Systematic review · 2026
Review of 18 trials finds oral ketamine mostly causes mild, short-lived side effects
- Original title
- Safety and tolerance of oral ketamine: A systematic review.
- Authors
- Novaretti N, Pessoa RMP, Hallak JEC, et al.
- Journal
- Psychiatry and clinical neurosciences, 2026
- Molecules
- Ketamine, Esketamine
- Conditions
- Treatment-resistant depression, Depression, Chronic pain, Healthy volunteers, Other
- Evidence grade
- Low
- Source
- Read the original paper
The question
How safe and tolerable is ketamine when it is swallowed rather than injected or given through a drip?
What they did
Researchers searched four large medical databases up to November 2025 for randomized placebo-controlled trials of oral ketamine or esketamine in any patient group. Eighteen trials met the criteria, covering adults, children and healthy volunteers. The main outcomes were safety and tolerability, meaning side effects and how well people put up with the drug. The team assessed each trial for bias and rated the overall certainty of the evidence using standard tools (RoB2 and GRADE).
What they found
In the five depression trials (427 participants), side effects were mostly mild and passed quickly. Trials using oral ketamine to calm children before procedures (239 participants) reported temporary neurological effects but no safety problems the authors judged clinically significant. Pain and experimental studies (372 participants) also showed mainly mild adverse events, with dissociation (a sense of detachment from one’s body or surroundings) appearing at higher doses. Compared with placebo, ketamine led to more dizziness, sedation and dissociative symptoms, while serious adverse events were rare.
The fine print
The review pooled very different groups, from children having procedures to adults with depression or pain, so the findings do not apply neatly to any single use. There is no standardized oral ketamine formulation, and doses varied across trials. The trials were short, so long-term safety remains unknown, and the authors rated the overall certainty of evidence as low. This summary is based on the abstract only.
What it means
Across the trials reviewed, oral ketamine appeared to cause mostly mild and temporary side effects in the short term, but the evidence is weak and nothing is known about what happens with prolonged use.
Evidence grade: Low. A systematic review of randomized placebo-controlled trials, but the populations and doses varied widely, no pooled analysis is reported, and the authors themselves graded the certainty of evidence as low.
This summary is based on the study’s published abstract.