Lifetime Cannabis Use, Brain Volume, and Cognitive Function in Middle-Aged and Older Adults

March 26, 2026

At the March CMCR Investigators’ Meeting, Anika Guha, Ph.D., of the Rocky Mountain Cannabis Research Center at the University of Colorado Anschutz Medical Campus, presented research on lifetime cannabis use and its associations with brain volume and cognitive functioning in middle-aged and older adults. Her talk examined whether cannabis may have different effects on the aging brain than those typically reported in younger populations.

Dr. Guha began by noting that cannabis use is increasing among older adults, many of whom report using it to address pain, sleep problems, and anxiety. At the same time, relatively little is known about the long-term effects of cannabis on brain health in aging populations. She emphasized that much of the existing literature has focused on adolescents and young adults, often highlighting adverse effects during periods of active brain development.

She then reviewed prior work from her group suggesting that age may moderate cannabis-related effects. In smaller studies of older adults, cannabis use was associated with differences in endocannabinoid responsivity, acute cognitive effects, and regional brain morphology. These findings helped motivate a larger analysis using UK Biobank data.

Using self-reported lifetime cannabis exposure in a large cohort of middle-aged and older adults, Dr. Guha and colleagues found that cannabis use was associated with larger volumes in several subcortical and limbic regions, including the putamen, hippocampus, amygdala, and caudate. Cognitive analyses also showed better performance among cannabis users than non-users across several domains, particularly among moderate users. Similar patterns were observed in a subgroup whose cannabis use reportedly occurred only before age 25.

In closing, Dr. Guha emphasized that these findings do not establish that cannabis is beneficial, but they do challenge overly broad assumptions about uniformly negative effects on the aging brain. They highlighted the need for future studies with better measures of dose, product type, biomarkers, longitudinal change, and dementia-related outcomes.

Anika Guha, PhD
Faculty Research Associate
University of Colorado Anschutz Medical Campus

Dr. Guha’s research examines the effects of cannabinoids and psychedelics on neurocognition and mental health across the lifespan, with a particular focus on adolescence and older adulthood. She previously worked with Dr. Beau Ances at Washington University in St. Louis, received her Ph.D. in Clinical Psychology from UCLA, and completed postdoctoral training at the University of Colorado Anschutz Medical Campus, where she focused on translational neuroimaging research. Dr. Guha currently works in the Cannabis, Health, and Addiction Over the Lifespan (CHAOS) Lab directed by Dr. Kent Hutchison.

Cannabis and Psychosis: A Genetically-Informed Perspective

February 26, 2026

At the February CMCR Investigators’ Meeting, Emma Johnson, Ph.D., Assistant Professor of Psychiatry at Washington University School of Medicine, presented a genetically informed perspective on the relationship between cannabis use and psychosis. She examined whether associations between cannabis use and schizophrenia reflect causal effects, shared genetic liability, or both.

Drawing on large genomewide association studies (GWAS), Dr. Johnson reviewed evidence that cannabis use behaviors are complex and polygenic. Both lifetime cannabis use and cannabis use disorder (CUD) show moderate genetic correlations with schizophrenia, suggesting overlapping genetic risk. Cross-trait analyses identified overlapping genetic regions linked to schizophrenia, cannabis use disorder, and tobacco use, many of which involve genes that are active in the brain.

However, shared genetic liability does not rule out causal effects. Epidemiologic data continue to support dose-response relationships, particularly for heavy, high-potency, or early-onset use. Dr. Johnson emphasized that causal and genetic vulnerability models are not mutually exclusive.

She then presented new findings from the All of Us Research Program. Lifetime and more frequent cannabis use were associated with psychotic-like experiences, including perceptual distortions and referential ideation. Modest evidence suggested that schizophrenia polygenic risk may amplify some associations. However, individuals with higher genetic risk were also more likely to use cannabis, indicating gene–environment correlation that complicates interpretation.

Finally, Dr. Johnson highlighted the importance of accounting for polysubstance use, noting independent associations of methamphetamine and tobacco use with certain psychotic-like symptoms.

