As Legal Use of Marijuana Spreads, Researchers Seek to Better Assess the Risks and Benefits

With a growing number of states allowing medical use of marijuana and, in several cases, recreational use as well, specialists told a AAAS-organized briefing that it is important to better understand both the benefits and risks of such legislation.

Nora D. Volkow, the director of the National Institute on Drug Abuse (NIDA), said she is concerned about increased access to marijuana by adolescents in states with laws that increase availability of the drug, even if a law may explicitly prohibit use by those under 21.

She noted that the average past month use of marijuana by teenagers in Colorado — one of four states that have legalized marijuana use — was just over 11% in 2013, compared to 7.6% in 2006. Voters in the state approved a ballot initiative in November 2012 that legalized marijuana for recreational purposes.

States are passing laws without studying the potential increased rates of exposure of teenagers to marijuana, Volkow said. As legal access to the drug becomes more widely available, she said, "There is an increased perception by the public that marijuana is not harmful," and that perception "may influence the extent to which teenagers experiment with the drug."

Marijuana is an addictive drug, Volkow said, and it can have negative effects on the still-developing adolescent brain. Frequent use of the drug before the age of 17 can impair cognition and is linked to lower rates of high school graduation and attainment of a college degree, she said.

Rosalie Liccardo Pacula, a senior economist for the RAND Corporation, said studies have found no significant change in general prevalence rates of marijuana use by adolescents in states that were among the first to adopt medical marijuana laws. But one study did find a positive association with passage of these laws and teen initiation of marijuana.

Volkow, Pacula, and Daniele Piomelli, professor of pharmacology and neurosciences at the University of California, Irvine, spoke at 12 May luncheon briefing on Capitol Hill on "Marijuana and the Brain." It was the latest in a series of neuroscience briefings hosted by AAAS in conjunction with Rep. Chaka Fattah (D-Pa.), and through the support of the Dana Foundation.

Pacula said is it important to sort out of the specific effects of each law. "Not all medical marijuana laws are likely to influence youth use the same way," she said. When a state allows home cultivation of marijuana plants for personal use, she said, it also increases potential access to the drug by youngsters who may know relatives or friends who are legally growing the plants.

States that provide legal protections for marijuana dispensaries and do not tightly monitor production and sales of marijuana products may also be opening the door to wider use by adolescents, she said, including the possibility of direct sales to minors or resale of dispensary products to minors by adults. State laws legally protecting dispensaries may also allow for marketing, which can inadvertently reach youth.

Although marijuana use has been correlated with adverse outcomes, it is more difficult to determine whether use of the drug causes those outcomes. A Lancet study last year found that frequent use of marijuana as an adolescent was associated with an increased risk of suicide by age 30, Volkow said. But she added: "This is an area that requires much more investigation to see if there is a causative risk."

Volkow said NIDA and eight other institutes and offices at the National Institutes of Health are mounting a ten-year longitudinal study involving 10,000 children and adolescents from the ages of 10 to 20. It will assess the effects of drugs, including marijuana, on the brain development of individuals as they grow to adulthood.

Using powerful brain imaging methods and other research tools, scientists are making progress in understanding the developing brain and the impacts of marijuana, both harmful and beneficial, on the human body.

THC, the principal psychoactive ingredient in cannabis — the marijuana plant — activates cannabinoid receptors throughout the brain that regulate memory and cognition, brain development, appetite, and other functions, Volkow said. It also increases levels of dopamine, a neurotransmitter, in a part of the brain's reward system called the nucleus accumbens. That process is believed to trigger some of the biochemical changes that lead to addiction, she said.

At the same time, THC has some positive effects that have fostered the widespread interest in medical marijuana use. Piomelli noted that the U.S. Food and Drug Administration has approved use of a synthetic version of THC to reduce nausea and stimulate eating in patients with cancer and HIV/AIDS. The synthetic THC also appears to be moderately effective in reducing chronic pain caused by nerve damage. It is estimated that one in 10 Americans suffer such neuropathic pain at at least once in their lifetimes. Piomelli said, however, that the pure THC seems to produce more side effects in patients than smoked marijuana.

FDA also has approved another drug containing a synthetic substance that acts similarly to compounds from marijuana but is not present in marijuana. The agency has not yet approved any drug product containing or derived from botanical marijuana. A marijuana extract spray is working its way through clinical trials in the United States and already is available in Europe, Canada, and Mexico. Piomelli said the oral spray has shown promise in the treatment of multiple sclerosis and anxiety disorders. But he stressed that these studies and others involving medical uses of marijuana "are preliminary and additional clinical studies are needed."

In another promising line of research, Piomelli has been studying naturally occurring marijuana-like chemicals in the brain — called endocannabinoids — that may play a key role in social behavior. He described his experiments in mice with an endocannabinoid called anandamide. The mice, who don't really like being alone, were socialized to hang out in groups, Piomelli said. He and his colleague measured levels of anandamide in the nucleus accumbens. The social mice had levels of the compound that were three times higher than the levels in mice kept in isolation.

Further, when the researchers prevented anandamide from acting in the brain, the affected mice preferred to be left in isolation. When they boosted levels of the compound, the animals preferred company.

"This opens a window, I think, on what the endocannabinoid system does in social behavior," Piomelli said. "Possibly it explains why some people may really need marijuana to feel social." It also suggests, he said, that drugs that boost anandamide levels in the brain might be helpful in situations where "our social nature is so profoundly undermined," such as autism and schizophrenia.

Piomelli was optimistic about researchers' ability to further unravel the effects of marijuana and its analogues on humans. In the next five years, he predicted, scientists should be able to "say the last word on marijuana's effectiveness in a number of medical conditions." During that same period, he said, scientists should have a better assessment of the risks associated with medical marijuana use. And, he said, "If we work hard, we can leverage our growing knowledge of the endocannabinoid system to make better medicines for a variety of conditions."

[Credit for related teaser image: Dank Depot/ CC BY 2.0]