NutriStack
Alprazolam and Melatonin, a caution.
Melatonin has mild sedative properties that can add to alprazolam's CNS depressant effects. While the interaction is generally less dangerous than with kava or valerian, the combination may cause increased daytime drowsiness, dizziness, and impaired coordination.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
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From the interaction database
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Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.
At a glance
- Substances
- Alprazolam and Melatonin
- Pair type
- Caution
- Evidence (highest tier)
- Moderate
- Source citations
- 4 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Moderate evidence
Caution
What is happening. Melatonin has mild sedative properties that can add to alprazolam's CNS depressant effects. While the interaction is generally less dangerous than with kava or valerian, the combination may cause increased daytime drowsiness, dizziness, and impaired coordination.
Mechanism. Melatonin activates MT1 and MT2 receptors in the suprachiasmatic nucleus and other brain regions, promoting sleep and reducing alertness. This adds to alprazolam's GABA-A mediated sedation, increasing overall CNS depression.
Recommendation. Use melatonin cautiously with alprazolam. Start with a low melatonin dose (0.5-1mg). Avoid driving or operating machinery until you know how the combination affects you. Discuss timing optimization with your prescriber.
Sources (4)
- Garfinkel D et al. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet. 1995;346(8974):541-544. PMID 7658780
- Fatemeh G, Sajjad M, Niloufar R et al.. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.. Journal of Neurology. 2022. PMID 33417003
- Tang BHY, Manalo J, Chowdhury SR et al.. Melatonin Use in the ICU: A Systematic Review and Meta-Analysis.. Critical Care Medicine. 2025. PMID 40662882
- Chan V, Lo K. Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis.. Postgraduate Medical Journal. 2022. PMID 33441476
Stack Score
How this pair moves the number.
Effect on the composite score
If both Alprazolam and Melatonin are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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