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Thursday, April 12, 2001
Scientists find munchies has physiological basis
By ROWAN HOOPER
The anecdotes and folklore that filter out from the hazy world of cannabis users attest to the drug's stimulating effect on the appetite as well as on the brain. Now scientists have confirmed that the munchies has a physiological basis, establishing the first firm link between cannabinoids (chemicals that occur in cannabis and also naturally in the body) and the normal regulation of body weight.
An international team of researchers from Italy, the United States and Japan show in today's issue of Nature that mice unable to process cannabinoids eat less than normal mice.
Physicians and dope smokers alike are aware of the drug's effect on appetite. Doctors use the major psychoactive component of cannabis, a cannabinoid called tetrahydrocannabinol (THC), to stimulate the appetites of seriously ill patients. What the new research has done is establish a link between cannabinoids and a hormone that regulates energy sources in the body.
Leptin is a hormone produced by fat tissue and affects the hypothalamus, a region of the brain important in weight regulation. Leptin acts to suppress the appetite. If there is a decrease in body fat, less leptin is produced and there is less suppression of the appetite. In other words, skinny mice will eat a lot. Conversely, lots of body fat means lots of leptin and stronger appetite suppression: Fat mice sleep, they don't eat.
But the system is more complicated than that. The new research shows that leptin also reduces the levels of cannabinoids in the brain. Cannabinoids act as neurotransmitters. The brain is equipped with CB1 receptors to detect them (incidentally, there are no such receptors for alcohol). Mice genetically engineered to lack leptin become obese, and mice with their CB1 receptors "knocked out" eat less than normal mice.
There is a complex interaction between the chemical signals that promote and suppress the appetite. Commenting on the work in Nature, Raphael Mechoulam and Ester Fride of Hebrew University, Jerusalem, ask, "Is a similar balance [between cannabinoids and leptin] important in controlling reproduction?"
There are many physiological processes where cannabinoids are already known to play a role, and it is likely that the new work will promote research in these areas, much like cannabis promotes the munchies in dope-heads.
Mechoulam was the scientist who discovered THC, the active ingredient of marijuana, in the 1960s. He was also the first to isolate, in the late 1980s, THC's natural analog in the brain. The dour, white-coated scientists called the substance anandamide, after the Sanskrit word ananda, meaning "bliss."
Work on the effects of cannabinoids was only taken seriously by mainstream scientists when this naturally occurring cannabinoid system was discovered. Cannabinoids were subsequently found to affect the activity of the brain's rostral ventromedial medulla, an area involved in pain sensitivity.
Groups established to care for multiple sclerosis patients advocate the use of cannabis to relieve pain, and research published last year in Nature shows that cannabinoids help control tremors and muscular spasticity in MS patients. Cannabinoids have also been successfully used to reduce the nausea suffered by chemotherapy patients.
Administration of the drug remains a problem. Smoking cannabis brings carcinogenic and toxic effects just as smoking tobacco does. Oral administration is currently unreliable because digestion and absorption of THC varies between individuals; and it is sometimes difficult to swallow for patients with muscular dysfunction. Spray-on methods and patches are among other options being developed.
If the neuroactive and medically beneficial aspects of cannabinoids have only relatively recently been acknowledged by mainstream scientists, it will take longer to convince the politicians (unless you live in the Netherlands). However, there is persuasive evidence that marijuana has long been used in pain relief.
At the beginning of the 1990s, Israeli archaeologists found, along with coins dating to around 315 A.D., the remains of a teenage girl. In her abdomen was the skeleton of a full-term fetus, indicating that the girl had probably died in childbirth. With the remains, the archaeologists also found gray ash containing trace amounts of THC. The supposition is that a midwife administered marijuana to relieve the girl's pain.
As usual, much work remains to be done before the medical and neural effects of cannabinoids are established and it can be safely prescribed. The research area is huge and of fundamental importance -- the broad-based effects of a neurotransmitter on brain function -- but the political hurdles are formidable.
E-mail Rowan Hooper at firstname.lastname@example.org