Not only is cannabis one of the world’s most widely used recreational drugs, it is also generating excitement for its potential to treat a range of health conditions from cancer to insomnia. But there is another side to the drug – it is associated with psychotic disorders, including schizophrenia.
at Yale University has been studying this relationship for decades. He spoke to ¿ìè¶ÌÊÓƵ about what his research, and the work of other scientists, has revealed – and why the link between cannabis and schizophrenia is so challenging to study.
Grace Wade: What do we know about the relationship between cannabis use and psychosis, specifically schizophrenia?
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Deepak D’Souza: There are roughly three distinct relationships between cannabis use and psychosis. The first is that when some people consume cannabis, they experience an with symptoms similar to schizophrenia. These can include delusions, hallucinations, blunted emotions and impairments in memory and speech. That psychotic episode is often sudden and dramatic. Sometimes it warrants going to the hospital. But it resolves fairly quickly, typically within hours or as soon as the drug wears off.
The second relationship is when . Unlike the first scenario, this psychosis persists beyond the typical period of intoxication, for days or weeks, before resolving. It often requires some intervention like the temporary use of anti-psychotic medications.
The third relationship is when someone uses cannabis and then days, weeks, months or years later, develops a psychotic disorder. We mostly see this in people who start using cannabis in adolescence.
We also know that in people who already have a psychotic disorder, cannabis worsens their symptoms. They become more paranoid, hear more voices and stop their medications.
The science of cannabis
As the use of marijuana and its compounds rises around the world, ¿ìè¶ÌÊÓƵ explores the latest research on the medical potential of cannabis, how it is grown and its environmental impact, the way cannabis affects our bodies and minds and what the marijuana of the future will look like.
Do we know for sure that it’s the cannabis causing the psychosis?
With the first two scenarios, we can say with confidence that cannabis causes the psychosis. One way of establishing causality is the temporal relationship. So, if I press down on your chest, and you experience pain, you know that my pressing is causing the pain. There is a clear temporal relationship. That relationship is seen in those two scenarios, especially with the first as psychosis stops once the cannabis wears off.
But, with the third scenario, we can only see an association. So, someone could have used cannabis, and then months and years go by before they develop schizophrenia. Research shows that, on average, people who use cannabis are as non-users. But it is very hard to prove a causal relationship here, especially to the degree we have with the first two scenarios.
So, in that third scenario, someone may develop schizophrenia even if they haven’t experienced an earlier psychotic episode. But what about the people in the first two scenarios – does cannabis-induced psychosis raise their risk of developing schizophrenia?
A number of studies in Scandinavian countries have followed people who visited the emergency room for cannabis-induced psychosis. They have found that of these individuals were diagnosed with schizophrenia in the 20 years after the incident. This suggests that if someone’s first psychotic episode occurs within the context of cannabis, that could be a harbinger of a chronic psychotic disorder.
Is this a risk for everyone, or mostly for a particular group? I’ve heard, for instance, that cannabis could trigger schizophrenia in people who are already genetically prone to developing it.
I don’t think we have enough data to support that, but it is a very reasonable hypothesis in my view. The issue is we know very little about risk factors for schizophrenia. The most obvious one is a family history of the condition. So, if you have an immediate family member or more than one extended family member with it, your risk of developing schizophrenia is much greater.
We also know now that there are – and the list continues to grow – that all confer some risk for schizophrenia. Individually, the risks associated with these genetic markers is tiny. But when you put them all together, it is sizeable. My research group just received funding from the US National Institute on Drug Abuse to investigate the extent to which someone’s genetic risk for schizophrenia influences their response to cannabis. Hopefully, we will have answers within a few years.
What about a cannabis user’s age – does that influence their risk of psychosis, and their likelihood of developing schizophrenia?
It appears use in early and mid-adolescence confers the highest risk. That is because a cell signalling network, called the endocannabinoid system, plays a crucial role in sculpting the brain during adolescence.
Compounds in cannabis, known as cannabinoids, bind to receptors in this network. So, smoking weed during this developmental period disrupts the system’s normal processes. That could impact neurodevelopment, and we know that schizophrenia is a neurodevelopmental illness. This might be the mechanism by which cannabis exposure in adolescence could lead to long-term consequences, like psychotic disorders.
That doesn’t mean other stages of brain development aren’t risky. For instance, people who use synthetic cannabinoids like spice or K2 can subsequently experience psychosis. These drugs are typically used by young adults, not adolescents.
Are there additional risk factors?
The more you use cannabis, the greater the likelihood of negative consequences. In adolescence, for instance, people who use cannabis five times a day are more vulnerable to later having schizophrenia than people who use it twice a day. Potency also plays a factor. A large, multinational study showed that people who smoke high-potency cannabis daily have compared with non-users.
But not everyone who has used cannabis develops schizophrenia, and not everyone who has schizophrenia used cannabis. There are probably lots of factors we don’t understand yet. I would say if you or your family members have serious mental illness – schizophrenia, bipolar disorder, major depression and related syndromes – try to refrain from using cannabis.
How easy is that advice to follow? Isn’t there a possibility that the people most prone to developing schizophrenia are also genetically predisposed to becoming regular cannabis users?Â
There have been attempts to answer that question. Some of these studies suggests that cannabis use does lead to schizophrenia while others suggest that schizophrenia leads to cannabis use. In short, there may be to both the likelihood of using cannabis and the likelihood of developing schizophrenia.
Can the risks be reversed if someone stops using cannabis?
We don’t know exactly. One study looked at the relationship between cannabis use and cognition by measuring the IQ of more than . The researchers did this before participants began using cannabis in adolescence, and again when they were in their late 30s.
They found that people who had used cannabis had lower IQ scores later in life than they did during adolescence. This was true even if they stopped using cannabis regularly in adulthood. That suggests cannabis use during critical periods of adolescence could have irreversible effects. Now, I’m not saying that is a widely held view. I would like to think that stopping cannabis at any time might be beneficial for someone who is vulnerable to schizophrenia. But the jury is still out.
What are the big unanswered questions when it comes to understanding the link between cannabis use and schizophrenia?
Well, we don’t know what schizophrenia is. It is probably an umbrella term for many different disorders that express themselves in a similar fashion. It could be that there is a type of schizophrenia specifically related to cannabis. There may be one that is methamphetamine related. There may be one that is related to certain genetic mutations and so on.
And we have not found a signature pathology of schizophrenia. What led to the conclusion that cigarettes increase lung cancer risk was findings from animal studies. Animals exposed to tobacco byproducts have the same changes in their lung cells that are seen in people with lung cancer. Because we don’t understand what is happening at that level in schizophrenia, we can’t begin to make similar conclusions about cannabis. That is why I worry that we are not prepared for the potential consequences of starting this grand experiment with cannabis legalisation.
Deepak D’Souza is a professor of psychiatry at Yale University and the director of the neuropsychiatry programme at VA Connecticut Healthcare System. His research focuses on new treatments for schizophrenia, mood disorders and cannabis use disorder.
