient, produces feelings of well-being and euphoria. In large doses, the drug can cause paranoia, hallucinations, and dizziness.

But recreation isn't the only reason people smoke marijuana. Many people suffering from glaucoma turn to illicitly obtained marijuana to help restore their vision. The Drug Enforcement Administration still considers marijuana a Schedule 1 drug, however - one that has no accepted medical use. That may change. Joycelyn Elders, the Arkansas state health official who has been tapped as President Clinton's Surgeon General, has gone on record supporting the use of marijuana in the treatment of diseases such as glaucoma.

Synthetic versions of THC are available with a doctor's prescription. In 1985, a lab-made THC received Food and Drug Administration (FDA) approval as an anti-nausea agent for cancer patients (SN: 6/15/85, p.377). And in December 1992, FDA approved the same drug to combat the weight loss that afflicts some people with AIDS. Physicians can also prescribe the synthetic THC for treatment of glaucoma, even though FDA has not specifically approved marketing the drug for that use. evane's search for "bliss" began in the 1980s, when he was completing his doctoral studies in pharmacology at the St. Louis (Mo.) University School of Medicine. In 1988, Devane, who had been working with cannabinoid researcher Allyn C. Howlett, discovered that the membranes of nerve cells contain protein receptors that bind THC. Once securely in place, THC kicks off a series of cellular reactions that ultimately lead to the "high" that users experience when they smoke a marijuana cigarette.

The very existence of such a receptor implied that the human brain manufactures a marijuana-like substance: It seemed unlikely that humans had a specialized receptor just waiting for the plant-derived THC to show up. Thus, the 1988 discovery had laboratories all over the world scouting for a THC look-alike.

Doctorate in hand, Devane left St. Louis for Jerusalem to pursue his search by working with Raphael Mechoulam, the Hebrew University chemist who had determined THC's structure.

Before Devane, Mechoulam, and their colleagues could begin looking for the body's version of THC, they had to design a radioactive THC-like drug, or marker, whose location could be traced during brain cell studies. They fashioned such a drug, then mixed it with THC receptors; they found that the marker locked onto its target.

The Israeli team needed a reliable source of brain cells. They couldn't get human brains, so Devane turned to a local butcher shop, where he bought pig brains. After grinding the brains up in a blender, the researchers had to sort through and separate thousands of brain chemicals. They tested each one to see if it would displace the radioactive THC from the receptor.