Cannabis, albeit widely used around the globe, remains poorly understood in terms of its long-term impacts on human health. Dr. Sandra Sanchez-Roige, associate professor of psychiatry at UC San Diego and the senior author of the study, emphasizes that despite its prevalence, much remains unknown about why some individuals transition from experimentation to problematic use, while others do not. A key objective of the team was to elucidate the genetic factors influencing early-stage behaviors that could indicate vulnerability to cannabis use disorder, a condition characterized by significant interference with daily functioning.

Epidemiological data indicate that approximately 30% of individuals who try cannabis eventually develop cannabis use disorder. This percentage is striking, given that most users do not progress to addiction. Dr. Sanchez-Roige highlights the urgency of identifying biological markers that distinguish those at higher risk. Understanding the genetic architecture of these intermediate behavioral traits stands to revolutionize interventions aimed at halting progression to disorder, potentially mitigating the rising health burden linked to cannabis misuse.

Utilizing a genome-wide association study (GWAS)—a powerful analytical tool to correlate genetic variants across the genome with specific traits—the team analyzed genetic and behavioral data from 131,895 volunteers who are part of 23andMe’s research cohort. Participants self-reported on their lifetime cannabis use and frequency of consumption, providing a robust dataset for interrogating the heritable elements associated with cannabis-related behaviors. GWAS technology permitted an unbiased scan for DNA regions linked with cannabis use, facilitating the discovery of novel genetic loci implicated in this complex trait.

Two genes emerged as primary loci that harbor significant associations with cannabis use. The first, Cell Adhesion Molecule 2 (CADM2), is renowned for its involvement in neuronal connectivity and signaling. This gene has been previously implicated in behavioral traits related to impulsivity and risk-taking, which align with predispositions towards substance use. The study confirmed CADM2’s association not only with whether an individual ever used cannabis but also with the intensity and frequency of use, underscoring its multifaceted role in the behavioral spectrum leading to cannabis engagement.

The second prioritized gene identified was Metabotropic Glutamate Receptor 3 (GRM3). This gene plays a vital role in synaptic communication and neuroplasticity—the brain’s ability to adapt structurally and functionally over time. GRM3’s linkage to psychiatric conditions such as schizophrenia and bipolar disorder has been established, suggesting shared neurobiological pathways across diverse neuropsychiatric phenotypes. Its association with cannabis use frequency offers intriguing insights into the potential neural mechanisms through which cannabis may influence or be influenced by underlying psychiatric vulnerabilities.

Beyond these two prominent genes, secondary analyses uncovered an additional 40 genes associated with lifetime cannabis use and four genes related to usage frequency. Remarkably, 29 of these genes had not been previously connected with cannabis-related behaviors, opening new frontiers for biological research and clinical exploration. This expanded genetic landscape highlights the polygenic and multidimensional nature of cannabis use, which intersects with a multitude of brain functions and systemic physiological processes.

Importantly, the researchers extended their genetic correlations by investigating links with thousands of traits cataloged in two expansive datasets: the National Institutes of Health’s All of Us Research Program and the Vanderbilt University Medical Center biobank. These comprehensive repositories allowed the team to chart the broad health consequences of genetic predispositions to cannabis use, unveiling associations with over 100 traits. These traits encompassed psychiatric disorders such as ADHD, anxiety, depression, and schizophrenia; cognitive attributes including executive function and risk-taking behavior; as well as physical health issues like diabetes, chronic pain, and coronary artery disease.

Further illuminating the complex interplay between cannabis use and other behaviors, genetic predisposition for cannabis consumption was also connected with increased tendencies toward tobacco use and susceptibility to infectious diseases including HIV and viral hepatitis. Moreover, autoimmune diseases emerged as part of the correlated health spectrum, revealing unexpected intersections between genetics of cannabis use and immune system regulation. These findings affirm cannabis use as a multifaceted phenotype with broad systemic implications beyond neural circuits alone.

