Hormone Takes the High Out of Weed, Rodent Study Finds

Researchers hope findings will lead to drug to treat marijuana abuse

Thursday, January 2, 2014

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THURSDAY, Jan. 2, 2014 (HealthDay News) -- In experiments with rodents, scientists have discovered that a steroid hormone blunts the effects of marijuana, virtually eliminating its high.

The hormone, pregnenolone, occurs naturally in the body. In the laboratory, it worked by reducing the reaction to THC (tetrahydrocannabinol), the intoxicating ingredient in marijuana, the researchers said.

"When the brain is stimulated by high doses of THC, it produces pregnenolone -- a 3,000 percent increase -- that inhibits the effects of THC," said senior researcher Dr. Pier Vincenzo Piazza of Neurocentre Magendie in Bordeaux, France.

Pregnenolone does this by blocking the activity of the type-1 cannabinoid receptor (CB1) in the brain, Piazza said.

Although research conducted in animals doesn't necessarily apply to humans, Piazza said he hopes a drug based on the hormone could combat marijuana addiction or allow researchers to isolate the medicinal properties of marijuana while blocking consequences such as memory impairment.

The findings, published in the Jan. 3 issue of the journal Science, might be timely since some observers fear that growing legalization of marijuana in the United States will increase marijuana addiction. Colorado and Washington state have voted to legalize marijuana for recreational use, and 20 states and Washington, D.C., are legalizing its medical use. In addition, many states are decriminalizing its use.

Piazza said his study points to the potential hazards of marijuana. "If we have a built-in mechanism that protects us from an over-activation of the CB1 receptor by THC, smoking cannabis cannot be that innocuous," he said.

The dose of THC needed to produce pregnenolone is greater than that usually found in cannabis users, he said. But in higher doses, he said, "we can use this natural protective mechanism to develop new therapies for cannabis abuse."

But pregnenolone by itself won't work because it quickly degrades after it's taken, Piazza said. However, his team has developed a class of compounds that retains pregnenolone's anti-cannabis effects and are stable and absorbed well in the body. "We hope to be able to test them in humans very soon," he said.

Some experts are skeptical of Piazza's conclusions.

Mitch Earleywine, a professor of psychology at the University at Albany, State University of New York, isn't convinced that a drug based on this hormone will work on humans or is even needed.

"Although the authors pitch this as a novel way to treat cannabis abuse, it's actually a superb -- if partial -- explanation for why cannabis appears to have no potential lethal dose and why its capacity for creating addiction is more like caffeine's than that of any illicit drug," he said.

Earleywine also said he's cautious about using data from rodent experiments to predict what will happen in humans.

"I'm always reluctant to generalize from rat studies, and some of these reactions only work with rats and not mice," he said. "We should be supremely careful before we start drawing conclusions for primates, let alone humans."

Moreover, a medication to treat marijuana problems is potentially unnecessary, Earleywine said.

Existing therapies, such as motivational interviewing and behavior therapy for relapse prevention, can be effective, he said.

"Behavioral interventions have no adverse side effects," he said. "We can't say the same for futzing around with pregnenolone or the complex, interconnected series of human hormones."

Dr. Scott Krakower, assistant unit chief of psychiatry at Zucker Hillside Hospital in Glen Oaks, N.Y., said a drug to treat marijuana abuse is needed.

"We don't have a lot of drug treatments for marijuana," he said. "However, I don't think we can say right now that pregnenolone is going to be helpful."

Krakower said he isn't sure how such a drug would be used -- whether it could curb an acute problem or provide a long-term therapy.

Like all other addictions, marijuana abuse needs both medication and counseling, he said.

"Right now, the treatments for marijuana addiction are therapy," Krakower said. "Research like this leads to hope that one day we are going to have drugs to help those suffering from marijuana addiction."

According to the American Cancer Society, use of pregnenolone pills and capsules is promoted by some people to increase energy and as an alternative treatment for fatigue. Others say pregnenolone supplements help treat various medical conditions. But scientific evidence is scant, and little is known about its long-term effects, according to the society.

SOURCES: Pier Vincenzo Piazza, M.D., Ph.D., INSERM, Neurocentre Magendie, Physiopathologie de la Plasticite Neuronale, Bordeaux, France; Mitch Earleywine, Ph.D., professor, psychology, University at Albany, State University of New York; Scott Krakower, M.D., assistant unit chief, psychiatry, Zucker Hillside Hospital, Glen Oaks, N.Y.; Jan. 3, 2014, Science

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