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Cannabis use has long been a topic of interest in both scientific and public health discussions. One emerging area of concern is the link between cannabis and psychosis risk, particularly how cannabis might influence the brain’s dopamine system. By examining new research, we can better understand the potential risks associated with cannabis use, especially for individuals who may be vulnerable to psychotic disorders.
The connection between cannabis use and psychosis is explored, with a focus on recent findings about its impact on the brain’s dopamine system. The importance of this research lies in understanding the mental health risks associated with cannabis use.
The Connection Between Cannabis and Dopamine
I
s cannabis linked to the dopamine pathway involved in psychosis?
Research shows that cannabis use, particularly in individuals with cannabis use disorder (CUD), affects the brain’s dopamine system. Dopamine, a neurotransmitter, plays a crucial role in motivation, reward, and emotional responses. It is also heavily implicated in psychotic disorders such as schizophrenia.
A recent study involving neuromelanin-sensitive magnetic resonance imaging (neuromelanin-MRI) has revealed an increased neuromelanin signal in the midbrain regions of individuals with CUD. Elevated neuromelanin levels often indicate changes in dopamine functioning, which is linked to psychosis. These findings suggest that cannabis use may affect the same pathways associated with psychosis symptoms.
Dopamine and psychosis
The dopamine hypothesis of psychosis proposes that excessive dopamine activity in certain brain regions contributes to psychotic symptoms. This hyperactivity, particularly in the midbrain areas like the substantia nigra/ventral tegmental area (SN/VTA), is often observed in individuals experiencing psychosis.
Cannabis use, especially when frequent or heavy, appears to disrupt dopamine regulation. Δ9-tetrahydrocannabinol (THC), the active compound in cannabis, can temporarily increase dopamine levels, potentially leading to psychotic episodes in vulnerable individuals. However, long-term effects of cannabis on dopamine function remain complex and not fully understood.
The Role of Neuromelanin-MRI in Research
Neuromelanin-MRI offers a non-invasive way to study dopamine activity in the brain over time. Neuromelanin accumulates in dopaminergic neurons, making it a useful marker for understanding changes in dopamine systems.
The study revealed that individuals with CUD exhibited higher neuromelanin signals in psychosis-related brain regions. Interestingly, these signals were even more pronounced in those with both CUD and first-episode schizophrenia (FES). Persistent cannabis use over time also maintained elevated neuromelanin signals, suggesting a lasting impact on dopamine pathways and psychosis risk.
How Cannabis Use Affects Psychosis Risk
Cannabis use and psychotic symptoms
Cannabis use disorder is linked to a higher risk of both positive and negative psychotic symptoms:
- Positive symptoms include hallucinations, delusions, and altered perceptions.
- Negative symptoms include diminished motivation, reduced social interaction, and emotional blunting.
Research indicates a dose-dependent relationship, meaning higher levels of cannabis use increase the risk of psychosis. Additionally, individuals with CUD frequently experience earlier onset of psychotic illnesses compared to non-users.
Dose-dependent risk
The study found that greater cannabis use severity correlated with higher neuromelanin signals in psychosis-related brain areas. This dose-dependent effect underscores the progressive risk associated with more frequent or prolonged cannabis use.
Long-term impact
Cannabis’ long-term effects on the brain remain under investigation. While THC temporarily elevates dopamine levels, continued use may alter dopamine regulation, potentially increasing susceptibility to psychosis. Persistent changes in neuromelanin signals support the idea of lasting effects.
The Role of Other Factors in Psychosis Risk
Interaction with other substances
The study noted that individuals with CUD had higher nicotine use. While cannabis appears to have a unique association with psychosis, other substances like tobacco may also contribute to changes in the dopamine system.
Individual vulnerability
Not everyone who uses cannabis develops psychosis. Genetics, environmental factors, and early-life stress may all play roles in determining a person’s vulnerability to cannabis-induced psychosis.
Implications of the Research
Why these findings matter
The findings of this study highlight the significant impact of cannabis on dopamine functioning and psychosis risk. They provide important insights into how cannabis interacts with the brain, adding to our understanding of its long-term effects on mental health.
Potential applications
Neuromelanin-MRI could become a valuable tool for identifying individuals at higher risk of psychosis due to cannabis use. It could also help in developing targeted interventions for CUD and psychotic disorders, potentially improving treatment outcomes.
Public health relevance
Cannabis is widely used, and its legalisation in many countries has led to increased accessibility. Understanding its potential mental health risks is essential for informed decision-making, both at an individual and societal level.
Key Takeaways From the Link Between Cannabis and Psychosis
- Cannabis use disorder is linked to increased neuromelanin signals in dopamine-rich brain areas.
- These signals are particularly elevated in individuals with psychosis, such as first-episode schizophrenia.
