AHA's new statement focuses on cannabis and brain health

Abstract

Cannabis, is used by hundreds of millions of people worldwide for recreational, medicinal, or other applications. According to a 2021 Gallup poll, 49% of Americans have tried cannabis, up from 45% in 2017 and 2019. “Despite its frequent use, few persons in the community understand what brain systems may be affected by marijuana and by what mechanisms,” said Philip Gorelick, MD, MPH, an adjunct professor at Northwestern University. Gorelick is coauthor of a new statement—The Use of Marijuana: Effect on Brain Health—by the American Heart Association (AHA), which provides a review of the safety of cannabis use from the perspective of brain health, describes mechanistically how cannabis may cause cognitive dysfunction, and advocates for a more informed health care worker and consumer about the potential for cannabis to adversely affect the brain. “Based on preclinical models, cannabis and its associated signaling pathways may influence key cerebral processes such as occurrence of brain inflammation, neurogenesis, neural migration, synaptic pruning—such as loss of synaptic contacts—and white matter development,” Gorelick said. Gorelick added that long-term exposure in adolescence to tetrahydrocannabinol—the chemical compound in cannabis responsible for its psychoactive quality—may disrupt certain neurotransmitter signaling systems and set the stage for later cognitive deficits and altered social and emotional behavior. Cannabinoids can also regulate metabolic processes that influence how drugs are absorbed in adults, which is especially relevant to pharmacists, said Gorelick. Even though data are lacking on how cannabis can affect many medications, it's well-understood currently that it interacts with several antiepileptic medications. While the research on medical cannabis is expanding, few randomized controlled trials have been conducted. If they do exist, they are small, said Kam Capoccia, PharmD, BCPS, CDCES, who spoke on the topic of cannabis and the implications for pharmacists at APhA2022 held in San Antonio, TX. Capoccia noted that people are using cannabis regardless of an FDA approval and companies are already making big profits, too. “We are not going to get the randomized controlled trials that we are used to and that we want,” she said. “It's really unprecedented that we have indications without any strong clinical data that are being included as acceptable.” Because uncertainty exists around cannabis products that may have been used in research, Capoccia said it's difficult for clinicians to look at a study and think there will be a benefit to patients. “It's hard to extrapolate the data,” said Capoccia, who is a clinical professor of community care at Western New England University College of Pharmacy. “Then there is so much drug variation because there is not standardization. Products are not regulated and can be made by so many different companies.” In 2018, FDA approved Epidiolex (Greenwich Biosciences) as the first-ever product containing cannabidiol—one of the 554 compounds in the cannabis plant that has no psychoactive properties. The drug is indicated for two rare and severe forms of epilepsy in patients ages 2 years and older. FDA has also approved 3 synthetic cannabis-related drug products for nausea associated with cancer chemotherapy. In early 2022, FDA approved an investigational new drug application for a clinical trial evaluating an investigational drug using CBD as an adjunctive treatment for opioid use disorder. Tabled 1Key points about cannabisAdapted from Testai FD, et al. Stroke. 2022.Actions of cannabis in animal models•THC disrupts endocannabinoid signaling pathways and affects synaptic plasticity. In the short term, this affects the strength of interneuronal connections; in the long term, it leads to changes in the functioning of neuronal networks.•Exposure to THC during adolescence can lead to structural, molecular, and functional alterations of brain circuits, particularly in areas involved in cognition and behavior.Effect of prenatal exposure to cannabinoid agonist•In preclinical models, THC disrupts the normal signaling of the endocannabinoid system during development and throughout ontogenesis and results in abnormal neurotransmission.•Prenatal THC affects neuroanatomic areas associated with cognition and emotional regulation, including the PFC, limbic system, and ventral tegmentum of the midbrain.Effects of cannabis use on human cognition•Acute intoxication with cannabis affects memory, behavior, and impulsivity.•The long-term effect of cannabis on cognition may be domain specific.•Neuroimaging studies have shown structural changes in cannabis users; however, the results are inconsistent.•Functional changes may be observed in areas of the brain involved in cognition among cannabis users.