This study stands among the pioneering genome-wide association efforts focusing on behaviors antecedent to cannabis use disorder. As Dr. Hayley Thorpe, a postdoctoral researcher and the study’s first author, explains, dissecting intermediate traits enables researchers to sketch a more granular map of the genetic risk trajectory, illuminating how predispositions unfold prior to the development of clinical addiction. This approach may ultimately furnish early biomarkers that predict and prevent the onset of cannabis-related disorders.

With no FDA-approved pharmacotherapies currently available to treat cannabis use disorder, the identification of the underpinning molecular systems marks a critical advance toward therapeutic discovery. The authors express hope that the genetic insights gleaned from this extensive GWAS will catalyze the design of future interventions—both pharmacological and behavioral—that target the biological pathways driving susceptibility. Such innovations could transform clinical practice by enabling precision medicine approaches tailored to individual genetic risk profiles.

The interdisciplinary nature of this research underscores the importance of collaboration between academic institutions and industry partners. Alongside UC San Diego’s team, contributors from 23andMe, Western University, Washington University in St. Louis, and Vanderbilt University Medical Center combined their expertise to produce a nuanced picture of cannabis genetics. This exemplifies how big-data approaches coupled with large-scale participant engagement can accelerate elucidation of complex behavioral traits.

Funding for the study was provided by prestigious sources including the National Institute on Drug Abuse at the NIH and the Tobacco-Related Disease Research Program. Ethical oversight was adhered to meticulously, with participant consent obtained through an AAHRPP-accredited protocol managed by the Salus Institutional Review Board, ensuring adherence to rigorous human research standards.

This landmark investigation fundamentally enriches our understanding of how genetic variation informs cannabis use and its broad impacts on mental and physical health. As cannabis legalization expands globally, these findings are particularly timely, equipping the medical and scientific communities with novel frameworks to confront the evolving landscape of cannabis consumption and its associated disorders.

Subject of Research: Genetic influences on cannabis use and associated health outcomes

Article Title: Genomic Insights into Cannabis Use Illuminating Psychiatric and Physical Health Links

News Publication Date: October 13, 2025

Web References:

• Molecular Psychiatry journal
• National Institutes of Health All of Us Research Program
• Vanderbilt University Medical Center biobank

References:

• Sanchez-Roige et al., Molecular Psychiatry, 2025
• NIH grants R01 DA050721, P50DA037844, P30DA060810
• Tobacco-Related Disease Research Program grant T32IR5226

Keywords: Cannabis, Addiction, Behavioral addiction, Behaviorism, Genetics

Insomnia and sleep disturbances affect roughly one-third of the global population at some point in their lives, with approximately 10 percent meeting the clinical criteria for insomnia disorder—a condition characterized by chronic difficulty in initiating or maintaining sleep that significantly impairs daytime functioning. Conventional pharmacological treatments, such as benzodiazepines or non-benzodiazepine hypnotics, often pose risks including tolerance, dependence, and adverse side effects, leaving a critical need for safer and more effective therapies.

Exploring cannabis-based medicinal products as an alternative treatment, the researchers analyzed patient-reported outcomes, focusing on subjective sleep quality, levels of anxiety and depression, and overall quality of life. These metrics provide a comprehensive understanding of how insomnia and associated symptoms respond to cannabis-based interventions over a substantial timeframe. The observational design of the study offers real-world evidence while acknowledging the necessity for future randomized controlled trials to confirm causality and further validate efficacy.

Patients enrolled in the study demonstrated significant, sustained improvements in self-reported sleep quality throughout the duration of the study. Notably, these benefits persisted for up to 18 months, suggesting that cannabis-based products may mitigate the issues of tolerance and diminishing effects observed with many traditional hypnotics. This sustained improvement points to a promising role for cannabinoids in sleep regulation pathways, potentially involving interactions with the endocannabinoid system, which is known to influence circadian rhythms and sleep architecture.

In addition to enhancements in sleep, the study participants showed marked reductions in anxiety and depression symptoms, conditions frequently comorbid with insomnia that exacerbate sleep difficulties. Such improvements are particularly relevant because psychoactive cannabinoids like THC and non-intoxicating compounds such as CBD have demonstrated anxiolytic and mood-stabilizing properties in other clinical contexts, implying a multifaceted therapeutic profile for medical cannabis in neuropsychiatric symptom management.