In closing, she argued that the cannabis–psychosis relationship likely reflects both shared genetic architecture and independent exposure effects. Larger, better-phenotyped studies will be essential to clarify mechanisms and guide clinical and public health decision-making.

Emma Johnson, Ph.D.

Assistant Professor of Psychiatry

Washington University School of Medicine

Dr. Johnson’s research leverages large-scale, genome-wide data to explore the genetic and environmental contributions to substance use behaviors and other behavioral psychiatric phenotypes. Much of her work has focused on characterizing the relationship between cannabis use and schizophrenia, supported by a career development award from the National Institute on Drug Abuse. She has been recognized with Early Career Investigator Awards from the Research Society on Alcohol and the Federation of Associations in Behavioral & Brain Sciences.

Cannabinoids for the Treatment of Pain: The Case of Sickle-Cell Anemia

January 22, 2026

At the January CMCR Investigators’ Meeting, Daniele Piomelli, Ph.D., Distinguished Professor at UC Irvine and Editor-in-Chief of Cannabis and Cannabinoid Research, presented findings on the potential of cannabinoids for treating pain associated with Sickle Cell Disease (SCD). While acknowledging a recent large-scale clinical trial for chronic low back pain, Dr. Piomelli focused on the urgent need to identify specific clinical pain conditions amenable to cannabinoid interventions using robust preclinical models.

Using a humanized mouse model of SCD, Dr. Piomelli’s team demonstrated that acute administration of low-dose THC (1 mg/kg) effectively normalized disease-specific hyperalgesia and allodynia. Interestingly, during subacute (14-day) administration, efficacy was maintained for mechanical allodynia without tolerance, whereas tolerance developed rapidly for cold hyperalgesia, suggesting modality-specific responses. The presentation also highlighted the efficacy of cannabidiol (CBD). Unlike the high doses typically used in epilepsy, lower doses of CBD (10 and 30 mg/kg) provided robust analgesic effects in the SCD model with no observed tolerance.

When THC and CBD were co-administered at low doses (0.45 mg/kg THC and 5.08 mg/kg CBD), Dr. Piomelli observed a synergistic effect. He detailed the potential mechanisms driving this interaction: pharmacokinetically, the combination appeared to slow metabolism, increasing circulating levels of both cannabinoids. Pharmacodynamically, the combination significantly elevated levels of the endocannabinoid 2-arachidonoylglycerol (2-AG), a phenomenon also recently observed in human subjects. At the molecular level in the spinal cord, the compounds showed complementary anti-inflammatory actions, with CBD reducing pro-inflammatory IL-1β and THC increasing anti-inflammatory IL-10.

Concluding his talk, Dr. Piomelli argued that these solid preclinical data justify the development of a properly designed, sufficiently powered clinical trial for SCD. He advocated for oral administration to ensure consistent dosing and metabolic activation, suggesting that a targeted, condition-specific approach is necessary to move beyond the failures of previous broad-spectrum clinical methodologies.

Daniele Piomelli, PhD, MD (hon) is the Louise Turner Arnold Chair in Neurosciences and Distinguished Professor of Anatomy & Neurobiology, Pharmacology & Biological Chemistry at UC Irvine. Dr. Piomelli is a world-renowned cannabis scientist who directs the NIDA Center of Excellence ICAL (Impact of Cannabinoids Across the Lifespan) and UCI's Center for the Study of Cannabis. Dr. Piomelli is Editor-in-Chief of Cannabis and Cannabinoid Research, a premier peer-reviewed journal entirely dedicated to the study of cannabis, its derivatives, and their endogenous counterparts in the human body. He is author of >470 peer-reviewed articles, three full-length books, and >38 patents.

Countermeasures and Strategies to Address Cannabis-Impaired Driving; A Multi-State Survey Study

October 23, 2025

At the October CMCR Investigators’ Meeting, Dr. Linda Hill, Distinguished Professor at UC San Diego and Director of the Transportation Research and Education for Driving Safety (TREDS) program, and Sarah Hacker, Research Program Manager and Data Analyst at the Herbert Wertheim School of Public Health, presented findings from a multi-state study conducted by UC San Diego’s TREDS team in collaboration with the AAA Foundation for Traffic Safety to understand how to reach drivers who use cannabis and still get behind the wheel.

