Schizophrenia is a disease that affects around 1% of the American population. It is characterized by positive and negative debilitating symptoms. Positive symptoms, such as hallucinations, delusions of grandeur, and paranoia, can be treated with medication to a certain degree. However, the negative symptoms have no way of being treated. These symptoms are negative because they take functions away from the victim of the disease. The symptoms reduce social behavior, cognition, and emotional intelligence. Without treatment, these symptoms progress with age and eventually, the person struggles to treat their positive symptoms. With each successive episode that doctors fail to prevent, there is a global strengthening of the patient’s symptoms. The causes of schizophrenia are an unknown combination of genetic and hereditary factors, however, neuroscientists like Masheel Sodhi are investigating the connection between mental illness and prenatal stressors.
Dr. Sodhi’s research argues in favor of the glutamate hypothesis of schizophrenia (SCZ). Although Dr. Sodhi studied brain tissue with depression, the likely comorbidity and similar symptoms lead to depression and schizophrenia possibly having similar mechanisms of action in the body. Depression is a disease characterized by periods of extreme emotional withdrawal and a loss of interest in daily activities. This is similar to schizophrenia’s emotionally withdrawing negative symptoms. Dr. Sodhi observed the preserved brain tissues of human postmortem specimens. There was a control group without any history of substance use disorders, a male major depressive disorder (MDD) group, a male MDD group with suicides, a female MDD group, and a female MDD group with suicides. The results of her study were that for the female MDD group, vesicular glutamate transporters (VGLUTs) were significantly increased in the dorsolateral prefrontal cortex (DLPFC) as well as the presence of excitatory amino acid transporters (EAATs) that can potentially transport glutamate (Sodhi). There was also a significant increase of ionotropic and metabotropic glutamate receptors in female DLPFCs with MDD. The male MDD group with violent suicides had decreased EAATs and normal levels of VGLUT in their DLPFCs. These results indicate that depression is a sexually dimorphic disorder where the brain regions affected have different genes expressed in women compared to men (Sodhi). This correlates with the fact that women are 2-3 times more likely to be diagnosed with MDD than men. Synthesizing Dr. Sodhi’s results indicates that MDD and suicide are caused by a decrease in DLPFC activity. She hypothesizes that the increase in transporters causes an increase in glutamatergic activity that is ultimately cytotoxic for neuronal and glial cells. This glutamatergic overexpression leads to signals in the dopaminergic system being overexpressed, a characteristic of schizophrenia.
After finding that increased glutamate could be a factor in the onset of MDD and SCZ, Dr. Sodhi did a follow-up study on schizophrenia. She investigated prenatal stress’s connection to the disease with mice models and found that increasing the stress of the mother increases the risk of schizophrenia for the child. Stress includes stressful life events, malnutrition, and/or infection. The prenatal stress was also connected to a reduction in an RNA editing process that converts adenosine to inosine, allowing adenosine to functionally act as a guanine and base pair with cytosine (Sodhi). This process is important for ionotropic channels in the neurons and by inhibiting or dysregulating it, the channels lose regulation and specificity. One example is of an unedited ubiquinone in the sodium-potassium ion channels, where when it is not edited, calcium ions flood unregulated into the cell. This is a mechanism that is altered by prenatal stress and could alter glutamatergic ion channels. Prenatal stress increases glutamatergic gene expression and decreases RNA editing of a protective allele, GluA2, in the DLPFC. The mice also show decreased spatial learning and social behavior when they are prenatally stressed. In humans, prenatal stress is hard to mitigate and environmental stressors have drastically increased. While prenatal stress does not trigger schizophrenia right away, Sodhi’s team’s data indicates that it could lead to a predisposition for the disease due to the lack of the stress-protective GluA2 allele (Sodhi). This predisposition is undetectable in the modern day but as the mental illness triggers of psychedelic drugs and cannabis are increasingly becoming legalized, this hidden vulnerable population will increasingly become victims of SCZ and MDD.
