Cannabis legalization & rising sales have not contributed to increase in substance abuse, study finds
BOSTON COLLEGE
The results, utilizing the most recent data on adolescent substance use to evaluate the effect of recreational cannabis legalization and retail sales on youth’s use of cannabis, tobacco, and alcohol, were reported in today’s issue of the Journal of the American Medical Association (JAMA) Pediatrics. See article here: https://jamanetwork.com/journals/jamapediatrics/article-abstract/2817566
The study authors — co-principal investigators Rebekah Levine Coley, a Lynch School of Education and Human Development professor; School of Social Work Professor Summer Sherburne Hawkins; and Christopher F. Baum, chair of the Economics Department — are among the first to evaluate associations between recreational cannabis legislation and recreational cannabis retail sales through 2021.
“Although studies of early-enacting states and Canada reported few effects of recreational cannabis legislation on adolescent substance abuse, experts have highlighted the need to further assess policy outcomes in youth as legislation and retail availability spread, and other policies targeting youth substance use shift,” the authors said. “We found limited associations between recreational cannabis legalization and retail sales with adolescent substance use, extending previous findings.”
Since 2012, 24 states and Washington, D.C. enacted recreational cannabis legislation, and 18 states implemented recreational cannabis sales.
According to the researchers, recreational cannabis legalization was associated with modest decreases in cannabis, alcohol, and e-cigarette use, while retail sales were associated with lower e-cigarette use, and a lower likelihood, but also increased frequency of cannabis use among youth consumers, leading to no overall change in cannabis use.
“The results suggest that legalization and greater control over cannabis markets have not facilitated adolescents’ entry into substance use,” noted the study co-authors.
The researchers analyzed data from nearly 900,000 high school students in 47 states over a10-year period between 2011-2021.
According to the Pew Research Center, 54 percent of Americans live in a state where the recreational use of marijuana is legal, while 74 percent of Americans live in a state where marijuana is legal for either recreational or medical use. Also, 79 percent of Americans live in a county with at least one cannabis dispensary; as of February 2024, there are nearly 15,000 dispensaries operating in the U.S.
Researchers who contributed to the study included Naoka Carey, a doctoral candidate in the Applied Developmental and Educational Psychology department of the Lynch School; and Claudia Kruzik, a postdoctoral research associate at the University of Maryland-College Park.
JOURNAL
JAMA Pediatrics
SUBJECT OF RESEARCH
People
ARTICLE TITLE
Recreational Cannabis Legalization, Retail Sales, and Adolescent Substance Use Through 2021
ARTICLE PUBLICATION DATE
18-Apr-2024
Protecting brain cells with cannabinol
Salk scientists observe cannabinol's neuroprotective properties in fruit flies and identify cannabinol analogs that could serve as promising future therapeutics for traumatic brain injury, Alzheimer's, and Parkinson's
IMAGE:
FROM LEFT: PAMELA MAHER AND ZHIBIN LIANG.
view moreCREDIT: SALK INSTITUTE
LA JOLLA (April 17, 2024)—One in every 10 individuals above the age of 65 develops an age-related neurological disorder like Alzheimer’s or Parkinson’s, yet treatment options remain sparse for this population. Scientists have begun exploring whether cannabinoids—compounds derived from the cannabis plant, like well-known THC (tetrahydrocannabinol) and CBD (cannabidiol)—may offer a solution. A third, lesser-known cannabinoid called CBN (cannabinol) has recently piqued the interest of researchers, who have begun exploring the clinical potential of the milder, less psychoactive substance.
In a new study, scientists at the Salk Institute help explain how CBN protects the brain against aging and neurodegeneration, then use their findings to develop potential therapeutics. The researchers created four CBN-inspired compounds that were more neuroprotective than the standard CBN molecule—one of which was highly effective in treating traumatic brain injury in a Drosophila fruit fly model.
The findings, published in Redox Biology on March 29, 2024, suggest promise for CBN in treating neurological disorders like traumatic brain injury, Alzheimer’s disease, and Parkinson’s disease, and also highlight how further studies of CBN’s effects on the brain could inspire the development of new therapies for clinical use.
