Open research questions in Cannabis and Cannabinoid Research

What the literature leaves open

• The paper identifies heterogeneity between studies as a challenge, with high I2 values for some outcomes. The paper also notes the limited number of included studies, which precluded the use of certain statistical methods, such as Egger's regression test. The paper highlights the risk of bias in some studies as a challenge, which was assessed using the RoB-2 tool.

  Efficacy and safety of cannabinoid-based interventions for behavioral and cognitive symptoms in dementia: systematic review and meta-analysis · 2026 · DOI

• Due to the limited number of included studies, fewer than 10 per analysis, it was not feasible to conduct Egger's regression test to assess publication bias or perform a meta-regression. The study had a small sample size of 334 participants. The certainty of evidence was low for cognition.

  Efficacy and safety of cannabinoid-based interventions for behavioral and cognitive symptoms in dementia: systematic review and meta-analysis · 2026 · DOI

• Findings cannot rule out a selection process outside the variables assessed, - The study did not assess all possible variables that could influence the results, - The study was limited to two separate studies

  Quasi-randomization to Cannabinoid Condition in Studies of US Legal Market Cannabis: Characteristics of Accepters Versus Decliners of Condition Assignment · 2026 · DOI

• There is a gap in research on legal market cannabis due to the federal classification of cannabis as a schedule 1 drug, which precludes true random assignment. Quasi-randomization is a potential solution to this gap.

  Quasi-randomization to Cannabinoid Condition in Studies of US Legal Market Cannabis: Characteristics of Accepters Versus Decliners of Condition Assignment · 2026 · DOI

• There is a gap in the literature on the relationship between cannabis use and adverse health outcomes in individuals with psychotic disorders. Prior studies have not fully examined the risks of cannabis use in this population.

  People with psychotic disorders are the most vulnerable to cannabis adverse health outcomes: a study in WA State, USA · 2026 · DOI

• The study does not investigate the long-term effects of THC, - The study uses a limited number of samples, - The study focuses on LPS-induced inflammation, - The study does not explore the effects of THC on other types of inflammation

  Delta-9-tetrahydrocannabinol alleviates inflammation by modulating immune responses in LPS-induced murine inflammation model · 2026 · DOI

• Investigate the precise mechanisms of THC's immunomodulatory effects, - Clarify the complex relationship between THC and inflammation, - Explore the effects of THC on other types of inflammation, - Examine the long-term effects of THC

  Delta-9-tetrahydrocannabinol alleviates inflammation by modulating immune responses in LPS-induced murine inflammation model · 2026 · DOI

• The study faced the challenge of conducting research in a context where medical cannabis remains banned. The study had to ensure the validity and reliability of the data collected through self-administered questionnaires and in-depth interviews.

  Knowledge, Attitudes, Beliefs, and Intention to Support Future Legalization of Medical Cannabis Among Vietnamese Nursing Students: A Convergent Parallel Mixed-Methods Study · 2026 · DOI

• The study identifies a gap in the literature on the association between cannabis potency and psychiatric harms at the population level. Prior studies have found associations between potency and individual-level psychiatric harms, but the study aims to examine this association at the population level.

  Changes in cannabis potency and cannabis-related psychiatric harms: a 23-year ecological study in Denmark · 2026 · DOI

• The study notes that evidence for the effectiveness of cannabis for physical and mental health conditions is limited. It also highlights the challenge of discussing risks related to products, potency, and adverse effects in healthcare encounters.

  The use of cannabis for medical reasons in the UK: Prescriptions, sources, products, and high-risk use · 2026 · DOI

• The effects of CBD on cellular lipid profiles are not well understood. Prior studies have not investigated the specific changes in lipid classes and species induced by CBD.

  Lipidomic Evidence for Cannabidiol-Induced Remodeling of Cellular Lipid Composition in SH-SY5Y Cells · 2026 · DOI

• social desirability and recall bias in self-reported measures, - lack of measures to assess the body's exposure to THC, - inconsistencies in findings due to different measurement methods, - limitations in generalizing the results due to the specific sample and context

  Cannabis use is associated with changes in psychological and functional well-being during young adulthood: evidence from self-reports and hair analyses · 2025 · DOI

• investigating the effects of cannabis use on psychopathology and functional outcomes in different populations and contexts, - developing more accurate and reliable measures of cannabis exposure, - examining the dose-response associations between cannabis use and psychopathology

  Cannabis use is associated with changes in psychological and functional well-being during young adulthood: evidence from self-reports and hair analyses · 2025 · DOI

• The study identifies a gap in understanding the interplay between childhood trauma, cannabis use, and paranoia. The study notes that prior research has not fully explored the relationship between childhood trauma, cannabis use, and paranoia.

  The impact of childhood trauma and cannabis use on paranoia: a structural equation model approach · 2025 · DOI

• Investigate nuanced subgroup differences in bidirectional relationships between cannabis and internalizing symptoms based on sexual orientation, - Examine the effects of adverse traumatic childhood experiences on bidirectional relationships

  Examining bidirectional associations between cannabis use and internalizing symptoms among high-risk emerging adults: A prospective cohort study · 2025 · DOI

• The study identifies a gap in the empirical evidence on bidirectional relationships between cannabis use and internalizing symptoms. The study aims to address the gap by investigating the relationships between cannabis frequency and consequences and internalizing symptoms.

  Examining bidirectional associations between cannabis use and internalizing symptoms among high-risk emerging adults: A prospective cohort study · 2025 · DOI

• The study faces challenges in dealing with missing data, with only 48% of participants having available data on all predictors and covariates. The paper notes that the efficacy of available psychosocial treatments for cannabis problems is modest, and long-term outcomes are unclear.