- There is a dose-response relationship, where higher cannabis use severity correlates with greater changes in dopamine pathways.
- Neuromelanin-MRI offers a promising method for studying the long-term effects of cannabis on the brain and its connection to psychosis.(Source: WRD News – JAMA Network)
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Question: Is chronic cannabis use associated with endothelial dysfunction? YES!
Findings: In this cross-sectional study of 55 participants, vascular endothelial function was impaired in both chronic marijuana smokers and tetrahydrocannabinol (THC)–edible users, whereas serum from marijuana smokers but not THC-edible users blunted nitric oxide production in cultured endothelial cells.
Meanings: Endothelial dysfunction was observed in otherwise healthy cannabis users, suggesting an increased risk of early development of vascular disease.
Abstract
Importance: Recreational and medicinal cannabis legalization has led to increased cannabis use. To understand the consequences for vascular health, we initiated the Cannabis: Does It Damage Endothelium (CANDIDE) study.
Objective: To investigate whether cannabis use is associated with vascular endothelial dysfunction.
Design, Setting, and Participants: In this cross-sectional study, sex- and age- matched healthy adults, aged 18 to 50 years, living in the San Francisco Bay Area, California, who neither smoke tobacco nor vape and were not frequently exposed to second-hand smoke were recruited into 3 cohorts: 2 chronic cannabis user groups (marijuana smokers and tetrahydrocannabinol [THC]–edible users) and 1 nonuser group. Participants were recruited from October 25, 2021, through August 1, 2024; analysis was completed September 2024. Participants’ arterial flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity (PWV) were measured. Human umbilical vein endothelial cells (HUVECs) were exposed to participant sera with and without vascular endothelial growth factor (VEGF) to assess the effects of user serum on endothelial nitric oxide production.
Conclusions: This cross-sectional study found that chronic cannabis smoking and THC ingestion were associated with endothelial dysfunction similar to that observed in tobacco smokers, although apparently occurring via distinct mechanisms. "vascular endothelial function was impaired in both chronic marijuana smokers and tetrahydrocannabinol (THC)–edible users" (Source: JAMA Network Cardiology)
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A tragic accident in Bexleyheath has shed new light on drug-driving risks as a bus driver, Martin Asolo-Agogua, pleaded guilty to causing the death of nine-year-old Ada Bicakci. The Bus driver cannabis death occurred when the driver, high on cannabis, struck Ada and her brother on Watling Street on the 3rd of August 2023. The heartbreaking incident resulted in Ada’s death two days later, while her younger brother survived the hit.
Ada, a bright and energetic gymnast and swimmer, has left her family and community grieving. She attended a local school and embraced her love of sports with an active spirit. Following her passing, her family donated her organs, saving the lives of six other children—a profound act of generosity during their darkest days.
Fatal Consequences of Cannabis Use While Driving : Driving under the influence of cannabis significantly reduces reaction times, coordination, and perception, all of which are crucial to safe driving. Court revelations showed that the driver, Martin Asolo-Agogua, had not slept the night before the crash and had consumed cannabis, an act that undoubtedly impaired his ability to drive safely. At Woolwich Crown Court, he pleaded guilty to causing death by dangerous driving and driving while unfit through drugs.
The court has informed Asolo-Agogua that a prison sentence is inevitable and has imposed an interim driving ban on him while he awaits sentencing on 9th June.
Rising Tragedy of Drug-Driving in the UK: The sad reality of Ada’s death is part of a broader issue that is escalating on UK roads. Deaths and injuries attributable to cannabis-related deaths and drug-driving crashes have increased sharply over the last decade.
Drug-Driving Fatalities on the Rise
- Drug-driving fatalities have increased by 164% over the last decade, with 124 deaths in 2023 compared to 47 in 2014.
- Such accidents now constitute 8% of all road fatalities in the UK, underscoring the urgent need for proactive measures to combat drug-driving.
- Among the most common drugs linked to these incidents are cocaine, cannabis, morphine, and ketamine, all of which severely impair driving capabilities.
Impact by Age Groups
Statistics reveal that the most affected age group is 20-29 years, followed by drivers aged 30-39. Many cannabis users in these age ranges often underestimate the significant dangers of impaired driving, believing false claims that driving under the influence of cannabis is safer.
Broader Implications of Drug-Driving: Drug use not only contributes to life-altering accidents but impacts countless families, leads to legal trouble, prison sentences, and spikes in insurance costs. Misconceptions around cannabis consumption being “harmless” have contributed to these issues, especially considering the drug’s legalisation in various contexts worldwide.
