Low-Dose Oral Ketamine for Pain Management: A Primer for Clinicians

To critically evaluate the available evidence for low-dose oral ketamine for analgesia and provide summary recommendations for clinicians on its use in practice.

A search of the primary literature was performed in PubMed from 2010 through 2025 using the following keywords: "Administration, oral," "Administration, sublingual," "ketamine," and "pain."

All studies and case reports involving the use of oral or sublingual ketamine for analgesia as the primary focus were included.

Oral ketamine was well tolerated in dose ranges from 25 to 300 mg/day, which were associated with reduced pain scores, improved quality of life, and decreased opioid requirements in line with low-dose infusions for pain management. Weight-based doses above 6 mg/kg corresponded with an increase in adverse effects. Optimal parenteral-to-oral dose conversions are not known; however, dose reductions by 75% from the daily infusion dose maintained analgesia in a small number of cases. Treatment durations ranged from single doses up to 12 years but were predominantly studied in less than 2 years of use.

There remains a dearth of safe and effective pharmacologic pain management options which serve as alternatives to opioids. Low-dose ketamine is an oft-overlooked analgesic with evidence dating back over 50 years, but clinical uptake is poor. Oral ketamine presents a pragmatic formulation, and this review uses the current evidence to address pertinent clinical queries raised by clinicians in practice.

Subanesthetic oral ketamine is an analgesic with continually growing evidence investigating use in a variety of acute and chronic pain syndromes. Based on the current evidence, ketamine may be helpful for refractory pain, as a component of multimodal analgesia, or in patients with high opioid requirements. Adverse effects are typically mild, but the risks of long-term use ultimately remain unclear.