  Association of childhood mental health and cognition with longitudinal patterns of cannabis problems in adolescence · 2025 · DOI

• Missing data was a limitation, with only 48% of participants having available data on all predictors and covariates, - The analysis was limited to a UK-based prospective birth cohort, - The study relied on parent report for some variables

  Association of childhood mental health and cognition with longitudinal patterns of cannabis problems in adolescence · 2025 · DOI

• The lack of understanding of the genetic and environmental contributions to the relationship between cannabis use and psychotic-like experiences. The need to investigate the underlying mechanisms of the relationship between cannabis use and psychotic-like experiences. The gap in current research on the role of the salience network in the relationship between cannabis use and psychotic-like experiences.

  The relationship between recreational cannabis use, psychotic-like experiences, and the salience network in adolescent and young adult twins · 2025 · DOI

• Further research is needed to fully account for the genetic correlation between CUD and SCZ, - Studies should aim to integrate genetic risk factors for heavy cannabis use to advance understanding of SCZ etiology, - Research should investigate the phenotypic co-occurrence of CUD and SCZ in target samples

  Investigating the polygenic relationship between heavy cannabis use and schizophrenia in the All of Us Research Program · 2025 · DOI

• The genetic characterization of the comorbidity between heavy cannabis use and schizophrenia remains incomplete. Prior studies have not fully accounted for the genetic correlation between cannabis use disorder and schizophrenia. The phenotypic co-occurrence of these traits in target samples has not been fully considered.

  Investigating the polygenic relationship between heavy cannabis use and schizophrenia in the All of Us Research Program · 2025 · DOI

• The underlying neurobiological mechanisms of psychotic disorders are still largely unknown. There is a lack of understanding of the relationship between endocannabinoid levels and neurotransmitters in patients with psychotic disorders.

  Endocannabinoid levels in plasma and neurotransmitters in the brain: a preliminary report on patients with a psychotic disorder and healthy individuals · 2024 · DOI

• The gap in the current understanding of the relationship between cannabis use and schizophrenia. The need to investigate whether use of antipsychotic medication, benzodiazepines, and psychiatric service use differs among patients with schizophrenia depending on whether psychosis was precipitated by a diagnosis of cannabis use disorder.

  Use of antipsychotic medication, benzodiazepines, and psychiatric hospitalization in cannabis-related versus cannabis-unrelated schizophrenia – a nationwide, register-based cohort study · 2024 · DOI

• Investigating the receptors through which CBD exerts its effects, - Delving into a detailed discussion of the intricate connections between CBD and liver diseases, - Exploring the potential therapeutic effects of CBD in clinical practice, - Investigating the molecular mechanisms of viral persistence and the risk factors for developing advanced liver disease and HCC

  The Role of Cannabidiol in Liver Disease: A Systemic Review · 2024 · DOI

• Further research is needed to understand the relationship between cannabis use and mental health outcomes, - Studies should investigate the mechanisms by which cannabis use affects individuals with psychotic disorders, - Research should examine the effectiveness of interventions aimed at reducing cannabis use among individuals with psychotic disorders

  People with psychotic disorders are the most vulnerable to cannabis adverse health outcomes: a study in WA State, USA · 2026 · DOI

Most-cited papers in Cannabis and Cannabinoid Research

• Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor · Science · 1992 · 4,582 citations
• Molecular characterization of a peripheral receptor for cannabinoids · Nature · 1993 · 4,138 citations
• Structure of a cannabinoid receptor and functional expression of the cloned cDNA · Nature · 1990 · 4,069 citations
• Unresponsiveness to Cannabinoids and Reduced Addictive Effects of Opiates in CB 1 Receptor Knockout Mice · Science · 1999 · 3,425 citations
• Adverse Health Effects of Marijuana Use · New England Journal of Medicine · 2014 · 2,129 citations
• Cannabinoids for Medical Use · JAMA · 2015 · 1,962 citations
• Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review · The Lancet · 2007 · 1,728 citations
• Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study · The Lancet · 2005 · 1,221 citations
• The Endocannabinoid System and the Brain · Annual Review of Psychology · 2012 · 911 citations
• An improved brief measure of cannabis misuse: The Cannabis Use Disorders Identification Test-Revised (CUDIT-R)☆ · Drug and Alcohol Dependence · 2010 · 848 citations

Most recent work

• Epilepsy, neuroinflammation and cannabidiol What do we know thus far? · Frontiers in Pharmacology · 2026
• Increasing use of cannabis edibles in response to recreational cannabis legalization in the United States · Preventive Medicine · 2026
• The Impact of Recreational Cannabis Legalization on Cannabis Use in U.S. Adults From 2016 to 2023: A Quasi-Experimental Study · American Journal of Preventive Medicine · 2026
• Trends in US adolescent cannabis use, 1991–2023 · Addictive Behaviors · 2026
• Prevalence and Correlates of Symptoms of Cannabinoid Hyperemesis Syndrome in the United States · medRxiv · 2026
• Association of Cannabis Use Disorder Versus Other Substance Use Disorders With Psychiatric Conditions: A Propensity-Matched Retrospective Cohort Analysis · American Journal of Psychiatry · 2026
• Cannabis use in pregnancy: Key findings from 2021-2023 National Survey on Drug Use and Health data · Addictive Behaviors · 2026
• Bridging reward and resilience: the endocannabinoid system as a unifying mechanism in exercise-induced protection against major depressive disorder · Frontiers in Psychiatry · 2026
• Rational design of Gi-biased CB1 agonist with reduced side effects · Cell · 2026
• Replik auf die gemeinsame Stellungnahme der DG-Sucht, DGKJG und DGPPN – Wann sind seriöse Aussagen über Auswirkungen der Teillegalisierung von Cannabis möglich? · SUCHT - Zeitschrift für Wissenschaft und Praxis / Journal of Addiction Research and Practice · 2026

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