Does Marijuana Change the Brain?

by Tia Ghose,

Credit: Stanimir G.Stoev | Shutterstock.com

The effects of marijuana on the brain may be more complicated than experts previously thought, and may depend on factors related to the person using the drug, such as their genetics, two new studies suggest.
Marijuana use does not lead to smaller brain size in teens, one of the new studies found. That finding contrasts with previous research suggesting the drug does have this effect.

But in people who are genetically prone to schizophrenia, marijuana could alter their brain development in potentially negative ways, according to the other new study.

Together, the two new studies point to a complicated and confusing picture of marijuana's effects on young brains. The studies suggest that a person's environment, culture and genes all play murky roles in the process.

Long-term effects
Dozens of studies have researched the differences between the brains of pot smokers and those of people who don't smoke marijuana. Overall, the research shows that heavy pot smokers — those who use pot at least three times a day — tend to have smaller gray-matter volumes in the orbitofrontal cortex, a brain region tied to addiction, but they also had greater connectivity between brain regions, according to a 2014 study in the journal Proceedings of the National Academy of Sciences.

Other studies have shown that people who smoke pot in their teen years have lower IQs later on. And several studies have found that people who smoke pot are more likely to develop schizophrenia than those who don't use the drug.
But the problem plaguing all of these studies is that people who smoke marijuana are different from those who don't in lots of ways, and untangling cause and effect can be incredibly tricky, the researchers said.

No obvious differences
To get a better picture of the effects of marijuana on the teenage brain, Arpana Agrawal, a geneticist at Washington University in St. Louis, and her colleagues looked at magnetic resonance imaging (MRI) studies of the brains of 241 pairs of same-sex siblings, including some who were twins.
In some pairs, only one sibling had smoked marijuana; in others, both had smoked pot; and in some, neither sibling had used cannabis. By studying such pairs, who share half their DNA, the team hoped to untangle the effects of marijuana from those of other factors, such genetics or the environment of a person's home.

The team found that teens who had smoked pot — even once — did have smaller brain volume in the amygdala, a region associated with emotion processing and reward seeking, compared with those who had not smoked pot. The pot smokers also had smaller volume in the right ventral striatum, a brain region tied to reward processing.
However, the siblings who did not smoke pot but who shared similar genes and environment with their pot-smoking siblings also tended to have smaller volume in these key brain regions, compared with siblings who both avoided marijuana.

"That suggests there might be common factors, genetic and environmental, that predispose us to using marijuana that also contribute to variations in our brain volumes," Agrawal told Live Science.

High risk factors
In a second study, Dr. Tomáš Paus, a neuroscientist at the Rotman Research Institute, Baycrest in Toronto, and his colleagues used MRI to study the brains of more than 1,500 teenage boys. In one subgroup, the team looked at the teenagers' brains at two points in time: when the youngsters were almost 15 and almost 19 years old.
They found that over the four years, those who had smoked pot and also had several genes that increased their risk of schizophrenia had thinning in the cortex — the outer, gray matter of the brain — compared with those who had the same genes but had not smoked pot.

It's not clear what the thinning in this brain region means for what's going on inside the brain. It could be that the pot smokers had less-connected brain cell networks, fewer capillaries nourishing blood vessels in the cortex or fewer support cells, such as glial cells, Paus speculated.
However, the findings do hint that marijuana itself could be responsible for the thinning in the cortex, Paus said.

The brain regions that showed the greatest cortical thinning also have high concentrations of cannabinoid receptors, which bind the active ingredients in marijuana, Paus said.
Schizophrenia is rare, and Paus noted that even among teens with the highest genetic risk of schizophrenia, only 4 percent actually develop the disease. About 1 percent of people in the general population have schizophrenia. In the study, the team didn't follow the teens long enough to see how many developed the disorder.

In addition, because schizophrenia is so rare, the study was too small to get a statistically meaningful answer to the question of whether smoking pot increased the teens' risk of the disorder, he added.
Still, the findings suggest that in susceptible people, smoking pot could alter brain development. "All we are saying is that if you combine cannabis use with the genetic risk, then the brain is maturing in a slightly different way," Paus told Live Science.

Jury still out
But scientists still aren't sure whether, and how, marijuana harms young brains.
"We really do not fully understand what impact marijuana use has on us, and I think, in particular, in youth," Agrawal said.
In an editorial accompanying the new studies in the journal, Dr. David Goldman, a neurogeneticist at the National Institute on Alcohol Abuse and Alcoholism in Rockville, Maryland, wrote that the effects of marijuana may vary among people.

"Because of diversity in genotype and environment, one person's sugar may be another's poison," Goldman wrote.
Still, that doesn't mean marijuana is safe for people with the "right" genes, Goldman added. Like other drugs, the effect of marijuana is dependent on the dose, and as high-concentration tetrahydrocannabinol (THC) weed becomes increasingly popular, the effect of the drug could change, he said.