New findings support marijuana-psychosis link

Nov 03 2017

New findings support marijuana-psychosis link

How does using marijuana effect the brain development of adolescents? This continues to be an important question for researchers, because teenage users may have a higher risk of developing psychosis. The drug may accelerate the development of psychosis in vulnerable individuals.

New findings appear to support those concerns. At the World Psychiatric Association’s World Congress in Berlin on October 9, Hannelore Ehrenreich of the Max Planck Institute of Experimental Medicine presented results of a study of 1,200 people with schizophrenia. The investigation analyzed a wide range of genetic and environmental risk factors for developing the debilitating mental illness. 

The results indicate people who had consumed cannabis before age 18 developed schizophrenia approximately 10 years earlier than others. The higher the frequency of use, the data indicated, the earlier the age of schizophrenia onset. In Ehrenreich’s study, neither alcohol use nor genetics were linked to earlier onset, but marijuana was. “Cannabis use during puberty is a major risk factor for schizophrenia,” Ehrenreich says.

Some other studies, but not all, support Ehrenreich’s findings. Speaking at the Berlin conference, Robin Murray, a professor of psychiatry at King’s College London, said “there is no doubt” that cannabis use in young people increases the risk of developing schizophrenia as an adult.

Murray, one of the first scientists to study the pot-psychosis connection, cited 10 studies that found a significant risk of young cannabis users developing psychosis. He also mentioned three other studies that indicated a trend but had a sample size that was too small to be statistically significant.

“The more (cannabis) you take — and the higher the potency — the greater the risk,” he contends, which makes today’s more potent, new strains of marijuana cause for concern.

In an interview with Scientific American, Murray said his research with users in London has shown that high-potency cannabis — approximately 16 percent THC (tetrahydrocannabinol) — was involved in 24 percent of all cases of a first episode of psychosis.

Still, there is not universal agreement among scientists on the canabis-psychosis connection.

“The available data on this subject is far from definitive — particularly with regard to any potential cause-and-effect relationship,” said Paul Armentano, deputy director of NORML, a U.S. organization that advocates marijuana legalization for adults. “For instance, increased cannabis use by the public has not been followed by a proportional rise in diagnoses of schizophrenia or psychosis.”

Another speaker at the Berlin conference, Beat Lutz, a neurochemist at the University of Mainz, described how marijuana can trigger harmful effects in a young person’s brain. The main psychoactive compound in marijuana, THC, interferes with the normal flow of signals among brain cells—a process normally regulated by chemicals called endocannabinoids.

These compounds occur naturally in the body and activate a type of cellular docking site (called the cannabinoid type 1, or CB1, receptor) to “act like a circuit breaker,” Lutz says, keeping the brain’s level of signaling activity or “excitation” within a normal range.

Too little endocannabinoid signaling results in excessive excitation of the nervous system, which can lead to anxiety disorders, impulsivity and epilepsy. Too much activity has the opposite effect and can trigger depression, for example. Interfering with the information flows regulated by the endocannabinoid system has also been tied to psychosis.

Unlike endocannabinoids. THC does not quickly break down in the body the way natural endocannabinoids do, Lutz says. This longer process of activation causes serious, wide-ranging disturbances in the brain. Low doses of THC may reduce anxiety but high doses can increase it.

Also, chronic overstimulation of CB1 receptors by THC shuts down the body’s natural endocannabinoid signaling system by eliminating the CB1 receptors from neurons, Lutz adds.

In addition, new research indicates that mitochondria — the organelles within cells that generate energy for cellular metabolism — also have CB1 receptors. THC inhibits mitochondrial activity, reducing the cells’ vital energy supply, he says, citing a 2016 paper published in Nature.

More importantly, he believes THC’s disruption of endocannabinoid signaling in the early teen brain can hinder key neuro-developmental processes that involve the CB1 receptors, which permanently impairs brain communication.

The researchers at the Berlin conference said the public needs to be informed of these new findings. “As physicians, we need to say clearly what is happening and what is not,” says Peter Falkai, a psychiatrist at the Munich Center for Neurosciences at Ludwig Maximilian University, told Scientific American. “Looking into the data, clearly yes, the data show increasing risk of psychosis.”