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THC-induced Psychosis as a Potential Marker of Schizophrenia Risk

Schizophrenia is a mental disorder that affects the way individuals perceive reality. While it is relatively uncommon (less than 1% of the population), the symptoms are devastating. Those suffering from schizophrenia often lose touch with reality, and may experience hallucinations and delusions. Other symptoms include withdrawing into an internal world, a “flat” affect, an inability to remember or use information, and trouble focusing or paying attention. While treatments exist, there is currently no cure.

There are many factors that lead to the development of schizophrenia. While it may run in families, many genes contribute to the disease, complicating genetic testing strategies. Environmental factors also play a major role. One of those factors is exposure to cannabis at a young age. Cannabis use has been linked to an earlier age of onset and increased severity of symptoms in those with schizophrenia. Certain healthy individuals may experience symptoms associated with the disease. These symptoms, including hallucinations and paranoia, are known as “transient psychotic effects”, or TPE. Further, THC exacerbates these symptoms in schizophrenic patients. Therefore, cannabis use presents a real risk to those susceptible to developing this disorder. 

Not everyone is prone to experience THC-induced psychosis. Very little research has been done to determine what is different between those who experience hallucinations and those who do not. In part this research is difficult because it is subject to many confounding factors, such as cannabis composition and individual genetic factors. Now, a study published in Psychological Medicine looks at physiological factors related to TPE susceptibility. This research not only highlights inter-individual differences that may predispose a person to these negative effects of THC, but it may also have uncovered a sign of increased schizophrenia risk.

THE STUDY

Schizophrenia causes cognitive impairments associated with a brain region known as the hippocampus. The hippocampus is involved in processing memory and has a high density of cannabinoid receptors. THC, in addition to potentially causing TPE, is also known to have permanent effects on recall memory. Therefore, the researchers chose to look at activation of the hippocampus in those known to experience TPE.

A group of 36 subjects were recruited for this study. They were chosen based on age, sex, and prior experience with cannabis and illicit drugs. Each subject had had at least one experience with cannabis prior to the study, but none were chronic users. Participants were given either 10mg of THC in pill form, or a placebo. Surveys were administered hourly for four hours after dosing. These surveys were designed to assess the subjects’ levels of impairment and anxiety levels. 

One hour after dosing, the subjects were given two memory-based tasks to complete. First, they were shown a pair of words and asked, “Do these words go together?” Then, in the second part of the test, they were shown one word of the pair, and asked to provide the other. The fMRI showed which parts of the brain were more or less active in each group during both tasks. This same set of tests was performed twice in each subject, once with THC, and once without, allowing the researchers to compare an individual’s performance under both conditions. 

Using the survey results, the authors were able to split the subjects into two groups, those that experienced TPE, and those that did not. Under placebo conditions, the TPE group had increased activity in the hippocampus compared to the non-TPE group. They also experienced more severe impairment and greater levels of THC-induced anxiety. These results link increased hippocampal activity to acute psychosis caused by THC. 

CONCLUSIONS

This work points to a potential physiological explanation for why some individuals experience THC-induced TPE, and others don’t. While it is possible that this susceptibility to TPE may be related to one’s schizophrenia risk, it is much to early to say so definitively. For one thing, these experiments were looking at the effects of a single dose of THC. It is only long-term, chronic use that is linked to schizophrenia. Further, these results may not apply to the public at large, because they used only male subjects for this study. Men are more likely to develop schizophrenia, and often do so at a younger age. Finally, they did not take into effect the varying methods of cannabis ingestion, dosage strength, and the modifying effects of CBD.

Nevertheless, the tendency to experience TPE under the influence of cannabis may be an early warning sign of developing schizophrenia. Only more research will tell if this is truly the case. In the meantime, this information may be helpful for doctors in deciding if cannabis presents an extra risk for their patients.

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