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JAMA Network: Open Published Online 2025;8;(1):e2457069. doi:10.1001/jamanetworkopen.2024.57069
Key Points
Question Are recent cannabis use and lifetime cannabis use associated with differences in brain function during cognitive tasks?
Findings In this cross-sectional study of 1003 young adults, heavy lifetime cannabis use was associated with lower brain activation during a working memory task; this association remained after removing individuals with recent cannabis use. These results were not explained by differences in demographic variables, age at first cannabis use, alcohol use, or nicotine use.
Meaning These findings suggest that cannabis use is associated with short- and long-term brain function outcomes, especially during working memory tasks.
Abstract
Importance Cannabis use has increased globally, but its effects on brain function are not fully known, highlighting the need to better determine recent and long-term brain activation outcomes of cannabis use.
Objective To examine the association of lifetime history of heavy cannabis use and recent cannabis use with brain activation across a range of brain functions in a large sample of young adults in the US.
Design, Setting, and Participants This cross-sectional study used data (2017 release) from the Human Connectome Project (collected between August 2012 and 2015). Young adults (aged 22-36 years) with magnetic resonance imaging (MRI), urine toxicology, and cannabis use data were included in the analysis. Data were analyzed from January 31 to July 30, 2024.
Exposures History of heavy cannabis use was assessed using the Semi-Structured Assessment for the Genetics of Alcoholism, with variables for lifetime history and diagnosis of cannabis dependence. Individuals were grouped as heavy lifetime cannabis users if they had greater than 1000 uses, as moderate users if they had 10 to 999 uses, and as nonusers if they had fewer than 10 uses. Participants provided urine samples on the day of scanning to assess recent use. Diagnosis of cannabis dependence (per Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) was also included.
Main Outcomes and Measures Brain activation was assessed during each of the 7 tasks administered during the functional MRI session (working memory, reward, emotion, language, motor, relational assessment, and theory of mind). Mean activation from regions associated with the primary contrast for each task was used. The primary analysis was a linear mixed-effects regression model (one model per task) examining the association of lifetime cannabis and recent cannabis use on the mean brain activation value.
Results The sample comprised 1003 adults (mean [SD] age, 28.7 [3.7] years; 470 men [46.9%] and 533 women [53.1%]). A total of 63 participants were Asian (6.3%), 137 were Black (13.7%), and 762 were White (76.0%). For lifetime history criteria, 88 participants (8.8%) were classified as heavy cannabis users, 179 (17.8%) as moderate users, and 736 (73.4%) as nonusers. Heavy lifetime use (Cohen d = −0.28 [95% CI, −0.50 to −0.06]; false discovery rate corrected P = .02) was associated with lower activation on the working memory task. Regions associated with a history of heavy use included the anterior insula, medial prefrontal cortex, and dorsolateral prefrontal cortex. Recent cannabis use was associated with poorer performance and lower brain activation in the working memory and motor tasks, but the associations between recent use and brain activation did not survive false discovery rate correction. No other tasks were associated with lifetime history of heavy use, recent use, or dependence diagnosis.
Conclusions and Relevance In this study of young adults, lifetime history of heavy cannabis use was associated with lower brain activation during a working memory task. These findings identify negative outcomes associated with heavy lifetime cannabis use and working memory in healthy young adults that may be long lasting.
(For complete Research: JAMA Network)
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Abstract
Importance: In the context of the US opioid crisis, factors associated with the prevalence of opioid use disorder (OUD) must be identified to aid prevention and treatment. State medical cannabis laws (MCL) and recreational cannabis laws (RCL) are potential factors associated with OUD prevalence.
Objective: To examine changes in OUD prevalence associated with MCL and RCL enactment among veterans treated at the Veterans Health Administration (VHA) and whether associations differed by age or chronic pain.
Design, setting, and participants: Using VHA electronic health records from January 2005 to December 2022, adjusted yearly prevalences of OUD were calculated, controlling for sociodemographic characteristics, receipt of prescription opioids, other substance use disorders, and time-varying state covariates. Staggered-adoption difference-in-difference analyses were used for estimates and 95% CIs for the relationship between MCL and RCL enactment and OUD prevalence. The study included VHA patients aged 18 to 75 years. The data were analyzed in December 2023.
