Use of Cannabidiol for the Treatment of Anxiety: A Short Synthesis of Pre-Clinical and Clinical Evidence

Abstract

Anxiety disorders have the highest lifetime prevalence of any mental illness worldwide, leading to high societal costs and economic burden. Current pharmacotherapies for anxiety disorders are associated with adverse effects and low efficacy. Cannabidiol (CBD) is a constituent of the Cannabis plant, which has potential therapeutic properties for various indications. After the recent legalization of cannabis, CBD has drawn increased attention as a potential treatment, as the majority of existing data suggest it is safe, well tolerated, has few adverse effects, and demonstrates no potential for abuse or dependence in humans. Pre-clinical research using animal models of innate fear and anxiety-like behaviors have found anxiolytic, antistress, anticompulsive, and panicolytic-like effects of CBD. Preliminary evidence from human trials using both healthy volunteers and individuals with social anxiety disorder, suggests that CBD may have anxiolytic effects. Although these findings are promising, future research is warranted to determine the efficacy of CBD in other anxiety disorders, establish appropriate doses, and determine its long-term efficacy. The majority of pre-clinical and clinical research has been conducted using males only. Among individuals with anxiety disorders, the prevalence rates, symptomology, and treatment response differ between males and females. Thus, future research should focus on this area due to the lack of research in females and the knowledge gap on sex and gender differences in the effectiveness of CBD as a potential treatment for anxiety.

Industrial Hemp (Cannabis sativa subsp. sativa) as an Emerging Source for Value-Added Functional Food Ingredients and Nutraceuticals

“…Concentrated CBD from hemp has been shown in both pre-clinical and clinical studies to possess anxiolytic or antianxiety characteristics due to its ameliorating effect on limbic and paralimbic areas of the brain [ 97 , 98 ]. Importantly, the anxiolytic effects of CBD are only induced with low concentrations; high concentrations may cause anxiogenic or panicogenic effects [ 99 ].…”

“…Comprehensive research on this topic is required to understand the broad-spectrum effects of hemp-seed-derived CBD-based nutraceuticals on anxiety [ 108 ]. Data is especially lacking on the differences between sexes in response to treatment; most pre-clinical studies used only male animals, and clinical studies that include females have yet to evaluate sex-differentiated responses [ 98 ]. Males and females experience anxiety differently, and they respond to psychotropics differently, so this is an important knowledge gap to fill with further studies [ 98 ].…”

“…Data is especially lacking on the differences between sexes in response to treatment; most pre-clinical studies used only male animals, and clinical studies that include females have yet to evaluate sex-differentiated responses [ 98 ]. Males and females experience anxiety differently, and they respond to psychotropics differently, so this is an important knowledge gap to fill with further studies [ 98 ]. There is also limited research on CBD treatment for the other anxiety-related disorders discussed above.…”

Cannabidiol has a unique effect on global brain activity: a pharmacological, functional MRI study in awake mice

“…CBD has anxiolytic properties, reducing the autonomic and emotional responses to stress and interfering with the consolidation and extinction of fearful memories [1], which has been associated with anxiety disorders [2], autism spectrum disorder [3], psychosis [4] and post-traumatic stress disorder [5]. It's potential as decreases in site-specific brain activity in response to various drugs [8][9][10][11].…”

Cannabidiol Has a Unique Effect on Global Brain Activity: A Pharmacological, Functional MRI Study in Awake Mice 

“…CBD has anxiolytic properties, reducing the autonomic and emotional responses to stress and interfering with the consolidation and extinction of fearful memories (1), which has been associated with anxiety disorders (2), autism spectrum disorder (3), psychosis (4) and post-traumatic stress disorder (5). It's potential as a therapeutic compound is emphasized by the fact that CBD is the primary active compound in the anti-epileptic drug, Epidiolex (6).…”