Matt Pernet, Head of Direct Line Motor Insurance, has reiterated the severe risks associated with drug-impaired driving, saying, “Anyone that gets behind the wheel after taking illegal drugs is making a terrible decision, which can have life-altering consequences for themselves and others.”
Educating Communities About Cannabis-Related Death Risks: The untimely loss of Ada Bicakci serves as a grave reminder of the need for more robust community awareness and legal measures to tackle drug-driving. It is vital to dispel myths around cannabis and its effect on individuals’ ability to drive safely.
Communities, law enforcement, and policymakers must collectively work to ensure drivers understand the legal and moral consequences of drug use. By implementing steadfast prevention efforts, enforcing stricter laws, and launching sustained education campaigns, they can protect lives, especially in response to incidents like the Bus driver cannabis death in Bexleyheath. (Source: WRD News)
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Astrogliosis Occurs Selectively in Amygdala of Adolescent Primate and Rodent Following Daily Δ9-Tetrahydrocannabinol
Among the advantages of this preclinical research is that there are no critical confounds (no family stress, no bad neighbourhoods, poor grades at school, no other drug use, dose and purity of THC are known, age of onset is fixed). Bear in mind: 13% of 12th graders in U.S. use marijuana daily. It's a complicated paper but here is the bottom line. In primate and rodent adolescent, daily THC caused:
- An increase in inflammatory cells (GFAP-astrogliosis) in a key region of the brain, the amygdala. This brain region is implicated in a large array of physiological functions (survival, sizing up feelings, threats, safety, generating anxiety fear, aggression, stress) and psychopathology related to marijuana use (depression, anxiety, psychosis, hyperreaction to stress, sleep problems and others).
- This response to daily THC was observed only in adolescent amygdala, not in adult amygdala treated daily with THC!
- This response to daily THC was observed only in adolescent amygdala, and not in two other brain regions examined.
- Other makers of inflammation were also elevated (complement factors). These are implicated in psychiatric disorders associated with adolescent cannabis exposure. Aberrant complement function has been linked to schizophrenia, depression, and anxiety, suggesting an overlapping contribution of this inflammatory pathway in cannabis associated psychiatric pathology.
- THC-induced increases in these inflammatory markers may drive abnormal pruning in the amygdala to the detriment of establishing appropriate connections, dysregulating its behavioural outputs.
- THC reduced two proteins that are critical for brain development and improve connections between nerve cells, but only in adolescent and not in adult amygdala.
- Cannabidiol (CBD) prevented astrogliosis but did not restore proteins implicated in connectivity.
- Increased inflammation correlated with fragmented sleep in primates. These changes may contribute to sleep disturbances observed in adolescent heavy marijuana users.
- Reduced markers for connectivity correlated with anxiety Behavior in rodents
- Same effects were found if specific brain cells (astrocytes) were isolated, cultured and exposed to THC.
- Effects required cannabinoid receptors
- THC reduced cannabinoid receptors in astrocytes in the adolescent brain, which may be the reason for these changes.
In summary: Results reveal that chronic THC exposure during a critical period of adolescent brain maturation elicited inflammatory activation of astrocytes and attenuated expression of certain proteins in the amygdala, together vital for regulation of sleep and anxiety. These mechanisms underscore the significant detrimental reorganization of the adolescent neuronal and glial landscape within the amygdala following chronic THC exposure, which does not occur in other brain regions or following comparable THC exposure in adult animals. Our results demonstrate a vital mechanism potentially underlying the increased risk of psychiatric disorders involving amygdala dysfunction following chronic cannabis use at a critical developmental stage.
(Click here for PDF Paper Source: ScienceDirect)
Bertha K Madras, PhD
Professor of Psychobiology, Department of Psychiatry
Harvard Medical School
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Marijuana is often portrayed as harmless, with countless individuals and media outlets emphasising its perceived benefits. However, the PBS documentary: Experts are sounding the alarm about the dark side of cannabis sheds light on an alarming concern overshadowed by the growing cannabis industry. This investigative feature explores the devastating impact of high-potency marijuana on mental health, particularly in young adults, and its link to cannabis-induced psychosis.
Through real-life stories and expert research, the documentary reveals how today’s marijuana—with THC concentrations reaching up to 100% in some products—is a far cry from the mild, recreational substance of decades past. Join us as we uncover the dangers of high-potency marijuana and the tragic consequences experienced by those featured in HIGH RISK.
Johnny Stack’s Story A Tragedy of Cannabis-Induced Psychosis: The documentary opens with the heartbreaking story of Johnny Stack, a once-aspiring, academically gifted teenager who spiralled into despair after falling victim to cannabis-induced psychosis. Johnny, who achieved a perfect SAT maths score, began using marijuana at the age of 14 during a high school party. Over time, he progressed from occasional use to consuming extremely potent THC products.