Main outcome and measures: International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) OUD diagnoses.
Results: From 2005 to 2022, most patients were male (86.7.%-95.0%) and non-Hispanic White (70.3%-78.7%); the yearly mean age was 61.9 to 63.6 years (approximately 3.2 to 4.5 million patients per year). During the study period, OUD decreased from 1.12% to 1.06% in states without cannabis laws, increased from 1.13% to 1.19% in states that enacted MCL, and remained stable in states that also enacted RCL. OUD prevalence increased significantly by 0.06% (95% CI, 0.05%-0.06%) following MCL enactment and 0.07% (95% CI, 0.06%-0.08%) after RCL enactment. In patients aged 35 to 64 years and 65 to 75 years, MCL and RCL enactment was associated with increased OUD, with the greatest increase after RCL enactment among older adults (0.12%; 95% CI, 0.11%-0.13%). Patients with chronic pain had even larger increases in OUD following MCL (0.08%; 95% CI, 0.07%-0.09%) and RCL enactment (0.13%; 95% CI, 0.12%-0.15%). Consistent with overall findings, the largest increases in OUD occurred among patients with chronic pain aged 35 to 64 years following the enactment of MCL and RCL (0.09%; 95% CI, 0.07%-0.11%) and adults aged 65 to 75 years following RCL enactment (0.23%; 95% CI, 0.21%-0.25%).
Conclusions and relevance: The results of this cohort study suggest that MCL and RCL enactment was associated with greater OUD prevalence in VHA patients over time, with the greatest increases among middle-aged and older patients and those with chronic pain. The findings did not support state cannabis legalization as a means of reducing the burden of OUD during the ongoing opioid epidemic. (for complete research https://pubmed.ncbi.nlm.nih.gov/40512510/)
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There is abundant scientific literature on the harms of marijuana use that will be discussed in this report. More than 20,000 peer-reviewed research articles have linked marijuana use to adverse mental health outcomes, ranging from depression to psychosis, as well as consequences for physical health and even negative outcomes for neonates exposed in utero. The connections between marijuana use and negative consequences for mental and physical health, among other risks, are often 2 3 lost in the debate surrounding legalization. The distinction between medical and recreational marijuana has been deliberately blurred by an industry with significant investments in both markets. A study found that despite evidence that lower THC dosage is more appropriate for medical purposes, the medical marijuana products that are advertised in retail stores contain around the same amount of THC as recreational marijuana products, which generally contain upwards of 15% THC (Cash et al., 2020). And a 2022 study suggests that the risk of developing a cannabis use disorder (CUD) increases as marijuana’s THC level increases (Petrilli et al., 2022).
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New research spanning three decades has revealed how experiences during childhood and adolescence significantly influence patterns of cannabis consumption well into adulthood. The French TEMPO cohort study, which followed 622 cannabis users over 30 years (1991-2021) from age 15 to 46, offers crucial insights for understanding and preventing sustained substance use.
Three Distinct Patterns Emerge
Researchers identified three clear trajectories amongst those who had tried cannabis during their teenage years. The majority—69.9%—showed declining consumption over time, naturally reducing their use as they matured. However, 13.7% demonstrated fluctuating consumption, characterised by an initial increase followed by a decrease around ages 27-30, whilst 16.4% exhibited persistent consumption throughout adulthood.
Understanding these childhood cannabis risk factors is essential for developing effective prevention strategies, particularly as the persistent use group began with the highest initial levels of consumption during adolescence.
Early Life Experiences That Matter
The study examined numerous early-life influences to determine which childhood experiences most strongly predicted long-term patterns. For those following the persistent consumption trajectory, three factors stood out prominently.
Academic difficulties emerged as a powerful predictor, with affected individuals 2.47 times more likely to maintain cannabis use into adulthood. This connection works both ways: struggling students may turn to substances as a coping mechanism, whilst cannabis use itself can impair thinking skills, attention and motivation—creating a cycle that perpetuates both academic challenges and continued use.
