Smoking marijuana is becoming increasingly legal and mainstream in the United States. More than 33 million adults identify as pot smokers, and teenagers in particular are feeling more comfortable with weed, thanks to its status as a safe drug.

That cultural shift may need some rethinking. A new study suggests that there can be potential negative long-term effects of heavy marijuana use — especially if people begin smoking at a young age. Published last November in the journal Biological Psychiatry: Cognitive Neuroscience, the findings are part of a larger effort by scientists at the National Institute on Alcohol Abuse and Alcoholism to better understand the effects of chronic smoking, a murky issue.

According to the study, heavy marijuana use was linked to changes in the parts of the brain that are involved in reward processing and habit formation. Cameron Carter, Ph.D., the editor of Biological Psychiatry, explained in a statement released Monday that this suggests “heavy use of this popular drug may lead to depression and other even more severe forms of mental illness.”

Long term cannabis use appears to alter the parts of the brain linked to negative emotion. Early onset cannabis use was associated with a higher risk for poor neuropsychiatric outcomes. Scientists analyzed resting brain data from 441 people between the ages of 22 and 35, already collected through the Human Connectome Project, a collaboration between the University of Southern California and Harvard University to map the structural and functional neural connections of individuals. Thirty of these study participants were already established as meeting the DSM criteria for marijuana dependence. The research team also assessed the brain scans of 30 people between the same ages who did not smoke marijuana as a control group.

They discovered that the individuals who had starting using cannabis early in life exhibited the most significant changes in their brain’s subcortical volumes, as well as changes to the functional connectivity density in the brain’s ventral striatum, midbrain, brainstem, and lateral thalamus. The scientists explain that these changes, described as “hyperconnectivity,” end up disturbing resting brain functions assocaited with habit formation, reward processing, and the development of psychosis (defined as when one’s emotions and thoughts aren’t in touch with reality).

These individuals also reported the highest levels of negative emotions. The study’s authors think that makes sense, since these brain alternations are often associated with heightened feelings of negativity and alienation — which they reason is why people who are dependent on marijuana often report that they feel a sense of rejection from others.

Scientists are still learning why these effects manifest, and they suspect THC, the most famous active chemical compound in cannabis, is to blame. Another chemical compound in cannabis, CBD, has been found to have the opposite effect: A study published in December found that CBD could be useful in treating psychotic disorders.

It’s clear these days marijuana use is not the death knell that health advocates early last century feared it was. On the other hand, new studies like this also emphasize that there’s still a ton we don’t know about how drugs affect the brain, especially in the long run.