The largest study of its kind now shows that the psychoactive ingredient in cannabis is associated with short-term paranoia in users. Scientists also determined those cognitive mechanisms responsible for initiating paranoia in subjects under the influence of marijuana.

Professor Daniel Freeman and colleagues at the University of Oxford identified worrying, poor self-esteem, anxiety, and unsettling changes in perceptions as most-correlated factors in prompting paranoia in human subjects injected with Δ9-tetrahydrocannabinol, or THC, the psychoactive ingredient found in marijuana.

“The study very convincingly shows that cannabis can cause short-term paranoia in some people,” said Professor Freeman in a statement. “But more importantly it shines a light on the way our mind encourages paranoia. Paranoia is likely to occur when we are worried, think negatively about ourselves, and experience unsettling changes in our perceptions.”

Paranoia is essentially unusually strong beliefs that others are conspiring to do one harm to the point of irrationality and delusion. Although cannabis has long been suspected of causing paranoia, this study marks the first conclusive link between THC and short-term paranoia in some subjects.

The researchers tested 121 subjects between the ages of 21 and 50, all of whom had a history of cannabis use but no mental illness. Roughly 67 percent of the subjects were injected with THC, while the remaining third received a placebo injection. Among the subjects that received THC, 50 percent reported having paranoid thoughts, compared with 30 percent of the placebo group. The paranoia in the THC group declined as the drug cleared from their systems.

Subjects who experienced paranoia also most commonly reported experiencing anxiety, worry, poor mood, negative thoughts of self, echoing thoughts, changes in perceptions of sound and color in the form of pronounced intensity, and disruptions in perceptions of time.

The report was published this week in the journal Schizophrenia Bulletin, an Oxford University Press publication.