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"For patients using cannabis or cannabinoids for treatment of medical conditions, clinicians should discuss harm reduction strategies, including avoiding concurrent use with alcohol or other central nervous system depressants such as benzodiazepines, using the lowest effective dose, and avoiding use when driving or operating machinery.
Evidence from randomized clinical trials does not support the use of cannabis or cannabinoids for mostconditions for which it is promoted, such as acute pain and insomnia.“
(For complete analysis https://pubmed.ncbi.nlm.nih.gov/41296368/)
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A groundbreaking study from the University of California San Diego has identified cannabis as a significant gateway to tobacco use among American youth and young adults. The research reveals that cannabis may be responsible for roughly 13% of new regular tobacco cases in the United States.
The study, published in the journal Tobacco Control, challenges traditional assumptions about the relationship between cannabis and tobacco amongst young people. It provides compelling evidence that cannabis serves as a gateway to tobacco addiction rather than the reverse.
Understanding the Cannabis Gateway to Tobacco Research
Researchers analysed national data from more than 13,800 respondents between the ages of 12 and 24 who had not previously been regular tobacco users. The data came from the Population Assessment of Tobacco and Health (PATH) study conducted in 2017.
Among those surveyed, 15% reported using cannabis within the previous year. Four years later, in 2021, cannabis users were significantly more likely to have taken up regular tobacco use compared to non-users.
“This study challenges long-held assumptions about the pathways between cannabis and tobacco use amongst youth,” said corresponding study author Karen Messer, PhD, professor at the UC San Diego Herbert Wertheim School of Public Health and Human Longevity Science.
The observational study tracked participants over four years to examine progression patterns. Researchers used propensity score matching to control for confounding factors including demographics, tobacco use history, perceived harmfulness of cigarettes, and mental health symptoms.
Striking Differences Between Age Groups
Among younger respondents aged 12 to 17, 32.7% of those who used cannabis had become regular tobacco users by 2021. This represented approximately 15 percentage points higher than their peers who did not use cannabis.
The cannabis gateway to tobacco effect proved particularly pronounced in this age group. Among youth who had never used tobacco at baseline, 24.0% of cannabis users reported current regular tobacco use four years later, compared with just 7.5% of matched controls who did not use cannabis.
Among youth who had experimented with but never regularly used tobacco, 36.8% of cannabis users progressed to regular tobacco use. This compared to 22.9% of their matched peers who did not use cannabis.
For young adults aged 18 to 24, the difference was smaller but still notable. Overall, 14% of cannabis users in this age group became regular tobacco users, representing a 5.4 percentage point increase over their matched controls.
National Impact of Cannabis as Gateway to Tobacco
When weighted on a national level, researchers estimate that more than 509,800 fewer young Americans might have avoided regular tobacco use in 2021 if they had not previously used cannabis.
The study attributed 13.0% of total new regular tobacco use in the United States to cannabis. This represents a substantial proportion of new cases amongst a population where tobacco use has historically declined.
Among the estimated 1.96 million never regular tobacco users aged 12 to 17 who used cannabis in 2017, 33.8% progressed to current regular tobacco use by 2021. The matched analysis estimates these numbers would have been reduced by 43.6% in the absence of cannabis.
Among 4.69 million never regular tobacco user young adults who used cannabis, 14.4% progressed to current regular tobacco use. These numbers would have been reduced by 32.6% without cannabis use.
The “Reverse Gateway” Phenomenon
The findings support an emerging “reverse gateway” effect, suggesting that using cannabis may lead to initiation of other addictive substances like tobacco. This challenges the traditional “gateway hypothesis” from the 1970s, which noted that adolescent cannabis users had almost all started by first smoking tobacco.
Public health action against tobacco led to dramatic declines in cigarette smoking amongst US youth. However, cannabis use did not decline in the same way. By 2005, 50% of US high school seniors had ever used tobacco, and 45% had ever used cannabis.
Cigarette smoking is now at historically low levels amongst American youth. However, electronic nicotine delivery systems (ENDS) have become the most popular tobacco product. Ever-use of any tobacco product has remained comparatively stable amongst US high school students at 23.4% in 2024.
