Psychosis in cannabis users: Dopamine system may be the link

Patients with cannabis use disorder (SUD) have increased dopamine functioning in the brain pathway associated with psychosis, a longitudinal cohort study has shown.

Cannabis is the most commonly abused drug among young people in Hong Kong. [www.info.gov.hk/gia/general/202103/29/P2021032900302.htm] “CUD is of particular concern due to the association between cannabis and psychosis,” said first author, Ms Jessica Ahrens, a PhD student of McGill’s University, Montreal, Canada. “For a long time, researchers across the world have been searching for a link between cannabis and the brain mechanism behind psychosis.”

Role of neuromelanin-MRI

Therefore, the researchers conducted an observational cohort study that included 25 participants with CUD (mean age, 22.3 years; male, 81 percent) and 36 without CUD (mean age, 24.3 years; male, 88 percent) recruited in 2019–2023 from an early psychosis service and the surrounding communities in Ontario. [JAMA Psychiatry 2025;82:609-617]

Using neuromelanin-MRI (a specialized brain scan), they measured participants’ neuromelanin signal, which reflects dopamine activity, in the psychosis-related region of interest. “We have so many new techniques to look at the brain, but many of these have not been applied in this special way where we compared SUD with psychosis,” highlighted co-author Dr Ali Khan of the Department of Psychiatry, McGill’s University, Montreal, Canada.

Shared dopamine pathway

Results showed that CUD was associated with elevated neuromelanin-MRI signal in the psychosis-related region of interest — specifically, the substantia nigra and ventral tegmental area (t₉₂, 2.12; p=0.04).

“Our findings of elevated signal in this region in CUD suggest that cannabis may be associated with the final common pathway of dopaminergic dysfunction relevant to psychotic symptoms,” noted the researchers. “This could help explain why cannabis use increases the risks of hallucinations and delusions, [which are the] key symptoms of schizophrenia and other psychotic disorders.”

Of note, the association was dose-dependent, with a higher burden of CUD symptoms associated with increased neuromelanin-MRI signal (F_{1, 96}, 4.89; p=0.03). “Those changes are directly linked to more frequent and more severe episodes of psychosis, which can have a devastating impact on young people’s lives,” commented Khan.

However, patients with first-episode schizophrenia did not exhibit a significant elevation in neuromelanin-MRI signal vs healthy controls (p=0.09), but there was a numerical trend in the relevant voxels. “Alongside the lack of power, the limited effect of first-episode schizophrenia on neuromelanin-MRI signal may be due to treatment effect as the patients with first-episode schizophrenia in our study had low symptom burden and were taking antipsychotics,” explained the researchers.

Educate youths about risks of frequent cannabis use

“The lack of clear biological evidence linking cannabis to psychosis has made it hard to persuade young people with psychotic symptoms to reduce their use,” said co-author Professor Lena Palaniyappan of the Department of Psychiatry, McGill University, Montreal, Canada.

“Our findings could help doctors and mental health professionals better educate patients with SUD about the potential risks of frequent cannabis use, especially for those with a family history of psychosis,” Khan remarked.