Over recent years, legal restrictions on cannabis use have been lifted in many U.S. states. In 11 states and the District of Columbia the drug has not only been decriminalized but is currently available commercially for “recreational use.”

This has raised concern among some experts on drug usage and addiction, including BBRF Scientific Council member Nora Volkow, M.D., who heads the National Institute on Drug Abuse. Dr. Volkow has warned for years about the risks of regular and heavy cannabis use, particularly as the potency of cannabis has multiplied, a function of the rising concentration of its psychoactive ingredient, THC. She has specifically warned of the dangers of vaping highly potent THC.

Dr. Volkow has also pointed out that for a small but important segment of the population—a subset of vulnerable adolescents—early exposure to marijuana followed by heavy and chronic use is a risk factor for onset of a first episode of psychosis. This is typically the start of a clinical course that culminates in a diagnosis of schizophrenia in late adolescence or early adulthood.

A considerable body of research, some of it performed by BBRF-funded investigators, has closely examined the risks that may be associated with heavy and regular cannabis use, generating scientific evidence not only for heightened risk of psychosis, but evidence, as well, about the drug’s impact on cognition – how the human brain performs routine and essential tasks such as verbal and visual processing and learning, executive function, and working memory, as well as psychomotor functions that are orchestrated by the brain.

A recent paper by 2013 BBRF Independent Investigator Dr. Deepak Cyril D’Souza of Yale University School of Medicine, and colleagues, adds new evidence to the argument that early, heavy, and chronic cannabis use does have substantive negative effects on the brain.

The study, published in Psychological Medicine, explores the impacts of early, chronic and especially heavy cannabis use in what the researchers describe as a unique population. With collaborators at the University of the West Indies in Jamaica, Dr. D’Souza and Yale colleagues conducted a clinical study that included 15 individuals whose use of cannabis “is central to their way of life ... used for enlightenment, social bonding, medicinal uses and rituals.”

These 15 study participants, whose average age was about 45, began using cannabis early in life—some as early as age 9, most around age 18. Nearly all being daily users, the group’s cumulative lifetime “exposures” averaged 30,000 – the equivalent of over 1,200 joints per year, or between 3 and 4 joints per day. The 15 participants, who came from diverse locations (not a single community), were matched with 12 controls from the same population, of Afro-Caribbean ethnicity who shared similar beliefs. Those in the control group were of the same culture, but did not use cannabis. Importantly, like the cannabis users, the controls were not users of other substances that might impact cognition, most notably tobacco and alcohol.

This is one aspect of the study that made it unusual. Dr. D’Souza and his team hoped to focus on the impacts of heavy cannabis use over many years, without having to guess the possible confounding effects of other substances. The study also looked at changes in a subset of the “user” group over 6 years, as well as comparisons of several of the cannabis users with siblings who were not users.

All participants in the study were given a 74-item questionnaire called the Schizotypal Personality Questionnaire, or SPQ. They were also given a battery of 13 standardized tests that measure various aspects of cognitive function. These tests were not given at the peak of the “high” immediately following cannabis use, but rather several hours after participants’ last use of cannabis, to minimize the chance that the results reflected being intoxicated.

The results: the 15 participants who were regular, heavy users of cannabis and had been since their youth “performed worse than controls on all cognitive tasks.” Moderate to large “effect-sizes”—measures of the statistical significance of the differences—were found between users and controls on tests that measured attention, psychomotor speed, working memory, cognitive flexibility, visuo-spatial processing and memory. In tests separated by 6 years, a subset of the “user” group registered a “small decline” over time in their capacity for immediate recall. Finally, in comparisons involving siblings of cannabis users who did not use cannabis, sibling scores on cognitive tests were comparable, the team found, with the scores of the study’s control participants.

Dr. D’Souza and the team were also able to discern significant differences between “users” and non-users on the SPQ test, which probes for the presence of symptoms that are associated with psychosis. The researchers concluded that differences in scores on the SPQ test suggested that heavy, chronic use of cannabis can lead to “psychosis-relevant phenomena.” These ranged from a propensity to indulge “odd beliefs,” to “magical thinking, unusual perceptual experience and odd and eccentric behavior.”

While cannabis use is generally thought to be a risk factor for psychosis in a small minority of the many millions of people who expose themselves to the substance—notably, young people at risk for psychosis—“it is possible that cannabis may increase the risk of psychosis along a continuum,” the researchers said, and that some of the symptoms they noted in the SPQ test of study participants who were heavy, chronic users may reflect what they call “attenuated psychotic syndrome.”

Acknowledging the small size of their study, the team said their results “warrant replication in a larger study” that would monitor a similar group of participants over a period of years.

Suhas Ganesh, M.D., a 2018 BBRF Young Investigator, and Jose Cortes-Briones, Ph.D., a 2015 BBRF Young Investigator, were among the members of the research team, as were Drs. Michael Campbell and Maisha Emmannuel of the University of the West Indies.