Over the last decade, the attitude toward drug usage has shifted. Psychedelics like psilocybin and stimulants like marijuana have risen in popularity, especially among young people. Author Dana G. Smith wrote an article warning the youth in the New York Times. She emphasizes that state laws are beginning to accept youth drug usage as the norm and they lift the laws preventing them from accessing it legally to prevent black market trade. Over 1.4 million Americans tried hallucinogens for the first time in 2020 (Smith). Smith argues the popularity comes from illusions about the drugs’ safety. Since dopamine does not increase as a result of taking hallucinogens, they are very unlikely to be addictive. There is also minimal risk of lethal overdose for the drugs, but psychological problems are at risk with even a single dose of hallucinogenic drugs. This increase in hallucinogen usage is triggering an outbreak of schizophrenia in the American population. One woman was diagnosed with the illness only after her second use of the drug psilocybin. Her doctor reported, “She had a full-blown psychotic episode for the first time in her life, (Smith)”. None of her friends experienced any long-lasting effects, indicating that they were not predisposed to the disease. This indicates that the woman had genetic and environmental factors that predisposed her to the disease. Even into adulthood, the long-lasting biological effects of prenatal stress and/or the lack of the GluA2 allele could lead to a pathological response after exposure to hallucinogens. Recently experts, like Dr. Sodhi, have connected the population with bipolar heredity and schizophrenia heredity, explaining that those with bipolar disorder in their family history are at risk for developing schizophrenia after trying hallucinogens. Many practitioners like Dr. Roth have seen many examples, although they are rare, where patients tried a hallucinogenic drug and then, “they’ve had schizophrenia ever since (Smith)”. Beyond schizophrenia, heart problems and a neurological condition called serotonin syndrome, which can affect those on monoamine oxidase inhibitors (MAOIs) or less commonly selective serotonin reuptake inhibitors (SSRIs), are risks associated with hallucinogen usage. Depending on the pressure within the skull, from traumatic brain injury, strokes are also a risk. Epilepsy can also occur during a hallucinogenic state depending on genetic predisposition. None of these risks from hallucinogenic drugs can be predicted reliably for unique users so the drugs are dangerous despite their increased popularity (Smith). Like psilocybin, Marijuana is another drug, often classified as hallucinogenic, that has risen in popularity among young people.
Marijuana use is proven to trigger schizophrenia and young men, a vulnerable population in the marijuana use outbreak, are especially at risk. As support for marijuana legalization continues to grow across America there is no doubt that it could soon become a federal policy. According to Ross Douthat, that is a huge mistake and a “social policy failure” for the country. While marijuana may have some disputed clinical benefits, the statistics that have arisen over the past ten years are disturbing. Since 2008, the amount of daily weed smokers has grown to over 16 million Americans in 2023. Without a way to screen for predispositions to neurological illnesses, each use of marijuana is a risk, particularly for people in their 20s when neurological diseases like schizophrenia develop. There are medical uses for marijuana that have given the population disillusionment about its safety. Studies have shown that legalized medical marijuana is associated with increased opioid deaths (Douthat). Presently, the increase in marijuana acceptance has led to a demotivated youth with decreased attention spans. Douthat explains that while these risks are not as worrisome as schizophrenia they still, “derail an awful lot of human lives (Douthat)”. A lack of motivation can lead to students performing poorly in school and becoming socially isolated. All of these consequences cannot be reliably predicted but they destroy people’s lives. The benefits of marijuana legalization are slim compared to the burdens. Marijuana legalization has given people the freedom to choose, lowered prices and safety risks from drug impurities, and increased the medicinal availability of the drug. However, the freedom to choose needs to come from proper knowledge about the risks of the drug, and young people often lack that knowledge.
Without a way to properly predict a hallucinogenic drug’s impact on someone’s mind, the increasing usage of drugs like marijuana and psilocybin will nourish the formation of a larger schizophrenic and mentally ill population. The increasing environmental stressors from modern processes like industrialization combined with the emotional stressors of pregnancy have led to many prenatally stressed people susceptible to the pathogenesis of schizophrenia among other mental illnesses. As this population is increasingly exposed to hallucinogens like psilocybin and marijuana, internal genetic issues like a lack of RNA editing could dysregulate ion channels and increase the transmission of excitatory neurotransmitters, like glutamate, resulting in a diseased state. Some of them may have a schizophrenia or bipolar family history and that indicates that they may not have the GluA2 stress protective allele leading them to be more vulnerable under the influence of hallucinogens. Mothers cannot simply reduce their stress and this predisposition will continue. The studies of Dr. Sodhi highlight the risks for the young population and the contemporary movement to legalize marijuana and take hallucinogenic drugs is concerning as young people are disproportionately affected. Young people need to be more aware that drug usage directly affects their brains and the effects on their unique brains will not always match the effects on the brains of the general population due to the differential predisposition of each brain to unique diseased states. Lifelong illness is never worth the temporary state that drugs can give, and the unpredictable dangers of these drugs must be emphasized to the American population.
Works Cited:
Smith, D. G. (2023, February 10). Psychedelics are a promising therapy, but they can be dangerous for some. The New York Times. https://www.nytimes.com/2023/02/10/well/mind/psychedelics-therapy-ketamine-mushrooms-risks.html?searchResultPosition=1
Douthat, R. (2023, May 17). Legalizing marijuana is a big mistake. The New York Times. https://www.nytimes.com/2023/05/17/opinion/marijuana-legalization-disaster.html?searchResultPosition=1
- Powers, B., Joyce, C., Kleinman, J. E., Hyde, T. M., Ajilore, O., Leow, A., & Sodhi, M. S. (2020). Sex differences in the transcription of glutamate transporters in major depression and suicide. Journal of Affective Disorders, 277, 244–252. https://doi.org/10.1016/j.jad.2020.07.055
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