Is it safe to combine zopiclone (a hypnotic) with cannabidiol (CBD) for insomnia?

Can You Take Zopiclone and CBD for Sleep?

No clear evidence exists to support combining zopiclone with CBD for insomnia, and this combination should be approached with significant caution due to potential additive CNS depression and lack of safety data.

Why This Combination Is Problematic

Additive Sedation Risk

• Combining multiple CNS depressants—including zopiclone and CBD—markedly increases the risk of respiratory depression, cognitive impairment, falls, and complex sleep behaviors such as sleep-driving and sleep-walking 1
• The FDA has issued warnings about combining sedating medications, noting possible serious effects including slowed or difficult breathing and death 2
• Both agents can potentiate central nervous system depression and decrease respiratory drive, substantially raising the likelihood of adverse outcomes 1

Lack of Evidence for CBD

• CBD is not recommended by any major sleep medicine guideline for insomnia treatment 1
• Herbal supplements and nutritional substances (which would include CBD) are explicitly not recommended by the American Academy of Sleep Medicine due to insufficient evidence of efficacy 1
• No controlled trials have established the safety or efficacy of CBD combined with prescription hypnotics like zopiclone 1

Evidence-Based Approach to Your Sleep Problem

First-Line Treatment: Cognitive Behavioral Therapy for Insomnia (CBT-I)

• All adults with chronic insomnia should receive CBT-I as initial treatment before or alongside any pharmacotherapy, as it demonstrates superior long-term efficacy with sustained benefits after medication discontinuation 1
• CBT-I includes stimulus control therapy, sleep restriction therapy, relaxation techniques, and cognitive restructuring—all of which can be delivered through individual therapy, group sessions, telephone, web-based modules, or self-help books 1

If Zopiclone Alone Is Insufficient

Instead of adding CBD, consider these evidence-based alternatives:

For Sleep-Onset Insomnia:

• Zaleplon 10 mg (5 mg if elderly) has an ultrashort half-life (~1 hour) with minimal next-day sedation 1, 3
• Ramelteon 8 mg is a melatonin-receptor agonist with no abuse potential and no DEA scheduling 1
• Zolpidem 10 mg (5 mg if elderly) shortens sleep-onset latency by ~25 minutes 1

For Sleep-Maintenance Insomnia:

• Low-dose doxepin 3–6 mg reduces wake after sleep onset by 22–23 minutes with minimal anticholinergic effects and no abuse potential 1
• Suvorexant 10 mg (orexin-receptor antagonist) reduces wake after sleep onset by 16–28 minutes with lower cognitive impairment risk than benzodiazepine-type agents 1

Zopiclone Safety Profile

• Zopiclone is a non-benzodiazepine hypnotic with efficacy comparable to benzodiazepines but with a more favorable safety profile 3, 4, 5
• It has a half-life of approximately 5 hours, longer than zaleplon but shorter than many benzodiazepines 3
• Zopiclone demonstrates selective action at omega₁ receptors (sedative effect) with less impact on omega₂ receptors (cognitive/memory effects) compared to traditional benzodiazepines 3
• The most common adverse effect is a bitter aftertaste (3.6% in postmarketing studies) 5

Critical Safety Considerations

Duration of Use

• FDA labeling indicates hypnotics are intended for short-term use (≤4 weeks) for acute insomnia 1
• Evidence beyond 4 weeks is limited, and long-term safety data are scarce 1
• Use the lowest effective dose for the shortest necessary duration 1

Monitoring Requirements

• Reassess after 1–2 weeks to evaluate efficacy on sleep parameters and daytime functioning 1
• Screen for complex sleep behaviors at every visit; discontinue immediately if they occur 1
• If insomnia persists beyond 7–10 days despite treatment, evaluate for underlying sleep disorders such as sleep apnea, restless-legs syndrome, or circadian-rhythm disorders 1

Drug Interactions with Zopiclone

• CYP inducers (rifampicin) significantly decrease zopiclone's sedative effects, requiring dose increases 6
• CYP inhibitors (ketoconazole, erythromycin, cimetidine) enhance zopiclone's sedative effects, requiring dose reductions 6
• Alcohol produces additive sedative effects and must be avoided 6

Common Pitfalls to Avoid

• Do not combine multiple sedative agents without clear medical justification—this markedly increases respiratory depression, cognitive impairment, and fall risk 1
• Do not use unproven supplements like CBD when evidence-based alternatives exist with established safety profiles 1
• Do not continue hypnotic therapy long-term without periodic reassessment every 2–4 weeks 1
• Do not skip CBT-I—pharmacotherapy should supplement, not replace, behavioral interventions 1

Bottom Line

If zopiclone alone is not adequately controlling your insomnia, optimize CBT-I first, then consider switching to or adding an evidence-based alternative such as low-dose doxepin (for sleep maintenance) or ramelteon (for sleep onset) rather than adding CBD, which lacks efficacy data and increases polypharmacy risks 1.