Pain—a notable contributor to sleep disruption—also lessened significantly among the study cohort. Chronic pain conditions often interfere with the onset and maintenance of restful sleep, and cannabinoids have been widely studied for their analgesic properties. The dual action on pain and sleep disturbances might explain the observed comprehensive improvements and highlight the potential for cannabis formulations tailored to complex symptom clusters.

Side effects associated with cannabis-based medicinal treatment were reported by approximately nine percent of patients, including fatigue, insomnia paradoxically, and dry mouth. Importantly, none were life-threatening or severe enough to warrant discontinuation in most cases. These findings underscore that while not without risk, the safety profile of cannabis-based products may compare favorably to that of conventional hypnotics, which often carry risks of dependence, cognitive impairment, and other adverse outcomes.

Dr. Simon Erridge, Research Director at Curaleaf Clinic and co-author of the study, underscored the significance of these findings in the clinical management of insomnia. He emphasized the importance of monitoring potential tolerance development over time and tailoring treatments on an individual basis to maximize efficacy while mitigating risks. The practical implications for clinicians include the possibility of integrating cannabis-based products as adjunctive or second-line therapy, particularly in patients unresponsive to or intolerant of standard pharmacological options.

The observational nature of this research is both a strength and a limitation. While allowing a realistic picture of patient experiences over an extended period, it inherently cannot establish cause-effect relationships. Confounding variables such as lifestyle changes, placebo effects, and the variability in product formulations and dosages require careful consideration. Nevertheless, the study’s real-world evidence broadens our understanding of medical cannabis’s therapeutic potential, encouraging further rigorously controlled investigations.

From a neurobiological perspective, it has been hypothesized that cannabinoids modulate sleep through their action on CB1 receptors in the central nervous system. These receptors influence neurotransmitters implicated in sleep cycles, such as GABA and glutamate. Moreover, the balance of THC and CBD in medicinal formulations could account for differential effects on sleep latency and maintenance, where THC’s sedative properties complement CBD’s anxiolytic and anti-inflammatory effects, possibly improving sleep architecture and subjective restfulness.

The complex interplay between insomnia, mental health, and pain highlights the multifactorial nature of chronic sleep disorders. Cannabis-based treatments potentially target these overlapping symptoms simultaneously, addressing the limitations of mono-target pharmacotherapeutics. Additionally, favorable patient-reported outcomes may promote adherence, an essential factor often overlooked in clinical trials but critical for real-world success.

As the legal and regulatory landscapes evolve, so too does the urgency to clarify the clinical role of cannabis-based medicinal products. The study’s findings contribute to a growing body of literature advocating for the thoughtful incorporation of these treatments into personalized medicine strategies. However, regulatory agencies and healthcare professionals must weigh these benefits against potential risks, emphasizing careful screening, dosing protocols, and longitudinal follow-up.

In conclusion, this pioneering investigation offers encouraging evidence that cannabis-based medical products can provide meaningful and sustained improvements in sleep quality and associated symptoms over an extended period. While not a panacea, these findings illuminate a promising avenue for patients grappling with the often intractable challenge of insomnia. The research paves the way for future randomized trials that will be critical in defining standardized treatment guidelines and integrating cannabinoid therapies into mainstream clinical practice.

For full access to the study and detailed data, the article appears freely available in PLOS Mental Health, reinforcing the commitment to open science and the dissemination of knowledge that may benefit insomnia patients worldwide.

Subject of Research: People

Article Title: UK Medical Cannabis Registry: A clinical outcomes analysis for insomnia

News Publication Date: 27-Aug-2025

Web References: https://doi.org/10.1371/journal.pmen.0000390

References:
Aggarwal A, Erridge S, Cowley I, Evans L, Varadpande M, Clarke E, et al. (2025) UK Medical Cannabis Registry: A clinical outcomes analysis for insomnia. PLOS Ment Health 2(8): e0000390. https://doi.org/10.1371/journal.pmen.0000390

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