People who use marijuana daily could be more likely to see hallucinations and have other psychotic experiences earlier in life, according to new research that strengthens our understanding of genetic vulnerabilities, environmental factors and the risk of schizophrenia among cannabis consumers.

A new study published April 9 in Translational Psychiatry takes researchers one step closer to proving causality between cannabis and psychosis. The researchers examined self-reported data from 109,308 individuals in the U.K. Biobank. The data combined information about genetics, mental illness and environmental factors with questions about how frequently people used cannabis and whether they ever experienced hallucinations or delusions. 

Cannabis is just one of many drugs that has a legitimate use in the medical field, lead author Michael Wainberg told The Academic Times. Marijuana is prescribed as a pain reliever, and certain compounds in cannabis, such as cannabidiol (CBD), show promise in treating anxiety. Other controlled substances with utility to medicine include opioids to treat pain, MDMA to treat post-traumatic stress disorder and psilocybin, the active compound in so-called magic mushrooms, to treat depression.

Opioids are already legal and widely available, though, "One can certainly make the argument that using opioids like OxyContin for pain was probably overprescribed, and has led to the current opioid crisis that the world is now facing," corresponding author Shreejoy J. Tripathy told The Academic Times. He thinks studying the addictive properties of opioids could have averted at least some of the epidemic, as OxyContin, broadly prescribed for decades, can be easily misused. That's one major reason why more research on drugs is needed.

"Knowing the harms allows you to better evaluate where these drugs should be deployed because it tells you the cost-benefit," said Wainberg. 

"From a public health standpoint, it's important to know these things so that the decision-makers can make" intelligent decisions about prescribing and legalizing drugs, Tripathy added. In their view, science can clarify which dangers are real and which are overstated.

A recurring question in the study of mental illness is whether people at risk of schizophrenia are more vulnerable to psychotic experiences after smoking or otherwise using marijuana. The current study "strengthens the amount of causal inference that we're able to make, though it's still not a true statement about causality," Wainberg noted. He sees their research as a small, but important, contribution to the long-studied hypothesis that cannabis can cause psychosis.

Wainberg, Tripathy and their colleagues in Toronto and London found that the frequency with which individuals use cannabis strongly correlates with the number of psychotic episodes they experience. The authors found that the likelihood of any psychotic event increased by 20% as the patient's frequency of use increased. For example, daily users were 20% more likely to have auditory or visual hallucinations or delusions than people who used marijuana weekly. Cannabis use is especially associated with persecutory delusions, where people believe that they are being followed or harmed by a plot that does not exist.

Cannabis use also affected the extent of individuals' psychotic experiences. People who used marijuana every day reported a higher rate of early-onset psychotic experiences – that is, hallucinations or delusions before the age of 18. They also reported more upsetting episodes overall. Though daily users showed "disproportionately greater rates of distressing" events, the authors noted that these participants did not seek help at a higher rate than other marijuana users or individuals who had a previous psychotic episode. 

Tripathy and Wainberg noted that even in a progressive place like California where marijuana is legal, there's still a lot of stigma around cannabis use. "You can imagine a government might not want to fund the use of cannabis because of a historical stigma," Tripathy noted. Wainberg believes that more research on cannabis will shed some of this stigma, both at the governmental level and among the public. 

Both Wainberg and Tripathy work at the Centre for Addiction and Mental Health in Toronto and seek to make their research more relevant to the care of psychiatric patients. Genetics is a very appealing way to do that, explained Tripathy.

Certain mutations in people's genomes can tell researchers about their increased risk of schizophrenia. As part of this study, the researchers looked at the polygenic risk of individuals, or how many similar mutations people have compared to the general population. These mutations are found at a higher frequency in people with schizophrenia and, though not a perfect predictor of accuracy, can give scientists a pretty good idea of a person's risk of mental illness, Wainberg said.

A stronger association was found between marijuana use and hallucinations for people who were genetically vulnerable to schizophrenia. For those with the highest polygenic risk scores, daily cannabis use was associated with a 1.58-fold increase in psychotic experiences. There was a 60% increase in delusions of reference — a belief that a force is communicating with one through signs or signals — between the bottom fifth and the top fifth of the same population.

The authors stress that it's important to consider the possibility of reverse causality in any study about cannabis. In this particular investigation, the researchers could not determine whether individuals were self-medicating or were more drawn to use marijuana in the first place because of their mental state. Participants in studies of this sort may also be less likely to truthfully report their use if they live in a country where cannabis isn't legal.

In future cannabis research, Tripathy would like to see even more data sets from diverse participants worldwide. Both he and Wainberg mentioned that some information that was not considered in this study would lead to more avenues for research — for example, knowing when people started to use cannabis or when they had their first psychotic experience. Tripathy plans to continue research with the U.K. Biobank database, using brain images to study different types of depression and mental illness.

The study, "Cannabis, schizophrenia genetic risk, and psychotic experiences: A cross-sectional study of 109,308 participants from the UK Biobank," published April 9 in Translational Psychiatry, was authored by Michael Wainberg, Centre for Addiction and Mental Health; Grace R. Jacobs and Shreejoy J. Tripathy, Centre for Addiction and Mental Health and University of Toronto; and Marta di Forti, King's College London and NHS Mental Health Foundation Trust.