The Effects of Cannabidiol (CBD) on Anxiety: A Comprehensive Review of Clinical and Preclinical Studies


Cannabidiol (CBD), a non-psychoactive component of the cannabis plant, has gained increasing attention in recent years due to its potential therapeutic effects on anxiety. This paper aims to provide a comprehensive review of both clinical and preclinical studies examining the effects of CBD on anxiety. While numerous studies have shown promise, it is essential to exercise caution when interpreting these results, as the field still requires more robust research. This review highlights the need for further investigation into CBD’s anxiolytic potential and its underlying mechanisms, taking into account the methodological limitations and inconsistencies across studies.


Anxiety is one of the most prevalent mental health disorders, affecting millions of people worldwide (Bandelow & Michaelis, 2015). Current pharmacological treatments, such as selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines, are often associated with adverse side effects and limited effectiveness (Baldwin et al., 2011). This has led to increased interest in exploring alternative therapeutic options, including cannabidiol (CBD), a non-psychoactive phytocannabinoid found in the cannabis plant (Iffland & Grotenhermen, 2017).

CBD has been proposed to exert anxiolytic effects via modulation of the endocannabinoid system, serotonergic, and other neurotransmitter systems (Russo et al., 2005). Preclinical and clinical studies have shown potential promise for CBD’s use in anxiety treatment. This paper aims to provide a comprehensive review of the available literature to understand the current state of knowledge on CBD’s effects on anxiety.

What This Means For You

Anxiety is a common mental health issue affecting millions of people, and current treatments may have side effects or be less effective for some individuals. CBD, a non-intoxicating substance found in the cannabis plant, has gained attention as a potential alternative treatment for anxiety. This review will explore the current research on CBD’s effects on anxiety to help you understand its potential benefits.

Preclinical Evidence

Rodent models have provided preliminary evidence for CBD’s anxiolytic effects. (Guimarães et al., 1990) found that CBD reduced anxiety-like behavior in rats subjected to the elevated plus-maze (EPM) test. Similarly, Moreira et al. (2006) demonstrated that CBD administration reduced marble-burying behavior in mice, a model of obsessive-compulsive disorder (OCD) and anxiety.

Moreover, CBD has been shown to have an inverted U-shaped dose-response curve in rodents, with lower and higher doses producing minimal anxiolytic effects, while moderate doses produce optimal results (Zuardi et al., 1993). This highlights the importance of optimizing CBD dosages to achieve therapeutic benefits.

What This Means For You

Animal studies have shown that CBD can help reduce anxiety-related behaviors in rats and mice. These studies also suggest that the right dosage is essential, as both low and high doses might not have the desired effects. While these findings are promising, it’s important to note that they are still preliminary and further research is needed.

Clinical Evidence

Several human studies have investigated the potential anxiolytic effects of CBD. A systematic review by Bergamaschi et al. (2011) found that acute CBD administration (300-600 mg) reduced anxiety in participants with social anxiety disorder (SAD) during a simulated public speaking task. Another study by Crippa et al. (2010) reported that a single dose of CBD (400 mg) reduced anxiety and cognitive impairment in individuals with SAD during a functional magnetic resonance imaging (fMRI) paradigm.

However, not all studies have reported positive effects. A clinical trial by Linares et al. (2018) found no significant differences in anxiety levels between participants treated with CBD (150-600 mg/day) and those treated with a placebo for generalized anxiety disorder (GAD) over four weeks.

These conflicting results may be due to methodological differences, including variations in study design, CBD dosages, and participant characteristics. Therefore, more large-scale, well-controlled clinical trials are needed to determine the optimal dosages and treatment durations for different anxiety disorders.

What This Means For You

Some human studies have found that CBD can help reduce anxiety in people with social anxiety disorder during public speaking or while undergoing brain scans. However, other studies have not found significant benefits for generalized anxiety disorder. These mixed results may be due to differences in study design, CBD dosages, and individual characteristics. More research is needed to determine the best dosage and duration of treatment for different types of anxiety.

Possible Mechanisms of Action

CBD’s anxiolytic effects are thought to be mediated through several mechanisms, including modulation of the endocannabinoid system, serotonergic, and other neurotransmitter systems. The endocannabinoid system plays a crucial role in the regulation of anxiety and stress responses (Hill et al., 2010). CBD has been shown to enhance the availability of endocannabinoids, such as anandamide, by inhibiting their degradation (Bisogno et al., 2001). This, in turn, may promote anxiolytic effects.

Additionally, CBD has been found to interact with the serotonergic system, particularly the 5-HT1A receptor, a key target for anxiolytic drugs (Russo et al., 2005). Studies have demonstrated that CBD can act as a partial agonist at 5-HT1A receptors, potentially contributing to its anxiolytic effects (Resstel et al., 2009).

Other neurotransmitter systems, such as the glutamatergic and GABAergic systems, have also been implicated in CBD’s effects on anxiety (Campos et al., 2013). However, the exact mechanisms underlying CBD’s anxiolytic properties remain to be fully elucidated.

What This Means For You

Researchers believe that CBD’s anxiety-reducing effects might be due to its interactions with various systems in the brain, including the endocannabinoid and serotonin systems. However, the exact ways CBD works to reduce anxiety are still not fully understood, and more research is needed to clarify these mechanisms.

Limitations and Future Directions

While the current evidence suggests potential anxiolytic effects of CBD, several limitations must be acknowledged. First, the number of high-quality clinical trials remains limited, and the sample sizes in many studies are small. Moreover, the majority of studies have focused on acute CBD administration rather than long-term treatment, which is more relevant to clinical practice.

Second, the optimal CBD dosages and treatment durations for different anxiety disorders have yet to be determined. The inverted U-shaped dose-response curve observed in preclinical studies highlights the importance of identifying the appropriate dosages for achieving therapeutic effects.

Finally, more research is needed to understand the mechanisms underlying CBD’s anxiolytic effects, as well as its potential interactions with other medications and possible long-term side effects.

What This Means For You

Although there is some evidence that CBD may help with anxiety, there are limitations to the current research. Many studies have small sample sizes or focus on short-term effects rather than long-term treatment. More research is needed to understand the ideal dosages, treatment duration, and potential interactions with other medications or side effects.


In conclusion, the available preclinical and clinical evidence suggests that CBD has potential anxiolytic effects. However, the field still requires more robust research to establish optimal dosages, treatment durations, and underlying mechanisms. Future studies should focus on large-scale, well-controlled clinical trials, exploring the long-term effects of CBD on anxiety and related disorders, and investigating its mechanisms of action. By addressing these limitations, researchers can better understand the therapeutic potential of CBD for anxiety and contribute to the development of more effective, safer treatment options.

What This Means For You

While current research suggests that CBD might have anxiety-reducing effects, more studies are needed to determine the best way to use CBD for treating anxiety. Future research should focus on larger, well-designed clinical trials to better understand the long-term effects and mechanisms of CBD’s action. In the meantime, if you are considering trying CBD for anxiety, it is essential to talk to your healthcare professional to ensure it’s a safe and appropriate option for you.


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