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Getting a good night's sleep the natural way

by: Roxane Tracey, roxane@exn.ca

May 17, 2000

Inducing a natural sleep

Ongoing research at a California research clinic might mean that drowning insomniac sorrows with sleeping pills and late night television could become a thing of the past. Chemists at the Scripps Research Institute in La Jolla, California have developed a new molecule that could induce a more 'natural' sleep, without all of the potentially dangerous side effects of sleeping pills.

Although sleeping pills can relieve anxiety and sleeping difficulties, their drawbacks include everything from addiction (possibly leading to depression) to impaired mental function. Because of their potential dangers, sleeping pills are usually only prescribed for short terms of seven to 10 days. Generally, the sedatives work by slowing down activity in the central nervous system. This triggers sleep that is almost like being under anesthesia instead of bringing about a more normal (physiological) rest.

Assistant professor Benjamin Cravatt, chemist Dale Boger and their colleagues have been working on a way to stimulate normal sleep since, 1995. At this time they isolated a molecule called oleamide in sleep-deprived cats and have used it to induce sleep in rats.

Cravatt was in charge of determining oleamide's chemical make-up and characterizing the enzyme that degrades it. "We saw that once oleamide was injected, not only was the time until first sleep decreased, but the sleep-like state that we got from EEG (electroencephalogram) monitoring appeared to be normal and didn't have the altered patterns associated with sedation."

But the researchers also found that during sleep an enzyme called fatty acid amide hydrolase (FAAH) breaks oleamide down, almost defeating its purpose. So the Scripps research team thought they would have more success in stimulating natural sleep if they could stop FAAH from doing its job. By 1996, researchers had developed molecules that could partially block the FAAH enzyme and now they have discovered blockers (or, enzyme inhibitors) that are up to 1,000 times more potent.

Although the new enzyme inhibitors have only been studied in a test tube so far, the Scripps research team will begin experimenting on living creatures in the next few months. Hopefully, this will bring them closer to uncovering any possible side effects that the inhibitors may have on humans.

"There are always potential side effects," says Cravatt. "They [the inhibitors] tend to lower body temperature quite a bit in rodents, but then again rodents regulate their body temperature in different ways than we do. So it is not clear yet whether that effect would be seen in higher mammals like humans."

Boger says despite the long road ahead, he is optimistic that their research could lead to helping people get a good night's sleep in a more natural way. "There is something intrinsically comforting about using something that's natural as opposed to a contrived synthetic molecule that produces the drugs that people might use."