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Marijuana and adolescence: what can we learn from primates?

Inan article published concurrently with this editorial, Verrico and colleagues (1) report that D9-tetrahydrocannabinol (THC), the active ingredient of marijuana, administered to monkeys for 6 months during their adolescence, impairs development of spatial working memory. Normal development of spatial working memory was observed in adolescentmonkeys administered only saline. The spatial working memory task entailed monkeys 1) looking at a screen that had a square displayed at random in one of four corners, 2) touching the square, 3) looking at a “fixation” cross for an interval of 1, 4, 8, or 16 seconds, and 4) then pointing to the corner where the monkey remembered the square was before. The effect of chronic administration of THC was specific to spatial working memory in the monkeys, as the recall of a colored object independent of location was not affected by THC in terms of either accuracy or reaction time. The exposure to THC in adolescent monkeys was similar to that obtained by a human smoking one to two marijuana cigarettes, five times per week, for 6 months. Verrico and colleagues earlier found that acute administration of THC similarly impaired spatial working memory (2). These prior data are consistent with an extensive literature showing that THC “challenge” leads to transient working and other memory impairment across species, including rodents, humans, and nonhuman primates (3). But while the transient cognitive effects of challenge or acute administration of THC can be studied in humans (specifically adults) to observe direct effects of marijuana, random assignment to chronic administration of marijuana cannot be done in human adolescents, perhaps the most vulnerable group. A model of chronic cannabis exposure in monkeys offers the opportunity to observe the direct biological effects of the active component of marijuana on the developing adolescent primate brain and its cognitive function, independent of the confounds that exist in observational studies of teens. The effect of marijuana on the developing adolescent brain and its cognitive function is an especially salient public health issue in 2014. The prescription of marijuana for medical conditions is legal in nearly half of our 50 states. The sale of marijuana for recreational use is legal now in both Colorado and Washington, with other states weighing this option. The market for marijuana is large. For example, while in 2013 the state of Colorado collected $9million in tax revenue from “medical marijuana” dispensaries (4), the projected state tax revenue in 2014 in Colorado for retail marijuana is $67 million, based on an estimated $578 million in sales (5). A recent Gallup poll shows that more than half of all Americans support the legalization of marijuana (6); therefore, it is likely that more states will join the trend of legalization and marijuana will become even more widely available. While marijuana can be sold legally only to adults in the United States, whether formedical or recreational purposes, it is nonetheless readily available to teens. The Even if performance of cognitive tasks does not seem to be affected in adolescent abusers, the brain’s reserve may already be compromised.