It probably won’t come as a surprise that smoking a joint now and then will leave you feeling … pretty good, man. But smoking a lot of marijuana over a long time might do just the opposite. Scientists have found that the brains of pot abusers react less strongly to the chemical dopamine, which is responsible for creating feelings of pleasure and reward. Their blunted dopamine responses could leave heavy marijuana users living in a fog—and not the good kind.

After high-profile legalizations in Colorado, Washington, and Uruguay, marijuana is becoming more and more available in many parts of the world. Still, scientific research on the drug has lagged. Pot contains lots of different chemicals, and scientists don’t fully understand how those components interact to produce the unique effects of different strains. Its illicit status in most of the world has also thrown up barriers to research. In the United States, for example, any study involving marijuana requires approval from four different federal agencies, including the Drug Enforcement Administration. Politics also plays a role in marijuana research.

One of the unanswered questions about the drug is what, exactly, it does to our brains, both during the high and afterward. Of particular interest to scientists is marijuana’s effect on dopamine, a main ingredient in the brain’s reward system. Pleasurable activities such as eating, sex, and some drugs all trigger bursts of dopamine, essentially telling the brain, “Hey, that was great—let’s do it again soon.”

Scientists know that drug abuse can wreak havoc on the dopamine system. Cocaine and alcohol abusers, for example, are known to produce far less dopamine in their brains than people who aren’t addicted to those drugs. But past studies had hinted that the same might not be true for those who abuse marijuana.

Nora Volkow, the director of the National Institute on Drug Abuse in Bethesda, Maryland, decided to take a closer look at the brains of marijuana abusers. For help, she and her team turned to another drug: methylphenidate (aka Ritalin), a stimulant known to increase the amount of dopamine in the brain. The researchers gave methylphenidate to 24 marijuana abusers (who had smoked a median of about five joints a day, 5 days a week, for 10 years) and 24 controls.

Brain imaging revealed that both groups produced just as much extra dopamine after taking the drug. But whereas the controls experienced increased heart rates and blood pressure readings and reported feeling restless and high, the marijuana abusers didn’t. Their responses were so weak that Volkow had to double-check that the methylphenidate she was giving them hadn’t passed its expiration date.

This lack of a physical response suggests that marijuana abusers might have damaged reward circuitry in their brains, Volkow and her team report online today in the Proceedings of the National Academy of Sciences. Unlike cocaine and alcohol abusers, marijuana abusers appear to produce the same amount of dopamine as people who don’t abuse the drug. But their brains don’t know what to do with it. This disconnect could be “a key mechanism underlying cannabis addiction,” says Raul Gonzalez, a neuropsychologist at Florida International University in Miami who was not involved with the research. The study “suggests that cannabis users may experience less reward from things others generally find pleasurable and, contrary to popular stereotypes, that they generally feel more irritable, stressed, and just plain crummy. This may contribute to ongoing and escalating cannabis use among such individuals.”

But do marijuana abusers smoke a lot because they feel crummy, or do they feel crummy because they smoke a lot? Volkow doesn’t know. Not being able to tease out cause and effect “is a limitation in a study like this one,” she says. Perhaps the abusers already had less reactive dopamine systems and started smoking a ton of pot to cope with their general malaise. Or maybe prolonged marijuana abuse is actually damaging their brains’ reward circuitry, leading to the apathy and social withdrawal that marijuana abusers often experience.

The lessons for recreational users of marijuana, if any, are unclear. This study used “hardcore volunteer[s]” who were “using quite a lot of cannabis,” says Paul Stokes, a psychiatrist at Imperial College London who wasn’t involved in the research. As such, “it probably tells you more about cannabis dependence than about recreational use.” But when he did a similar brain imaging study of people who smoked marijuana no more than once a week, he observed “similar themes” when it came to dopamine.

All of these are important questions to answer, Volkow says. As availability of the drug increases, she says, it’s something “we all need to know.”