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Not Your Average Hazard: Cannabis Use, Psychosis, and the Youthful Brain
Cannabis use during adolescence can profoundly impact brain development.
The Allery/AdobeStock
SPECIAL REPORT: ADDICTION
Case Study
“Valerie” is a 17-year-old adolescent girl living in an urban area. She works evenings at a department store and babysits to help her family make rent for the month. She avoids bringing friends home, as her parents are often physically and verbally abusive to each other. Two years ago, a friend introduced her to synthetic cannabis vaping. These products seemed cooler than nicotine, and she felt she was self-medicating her stress. After all, medical cannabis was listed on her state’s compassionate registry to treat posttraumatic stress disorder, so she believed it could not be that risky. To Valerie, vaping was not even real cannabis use.
One day after school, her friend raced through the halls and shoved a vape pen in her hand. She was stunned. The school principal found Valerie still holding the vape pen in her hand. Valerie was asked to show the principal the contents of her backpack, which included another cannabis vape pen.
Valerie was suspended and transferred to an alternative school. At the new school, she avoided the other students, as she considered them troublemakers. Valerie continued to go on walks by herself late at night while her parents fought and would vape cannabis. Over the course of the school year, Valerie withdrew further and remained in her room, not showering or brushing her teeth consistently. She presents now to psychiatry clinic with her mother after the school notified child protective services (CPS) about school truancy.
Valerie’s experience with cannabis is not unusual. Most teenagers do not know the contents of the vape products they consume. Prevalence is also high in Valerie’s age group. The Monitoring the Future survey of 2023 found that the percentage of youth using marijuana in the last year was 29% in 12th grade, 18% in 10th grade, and 8% in 8th grade.1 Similarly, the percentage of 12th graders vaping marijuana remains at about 20% and has not varied since 2019. Vaping marijuana serves as a way for users to avoid detection by adults, and/or it could be a way for users to supplement their combustible marijuana use.1
Cannabis Use in Adolescence
Cannabis use during adolescence can profoundly impact brain development. The brain develops until age 25, with evolution in gray and white matter. In adolescence, gray matter diminishes while white matter increases, impacting cognitive development. Synaptic pruning takes place, promoting learning and brain efficiency. The prefrontal cortex also develops during adolescence and is responsible for the development of impulse control and appropriate social behavior. Substance use, including cannabis use, may lead to loss of gray matter in areas such as the medial prefrontal cortex, compromising decision-making skills and impulse control.2 In addition, cannabis may negatively affect other cognitive domains, particularly learning, memory, attention, and working memory. Regular cannabis use is also associated with amotivational syndrome, defined by apathy and decreased goal-directed behavior.3 These effects may result in decreased occupational achievement, such as college matriculation, among adolescents who use cannabis regularly, leading to significant economic costs to the general population. All of these factors could be pertinent to teenagers like Valerie.
Among the risks of cannabis are its detrimental effects on mental health, including the bidirectional link of cannabis use with psychosis and an increased risk of comorbid substance use disorders (SUDs). In patients with preexisting psychosis, cannabis is associated with worse health outcomes and greater disease severity. In adolescents, cannabis is also believed to affect synaptic plasticity and N-methyl-d-aspartate receptor–mediated memory formation. Since adolescence to early adulthood is the time frame associated with the onset of schizophrenia, this can be a particularly fraught period.
