Google the three-letter acronym “CBD,” and you will receive 177 million results. For comparison, a search for “FBI” produces 213 million hits, “IBM,” 305 million, and “FDR,” just 51.3 million. Do you know what CBD is? More important, do you know what it does?CBD is short for cannabidiol, a seemingly non-intoxicating compound of the cannabis plant, as opposed to tetrahydrocannabinol (THC), the major psychoactive component responsible for the drug’s euphoric effect.CBD is the main active ingredient in a growing category of products sold in all 50 states with little regulation. The substance can be found in nasal sprays, food supplement powders, skin patches, suppositories, capsules, chocolates, coffee, beer, gummies, lollipops, macaroni and cheese, hummus, honey, jelly beans, cereal, gum, popcorn, peanut butter, massage oil, lotions, face masks, deodorant, pet treats, and bath bombs.In 2019, more than 64 million Americans reported trying CBD, the majority of whom are female.Manufacturers of these products have claimed they can help alleviate anxiety and pain, promote sleep, and treat depression, post-traumatic stress disorder, and more. But there is little research to support these claims or the safety of regularly using such products over time. Currently, the U.S. Food and Drug Administration has only approved the use of CBD to treat two rare, severe forms of epilepsy.Now, with a grant from Women’s Health Research at Yale, Dr. Sarah Lichenstein is leading a study on how CBD may affect behavior and the brain to determine how it affects women and if it affects women and men differently.“The majority of research on the neurological effects of CBD in healthy adults derives from a single small study conducted entirely on men,” said Lichenstein, Assistant Professor of Psychiatry at Yale School of Medicine. “If we are to make sure these products are safe and effective — and, if so, determine correct dosing — it is important to complement what has been done in men to understand how CBD affects the brain in women.”We need to know much more about what CBD is doing, how it might operate in women, and if this is different in women and men.Dr. Sarah LichensteinIn collaboration with Drs. Sarah Yip and Ayana Jordan, Dr. Lichenstein is focusing on CBD’s potential to treat anxiety disorders, the most common reason cited by CBD users for their interest in these products and a condition that is twice as prevalent among women than men. One in three women will meet the criteria for an anxiety or related disorder in their lifetime. In addition to direct negative impact on well-being, these disorders increase the risk of other significant harmful effects, including interpersonal difficulties, major depression, and suicide, as well as higher health care costs and higher rates of unemployment.“We know that other substances used by women to manage anxiety, such as tobacco smoking, were once portrayed as non-addictive,” said WHRY Director Carolyn M. Mazure, Ph.D. “Yet smoking is in fact addictive and harder to quit for women compared to men.”Currently, the most common medical treatment for anxiety disorders are benzodiazepines, medications which are twice as likely to be prescribed to women as men. These medications have been associated with a significant risk of abuse and fatal overdose when combined with alcohol or opioids.“CBD presents a potentially promising alternative to benzodiazepines for treating anxiety, but there is a huge mismatch between the way these products are being marketed and the state of the science,” Lichenstein said. “We need to know much more about what CBD is doing, how it might operate in women, and if this is different in women and men — particularly as millions of Americans are already using it.”Needed Research on CBD, Behavior, the Brain, and WomenDr. Lichenstein’s study seeks to determine brain mechanisms behind how CBD affects the behavior of women, building on currently limited evidence showing that a single dose of CBD affects functional brain responses in healthy men and evidence that sex may influence how cannabis and its constituent compounds affect these responses.\n “Most of what we know about how CBD acts on the brain comes from research on animals,” Lichenstein said. “There is evidence it acts on many different neural systems through diverse mechanisms of action, which makes it interesting to study. But also hard to pin down.”Study participants will take either the FDA-approved CBD oral solution known commercially as Epidiolex or a similarly appearing and tasting but inert placebo. They will then undergo tasks proven to reliably induce low levels of stress in most healthy individuals while inside of a magnetic resonance imaging (MRI) scanner. Researchers will gather data on self-reported measures of anxiety and subjective and physiological effects following the administration of CBD or the placebo while observing and recording activation of the insula and amygdala, areas of the brain associated with stress and anxiety.Crucially, all participants will be female, providing necessary data to compare with existing male data and to prepare applications for additional external funding for a larger study that can directly compare the effect of CBD on women and men.Dr. Lichenstein anticipates that CBD’s effects on the insula and amygdala — and associated reduction in perceived anxiety — could be greater in women than in men.“Women seem to have more exposure from the same dose of CBD,” Lichenstein said. “Preliminary data suggest that women reach peak concentrations more quickly and reach higher concentrations than men.”However, it is also possible that greater exposure among women could interfere with CBD’s effects on anxiety based on preclinical studies suggesting that neurobiological channels may block the effects of CBD at higher doses and are modulated by the female sex hormone estradiol.“If there is a point at which higher doses trigger a neurobiological mechanism that blocks the anti-anxiety effects of CBD, that could very likely lead to different effects for women and men,” Lichenstein said.Such differences, if found in the brain and through an observed effect on anxiety reduction, would indicate the need to establish sex-specific dosing recommendations for CBD.“We don’t know if or where a dosing cutoff exists for humans in terms of safety or reducing anxiety,” Lichenstein said. “We need research in people with anxiety disorders and research on dosing over long periods of time. But first, we need to take this initial, essential step toward understanding what exactly happens to the behavior and in the brains of women when using this popular but largely unexamined substance.”CBD FactsCBD is an abbreviation for cannabidiol, a naturally occurring compound of the cannabis plant. Unlike THC (tetrahydrocannabinol), CBD is not known to produce the euphoric “high” associated with the plant.\n The 2018 federal Farm Bill removed CBD from the list of controlled substances, making CBD products with little or no THC content legal to sell in all 50 states.\n Although many people say they consume CBD products to treat pain, anxiety, and other conditions, the U.S. Food and Drug Administration (FDA) has approved CBD only to treat two rare forms of epilepsy and has not approved CBD for any use in pets.\nThe CBD market reached an estimated $4.7 billion in sales in 2020, on a trajectory to reach $16.8 billion by 2025, according to CBD data-collecting company The Brightfield Group.\n 14 percent of U.S. adults reported using CBD products in a 2019 Gallup poll, with women more likely to use them for anxiety and men more likely to use them for help sleeping.