Ultra-low Dose Oral Ketamine for Chronic Pain in the Primary Care Setting

Chronic pain is a major national public health issue, affecting about 100 million adults in
the United States. Opioid pain medications are commonly used for treatment of chronic pain,
but their use is fraught with consequences including an increasing prevalence of misuse,
abuse, and overdose death, and side effects which lead to a reduced quality of life. An
effective and safe medication that would improve control of chronic pain while reducing
reliance on opioid medications would be valuable for patients, medical providers and society
at large.

Ketamine, commonly used as an intravenous anesthetic agent, has been shown to have analgesic
and opioid-sparing effects in the peri-operative period and in the palliative care setting.
Based on promising preliminary data from an open-label treatment trial, this project is a
pilot study to evaluate the analgesic and opioid-sparing effects of ketamine in an ultra-low
dose oral formulation as a novel intervention for treatment of chronic non-cancer pain in
the primary care outpatient setting.

The design of the proposed study is a randomized controlled two week parallel-group trial,
with 32 patients receiving either the active treatment or placebo twice daily.

Inclusion Criteria:

- Age 18 years or older

- Routine use of an opioid medication for non-cancer pain for more than six months

- A current average daily dose of greater than or equal to 20 mg morphine or equivalent

- Current prescription of an as-needed opioid suitable for downward titration during
the study period

- Ability to provide informed consent Ability to adhere to the study protocol

Exclusion Criteria:

- Uncontrolled hypertension, cardiac arrhythmia or other known cardiac disease,

- elevated intracranial pressure,

- severe glaucoma,

- schizophrenia,

- diagnosed substance use disorder, or

- other unstable medical or psychiatric illness or pregnancy.