Early initiation proved particularly concerning. Young people who began using both tobacco and cannabis early were 3.07 times more likely to follow a persistent use path, whilst those who started cannabis early alone were 2.31 times more likely. The study defined early use as age 14 or younger for tobacco and age 16 or younger for cannabis. This finding underscores how the developing teenage brain responds differently to substances, with early exposure potentially changing the brain’s reward systems and increasing the risk of long-term dependency.
Gender also played a significant role, with males 3.66 times more likely to maintain persistent use patterns. This aligns with broader substance use trends, though the gap between males and females has been narrowing in recent years.
Family Environment and Fluctuating Use
For those showing fluctuating consumption patterns—the group that increased use initially before reducing it in their late twenties—family dynamics during childhood proved particularly influential as childhood cannabis risk factors.
Individuals who experienced parental conflict, stress or frequent parental absence before age 17 were 1.93 times more likely to follow this pattern. The family environment serves as a crucial foundation during formative years, and disruption to that stability appears to increase the risk of substance experimentation during adolescence and early adulthood.
Parental smoking also increased the likelihood of fluctuating use patterns significantly—children of smoking parents were 2.18 times more likely to follow this trajectory. Children naturally copy behaviours they observe at home, and parents who use substances—even legal ones like tobacco—may inadvertently signal acceptance of substance use to their children. Research shows that parental substance use not only directly influences children’s behaviour but also shapes their fundamental attitudes towards drugs and alcohol.
Additionally, males were 2.15 times more likely to follow the fluctuating pattern compared to females.
The eventual decline in use amongst this group around ages 27-30 likely reflects major life transitions: entering stable employment, forming committed relationships, pregnancy and parenthood. These milestones often prompt individuals to reassess their substance use, particularly when considering workplace responsibilities and family wellbeing.
Prevention Implications
These findings carry significant implications for prevention efforts. Rather than waiting until problems develop, identifying early cannabis use risk factors allows for targeted intervention during childhood and adolescence—when patterns are still forming.
Schools represent a crucial frontline for prevention. Supporting students who struggle academically, rather than viewing them solely through a disciplinary lens, may help prevent the turn to substances as a coping mechanism. Early screening for behavioural difficulties can identify at-risk young people before substance use begins.
Family support services prove equally vital. Families experiencing conflict, stress or instability need accessible resources to strengthen their functioning. When parents recognise how their own substance use—including seemingly benign behaviours like smoking—influences their children’s choices, they become powerful agents of prevention.
Understanding Childhood Cannabis Risk Factors for Better Outcomes
Education programmes must convey accurate information about cannabis risks, particularly concerning brain development. Many young people underestimate the dangers, believing cannabis to be relatively harmless. Correcting these misperceptions during the crucial window before first use can shift attitudes and delay or prevent initiation.
The study found that individuals born after 1980 were 37% less likely to engage in heavy cannabis use—suggesting that evolving social attitudes, policy changes and prevention programmes can make a difference. This offers hope that sustained prevention efforts targeted at early cannabis use risk factors can continue to shift patterns positively.
For young people who have already begun experimenting, early intervention remains critical. The research confirms that early, regular use dramatically increases the likelihood of persistent consumption. Catching use early and providing support to stop can alter the trajectory before patterns become entrenched.
The Broader Context
Whilst approximately 70% of adolescent cannabis users naturally reduce consumption as they mature, the 16.4% who maintain persistent use face significant long-term consequences. Extended cannabis consumption correlates with reduced educational attainment, lower income levels, higher unemployment rates, relationship difficulties, and both mental and physical health challenges.
The impact extends beyond individual users. Communities bear the costs through healthcare systems, lost productivity, and the ripple effects on families. Preventing persistent use patterns thus represents not just an individual health priority but a broader societal imperative.
Understanding that these patterns often originate in childhood experiences—academic struggles, family instability, parental substance use, early first use—shifts the focus towards prevention rather than dealing with problems after they emerge.
Looking Forward
This comprehensive research reinforces a fundamental principle: the earlier we can identify and address risk factors, the greater our chance of preventing long-term substance use patterns. Childhood and adolescence represent windows of both risk and opportunity.
At risk because developing brains respond differently to substances, early use can change brain connections, and formative experiences shape lifelong behaviours. Yet these years also offer opportunity—the chance to provide support before patterns become fixed, to strengthen protective factors, and to equip young people with skills and knowledge that serve them throughout life.
