The growing popularity of medical cannabis coupled with increased rates of anxiety, especially in relation to the COVID-19 pandemic, has reignited a long-standing conversation about the potential effects of cannabis on psychiatric symptoms. While there are numerous pharmacological treatments available for anxiety, limited response rates and frequent presence of residual symptoms underscore the need for alternative treatments. Cannabidiol (CBD) is a cannabinoid compound naturally found within the Cannabis sativa L. plant. Previous studies suggest CBD may reduce anxiety, indicating potential for novel treatment strategies. Further, preliminary research suggests that whole-plant, full-spectrum products with diverse cannabinoid profiles may yield therapeutic response at lower doses relative to single extracted compounds (i.e., isolates), potentially due to the synergistic effects of multiple cannabinoids and the presence of other compounds1.
Our recent publication2 in Communications Medicine presents data assessing the efficacy and tolerability of a custom-formulated, full-spectrum, high-CBD product for anxiety. These data were from the open-label stage of a larger clinical trial, so all patients knew that they were taking a high-CBD product. In total, 14 patients with moderate-to-severe anxiety defined as ≥16 on the Beck Anxiety Inventory (BAI) or ≥11 on the Overall Anxiety Severity and Impairment Scale (OASIS) were included in the analyses. All patients were treated for four-weeks with a custom-formulated, high-CBD product administered under their tongue 3 times each day for a total daily dosage of ~30mg of CBD per day.
Following four weeks of treatment, patients reported significantly reduced anxiety, with BAI scores decreased by an average of 80% and OASIS scores by 70%. Treatment response analyses revealed a rapid onset of clinically significant reductions in anxiety (≥15% symptom reduction), with most patients achieving and maintaining treatment response after 1 week and all patients achieving and maintaining treatment response by week 3. This rapid response has been observed in previous clinical trials of cannabinoid-based products3, and is a marked improvement over the typical time course (up to 12 weeks) often required for full treatment response using conventional pharmacotherapy4.
The study drug was well-tolerated with no reported intoxication or serious adverse events. Some minor side effects were noted, with sleepiness/fatigue, increased energy, and dry mouth most frequently endorsed (21% of patients). Side effect severity was predominantly ranked as mild, and throughout the trial, no side effects were rated as severe. Interestingly, several side effects were actually reported as beneficial in addressing anxiety-related issues (e.g., sleeping more). The reported tolerability of CBD is a benefit relative to conventional medications, which are often associated with burdensome side effects4.
Interestingly, in the current study, treatment response was observed at a much lower dosage (~30mg/day) than a previous trial using a single extracted CBD isolate (~300mg/day)3. This difference may be related to the entourage effect, a term used to describe the potentially enhanced effects of cannabinoids when a variety of compounds (e.g., cannabinoids, terpenoids, flavonoids) work together synergistically1. While few studies have directly compared full-spectrum and single extracted, isolate products, research suggests that for some conditions, full-spectrum products may yield therapeutic response at lower doses and with fewer side effects5,6.
Additionally, following treatment, patients also demonstrated significant improvements in cognitive performance, particularly on measures of executive function reflecting their self-control and ability to think flexibly. Interestingly, these findings are in contrast with research on chronic, recreational cannabis use, which is typically associated with poorer cognitive performance. Importantly, however, differences in cognitive outcomes between recreational consumers and medical cannabis patients are likely related to differences in cannabis-related variables, such as age of onset and notable differences in exposure to specific cannabinoids based on product selection7. For example, the majority of recreational cannabis products contain higher levels of tetrahydrocannabinol (THC), the primary intoxicating constituent in cannabis, and very low to no discernible CBD. Lastly, extensive research indicates that anxiety impairs cognitive function, suggesting that patients’ performance is likely to improve with reduction of clinical symptomatology8. Future studies should continue to assess the impact of CBD and other cannabinoids on cognition as well as the role of symptom alleviation.
Overall, the initial results from the open-label stage of this clinical trial demonstrated significantly reduced anxiety, providing preliminary evidence that a full-spectrum, high-CBD product may be efficacious for treating anxiety with few side effects. A more definitive assessment of the impact of this novel treatment on clinical symptoms and cognition will be ascertained in the ongoing double-blind, placebo-controlled stage of this clinical trial, which includes larger sample sizes.
- Russo EB. The case for the entourage effect and conventional breeding of clinical cannabis: No “strain,” no gain. Front Plant Sci 2018;9:1969; doi: 10.3389/fpls.2018.01969.
- Dahlgren MK, Lambros AM, Smith RT, et al. Clinical and cognitive improvement following full-spectrum, high-cannabidiol treatment for anxiety: open-label data from a two-stage, phase 2 clinical trial. Commun Med 2022;2(1):1–10; doi: 10.1038/s43856-022-00202-8.
- Masataka N. Anxiolytic effects of repeated cannabidiol treatment in teenagers with social anxiety disorders. Front Psychol 2019;0; doi: 10.3389/fpsyg.2019.02466.
- Katzman MA, Bleau P, Blier P, et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry 2014;14(1):S1; doi: 10.1186/1471-244X-14-S1-S1.
- Pamplona FA, da Silva LR, Coan AC. Potential clinical benefits of CBD-rich cannabis extracts over purified CBD in treatment-resistant epilepsy: Observational data meta-analysis. Front Neurol 2018;9:759; doi: 10.3389/fneur.2018.00759.
- Gallily R, Yekhtin Z, Hanuš LO. Overcoming the bell-shaped dose-response of cannabidiol by using cannabis extract enriched in cannabidiol. Pharmacol Pharm 2015;06(02):75–85; doi: 10.4236/pp.2015.62010.
- Sagar KA, Gruber SA. Marijuana matters: reviewing the impact of marijuana on cognition, brain structure and function, & exploring policy implications and barriers to research. Int Rev Psychiatry Abingdon Engl 2018;30(3):251–267; doi: 10.1080/09540261.2018.1460334.
- Eysenck MW, Derakshan N, Santos R, et al. Anxiety and cognitive performance: Attentional control theory. Emotion 2007;7(2):336–353; doi: 10.1037/1528-35126.96.36.1996.
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