Ketamine nasal spray does carry a real potential for addiction, which is why it’s classified as a Schedule III controlled substance and surrounded by strict safety protocols. But the risk depends heavily on which form you’re using and how it’s administered. The FDA-approved version (Spravato, which contains esketamine) has significantly lower rates of reported abuse and dependence than off-label ketamine, largely because of built-in safeguards that limit unsupervised access.
Why Ketamine Has Addictive Properties
Ketamine produces feelings of euphoria and dissociation, both of which can make a drug appealing to use beyond its medical purpose. In the brain, it increases activity in reward-processing areas, particularly the nucleus accumbens and putamen, regions closely tied to how you experience pleasure and motivation. A phase 1 study submitted to the FDA during the approval process confirmed that people given esketamine reported “drug-liking” scores similar to those given IV ketamine and significantly higher than placebo. In other words, the drug feels good in ways that go beyond its antidepressant effect, and that creates a foundation for misuse.
This doesn’t mean everyone who uses ketamine nasal spray will develop a problem. It means the biological mechanism for habit formation exists, and the drug’s rewarding qualities are well-documented enough that regulators took them seriously.
Approved Esketamine vs. Compounded Ketamine Spray
There’s an important distinction between the FDA-approved esketamine nasal spray (Spravato) and compounded ketamine nasal sprays that some clinics prescribe off-label. The approved version can only be used in a certified healthcare setting under direct observation. You cannot take it home. Compounded versions, by contrast, are sometimes dispensed for home use, which removes a critical layer of oversight.
An analysis of the FDA’s adverse event reporting system found strikingly different patterns between the two. Ketamine (including compounded and off-label forms) was associated with significantly elevated reports of drug abuse, drug dependence, and substance use disorder. Esketamine showed the opposite pattern: reports of drug abuse, drug dependence, and substance abuse were significantly lower than expected. The researchers attributed this gap largely to the controlled clinical setting in which esketamine is administered, not to a fundamental difference in the drug’s chemistry.
The FDA has issued a specific safety alert about compounded ketamine nasal sprays, identifying cases of abuse, misuse, delusions, dissociation, visual hallucinations, and panic attacks reported between 2016 and 2021. If you’re using a compounded ketamine spray at home without supervision, the risk profile is meaningfully different from what you’d experience with the approved product.
How the Safety System Works
The FDA approved esketamine with a Risk Evaluation and Mitigation Strategy (REMS), a set of mandatory safeguards specifically designed to reduce the chance of addiction and diversion. In practice, this means:
- Supervised administration only. You spray the medication yourself, but a healthcare provider watches you do it. The drug never leaves the clinic.
- Two-hour monitoring period. After each dose, you’re observed for at least two hours before you can leave.
- No take-home prescriptions. The medication cannot be dispensed for use outside a certified setting. It cannot be transferred, loaned, or sold.
- Patient enrollment. Your enrollment in the REMS program is verified before every single administration.
- Secure storage. Clinics must store the drug according to DEA requirements for controlled substances, and any unused patient-specific doses must be destroyed within 14 days.
These restrictions exist because regulators recognized the abuse potential and decided the drug’s benefits for treatment-resistant depression justified approval only if access was tightly controlled.
What the Withdrawal Data Shows
One reassuring finding from clinical trials: researchers specifically looked for withdrawal symptoms in patients who stopped esketamine after up to a year of intermittent use. They tracked both physical signs (nausea, tremor, dizziness, sweating, poor coordination, tingling sensations) and psychological ones (anxiety, irritability, insomnia, difficulty concentrating, fatigue, depersonalization). The conclusion was that no drug-specific withdrawal symptoms emerged after stopping treatment.
This is a meaningful distinction. Many addictive substances create physical dependence, where your body adapts to the drug and protests painfully when it’s removed. The absence of a clear withdrawal syndrome with esketamine suggests that physical dependence is not a prominent feature of its use at prescribed doses and schedules. That said, the intermittent dosing schedule (typically twice a week initially, then weekly or biweekly) may itself help prevent the kind of daily exposure that drives physical dependence with other substances.
Who Faces Higher Risk
The biggest risk factor for developing a problem with ketamine nasal spray is a personal history of substance use disorder. If you’ve struggled with alcohol, opioids, stimulants, or other drugs in the past, the euphoric and dissociative effects of ketamine may be more reinforcing for you than for someone without that history. This is true of most Schedule III controlled substances, but it’s especially relevant here because ketamine is being prescribed to people with severe depression, a population that has higher-than-average rates of co-occurring substance use problems.
Other factors that increase risk include using compounded (non-FDA-approved) ketamine products at home without clinical supervision, using the drug more frequently than prescribed, and seeking out the dissociative or euphoric effects rather than the antidepressant benefit. Signs that use may be shifting from therapeutic to problematic include looking forward to sessions primarily for how the drug feels rather than for mood improvement, feeling disappointed when the dissociative effects are mild, or attempting to obtain ketamine from sources outside your treatment plan.
The Bottom Line on Risk Level
Esketamine nasal spray, used as approved in a supervised clinical setting, has a lower practical addiction risk than its Schedule III classification might suggest. The combination of intermittent dosing, clinical supervision, and no take-home supply creates meaningful barriers to the pattern of escalating, unsupervised use that typically drives addiction. Clinical trials lasting up to a year found no evidence of withdrawal symptoms upon stopping.
The drug’s underlying pharmacology, however, is genuinely rewarding to the brain. It produces euphoria and dissociation at levels comparable to IV ketamine, a well-established drug of abuse. The safety of the approved product depends almost entirely on the controlled conditions under which it’s given. Remove those conditions, as happens with some compounded ketamine products used at home, and the risk equation changes substantially.