Cannabis use has also remained stable, at 47% amongst US high school students in 2024. This rate is higher than tobacco use rates.
Shared Risk Factors and Common Liabilities
Cannabis and tobacco share many common risk factors in this cohort. These included prior experimentation with tobacco products, living with a smoker in the home, reported mental health symptoms, and residence in certain US regions.
Common liabilities for initiation of both substances include individual factors such as anxiety, depression, conduct disorder, and attention-deficit/hyperactivity disorder. Environmental factors include stress, drug use modelling in the family, social norms of friendship groups, and easy access to products.
Twin studies have identified overlapping genetic influences in cannabis and tobacco use. These include genes influencing dopamine signalling and genetic factors predisposing people to impulsivity and risk-taking.
The study found that past-hour substance use was the strongest indicator that someone would use the next day. Situational risk factors, such as seeing drugs or being near substances, also strongly predicted use.
Implications for Prevention Efforts
“These findings underscore the importance of investigating not only the direct effects of cannabis, but also its broader influence on patterns of tobacco initiation and dependence,” Messer explained.
The finding that prior cannabis use is a major risk factor for initiation of current regular tobacco use amongst youth suggests important policy implications. The effect occurs independent of whether young people have tried tobacco, indicating cannabis represents a primary risk factor.
The research suggests that tobacco control programmes should include cannabis prevention as a key goal. Successful teenage tobacco control activities have shown spillover effects in reducing teenage cannabis use in some instances.
However, although major health agencies recognise early cannabis use as a significant public health problem, they have not adequately addressed its potential to increase future regular tobacco use.
Study Methodology and Strength
The study centred on 13,851 respondents aged 12 to 24 years who had never or never regularly used tobacco in 2017. All participants completed follow-up surveys in 2019 and 2021.
Researchers used propensity score matching to create comparable groups. The researchers matched each cannabis user with up to two similar non-users based on demographics, tobacco use history, perceived cigarette harm, mental health symptoms, and other baseline measures.
Most cannabis users (93%) were successfully matched. After matching, the exposure groups were well balanced on all confounders, strengthening the validity of the comparisons.
The comprehensive list of baseline covariates helped control for confounding. Survey weights adjusted for sampling design, longitudinal dropout, and non-response to ensure estimates represented the civilian non-institutionalised US population.
Study Limitations Acknowledged
Researchers noted that the observational study does not prove that cannabis directly causes tobacco use. It demonstrates a strong association whilst controlling for known confounding factors.
Additional factors such as peer influences, socioeconomic status, and general susceptibility to substance use were not fully accounted for and could play a role. Cannabis use may in part be a marker for these underlying factors rather than solely a cause of increased tobacco use.
The study used self-reported measures of tobacco and cannabis use, though such measures have been validated with biomarkers. Attrition and non-response in longitudinal surveys present challenges, though survey weights help mitigate these issues.
The exposure measure of “past 12 months” cannabis use is likely to underestimate effect sizes compared to a more proximal measure such as current cannabis use. This suggests the true association may be even stronger than reported.
Call for Integrated Prevention Strategies
The authors conclude that cannabis use amongst youth should be considered a major risk factor for later tobacco addiction. They recommend that prevention efforts should address both substances together.
Cannabis prevention should be incorporated as a synergistic strategy within tobacco control programmes. Regulatory approaches, school-based interventions, and targeted public health messaging campaigns should address both substances.
The study provides evidence that failure to address cannabis use amongst young people has potential to undermine progress tobacco control efforts have made in reducing tobacco initiation and progression to regular use.
Strategies for integrating the understanding of cannabis as a gateway to tobacco into prevention programmes should be considered urgently. The identification of high-risk groups, the estimated impact of reducing risk factors, and the relative contribution to overall cases all support cost-effective intervention approaches.
The research was funded in part by the Tobacco-Related Disease Research Programme of the University of California and the National Cancer Institute. It represents an important contribution to understanding substance use patterns amongst young people. (Source: WRD News)
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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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