Psychosis
The link between cannabis use and the onset of psychosis has long been an area of interest and speculation. Observational studies have consistently pointed to an association between cannabis use and schizophrenia; however, the nature and mechanisms of this relationship remain poorly understood.4 One hypothesis is that tetrahydrocannabinol (THC) may augment psychosis via alteration of dopamine and glutamate activity.5 Of note, unique individuals may respond differently to cannabis, suggesting that genetic and epigenetic factors may impact one’s susceptibility to psychosis. Several plausible genes and risk factors for cannabis-induced psychosis are listed in the Figure.6
Figure. Contributing Factors to Cannabis Use Disorder6
A genome-wide association study of 184,765 participants found 8 unique single nucleotide polymorphisms associated with lifetime cannabis use. The study found genetic overlap in risk for cannabis use and schizophrenia.7 Another study used a Mendelian genetic analysis to find a causal relationship of cannabis use with increased schizophrenia risk (OR, 1.37).8
Inconsistencies and Safety
The risks of modern cannabis products are exacerbated by inconsistencies in product composition, such as cannabinoid concentrations, and lack of US Food and Drug Administration oversight. Variations in THC content of cannabis products may be influenced by factors including cultivation methods, processing techniques, and storage conditions. Due to lack of consistent regulation, cannabis products may contain incorrect labeling and be of varied potency, contributing to heterogeneous effects and safety problems.9 Additionally, the increased popularity of synthetic cannabinoids has led to dangerous consequences. Synthetic cannabinoids are artificial compounds that have effects similar to those of THC but with significantly greater potency. Synthetic cannabinoids, sometimes known as Spice or K2, act as full agonists of cannabinoid receptors—unlike THC, which is a partial agonist. These products are difficult to detect due to structural diversity and rapid metabolism and are associated with severe intoxications and even fatalities.10 Highly potent synthetic cannabis may therefore promote development of psychotic symptoms.
Reduced Perception of Harm
The public may tend to focus on the medical benefits of cannabis products while underemphasizing its potential harms. The belief that cannabis is a medicine has likely led to increased adoption. Several formulations have been developed as medical cannabis products, with some evidence supporting therapeutic benefits in specific conditions. Medical cannabis products vary in their composition and include dronabinol (THC), nabilone (synthetic cannabinoid similar to THC), cannabidiol (CBD), and nabiximols (cannabis-derived extracts with equal parts THC and CBD). These products collectively have been shown to have benefits in epilepsy, chronic pain, spasticity, appetite, Parkinson disease, sleep, SUDs, and Tourette syndrome. However, these products can have adverse effects that may limit their use.11
On May 16, 2024, the US Department of Justice proposed transfer of marijuana from Schedule I of the Controlled Substances Act (CSA) to Schedule III of the CSA. While Schedule I drugs are those with no medical use that cannot be prescribed by a physician, Schedule III drugs are those with medical use and low to moderate potential for physical and psychological dependence. A change in scheduling would not legalize medical or recreational use of marijuana under federal law, but it would instead subject marijuana and cannabis-derived products to the Federal Food, Drug, and Cosmetic Act. Rescheduling of cannabis undoubtedly would have an impact on perception of harm posed by cannabis use, as it would then be researched for potential medical properties. Already, cannabis is approved for medical use in at least 38 states. In some states, it is also decriminalized or even legalized. The contradiction between state and federal laws concerning cannabis use can be confusing.
Case Study Continued
For youth like Valerie, cannabis can be life-changing. By the end of the case study, Valerie begins to demonstrate symptoms of prodromal schizophrenia and/or severe depression, and it is highly possible that these disorders are cannabis induced. With first the transfer to an alternative school and then isolation followed by issues of absenteeism, Valerie faces educational prospects that seem grim. However, linkage to child psychiatry through CPS and addiction-focused care engagement can improve her prognosis.
Concluding Thoughts
It is unsurprising that the perceived risk of harm from cannabis has decreased over time and that the concept of cannabis as a medicine is gaining traction. Studies suggest that perception of cannabis-related risk decreased among all adult age groups from 2002 to 2019.12 Interestingly, illicit cannabis use and the prevalence of cannabis use disorders increased significantly more in states that passed medical marijuana legalization laws than in states that did not,13 illustrating the impact of politics on public health. This is relevant, as adolescents are particularly vulnerable while their brains are undergoing maturation until young adulthood. They may be unaware of both the general harms posed by cannabis and the true composition of the substances they are vaping and consuming. Furthermore, chronic cannabis use is associated with increased schizophrenia risk, and schizophrenia has its onset in early adulthood.
Unfortunately, addiction and mental health services are not accessible to all adolescents and young adults. In fact, per the American Academy of Child and Adolescent Psychiatry, only half of children and adolescents with general diagnosable mental health problems, let alone those with SUDs, receive the care they need.14 It is thus even more important that psychiatrists and primary care providers screen for cannabis use and cannabis use disorders and stay abreast of cannabis-related legislation that can impact patient health and safety. The cost is too great not to.
