Schizophrenia and Cannabis: A New Blood Test Could Reveal the Risk

Scientists have analyzed the blood of people with schizophrenia, excessive cannabis use, or both to understand how these conditions affect metabolism. They found changes in certain fat molecules, suggesting that cannabis may influence processes linked to schizophrenia. These findings could help in the development of new treatments in the future.

Schizophrenia (SZ) is a serious and chronic psychiatric illness that affects approximately 1% of the world's population over the course of their lives. It is a disorder that impairs the perception of reality, and can cause hallucinations, delusions, and cognitive difficulties.

In addition to the emotional and social impact, schizophrenia reduces the life expectancy of patients by up to 15 years, mainly due to associated complications such as suicide, cardiovascular disease, and lack of adequate access to treatment.

There is currently no cure for schizophrenia, and available treatments only aim to control the symptoms. Many factors can contribute to the development of schizophrenia, including genetic predisposition and environmental influences.

Although symptoms of the disease usually appear in late adolescence or early adulthood, it is believed that the disorder has its origins long before the first signs appear, possibly during fetal development. However, science has not yet been able to accurately identify the exact biological mechanisms that trigger schizophrenia. 

Cannabis, one of the most widely used psychoactive substances in the world, has been associated with an increased risk of developing schizophrenia, especially when use begins in adolescence.

An estimated 10% of regular cannabis users develop cannabis use disorder (CUD), a condition characterized by dependence and difficulty controlling consumption. In addition, about a third of people diagnosed with schizophrenia also have CUD.

However, it is still unclear why some people develop schizophrenia after using cannabis, while others only develop substance use disorder.

In recent years, scientists have used metabolomics, an approach that analyzes small molecules called metabolites, to better understand the differences between individuals with schizophrenia and those who use cannabis.

One focus of this research is on lipids, a group of molecules that includes fats and oils and plays an essential role in brain function. Lipids are part of the membranes of nerve cells and are involved in communication between neurons.

In this study, researchers investigated the blood lipid profiles of three groups of individuals:

1. Patients diagnosed with schizophrenia only.

2. Individuals with cannabis use disorder (CUD).

3. Patients who had both disorders (schizophrenia and CUD).

To identify potential biomarkers that differentiate these groups, scientists used a technique called liquid chromatography coupled with high-resolution mass spectrometry (LC-MS). This technique allows the detection and quantification of hundreds of metabolites (small particles) in blood plasma.

Blood was chosen as the biological matrix because its collection is minimally invasive and reflects metabolic changes throughout the body.

The approach used in the study was untargeted lipidomics, meaning that researchers were not looking for a specific metabolite, but rather analyzing globally the variations in lipid profiles between the groups studied.

The scientists identified 119 metabolites, of which 16 were validated with a high level of confidence. Among the most relevant findings:

• Reduction in acylcarnitines (molecules involved in energy metabolism), such as octanoylcarnitine and decanoylcarnitine, in all patient groups compared to healthy controls.

• Decrease in N-acyl amino acids (NAAAs), such as N-palmitoyl threonine and N-palmitoyl serine, in individuals with cannabis use disorder. This same pattern was observed in patients with schizophrenia and in the dual diagnosis group.

• Increased levels of 7-dehydrodesmosterol, a metabolite involved in cholesterol production, in patients with schizophrenia and dual diagnosis.

These findings suggest that both schizophrenia and chronic cannabis use may be associated with important metabolic alterations, especially in lipid metabolism.

A reduction in acylcarnitines, for example, may indicate a problem in the use of energy by brain cells. A decrease in NAAAs suggests a possible dysfunction in the endocannabinoid system, which regulates several brain processes and is strongly influenced by cannabis use.

By identifying these metabolic patterns, researchers hope to pave the way for the development of new biomarkers for the early detection of schizophrenia and cannabis use disorder. In addition, understanding these changes may help in the creation of therapeutic strategies that act on specific metabolic pathways, improving the treatment of these psychiatric disorders.

READ MORE:

Uncovering metabolic dysregulation in schizophrenia and cannabis use disorder through untargeted plasma lipidomics

Aitor Villate, Maitane Olivares, Aresatz Usobiaga, Paula Unzueta-Larrinaga, Rocío Barrena-Barbadillo, Luis Felipe Callado, Nestor Etxebarria and Leyre Urigüen

Scientific Reports. 14, Article number: 31492 (2024)

DOI: 10.1038/s41598-024-83288-5

Abstract: 

Cannabis use disorder affects up to 42% of individuals with schizophrenia, correlating with earlier onset, increased positive symptoms, and more frequent hospitalizations. This study employed an untargeted lipidomics approach to identify biomarkers in plasma samples from subjects with schizophrenia, cannabis use disorder, or both (dual diagnosis), aiming to elucidate the metabolic underpinnings of cannabis abuse and schizophrenia development. The use of liquid chromatography-high resolution mass spectrometry enabled the annotation of 119 metabolites, with the highest identification confidence level achieved for 16 compounds. Notably, a marked reduction in acylcarnitines, including octanoylcarnitine and decanoylcarnitine, was observed across all patient groups compared to controls. In cannabis use disorder patients, N-acyl amino acids (NAAAs), particularly N-palmitoyl threonine and N-palmitoyl serine, showed a strong downregulation, a pattern also seen in schizophrenia and dual diagnosis patients. Conversely, elevated levels of 7-dehydrodesmosterol were detected in schizophrenia and dual diagnosis patients relative to controls. These findings suggest a potential link between metabolic disruptions and the pathophysiology of both disorders. The untargeted lipidomics approach offers a powerful tool to identify novel biomarkers, enhancing our understanding of the biological relationship between cannabis abuse and schizophrenia, and paving the way for future therapeutic strategies targeting metabolic pathways in these conditions.