For parents, educators, healthcare providers and communities, the message is clear: attention to children’s wellbeing during formative years—their academic success, family stability, behavioural health and delay of substance initiation—represents our most powerful tool for preventing sustained cannabis use.
By identifying childhood cannabis risk factors early and responding with appropriate support, we can help ensure that the natural trajectory towards reduced use, followed by 70% in this study, becomes the norm rather than the exception. The goal isn’t simply preventing experimentation—adolescents will be curious—but preventing that experimentation from becoming a persistent pattern that compromises their health, opportunities and futures.
The three-decade span of this research demonstrates that choices and experiences during childhood genuinely matter for decades to come. That reality should inform how we prioritise prevention, early intervention and support for young people and families navigating these critical years.
(Source: WRD News)
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The therapeutic application of cannabis has become increasingly prevalent across developed nations, yet the scientific evidence supporting its medical use remains surprisingly limited. A recent JAMA Clinical Reviews podcast featuring Dr Kevin Hill from Harvard Medical School reveals critical information that healthcare professionals and patients need to understand about the therapeutic use of cannabis and its associated risks.
According to recent data, approximately 27% of adults in the United States and Canada have used cannabis for medical purposes, whilst just over 10% have tried cannabidiol (CBD) for therapeutic reasons. This widespread adoption has occurred despite minimal regulatory approval and mounting evidence of significant health risks.
Understanding Cannabis and Its Components
Cannabis is a complex plant containing hundreds of chemical compounds, including flavonoids, terpenes, and cannabinoids. Whilst over 140 cannabinoids exist within the plant, medical discussions typically focus on two: delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the psychoactive compound responsible for the “high” associated with cannabis use and can also trigger psychotic episodes. CBD, conversely, is not intoxicating, though it does affect how users feel.
The complexity of the therapeutic use of cannabis stems partly from its numerous formulations. People can smoke cannabis flower, consume edible products, vaporise the substance, or apply topical ointments. Each formulation delivers different potencies and onsets of action, with THC content being the critical variable across all forms.
Limited FDA Approvals for Therapeutic Use of Cannabis
Currently, only three cannabinoid medications have received approval from the US Food and Drug Administration. Dronabinol (pure THC) and nabilone (a CB1 receptor agonist) are approved for treating nausea and vomiting associated with cancer chemotherapy, as well as appetite stimulation in conditions like HIV. In 2018, one particular CBD formulation gained approval for treating two paediatric epilepsy conditions (Lennox-Gastaut and Dravet syndrome) and seizures associated with tuberous sclerosis in adults.
These limited approvals stand in stark contrast to the numerous conditions for which people currently use cannabis, often without solid scientific evidence supporting its efficacy.
Rising Potency and Escalating Risks
One of the most concerning trends in medicinal cannabis use involves dramatically increasing potency levels. During the 1960s, 1970s, and 1980s, typical cannabis contained three to four percent THC. Published research from the University of Mississippi now shows typical potency hovering near 20 percent THC. This fivefold increase has profound implications for both acute and chronic health effects.
Acute risks associated with cannabis use include impaired judgement, motor skill deficits, elevated heart rate, and transient psychosis. These immediate effects can compromise driving ability and decision-making, posing risks not only to users but to those around them.
Chronic Health Effects and Medicinal Cannabis
The chronic effects of cannabis prove particularly problematic for individuals using daily or near-daily. Dr Hill emphasised that most adverse effects relate to THC rather than CBD, though CBD can cause problems as well. Brain-related complications include addiction, cannabis hyperemesis syndrome (severe cyclical vomiting), and worsening of various psychiatric conditions.
Recent epidemiological research published in JAMA Psychiatry revealed a striking statistic: 34.8% of adult cannabis users develop cannabis use disorder. This represents a significant increase from previous estimates of 10 to 30 percent. For those using cannabis for medical purposes specifically, approximately 29% develop use disorder.
Physical health impacts have become increasingly well-defined through research. Cardiovascular adverse effects, pulmonary complications, and chronic neurocognitive deficits all occur with regular cannabis use. These risks accumulate over time, particularly amongst daily users.