The project unfolded in three parts: interviews with national subject-matter experts; a broad, anonymous survey of 2,000 adults from eight states spanning fully legal, medicinal-only, and illegal cannabis laws; and a second survey (n ≈ 846) testing specific public-safety messages among medium- to ultra-high-risk same-day users.

Key patterns emerged. First, legality didn’t neatly predict use: self-reported cannabis prevalence was similar across legal and illegal states. Risky driving behavior was common—about half of users reported driving within an hour of use. Many believed cannabis did not worsen their driving, and a sizeable minority believed it improved it. Knowledge gaps were striking: in medicinal-only and illegal states, many participants misunderstood their state’s legal status and driving restrictions, and few cited fear of being stopped by police as influencing wait times before driving.

Message testing offered practical direction. Three messages consistently resonated: “Driving high is driving impaired,” “If you feel different, you drive different,” and “THC slows reaction time.” Pairing messages with images emphasizing consequences and community safety—along with clear alternatives such as rideshares—enhanced impact. Trust mattered: safe-driving advocates, healthcare providers, and science organizations were more credible than influencers or polarizing law-enforcement imagery. The toughest audience was the ultra-high-risk group (often younger, male, frequent users), who tended to be less trusting and more likely to feel “immune” to impairment; however, medium-risk users showed meaningful openness to changing behavior.

Bottom line: Broad, evidence-based campaigns already in use work, especially when they highlight impairment, promote alternatives to driving, and come from trusted messengers. To reduce cannabis-related crashes, prioritize targeted education in lower-knowledge states and tailor outreach to move medium-risk drivers toward safer choices.

Dr. Linda L Hill, MD, MPH
Dr. Linda L Hill, MD, MPH, is a Distinguished Professor and Founding Faculty of the Herbert Wertheim School of Public Health, where she is also Associate Dean. Dr. Hill obtained her MD from the University of Ottawa, in Ottawa, Canada in 1978 and completed a transitional internship at McGill University in 1979. She completed her residency in Preventive Medicine from the University of California San Diego (UCSD)/San Diego State University (SDSU) General Preventive Medicine Residency in 1985. She is a Fellow of the American College of Preventive Medicine. She was the founding Medical Director of the Exercise and Physical Activity Resource Center at UCSD at Qualcomm Institute. She is Faculty and immediate past Program Director of the UCSD/SDSU General Preventive Medicine Residency since 1989. San Diego Family Care, a Federal 330 Community Health Center, is the site of her clinical activities, as Medical Director 1980 to 2001, and Senior Staff Physician since 2001. She is the Director of the UCSD Training, Research and Education for Driving Safety (treds.ucsd.edu) and Co-Director of the UCSD Center for Human and Urban Mobility. She is the Executive Director of the Asylum-Seeker Shelter Health Assessment Program. Dr. Hill is engaged in prevention research and teaching, with current and past support from the NIH, the California Office of Traffic Safety, Robert Wood Johnson, American Cancer Society, Health Services Resource Administration, Caltrans, Federal Motor Carriers Service Association, and AAA Foundation for Traffic Safety, Caltrans, and the Bureau of Cannabis Control and is the author of 110+ peer reviewed papers, 4 book chapters, and 140+ abstracts. Her hobbies include classical piano and ocean sports.

Sarah Hacker 
Sarah Hacker is currently a Research Program Manager and Data Analyst at the Herbert Wertheim School of Public Health at UC San Diego. Sarah currently works with Dr. Linda Hill and TREDS (Transportation Research and Education for Driving Safety) on a variety of transportation safety projects. Her educational background is in psychology (cognition and neuroscience) and statistics, and she has used this to study driving behavior in a variety of populations. She has produced several grants, technical reports, and presentations on impaired driving, including cannabis-impaired driving.