The Role of Cannabis in Treating Anxiety: An Update

Michael Van Ameringen; Jasmine Zhang; Beth Patterson; Jasmine Turna


Curr Opin Psychiatry. 2019;33(1):1-7. 

In This Article

The Effects of Cannabis in Animal Models of Anxiety

Animal models are typically the first venture into clinical research. In preclinical anxiety research, the most common paradigm used is the Elevated Plus Maze (EPM), which exploits a conflict between rodents' innate tendency to explore novel environments and their fear of bright, elevated environments.[9] In the EPM, mice are placed on an elevated platform consisting of four sections arranged in a 'plus'-shaped formation with two open and enclosed arms. More time spent in the 'open', low-walled arms is indicative of lower anxiety.[9]

The literature has generally described CBD to be anxiolytic in mice [reviewed in 9] rather than the contrary.[9,11] More specifically, a bell-shaped dose-response curve has been described of CBD's effects on anxiety: moderate doses show anxiolytic effects, while higher doses have minimal effect.[9] However, studies published in the past year draw a more equivocal conclusion. In one study, mice who received a single dose of 20 mg/kg CBD explored the open arms of the EPM significantly longer than those treated with placebo or 5 mg/kg, signifying an anxiolytic effect of 20 mg/kg CBD.[12] In a different study, mice were injected with placebo or 20 mg/kg CBD daily for 6 weeks.[7] Within both groups, some mice began treatment at 3 months old whereas others began treatment at 5 months old. At 6 months of age, all mice were test for a range of physiological and behavioural functions, including anxiety. In the EPM, only mice who received CBD starting at 5 months of age spent more time in the open arms compared to the placebo group.[7] These studies suggest that a high dose of CBD may have anxiolytic potential, but effects may vary based on treatment duration.

Another EPM study suggested that CBD's anxiolytic effect may only be relevant when in the presence of THC.[13] Mice were injected with various concentrations of THC, CBD, combined THC and CBD, or a vehicle control. Based on the EPM, the anxiety levels of mice injected with 100 ng/500 nl CBD did not differ from the control group. On the contrary, mice injected with 100 ng/500 nl THC spent significantly less time in the open arms of the maze compared to control mice, supporting a previously documented anxiogenic effect of THC.[14] In CBD and THC co-administration, 100 ng/500 nl CBD did not affect THC-induced anxiety, while 500 ng/500 nl CBD appeared to block the anxiogenic effect of 100 ng/500 nl THC.[13] Another study explored the effect of synthetic cannabinoids (AB-FUBINACA, TAB-CHMINACA, and PB-22; potent CBR1 and CB2R agonists) and THC on anxiety using the EPM. Treatment with all compounds led mice to spend more time in the open arms of the maze compared to vehicle controls;[15] however, the anxiolytic effects were dose-dependent. For instance, AB-FUBINACA was anxiolytic anxiety at 3 mg/kg but anxiogenic at 4 mg/kg; only 1 mg/kg AB-CHMINACA showed anxiolytic effects, while PB-22 significantly decreased anxiety at 0.05, 0.1, and 0.4 mg/kg doses. THC demonstrated anxiolytic effects at a high dose of 25 mg/kg, which contradicts the general understanding that THC is anxiogenic.[9,14]