New research helps to explain how marijuana works in the brain, with study participants responding differently to THC and CBD.

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Marijuana can have very different effects on people's behavior, producing a mellow calm in some and anxiety or even paranoia in others. Researchers have not been clear on why this variation exists, but a new study suggests that the different -- virtually opposing -- actions of the two key chemicals in marijuana, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), may be the answer.

Researchers had 15 men who had only smoked pot a few times in their lives take pills that contained THC, CBD, or a placebo (a flour-filled capsule). Then they had the participants complete a computer task that measured their reaction times to typical vs. "oddball" stimuli. Most people react more strongly to unexpected stimuli, so the men's reaction times would give researchers a clue into how their responses to environmental triggers may shift when they are exposed to the different compounds.

The men underwent brain scans while they carried out the computer test, so that the team could see which areas of the brain were more active under the different treatments. They also filled out questionnaires about their subjective experiences, including whether they experienced delusional thoughts or hallucinations.

When men took THC, they had faster reaction times to the typical items in the computer test, compared to the "oddball" ones. This difference suggested that there was a fundamental shift in what the men saw as salient, or prominent, cues in the environment. The activity patterns in the brain reflected these changes in behavior. The men also reported more delusional thoughts after taking THC, compared to CBD and placebo.

On the other hand, CBD had a very different effect. Men who had taken this compound had faster responses to the "oddball" items, which would be expected under normal circumstances. Interestingly, previous research by the same team had shown that CBD can counteract the effects of THC when it is given beforehand, suggesting its possible use as an anti-psychotic medication.

The study is especially important since people who take marijuana appear to be at increased risk for mental health problems, including schizophrenia. If marijuana (or, specifically, THC) brings about altered or abnormal perceptions about what's relevant in one's environment, as seen in this study, then paranoid or delusional thinking might be triggered.

The study also helps explain why the synthetic form of marijuana, K2, may have such harmful effects, including increased agitation and hallucination. The drug K2 is thought to include only a substance related to THC, but nothing akin to CBD.

While the research makes some strides in explaining how marijuana works in the brain, it brings up almost as many questions as it answers, like why taking both THC and CBD together (that is, smoking pot proper) would have different effects on a user on different occasions. The study will surely be the source of great debate among the medical community, the general public, and advocates for the legalization of marijuana.

The study was carried out by a team at the Institute of Psychiatry at King's College London and published in the January 2012 issue of Archives of General Psychiatry.

Image: Yarygin/Shutterstock.

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