Anxiety: Cannabidiol as a Potential Treatment for Anxiety Disorders

Cannabidiol as a Potential Treatment for Anxiety Disorders

E. Blessing, M. M. Steenkamp, J. Manzanares, C. R. Marmar           

2015

KEY TAKEAWAYS:

• Preclinical evidence strongly supports the potential of CBD as a treatment for anxiety 
• In dogs, anxiety is responsible for depression, aggressiveness, restlessness and destructive and compulsive behaviors; it also impacts dogs’ quality of life in a significant and negative way
• Cats have similar anxiety-related behaviors, with restlessness, trembling, aggression and decreased appetite being the most worrying problems. Isolation and anti-social attitudes are also common
• 68.75% of the studies reviewed demonstrated the anxiolytic effects of CBD
• CBD reduced experimentally-induced anxiety in healthy subjects and reduced anxiety in patients with social anxiety disorders (SAD)
• Systemically administered CBD reduced acute increases in heart rate and blood pressure produced by states of heightened anxiety
• CBD blocked reconsolidation of unpleasant memories in rats and enhanced extinction of fear memories in healthy humans
• Human experimental studies put into evidence CBD’s excellent safety profile and minimal sedative effects

OBJECTIVES & HYPOTHESIS → ​Anxiety-related disorders are associated with diminished sense of well-being. In dogs, anxiety is responsible for a series of disturbed behaviors, including depression, aggressiveness, restlessness and destructive and compulsive behaviors. Moreover, it impacts dogs’ quality of life in an important and negative manner. Cats have similar anxiety-related behaviors, with restlessness, trembling, aggression and decreased appetite being the most worrying problems. Isolation and anti-social attitudes are also common. Current medications used to manage anxiety and stress have limited response rates and the adverse effects are very often intolerable. For these reasons, the purpose of the current review was to determine CBD’s potential as a treatment for anxiety-related disorders, by assessing evidence from existing studies.

METHODS → A search of MEDLINE, PsycINFO, Web of Science Scopus, and the Cochrane Library databases was conducted for English-language papers published up to 1 January 2015. In total, 49 primary preclinical, human experimental, clinical and epidemiological studies were included. 

RESULTS → Of the 32 preclinical studies included in the review, 68.75% of them demonstrated the anxiolytic effects of CBD, 15.63% showed panicolytic (anti-panic) effects; 9.34% demonstrated anticompulsive effects and 12.5% no effect; no anxiogenic effects have yet been reported. In a stress-induced anxiety model, systemic CBD reduced acute increases in heart rate and blood pressure as well as the delayed (24h) anxiogenic effects. In a subchronic study, CBD administered daily 1h after predator stress reduced the long-lasting anxiogenic effects of chronic predator stress. In a chronic study, systemic CBD prevented increased anxiety produced by chronic unpredictable stress. In a compulsive behavior model, CBD showed panicolytic effects in two proposed models of panic attacks and also in the predator–prey model. Anticompulsive effects of CBD were investigated in marble-burying behavior (OCD model); acute systemic CBD reduced marble-burying behavior for up to 7 days. Finally, in fear models, systemic CBD reduced conditioned cardiovascular responses; enhanced extinction of contextually conditioned fear responses and even blocked reconsolidation of aversive memories in rats. In summary, CBD exhibits a broad range of actions, including anxiolytic, panicolytic, anticompulsive actions, decrease in autonomic arousal, decrease in conditioned fear expression, enhancement of fear extinction, reconsolidation blockade, and prevention of the long-term anxiogenic effects of stress. Moreover, the preclinical evidence suggests that CBD has the advantage of not producing anxiogenic effects at higher doses, as distinct from other agents.

Moving to the human experimental and clinical studies, evidence demonstrates that CBD potently reduced experimentally induced anxiety or fear and anxiety associated with a simulated public speaking test in healthy subjects and in subjects with social anxiety disorder (SAD). Finally, CBD enhanced extinction of fear memories in healthy volunteers, suggesting potential for the treatment of PTSD. Regarding chronic studies, no outcome data are currently available regarding the chronic effects of CBD on humans. Human experimental findings support preclinical findings, and also suggest a lack of anxiogenic effects, minimal sedative effects, and an excellent safety profile.