There is currently no compelling evidence that a combination of melatonin and cannabidiol (CBD) improves sleep beyond what can be explained by melatonin alone.
Melatonin and CBD is a popular supplement combo for improving sleep, based on supposedly complementary mechanisms of action (i.e., melatonin promoting sleep onset and CBD theoretically reducing sleep disruption). However, there is little evidence that CBD can improve sleep quality on its own.[1] But what about when combined with melatonin?
One 4-week randomized controlled trial examined the effect of melatonin and several cannabinoids (including CBD), alone or in combination, on sleep in 1,784 people with sleep disturbances.[2] Ultimately, taking a combination of CBD, cannabinol (CBN), and melatonin did not clearly reduce sleep disturbances compared to taking melatonin alone. Unfortunately, the lack of placebo group and the inclusion of other cannabinoids (e.g., CBN) limits the generalizability of this study.
It’s possible that taking CBD could increase melatonin levels by inhibiting the enzyme CYP1A2,[3] which metabolizes melatonin.[4] In theory, this could mean CBD would make melatonin supplements more potent. However, this has not yet been directly confirmed in humans.
References
- ^Rainer Spanagel, Ainhoa BilbaoApproved cannabinoids for medical purposes - Comparative systematic review and meta-analysis for sleep and appetiteNeuropharmacology.(2021 Jun 26)
- ^Saleska JL, Bryant C, Kolobaric A, D'Adamo CR, Colwell CS, Loewy D, Chen J, Pauli EKThe Safety and Comparative Effectiveness of Non-Psychoactive Cannabinoid Formulations for the Improvement of Sleep: A Double-Blinded, Randomized Controlled Trial.J Am Nutr Assoc.(2023-May-10)
- ^Thai C, Tayo B, Critchley DA Phase 1 Open-Label, Fixed-Sequence Pharmacokinetic Drug Interaction Trial to Investigate the Effect of Cannabidiol on the CYP1A2 Probe Caffeine in Healthy Subjects.Clin Pharmacol Drug Dev.(2021-Nov)
- ^Härtter S, Nordmark A, Rose DM, Bertilsson L, Tybring G, Laine KEffects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity.Br J Clin Pharmacol.(2003-Dec)