It's hard to argue with the science; decades of research has made it all but incontrovertible that use of cannabis and the emergence of schizophrenia and psychosis in some people are linked, on some level.
What that level is and how that relationship functions isn't so easy to unravel, with mental health and drug use commonly locked in a tug-of-war that makes cause-and-effect hard to tease apart.
According to a 2021 study conducted by a team of researchers from the Centre for Addiction and Mental Health (CAMH) and King's College London in the UK, the genes for schizophrenia could prove to be the key to explaining why some cannabis users develop psychosis while others don't.
"These results are significant because they're the first evidence we've seen that people genetically prone to psychosis might be disproportionately affected by cannabis," said CAMH psychiatrist Michael Wainberg when the findings were published.
Psychosis is a serious mental health condition affecting how the brain builds a perception of the world around it.
The consequences can range from the merely confusing to the downright distressing, interpreting or correlating sights and sounds in ways that make it hard to tell what's real and what isn't.
Psychotic episodes – a key symptom of severe depression, bipolar disorder, and schizophrenia – can also be induced by various psychoactive substances, including the active compound in cannabis, delta 9-tetrahydrocannabinol (delta9-THC).
In fact, research suggests those who've used cannabis are nearly four times as likely to experience some form of psychosis, compared to people who've abstained.
Keeping an open mind, the same numbers could emerge in populations where people with mental health conditions disproportionately use cannabis to treat psychotic episodes.
However, further research suggests self-medication is unlikely to play a significant role in this relationship, with studies consistently finding most people start to use cannabis not to treat the symptoms of psychosis, but simply to get high.
Even when controlling for personality disorders and use of antipsychotics, the risk remains, making it harder to refute the fact cannabis appears to be the trigger for experiences of psychosis.
Still, taken from a different perspective, most people who use cannabis never come close to experiencing a psychotic episode, making it important to work out exactly where the differences lie.
Using 100,000 participant records from the UK Biobank, the scientists behind this latest study analyzed the relationship between genetics, cannabis use, and psychotic experiences.
Records contained details on frequency of past cannabis use and experiences of auditory or visual hallucinations, delusions of persecution, or delusions of reference. Crucially, the Biobank also provided evidence of key mutations on genes associated with schizophrenia, giving the team a score indicating the likelihood of developing schizophrenia.
In total, just over 4 percent of records with no report of cannabis-use presented some sort of delusional or hallucinatory experience. This figure jumped to 7 percent for those who'd used cannabis in their past, a result that comes as no real surprise.
On digging deeper, the increase was most pronounced for those with a high genetic score for schizophrenia. Among records with the fifth highest scores, the increase was around 60 percent. Among those with the fifth lowest, it was around 40 percent.
"And because genetic risk scoring is still in its early days, the true influence of genetics on the cannabis-psychosis relationship may be even greater than what we found here," says Wainberg.
Studies on schizophrenia have progressed in leaps in bounds in recent years, with evidence revealing a genetic condition that puts neurological development at risk of subtle disturbances in the environment, especially while in the womb.
Given most of what we know of the condition is biased by a focus on westernized, largely white populations, we have a long way to go before we can make generalized claims.
But with the legalization of cannabis putting the drug on par with alcohol and tobacco in an ever greater number of jurisdictions, it's becoming increasingly important to learn as much about the potential risks as possible.
This research was published in Translational Psychiatry.
An earlier version of this article was published in April 2021.