Therapeutic Use of Cannabis and Addiction Risk
Cannabis use disorder represents a significant concern that clinicians must monitor carefully. Warning signs include tolerance (requiring increasingly larger amounts to achieve the same effect), withdrawal symptoms upon cessation, and spending excessive time obtaining or using cannabis at the expense of work, school, or relationship responsibilities.
Diagnostic criteria specify that experiencing two or more of eleven specific factors within a 12-month period indicates cannabis use disorder. Healthcare professionals working with patients considering the therapeutic use of cannabis must remain vigilant for these signs, as addiction can develop even when use begins for legitimate medical reasons.
Particular Concerns for Young People
The developing brain faces unique vulnerabilities to cannabis exposure. Human brains continue developing into the mid-20s, and research demonstrates that early and regular cannabis use can significantly impair cognitive abilities. A 2012 study published in the Proceedings of the National Academy of Sciences found that young people using cannabis daily or near-daily experienced up to an eight-point decline in IQ over time. This represents more than one standard deviation, a statistically and clinically significant reduction.
These findings underscore the importance of preventing cannabis use amongst adolescents and young adults, whose neural development remains incomplete and particularly susceptible to disruption.
The Evidence Gap in Medicinal Cannabis Use
A critical issue confronting healthcare professionals involves patients using cannabis for conditions lacking solid scientific support. Whilst people suffering from chronic medical conditions naturally seek relief, the evidence base for the therapeutic use of cannabis remains limited primarily to the FDA-approved conditions mentioned earlier.
Dr Hill emphasised the importance of clinicians engaging in evidence-based conversations with patients. When patients express determination to use cannabis despite limited evidence, healthcare professionals face the challenging task of providing informed guidance whilst acknowledging the significant risks involved.
Concerns About Concurrent Substance Use
Cannabis use becomes particularly dangerous when combined with alcohol or benzodiazepines. These combinations amplify impairment and increase risks of accidents, respiratory depression, and poor decision-making. Healthcare professionals must clearly communicate these dangers to any patients considering medicinal cannabis.
Changing Legal Landscape and Public Health Implications
As of the podcast recording, 38 US states had implemented medical cannabis policies, with 24 states legalising recreational use. This shifting legal landscape has contributed to increased cannabis use overall, creating what Dr Hill described as a situation where “the train’s left the station.”
However, legal availability should not be confused with medical safety or efficacy. The rise in cannabis use has coincided with increases in cannabis use disorder, emergency department visits related to cannabis, and various other adverse outcomes.
Clinical Guidance for Healthcare Professionals
Healthcare professionals must balance acknowledging patient autonomy with providing evidence-based guidance about the therapeutic use of cannabis. Key points for clinical discussions include the limited scope of FDA approvals for cannabinoid medications, the lack of robust evidence for most conditions people treat with cannabis, the significant risk of developing cannabis use disorder (affecting roughly one-third of users), the particular dangers for young people whose brains are still developing, and the inadequacy of current treatments for cannabis use disorder.
Dr Hill noted that whilst many adverse effects exist, addiction itself is on the rise, and the medical community lacks effective treatments for cannabis use disorder. This reality makes prevention all the more critical.
Understanding the Risks
The therapeutic use of cannabis and cannabinoids represents a complex intersection of patient demand, limited scientific evidence, changing social attitudes, and concerning health risks. Whilst three FDA-approved cannabinoid medications exist for specific conditions, widespread cannabis use for medical purposes extends far beyond these narrow indications.
The dramatic increase in cannabis potency over recent decades, combined with rising rates of cannabis use disorder, creates a public health challenge that demands attention. Healthcare professionals must remain informed about both the limited evidence supporting medicinal cannabis and the well-documented risks associated with regular consumption.
For young people in particular, the potential for lasting cognitive impairment and the high risk of developing addiction make cannabis use a serious concern. As legal barriers continue falling, the importance of education about risks becomes paramount.
Understanding these realities allows healthcare professionals to engage patients in meaningful, evidence-based discussions about the therapeutic use of cannabis. Such conversations must acknowledge patient suffering and desire for relief whilst honestly presenting the limited evidence base and substantial risks that accompany cannabis consumption.
(Source: WRD NEWS)
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