A new review offers further insight into how long-term marijuana use might have a negative impact on mental health, after finding “substantial evidence” that the drug alters the brain’s reward system to increase negative emotions and decrease motivation.

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Researchers say long-term marijuana use lowers dopamine levels in the brain, which could explain why some users develop mental illness.

The study says there is sufficient evidence to suggest marijuana, or cannabis, reduces levels of dopamine in the brain – a neurotransmitter that plays a key role in learning, movement, motivation, emotion, and reward.

Low dopamine levels have been associated with mood changes, fatigue, depression, and lack of motivation; dopamine deficiency is present in a number of neurological conditions, including Parkinson’s disease and attention deficit hyperactivity disorder (ADHD).

Study leader Prof. Oliver Howes, of the Medical Research Council (MRC) Clinical Sciences Center at Imperial College London in the United Kingdom, and team recently published their results in the journal Nature.

According to the 2014 National Survey on Drug Use and Health, there are around 22.2 million marijuana users in the United States, making it the most commonly used illicit drug in the country.

Long-term marijuana use has been linked to a number of mental health conditions, including schizophrenia, anxiety, and depression, but the mechanisms underlying this association have been unclear.

Given the increased legalization of marijuana for medicinal and recreational purposes, researchers are keen to learn more about how the drug affects the brain.

For this latest study, Prof. Howes and team conducted a review of numerous studies investigating how the primary psychoactive compound in marijuana – tetrahydrocannabinol (THC) – affects the brain.

According to the researchers, there is now “substantial evidence” in animal and human studies that long-term exposure to THC leads to a decrease in levels of dopamine.

“The available evidence indicates that THC exposure produces complex, diverse and potentially long-term effects on the dopamine system,” the authors explain. “These include increased nerve firing and dopamine release in response to acute THC, and dopaminergic blunting associated with long-term use.”

The team believes this effect may explain why people who engage in long-term marijuana use are at increased risk for mental health problems.

In animal models, current research shows that marijuana use initially raises dopamine levels, fueling a sense of reward, which the team says may offer an explanation for why some users become addicted to the drug.

However, the authors point to some limitations in this area. “Fundamentally, animal studies are too short, and don’t give cannabis repeatedly or in combination with other substances,” notes Prof. Howes.

The researchers also noticed some other gaps in research, such as studies assessing what happens to the dopamine system when marijuana use is ceased.

What is more, the team notes it is important to learn more about how marijuana use affects brain development, as some women may use the drug in early pregnancy, before realizing they are expecting.

“Given the increasing use of cannabis, particularly in young people and women who may be pregnant, animal studies are needed to understand the effects of long-term cannabis use on the developing brain in a controlled way that is not possible in human studies.” says Prof. Howes.

“These studies also need to use techniques that can be translated into human studies, and to better represent human patterns of use.”

While further investigation into the effects of marijuana is clearly warranted, the researchers believe their current study helps broaden our understanding.

The changing patterns of cannabis use, including ‘cannavaping’ and edible products, mean it’s vital that we understand the long-term effects of cannabis on the brain.

This new research helps to explain how some people get addicted to cannabis, by showing that one of its main components, called THC, alters a delicate balance of brain chemicals.”

Co-author Dr. Michael Bloomfield, Clinical Sciences Centre, Imperial College London

Read about a study that sheds light on how marijuana causes memory loss.