Blood Fat Profiles Reveal Why Some Cannabis Users Develop Schizophrenia While Others Don’t

Scientists have identified distinct metabolic fingerprints in the blood that may finally explain why some cannabis users develop schizophrenia while others don’t – despite similar levels of exposure to the drug.

The groundbreaking research, published in Scientific Reports, reveals how specific fatty acid patterns in blood samples could potentially serve as early warning signals for those at heightened risk of developing psychosis from cannabis use.

For the millions who use cannabis worldwide, the findings may eventually lead to personalized risk assessments that could help users make more informed decisions about consumption.

“We found considerable differences between these groups of individuals. By comparing the quantities of certain metabolites (fatty acids), we were able to perfectly differentiate between the three patient populations,” stressed Leyre Urigüen, coordinator of the study from the University of the Basque Country (UPV/EHU). “This indicates that there is an altered or different metabolism between these three groups.”

The researchers analyzed blood samples from four distinct groups: individuals with schizophrenia who didn’t use cannabis, people who used cannabis and developed cannabis use disorder, patients with both schizophrenia and cannabis use disorder (dual diagnosis), and a control group of healthy individuals who neither had psychiatric disorders nor used drugs.

Using advanced lipidomics – a comprehensive study of fatty acids and related compounds – the team identified 119 different metabolites in the blood samples, with several showing significant differences between groups.

Among the most striking findings was a marked reduction in compounds called acylcarnitines – specifically L-octanoylcarnitine and L-decanoylcarnitine – across all patient groups compared to controls. These molecules play crucial roles in energy metabolism, neuroprotection, and maintaining cell membrane stability in the brain.

Cannabis users without schizophrenia showed significant decreases in compounds called N-acyl amino acids, particularly N-palmitoyl threonine and N-palmitoyl serine – molecules that help modulate brain signaling and provide neuroprotection. Interestingly, patients with schizophrenia displayed similar reductions, suggesting a common disruption in these protective pathways.

Meanwhile, patients with schizophrenia (both with and without cannabis use) showed elevated levels of 7-dehydrodesmosterol, a compound involved in cholesterol synthesis – though this change may be related to antipsychotic medications rather than the disorders themselves.

The research provides some of the first concrete evidence that cannabis use and schizophrenia may share underlying metabolic disruptions, potentially explaining their frequent co-occurrence. Nearly a third of people diagnosed with schizophrenia also meet criteria for cannabis use disorder, and up to 42% of individuals with schizophrenia are affected by cannabis use disorder.

“We are proposing that some fatty acids differentiate between the cannabis-using group and the groups with schizophrenia and dual-diagnosis patients. These molecules could potentially be biomarkers,” said Urigüen.

The research team employed liquid chromatography coupled with high-resolution mass spectrometry to detect subtle differences in these metabolic compounds. This sophisticated analytical approach was developed by the UPV/EHU’s IBeA research group under the direction of Professor Nestor Etxebarria, who collaborated closely with Urigüen’s Neuropsychopharmacology group.

For Dr. Urigüen, the findings mark an important starting point: “I think it is important to be capable of finding blood biomarkers that can help predict the risk of developing a psychiatric disorder, such as schizophrenia due to cannabis use, and this study has proven to be the start of this way forward. Now this has to be disproved by studies with a larger cohort of people than the one we have analysed.”

While the study’s sample size was relatively small – 24 individuals with cannabis use disorder, 18 with schizophrenia, 12 with dual diagnosis, and 50 controls – the researchers believe their methodology provides a template for larger investigations that could confirm these potential biomarkers.

The implications extend beyond predicting risk. Understanding the shared metabolic pathways between cannabis use and schizophrenia could potentially lead to new therapeutic approaches that target these disruptions directly, possibly preventing or mitigating psychosis development in vulnerable individuals.

With cannabis legalization expanding globally and usage rates climbing, identifying those at heightened risk for adverse psychiatric effects has taken on new urgency. This metabolic approach offers a promising avenue toward that goal – one that looks beyond genetics to the actual biochemical processes that may link cannabis use to schizophrenia development in susceptible individuals.

As these researchers continue refining their understanding of these metabolic signatures, the day may come when a simple blood test could help cannabis users assess their personal risk of developing serious psychiatric disorders – potentially transforming how we approach both cannabis use and schizophrenia prevention.