•Early exposure to cannabis may have a negative effect on cognitive function.Effects of cannabis use on cerebrovascular risk and disease•Several studies have described an association between cannabis use and increased risk of stroke.•Data from population survey studies indicate that the pattern (heavy vs. less) and frequency (> 10 days/month) of cannabis use may increase the risk of stroke.•Cigarette smoking is common in cannabis users and may be an important modifier or confounder of the relationship between cannabis use and stroke risk.•Given the potential role of cannabis as a vasoactive substance and its potential role in cardiac pathology and atherosclerosis development, cannabis use also may increase stroke risk via reversible cerebral vasoconstriction syndromes or may indirectly increase stroke risk.•It is possible that differences among some study findings may be attributable to the years in which population cohorts were studied or recruited because most population cohorts were assembled before 2012. Over the past decade, strains of cannabis have been evolving, resulting in plants with high THC concentrations and some preparations that may have synthetic cannabinoids such as Spice, which may influence the association of cannabis use with stroke.Education and future directions•The cumulative evidence collected in clinical and preclinical studies suggests that the consumption of cannabis can have a detrimental effect on brain health. The exact ramifications, however, have not been precisely established.•Emerging evidence questions the widely accepted belief that cannabis is innocuous and suggests that cannabis, particularly THC, negatively affects brain health through direct and indirect mechanisms.•Health care professionals and consumers should receive education on the potential beneficial and harmful effects associated with the use of cannabis, including the increased risk of stroke and cognitive decline.Abbreviations: CBD, cannabidiol; PFC, prefrontal cortex; THC, Δ9-tetrahydrocannabinol. Open table in a new tab Abbreviations: CBD, cannabidiol; PFC, prefrontal cortex; THC, Δ9-tetrahydrocannabinol. Gorelick said that most of the evidence used to inform AHA's new statement came from observational studies, which have their limitations. “As the field is evolving, more well-designed and robust studies are needed to identify new findings and validate previously published results,” he said. But taken together with the preclinical evidence, Gorelick said one can begin to piece together a picture of the mechanisms and safety concerns that may be associated with cannabis use. “The state-of-the-art is such that there are a number of key areas with limited information that are in need of additional research,” he said. For example, there is limited information about possible differential effects of recreational, medicinal, and illicit uses of cannabis and specific types of cannabis products, as well as different effects of social determinants of health and race and ethnicity with cannabis use and brain health. “Because marijuana use is so prevalent in the community, it will be important to educate public health and health care professionals about the potential risks and benefits of marijuana use to empower community members to make informed decisions about its possible use,” Gorelick said. What is cannabis?The cannabis plant contains many active chemicals including 113 cannabinoids. Two of these active chemicals, tetrahydrocannabinol (THC) and cannabidiol (CBD), are responsible for the effects of cannabis in the body.Although it's still an area of evolving research, THC and CBD are known to have different effects. THC binds to cannabinoid receptors in the body, while CBD may interact indirectly with cannabinoid receptors.THC is responsible for the psychoactive quality of cannabis, but it also has antinausea and analgesic effects. CBD, which has no psychoactive properties, is said to help with inflammation. Other compounds in the plant, such as terpenes and flavonoids, may play a synergistic role in the therapeutic effects of cannabis through what's known as the “entourage effect.” The cannabis plant contains many active chemicals including 113 cannabinoids. Two of these active chemicals, tetrahydrocannabinol (THC) and cannabidiol (CBD), are responsible for the effects of cannabis in the body. Although it's still an area of evolving research, THC and CBD are known to have different effects. THC binds to cannabinoid receptors in the body, while CBD may interact indirectly with cannabinoid receptors. THC is responsible for the psychoactive quality of cannabis, but it also has antinausea and analgesic effects. CBD, which has no psychoactive properties, is said to help with inflammation. Other compounds in the plant, such as terpenes and flavonoids, may play a synergistic role in the therapeutic effects of cannabis through what's known as the “entourage effect.”