Frequently Asked Questions

Yes. In this open-label trial, adjunctive cannabidiol was associated with a mean reduction in OASIS score of 4.6 points, or 42.6%, at 12 weeks in the intention-to-treat analysis (Cohen d = -1.07). Twelve of 30 participants (40%) had at least a 50% reduction in OASIS scores, and 18 of 30 had at least a 33% reduction by week 12.

Participants received oral cannabidiol for 12 weeks using a fixed-flexible titration schedule that started at 200 mg/day. The dose could be increased by 200-mg increments if there was no clinically meaningful improvement, with maximum doses of 400 mg/day at week 1, 600 mg/day at week 4, and 800 mg/day at week 8. By week 12, 19 participants had been titrated to 800 mg/day, 9 to 600 mg/day, and 1 to 400 mg/day.

Yes. By week 12, 26 of 30 participants (86.7%) were rated as improved on the Clinical Global Impressions–Improvement scale, and 16 of 30 (53.3%) were rated as substantially improved. The proportion rated as markedly or severely ill fell from 17 of 30 (56.7%) at baseline to 5 of 30 (16.7%) at the end of treatment.

Yes. Over 12 weeks, depressive symptom severity on the QIDS-A17 decreased by a mean (SD) of 3.5 (4.2) points, or 29.9% (Cohen d = -0.83), and social and occupational functioning on the SOFAS improved by a mean (SD) of 6.4 (8.9) points, or 11.3% (Cohen d = 0.69). The study also found that these improvements were not sustained at 6 months in the subset assessed at follow-up.

Cannabidiol was generally well tolerated in this trial, with no serious adverse events and no clinically significant changes in red or white blood cell counts, renal function, or liver function. Adverse events were reported by 25 of 31 participants (80.6%), and events considered related or possibly related to cannabidiol were reported by 19 of 31 (61.3%). All adverse events were mild or moderate and resolved spontaneously during the study.

Adverse events considered related or possibly related to cannabidiol included fatigue, low mood, increased or decreased appetite, drowsiness, nausea, diarrhea, dry mouth, insomnia, and hot flushes or cold chills. The most common adverse events highlighted in the discussion were fatigue, low mood, and hot flushes or cold chills. One participant withdrew because of a skin rash deemed possibly related to cannabidiol.

Yes. Participants prescribed antidepressants were more likely to experience at least one adverse event, with an odds ratio of 6.4 (95% CI, 1.16-35.44; P = .03). In addition, 5 of 6 participants taking citalopram or escitalopram showed increased plasma concentrations of those antidepressants after 12 weeks of cannabidiol treatment.

No clear relationship was found. Plasma cannabidiol concentrations at week 12 were not correlated with reduction in OASIS scores (r = -0.14, P = .46), and maximum cannabidiol plasma concentrations during treatment were also not correlated with OASIS improvement (r = -0.004, P = .83). The number of adverse events was likewise unrelated to maximum CBD dose, week-12 plasma CBD concentration, or maximum plasma CBD concentration during the trial.

The trial enrolled young people aged 12-25 years with a DSM-5 anxiety disorder who had not improved during their current episode of care despite standard treatment with cognitive-behavioral therapy and/or antidepressant medication. This was a treatment-resistant group: the median duration of prior treatment as usual was 25.5 months, and among the 21 participants taking antidepressants, the median duration of antidepressant treatment was 19 months with a median of 2 medication changes because of lack of efficacy or side effects.

The results suggest that adjunctive cannabidiol may have clinically meaningful anxiolytic effects in young people with treatment-resistant anxiety disorders, but the findings should be interpreted cautiously because the trial was open-label and had no control group. The authors state that causal inferences about efficacy cannot be made from this design and that randomized clinical trials are needed to confirm the effect.