They found that HU210 seemed to induce new brain cell growth, just as some antidepressant drugs do, they report in the Journal of Clinical Investigation 1 . This suggests that they could potentially be used to reduce anxiety and depression, Zhang says. He adds that the research might help to create new cannabinoid-based treatments.
Eisch adds that much more work must be done before scientists can reach any definitive conclusions about the benefits and costs of marijuana. First and foremost, researchers need to establish that THC has the same positive effects as the synthetic HU210. Then they must develop more sophisticated experiments to firm up the correlation between neuron growth in the hippocampus and emotional balance.
Finally, she says, scientists must understand why cannabinoids have a different effect on the brain than other addictive drugs.
He says his group’s next studies will examine this more unpleasant side of the drug. Other addiction researchers will be keenly interested in the results, because this cannibinoid acts so differently on the hippocampus than other drugs.
“I think it’s a very exciting study,” says Amelia Eisch, an addiction researcher at the University of Texas Southwestern Medical Center in Dallas. “It makes marijuana look more like an antidepressant and less like a drug of abuse.”
Expanding the mind
The researchers injected rats with HU210, a synthetic drug that is about one-hundred times as powerful as THC, the high-inducing compound naturally found in marijuana. They then used a chemical tracer to watch new cells growing in the hippocampus.
A large longitudinal study in New Zealand found that persistent marijuana use disorder with frequent use starting in adolescence was associated with a loss of an average of 6 or up to 8 IQ points measured in mid-adulthood. 43 Those who used marijuana heavily as teenagers and quit using as adults did not recover the lost IQ points. People who only began using marijuana heavily in adulthood did not lose IQ points. Two shorter-duration prospective longitudinal twin studies found that youth who used marijuana showed significant declines in verbal ability (equivalent to 4 IQ points) and general knowledge between the preteen years (ages 9 to 12, before use) and late adolescence/early adulthood (ages 17 to 20); however those who went on to use marijuana at older ages already had lower scores on these measures at the start of the study, before they started using the drug. Also, no predictable difference was found between twins when one used marijuana and one did not. 44
Also, the ability to draw definitive conclusions about marijuana’s long-term impact on the human brain from past studies is often limited by the fact that study participants use multiple substances, and there is often limited data about the participants’ health or mental functioning prior to the study. Over the next decade, the National Institutes of Health is funding the Adolescent Brain Cognitive Development (ABCD) study—a major longitudinal study that will track a large sample of young Americans from late childhood (before first use of drugs) to early adulthood. The study will use neuroimaging and other advanced tools to clarify precisely how and to what extent marijuana and other substances, alone and in combination, affect adolescent brain development.
Distribution of cannabinoid receptors in the rat brain. Brain image reveals high levels (shown in orange and yellow) of cannabinoid receptors in many areas, including the cortex, hippocampus, cerebellum, and nucleus accumbens (ventral striatum).
Marijuana, Memory, and the Hippocampus
Memory impairment from marijuana use occurs because THC alters how the hippocampus, a brain area responsible for memory formation, processes information. Most of the evidence supporting this assertion comes from animal studies. For example, rats exposed to THC in utero, soon after birth, or during adolescence, show notable problems with specific learning/memory tasks later in life. Moreover, cognitive impairment in adult rats is associated with structural and functional changes in the hippocampus from THC exposure during adolescence.
Some studies have also linked marijuana use to declines in IQ, especially when use starts in adolescence and leads to persistent cannabis use disorder into adulthood. However, not all of the studies on the link between marijuana and IQ have reached the same conclusion, and it is difficult to prove that marijuana causes a decline in IQ when there are multiple factors that can influence the results of such studies, such as genetics, family environment, age of first use, frequency of use, having a cannabis use disorder, duration of use, and duration of the study. Key research in this area to date is described below.
Among nearly 4,000 young adults in the Coronary Artery Risk Development in Young Adults study tracked over a 25-year period until mid-adulthood, cumulative lifetime exposure to marijuana was associated with lower scores on a test of verbal memory but did not affect other cognitive abilities such as processing speed or executive function. The effect was sizable and significant even after eliminating those involved with current use and after adjusting for confounding factors such as demographic factors, other drug and alcohol use, and other psychiatric conditions such as depression. 42
More research will be needed to answer definitively whether marijuana use causes long-term IQ losses and whether factors that weren’t measured in the prior research, such as the increasing amounts of THC in cannabis and the emergence of new cannabis products, are relevant.