A global analysis has found the gap in psychosis onset widened progressively with age, challenging assumptions about who is most vulnerable and when cannabis use is most harmful.
It’s well-established that cannabis use is associated with earlier-onset psychosis, but new research challenges the long-held idea that it’s the developing brains of people under 25 that are most at risk.
University of New South Wales (UNSW) researchers have found that in people who developed psychosis in their 20s, cannabis users developed it nearly four and a half years earlier on average. Among those who developed psychosis after age 30, the gap widened to around six and a half years.
The global meta-analysis of 149 studies involving more than 71,000 people – largely in Europe, North America, and Australia – was consistent with previous findings that cannabis users were developing psychosis several years earlier than non-users.
The work built on an analysis published in JAMA 15 years ago and encompassed five times the amount of data available at that time.
“Despite this massive increase in sample size, we found a strikingly similar result: just like in 2011, we found that on average, cannabis users tended to develop psychosis earlier by about two and a half years,” said Carly Stevens, PhD candidate at the UNSW School of Biomedical Sciences, trainee doctor, and lead study author.
“At this point, we can pretty confidently say this is a robust association, but this was actually the least interesting aspect of our research.
“Because of the increase in data, we were able to see if this association varied across different life stages, and we found that it did, but not in the way that we thought it would.”
She said the assumption was that the results would be seen largely in young people, given the vulnerability of the adolescent brain and some prior experimental evidence about cannabis exposure in animals, but this was not the case.
“We found no evidence that cannabis users had an early onset of psychosis in that age group [under 20s], but in contrast, you can see that as the groups got older, there was a progressive widening of the gap in psychosis onset between people who had used cannabis and hadn’t, and this became particularly clinically meaningful for people who developed psychosis in their late 20s or older,” she said.
“That’s a lot of years of healthy life lost,” she emphasised, detailing the immense burden of earlier onset of psychosis, widely associated with worse clinical outcomes.
“These people relapse more frequently, their episodes are characterised by more severe symptoms, they have a higher risk of suicide, they’re hospitalised more frequently, and day-to-day life on average is much more difficult for them.
“People who develop chronic psychotic disorders earlier in life are missing out on years of life that could otherwise be spent on enriching life experiences or obtaining educational milestones.”
Ms Stevens said that for those who develop psychosis in the late 20s or 30s, using cannabis could possibly make the difference in terms of having career opportunities that could set them up for life, building strong relationships and a support network, discovering hobbies, travelling, and much more.
“And more broadly, extending beyond the individuals and the people they love, there’s also an impact on society as a whole. Psychotic disorders account for about 3% of total healthcare expenditure in developed nations, so it’s very expensive to care for people with chronic psychotic disorders.”
She emphasised that the lack of an association with earlier onset of psychosis and cannabis use in under 20s in the analysis did not indicate that it was safe to use as a teenager, noting the possibility of a floor effect.
“Psychosis before the time of mid adolescence is extraordinarily rare, so it’s possible that there’s limited capacity for cannabis to accelerate psychosis in this age group,” Ms Stevens said.
“It’s also likely that other factors play a bigger role in the onset of psychosis in young people, such as genetics.”
She also said it was possible that ongoing cannabis exposure could regressively lower your threshold for psychosis onset and may lead to an earlier emergence.
“This isn’t unlike tobacco and earlier emergence in certain types of lung cancer. So, on the surface, a few years might not sound like much, but the sad reality is that psychosis emerging several years earlier, especially for patients living with schizophrenia, can derail their entire lives,” she said.
“There seems to be this predominant idea of the adolescent brain being very vulnerable, which is true. But also, this prevailing myth that if you wait until your brain develops and then you engage in these kinds of behaviours, that you’ll be okay.
“We really do need to have clear public health warnings, so people don’t buy into this myth. The idea is that really no one is safe when it comes to using cannabis [and] that it might be using that that then results in years of [additional] illness later down the track.”
Ms Stevens said the findings were particularly relevant given the use of medical cannabis, including for conditions for which evidence of benefit remains limited.
“I think prescribers need to make sure that patients are well informed about what evidence we have and what we don’t, and from there they can make a decision with the patient,” she said.
“For example, when you look at people who have actually been prescribed medical cannabis, about 30% is for anxiety, and there’s very little evidence that that works at all. In fact, we have plenty of evidence that shows the opposite. It makes people a lot of people paranoid, worsens their anxiety.”
UNSW Conjoint Professor Matthew Large, medical superintendent of Mental Health in the Eastern Suburbs Mental Health Service and co-author of the study (and the 2011 paper), echoed Ms Steven’s sentiments, highlighting pain, anxiety, depression, and insomnia as the most common indications for medical prescribing, “all of which are either worsened or not helped by cannabinoids”.
“Our results make cannabis look much more like a sort of long-term cumulative neurotoxin,” Professor Large said.
“I personally think that the medicalisation has quashed discussions of the toxicity of cannabis, and it’s that part of public policy that I think will quite likely prove to be one of the biggest public health bungles in Australian history.
“The survival strategy of the cannabis plant is to make humans love it, which they do. And in my view, I think it’s quite likely that that love of cannabis has seeped all the way up to decision makers and has meant that there’s this incredible double standard where, in order to pass muster as a scientist explaining the harms of cannabis, people require proof.
“And of course, you can’t randomise cannabis to 12-year-olds and see what happens. Yet the benefits of cannabis medically are little more than anecdotal.”
Ms Stevens also noted another key misconception in the narrative around cannabis use.
“It’s really common that people push this idea that it comes from a plant, it’s natural, so how bad can it be?” she said.
“You can argue at this point it’s not natural anymore… with selective breeding, with certain techniques that are being used, any kind of naturalness is really being lost, especially when you’re looking at cannabis edibles with ginormous doses.
“At this point, it’s not really what I would consider to be a natural substance. And also, even more broadly, it’s not a real argument in in my opinion.
“There’s a lot of natural things that can kill you very easily, like death cap mushrooms, for example. It’s an unfortunate point that people push when really, it’s quite meaningless.”
