Ketamine infusions carried out in a clinical setting have a low addiction potential, though the risk is not zero. In the handful of case reports published so far, a small number of patients have developed compulsive use patterns after being prescribed repeated low-dose ketamine for depression. But large clinical trials, particularly those tracking the nasal spray form esketamine for up to a year, have reported no instances of abuse, misuse, or addiction, even among patients with a history of substance use problems.
The honest answer is nuanced: the drug itself can be addictive at high, frequent doses, but the way clinical infusions are dosed and spaced makes that outcome uncommon. Understanding why requires looking at what ketamine actually does in your brain at different doses, what the clinical data shows, and which personal risk factors matter most.
Why Dose and Setting Change the Risk
Ketamine’s antidepressant effect works through a surprisingly narrow dose window. The standard infusion for depression is 0.5 mg/kg delivered intravenously over about 40 minutes. At this dose, ketamine briefly blocks certain receptors on inhibitory brain cells, which triggers a burst of glutamate, the brain’s primary excitatory chemical messenger. That glutamate surge kicks off a cascade of changes that help damaged neural connections regrow, and this appears to be the mechanism behind the rapid mood improvement many patients experience.
What’s interesting is that higher doses don’t work better. At 1.0 mg/kg, patients experience stronger dissociative effects (the floating, out-of-body sensation) without any additional antidepressant benefit. At full anesthetic doses, ketamine actually loses its antidepressant effect entirely because it shuts down the very glutamate release that makes the treatment work. Recreational users typically consume far higher and more frequent doses than clinical patients receive, and it’s at those levels that the brain’s reward circuitry gets hijacked in ways that drive compulsive use. Animal research supports this distinction: in one model, ketamine administered at clinical-range doses did not establish addiction-like behavior and did not produce the reward-system changes in the brain linked to drug craving.
What the Clinical Evidence Shows
No large study has produced a reliable incidence rate for addiction following medically supervised ketamine infusions. What exists are a few published case reports describing patients who developed full-blown ketamine addiction after being treated with repeated low-dose infusions for depression. These cases are notable precisely because they’re rare enough to be individually documented in the medical literature.
The strongest safety data comes from esketamine, a more potent version of the molecule approved as a nasal spray and administered under medical supervision. In the SUSTAIN-2 trial, which followed patients for up to one year, no indication of abuse was reported. A 2025 review of all available clinical trials, real-world studies, and case reports concluded that esketamine has proven safe and well tolerated without fostering new-onset substance use, even in patients with a history of alcohol or drug problems. Only a single case report of esketamine craving has been documented since the drug came to market.
A systematic review of maintenance ketamine treatment for depression, published in The Lancet Psychiatry, found that addiction “seems uncommon” among patients receiving ongoing infusions, though the authors noted that longer and larger studies are still needed.
Tolerance, Dependence, and Withdrawal
Tolerance (needing more of a drug to get the same effect) is well documented in heavy recreational ketamine users, but it has not emerged as a significant pattern in clinical infusion patients. The Lancet Psychiatry review described tachyphylaxis, the clinical term for rapidly developing tolerance, as uncommon in maintenance treatment settings.
Physical withdrawal from ketamine is poorly understood. Rates of clinically significant withdrawal have not been well characterized, partly because so few clinical patients use ketamine at the dose and frequency required to produce physical dependence. There is evidence that regular recreational users can experience dysphoria, anxiety, and cravings when they stop. The single detailed report in the medical literature of a patient with ketamine addiction and probable withdrawal describes tremor, sweating, irritability, and sleep disturbances. One case published in the American Journal of Psychiatry described a patient receiving clinical ketamine who became intensely agitated, dysphoric, and suicidal when doses were missed, with symptoms that resolved only when ketamine was resumed.
These cases are important to take seriously, but they represent a very different picture from opioid withdrawal, which affects a large percentage of patients who take the drugs as prescribed for even a few weeks.
How Ketamine Compares to Opioids
The comparison matters because ketamine is increasingly used as an alternative to opioids for pain management. In the United States, an estimated 10.1 million people aged 12 and older misused opioids in a single recent year, and two out of three drug overdose deaths involve an opioid. Opioids also carry risks of respiratory depression, dangerously low blood pressure, and severe sedation.
Ketamine does not suppress breathing the way opioids do, and its addiction liability is considered low by comparison. A randomized clinical trial comparing intravenous ketamine to morphine for traumatic pain found ketamine to be a viable alternative, and the researchers specifically highlighted ketamine’s lower addiction risk as a reason to consider it. That said, “lower risk than opioids” is a low bar. The more relevant question for most readers is the absolute risk in a supervised clinical setting, which current evidence suggests is small but not nonexistent.
Who Faces Higher Risk
Clinics offering ketamine infusions should screen patients for substance use history before treatment begins. Standard screening tools used in primary care, such as the NIDA Quick Screen or the TAPS Tool, can help identify people who may need closer monitoring. Some of these tools explicitly ask about ketamine use if an initial screen comes back positive.
If you have a personal history of addiction to any substance, that doesn’t automatically disqualify you from ketamine treatment, but it does mean the decision requires more careful consideration. Providers should ask about urological and gastrointestinal symptoms (chronic heavy ketamine use can damage the bladder), cognitive changes, and patterns of use. A history of seeking dissociative or psychedelic experiences recreationally is a relevant factor worth discussing honestly with your provider.
The structure of treatment itself acts as a safeguard. Clinical infusions are administered in a medical office, typically spaced days or weeks apart, at a fixed dose you don’t control. This is fundamentally different from having a supply at home. Clinics that send patients home with oral or nasal ketamine for unsupervised use remove some of those guardrails, which is worth factoring into your choice of provider.
What a Typical Protocol Looks Like
For depression, the standard approach is a series of six infusions over two to three weeks, each delivering 0.5 mg/kg intravenously over 40 minutes. Patients who respond well may then receive maintenance infusions spaced weeks or months apart. For acute pain, doses are generally lower: a bolus of 0.1 to 0.5 mg/kg followed by a slow drip of 0.1 to 0.6 mg/kg per hour, with guidelines recommending that infusion rates stay below 1 mg/kg per hour outside of intensive care settings.
These protocols are designed to stay well within the subanesthetic range, the zone where ketamine’s therapeutic effects occur without the full dissociative or euphoric experience that drives recreational use. You may still feel floaty, detached, or mildly altered during an infusion, but these sensations typically resolve within an hour or two of the drip ending. Enjoying that experience does not mean you’re becoming addicted. Feeling like you need the infusion more frequently than scheduled, or finding yourself seeking ketamine outside your clinic, would be signs worth taking seriously.