At the age of 18, Johnny obtained a medical marijuana card under dubious circumstances, as he had no chronic conditions or disorders. This escalation marked the beginning of a sharp decline in his mental health. “It was like an alien came and took my child,” recalled Laura Stack, Johnny’s mother. She described the harrowing transformation in her son’s personality, moving from kind-hearted to toxic and aggressive.
Despite multiple hospitalisations for cannabis-induced psychosis, Johnny repeatedly relapsed, convinced that his brain had healed. Tragically, his final psychotic episode involved extreme paranoia about the Russian mob and FBI surveillance, leading him to take his own life by jumping from a six-storey car park. He left his mother with these haunting final words, “Marijuana has ruined my mind and my life, and I’m sorry, Mama, I love you.”
Grace Davis Offers a Peer Perspective: Grace Davis, Johnny’s university friend, provides another perspective on the prevalence of marijuana use among young adults. She speaks candidly about the normalisation of cannabis use on college campuses, the ease of access through social media, and her personal struggles with addiction.
Grace shared how Johnny’s high tolerance for potent cannabis products contributed to his psychosis. She witnessed his paranoia firsthand, including beliefs that the “Russian mob was coming to get him” and that “the FBI was tracking his phone.” Despite her warnings to Johnny, she herself fell into daily use, leading to lasting paranoia even after two years of sobriety. “I know it wouldn’t have been this bad without marijuana,” Grace admits.
Bryn Spejcher’s Harrowing Experience: The documentary also focuses on Bryn, a Californian audiologist whose life took a tragic turn after experiencing cannabis-induced psychosis. After taking just two hits from a high-potency bong, Bryn fell into a psychotic episode marked by intense hallucinations and violent behaviour. This resulted in the tragic death of her friend Chad, whom she stabbed 108 times. Bryn’s case challenges the misconception that cannabis-induced psychosis only affects regular or heavy users.
Marijuana’s Escalating Potency
One of the most shocking revelations in the documentary is the dramatic rise in the potency of marijuana in recent decades. THC levels have surged from less than 3% in the 1980s to nearly 100% in modern concentrates like dabs, waxes, and shatter. Experts explain how these ultra-potent products are linked to severe mental health consequences, particularly in adolescents and young adults.
Dr. Sam Wang, a paediatric emergency doctor, emphasises the extraordinary risks for developing brains. The prefrontal cortex, which governs critical decision-making and emotional regulation, is highly susceptible to damage from THC. Dr. Wang warns, “Nearly 50% of individuals with cannabis-induced psychosis may go on to develop schizophrenia or bipolar disorder.”
Colorado Lessons in Legal Marijuana
The documentary uses Colorado, the first state to legalise recreational marijuana, as a case study. While the move was initially celebrated for generating significant tax revenue, unforeseen public health challenges quickly emerged. For example, cannabis-related emergency room visits became daily occurrences, with cases of “cannabis hyperemesis syndrome” (extreme nausea and abdominal pain) becoming alarmingly common.
Efforts to address these issues culminated in Colorado House Bill 1317, which introduced mandatory warning labels about mental health risks, restricted medical marijuana cards for young people aged 18–20, and allocated funding for public health research. Although initial proposals to cap THC levels faced resistance from the marijuana industry, these regulatory measures marked a significant step forward.
The Shadow of Synthetic Cannabinoids
Adding to the complexity, synthetic cannabinoids like Delta-8 and Delta-9 present another layer of danger. These substances often bypass state-level restrictions, leading to more widespread accessibility and severe mental health outcomes. Lawmakers and healthcare providers express frustration over the regulatory challenges, with Wyoming officials describing the mental health crisis and soaring suicide rates linked to Delta-8 products.
Advocacy and Education Efforts
Following Johnny’s tragic death, his mother Laura founded Johnny’s Ambassadors, a nonprofit organisation dedicated to raising awareness about the dangers of high-potency marijuana. She now speaks at schools, warning that cannabis is a contributing factor in adolescent suicides. Laura implores parents, “Education and regulation are essential to prevent further tragedies like Johnny’s.”
The documentary closes with Grace’s heartfelt letter to Johnny, encapsulating the devastating personal loss caused by cannabis-induced psychosis. She writes, “Your love could swell my mind whole… but then you died, and so did I.”
Shedding Light on High Potency Marijuana Dangers
HIGH RISK highlights an undeniable truth that challenges the narrative of marijuana as a harmless drug. The rise of high-potency THC products demands greater public awareness and stricter regulations. By documenting real-life tragedies, backed by scientific research, the documentary underscores the severe mental health risks posed to young adults.
Johnny Stack’s story, Grace’s testimony, and Bryn’s loss serve as poignant reminders of the human cost of ignoring these warnings.