Ketamine and Melatonin: what the published research says
PubMed indexes 8 records that name Ketamine and Melatonin together, either in the title or in an interaction, co-administration, or pharmacokinetic context. Each one is listed below with its study design and, where the abstract states one, the authors’ own conclusion, quoted and linked. This page reports that literature. It does not tell you whether to combine them.
Every statement below is attributed to a named, dated, linked source.
This page lists published research relevant to Ketamine and Melatonin. It deliberately does not state whether the combination is safe, whether it interacts, in which direction, at what dose, or how far apart to take them.
A study appearing here is not proof that an interaction exists. Two substances can be named together in a paper that never tested them in combination, and a source listed as background may cover only one of them.
Findings are quoted from each abstract as the authors wrote them. NutriStack has not re-analysed, pooled, or reconciled them, and they may disagree with each other.
NutriStack’s own interaction assessment for this pair is not published here. It has not completed qualified-human clinical review, so it is withheld from search. See the publication gate.
Nothing here is medical advice. Decisions about prescription medication and supplements belong with your prescriber or pharmacist, who can see your full regimen.
The research
8 studies naming Ketamine and Melatonin.
Strongest relevance first: papers naming both substances in the title, then human trials and systematic reviews.
Biological signals and receptors · 2001 · PMID 11490096
Comparative StudyAnimal study
“Our results indicated that halothane attenuated the release of melatonin and pentobarbital had no apparent effect, whereas ketamine potentiated the release of melatonin. These findings suggest that melatonin levels may be affected in patients anaesthetized with halothane or ketamine, resulting in disturbed biological rhythms, especially the sleep-wake cycle following recovery.”
“Luzindole, a non-selective MT1 and MT2 receptor antagonist, abolished these effects, suggesting that CaMKII is downstream of the melatonin receptor pathway that causes the antidepressant-like effects. These findings provide molecular insights into the combined effects of melatonin and ketamine on neuronal plasticity-related signaling pathways and pave the way for combating depression using combination therapy.”
Perioperative medicine (London, England) · 2025 · PMID 40846975
“This randomized controlled trial demonstrated the feasibility of recruiting and retaining surgical patients for a multi-arm perioperative intervention study. Although the interventions did not significantly reduce the incidence of POD, the study design and procedures were feasible, with acceptable recruitment and attrition rates.”
“Moreover, the mechanism by which the combination elicits neurogenesis is meditated by melatonin receptors, CaM Kinase II and CaM antagonism. This could have clinical advantages for the fast treatment of depression.”
“Ketamine has opposite phase-shifting effects on circadian rhythms according to the time of administration, whereas pentobarbital has no effect. Furthermore, both anesthetics decrease the postoperative amplitude of pineal melatonin secretion if administered during the active, but not the resting, phase of the 24-hour rest-activity cycle.”
Methods and findings in experimental and clinical pharmacology · 2005 · PMID 16395419
Animal study
“Melatonin failed to alter anesthetic effects of ether (2 mg/kg by open method) in rats. This study suggests that melatonin modulate mechanisms involved in induction of thiopental sodium and ketamine anesthesia.”
Names both Ketamine and Melatonin in its title.
Limitations
What this evidence cannot tell you.
Search-based evidence indexes have real limits, and it is worth being explicit about them:
Selection. These records were found by searching PubMed titles and abstracts for both substance names alongside interaction and pharmacokinetic terms. Relevant work that phrases things differently, or is not indexed in PubMed, will be missing.
No effect size. The quoted conclusions are the authors’ words about their own study. We have not extracted effect direction or magnitude, and a single study’s conclusion is not a consensus.
Population mismatch. Findings in healthy volunteers, animals, or a specific patient group may not transfer to you, your dose, or your formulation.
Absence is not safety. Few published studies means the combination is under-studied, which is not the same as established as safe.
Nearby evidence
Other pairs with published research.
Pages covering Ketamine or Melatonin alongside a different substance.
NutriStack is a free iPhone app for organising a supplement routine: what you take, when, and what the published record says about it. Its exploratory interaction checker covers Ketamine, Melatonin, and several hundred other substances.
The checker is a research and organisation tool, not a clinical decision aid, and its per-pair assessments are excluded from search until they pass claim-level review.
NutriStack is an informational and organizational tool, not a medical service, and not a substitute for professional advice. Always consult a qualified healthcare professional before starting, stopping, or changing any supplement or medication.
