Clinical Summary
Clinical Summary: Cannabidiol for Treatment-Resistant Anxiety Disorders in Young People: An Open-Label Trial
Many young people with anxiety disorders remain significantly symptomatic despite cognitive-behavioral therapy and selective serotonin reuptake inhibitors, leaving clinicians with few next-step options. This trial addresses whether adjunctive cannabidiol can reduce anxiety in a treatment-resistant youth population while remaining tolerable enough for real-world use.
Design
an open-label, single-arm Phase II trial
N
31
Population
young people aged 12–25 years with anxiety disorders who do not respond to standard treatment
Duration
12 weeks
Key Findings
- In the intention-to-treat analysis, the mean (SD) change in OASIS score was −4.6 (4.2) points, or −42.6%, from baseline to week 12 (Cohen d = −1.07).
- Twelve (40%) of 30 participants had a reduction of at least 50% in OASIS scores by week 12, and 18 of 30 participants had a reduction of at least 33%.
- Clinician-rated improvement was substantial at week 12: 26 (86.7%) of 30 participants had improved, 16 (53.3%) of 30 participants had substantially improved, and those rated as markedly or severely ill decreased from 17 (56.7%) to 5 (16.7%).
- Secondary outcomes also improved over 12 weeks, with a mean (SD) HARS decrease of −11.1 (10.6) points, or 50.2% (Cohen d = −1.00), a mean (SD) QIDS-A17 reduction of −3.5 (4.2) points, or 29.9% (Cohen d = −0.83), and a mean (SD) SOFAS increase of 6.4 (8.9) points, or 11.3% (Cohen d = 0.69).
- Adverse events were reported by 25 (80.6%) of 31 participants, adverse events deemed related or possibly related to the study drug were reported by 19 (61.3%) of 31 participants, no serious adverse events were observed, and antidepressant use was associated with at least one adverse event (OR = 6.4; 95% CI, 1.16–35.44; P = .03).
Clinical Bottom Line
Adjunctive cannabidiol at daily doses up to 800 mg was associated with clinically meaningful 12-week reductions in anxiety severity in treatment-resistant young people and was generally well tolerated. When cannabidiol is combined with antidepressants, closer monitoring for adverse effects and drug interactions is warranted.
Practice Implications
- Consider cannabidiol only as an adjunctive option in young people with anxiety disorders who have not improved with CBT and/or antidepressant medication, mirroring the treatment-resistant population studied here.
- Use active follow-up during titration, as most participants required dose escalation and 19 participants were titrated to the maximum CBD dose of 800 mg/d.
- Monitor adverse effects and concurrent antidepressant treatment closely, because participants prescribed antidepressants were more likely to experience at least one adverse event (OR = 6.4; 95% CI, 1.16–35.44; P = .03).
- Be alert to pharmacokinetic interactions with SSRIs, particularly citalopram or escitalopram, because 5 of 6 participants taking citalopram or escitalopram showed increases in plasma concentrations of the two drugs after 12 weeks’ treatment with CBD.