Dr Shenoi is an assistant professor of psychiatry at Baylor College of Medicine in Houston, Texas, and a recent graduate of Baylor College of Medicine’s addiction psychiatry fellowship program. Dr Vijayvargiya is an assistant professor of psychiatry at the University of Florida, Gainesville, where she serves as the director of the University of Florida Health Shands Hospital consultation-liaison psychiatry service.
References
1. Miech RA, Johnston LD, Patrick ME, et al. Monitoring the Future: National Survey Results on Drug Use: 1975-2023: Secondary School Students. University of Michigan Institute for Social Research; 2023. Accessed July 2, 2024. https://monitoringthefuture.org/wp-content/uploads/2023/12/mtf2023.pdf
2. Dhein S. Different effects of cannabis abuse on adolescent and adult brain. Pharmacology. 2020;105(11-12):609-617.
3. Volkow ND, Swanson JM, Evins AE, et al. Effects of cannabis use on human behavior, including cognition, motivation, and psychosis: a review. JAMA Psychiatry. 2016;73(3):292-297.
4. Gage SH, Hickman M, Zammit S. Association between cannabis and psychosis: epidemiologic evidence. Biol Psychiatry. 2016;79(7):549-556.
5. Colizzi M, McGuire P, Pertwee RG, Bhattacharyya S. Effect of cannabis on glutamate signalling in the brain: a systematic review of human and animal evidence. Neurosci Biobehav Rev. 2016;64:359-381.
6. Carvalho C, Vieira-Coelho MA. Cannabis induced psychosis: a systematic review on the role of genetic polymorphisms. Pharmacol Res. 2022;181:106258.
7. Pasman JA, Verweij KJH, Gerring Z, et al. GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia. Nat Neurosci. 2018;21(9):1161-1170.
8. Vaucher J, Keating BJ, Lasserre AM, et al. Cannabis use and risk of schizophrenia: a Mendelian randomization study. Mol Psychiatry. 2018;23(5):1287-1292.
9. Bero L, Lawrence R, Oberste JP, et al. Health effects of high-concentration cannabis products: scoping review and evidence map. Am J Public Health. 2023;113(12):1332-1342.
10. Roque-Bravo R, Silva RS, Malheiro RF, et al. Synthetic cannabinoids: a pharmacological and toxicological overview. Annu Rev Pharmacol Toxicol. 2023;63:187-209.
11. Bilbao A, Spanagel R. Medical cannabinoids: a pharmacology-based systematic review and meta-analysis for all relevant medical indications. BMC Med. 2022;20(1):259.
12. Waddell JT. Age-varying time trends in cannabis-and alcohol-related risk perceptions 2002–2019. Addict Behav. 2022;124:107091.
13. Hasin DS, Sarvet AL, Cerdá M, et al. US adult illicit cannabis use, cannabis use disorder, and medical marijuana laws: 1991-1992 to 2012-2013. JAMA Psychiatry. 2017;74(6):579-588.
14. Severe shortage of child and adolescent psychiatrists illustrated in AACAP workforce maps. American Academy of Child and Adolescent Psychiatry. May 4, 2022. Accessed July 2, 2024. https://www.aacap.org/AACAP/zLatest_News/Severe_Shortage_Child_Adolescent_Psychiatrists_Illustrated_AACAP_Workforce_Maps.aspx
Articles in this issue
Addressing Alcohol or Cannabis Use in Patients With Anxiety Disorders
Not Your Average Hazard: Cannabis Use, Psychosis, and the Youthful Brain
Social Media and Substance Use: What Clinicians Need to Know
Increasing Our Knowledge of Addiction and Substance Use Disorders
The Hidden Suffering of Social Anxiety Disorder
The Safety of Psychostimulants or Atomoxetine for Patients With Psychotic Disorders
Antidepressants Prescribed in the US Ranked on 3 Safety Indices
Tango Without Touching: Defusing Pediatric PTSD in the Emergency Department
Suicide Risk After Brain Injury
We’ve Only Just Begun…
Summertime Sadness
Outpatient Civil Commitment: A Look at Maryland’s New Legislation
The Perinatal Mental Health Crisis
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