“Not only does CBN have neuroprotective properties, but its derivatives have the potential to become novel therapeutics for various neurological disorders,” says Research Professor Pamela Maher, senior author of the study. “We were able to pinpoint the active groups in CBN that are doing that neuroprotection, then improve them to create derivative compounds that have greater neuroprotective ability and drug-like efficacy.”
Many neurological disorders involve the death of brain cells called neurons, due to the dysfunction of their power-generating mitochondria. CBN achieves its neuroprotective effect by preventing this mitochondrial dysfunction—but how exactly CBN does this, and whether scientists can improve CBN’s neuroprotective abilities, has remained unclear.
The Salk team previously found that CBN was modulating multiple features of mitochondrial function to protect neurons against a form of cell death called oxytosis/ferroptosis. After uncovering this mechanism of CBN’s neuroprotective activity, they began applying both academic and industrial drug discovery methods to further characterize and attempt to improve that activity.
First, they broke CBN into small fragments and observed which of those fragments were the most effective neuroprotectors by chemically analyzing the fragment’s properties. Second, they designed and constructed four novel CBN analogs—chemical look-alikes—in which those fragments were amplified, then moved them on to drug screening.
“We were looking for CBN analogs that could get into the brain more efficiently, act more quickly, and produce a stronger neuroprotective effect than CBN itself,” says Zhibin Liang, first author and postdoctoral researcher in Maher’s lab. “The four CBN analogs we landed on had improved medicinal chemical properties, which was exciting and really important to our goal of using them as therapeutics.”
To test the chemical medicinal properties of the four CBN analogs, the team applied them to mouse and human nerve cell cultures. When they initiated oxytosis/ferroptosis in three different ways, they found that each of the four analogs 1) were able to protect the cells from dying, and 2) had similar neuroprotective abilities compared to regular CBN.
The successful analogs were then put to the test in a Drosophila fruit fly model of traumatic brain injury. One of the analogs, CP1, was especially effective in treating traumatic brain injury—producing the highest survival rate after condition onset.
“Our findings help demonstrate the therapeutic potential of CBN, as well as the scientific opportunity we have to replicate and refine its drug-like properties,” says Maher. “Could we one day give this CBN analog to football players the day before a big game, or to car accident survivors as they arrive in the hospital? We’re excited to see how effective these compounds might be in protecting the brain from further damage.”
In the future, the researchers will continue to screen and characterize these CBN analogs and refine their chemical designs. They will also begin looking more closely at age-related neurodegeneration and changes in brain cells, particularly in mitochondria, asking how we can better suit these drug-like compounds to promote cellular health and prevent neuronal dysfunction with age.
Other authors include David Soriano-Castell and Wolfgang Fischer of Salk; and Alec Candib and Kim Finley of the Shiley Bioscience Center at San Diego State University.
The work was supported by the Paul F. Glenn Center for Biology of Aging Research at the Salk Institute, the Bundy Foundation, the Shiley Foundation, the National Institutes of Health (R01AG067331, R21AG064287, R01AG069206, RF1AG061296, R21AG067334, NCI CCSG P30CA01495, NlA P30AG068635, S10OD021815), and the Helmsley Center for Genomic Medicine.
About the Salk Institute for Biological Studies:
Unlocking the secrets of life itself is the driving force behind the Salk Institute. Our team of world-class, award-winning scientists pushes the boundaries of knowledge in areas such as neuroscience, cancer research, aging, immunobiology, plant biology, computational biology, and more. Founded by Jonas Salk, developer of the first safe and effective polio vaccine, the Institute is an independent, nonprofit research organization and architectural landmark: small by choice, intimate by nature, and fearless in the face of any challenge. Learn more at www.salk.edu.
Mouse neuronal cells with mitochondria (red) and nuclei (blue).
The outline of a person and their brain facing a cannabis leaf and symbolic CBN pill, demonstrating the potential for CBN to treat neurological disorders in the future.
The outline of a person and their brain facing a cannabis leaf and symbolic CBN pill, demonstrating the potential for CBN to treat neurological disorders in the future.
CREDIT
Salk Institute
Salk Institute
JOURNAL
Redox Biology
ARTICLE TITLE
Fragment-based drug discovery and biological evaluation of novel cannabinol-based inhibitors of oxytosis/ferroptosis for neurological disorders
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