The Clinic on Every Corner: Ketamine Is Treating Depression and Creating New Addictions Simultaneously

In January 2015, there were fewer than 100 ketamine infusion clinics in the United States. By early 2026, that number had grown to more than 1,500 — a roughly 15-fold expansion in a decade. Johnson & Johnson’s esketamine nasal spray (Spravato) now operates through more than 7,000 certified administration sites, up from 2,800 just two years ago. The company projects $2.3 billion in Spravato revenue for 2026 alone. The market for esketamine — the S-enantiomer of ketamine, FDA-approved since 2019 for treatment-resistant depression — is expanding at 10.8% annually and is projected to reach $2.5 billion by 2030.

Ketamine, the Schedule III anesthetic that has been used off-label for depression, suicidal ideation, PTSD, and chronic pain for the better part of a decade, is now a mainstream treatment. And mainstream treatments attract mainstream problems: inconsistent oversight, expanding access that outpaces regulatory infrastructure, and a patient population that includes people whose psychiatric histories make them specifically vulnerable to the substance’s abuse potential.

This is not an argument against ketamine treatment. The evidence for its efficacy — particularly in treatment-resistant depression and acute suicidal ideation — is real and meaningful. It is an argument for understanding what ketamine actually does in the brain, who it helps, who it might harm, and what the current regulatory landscape does and does not protect against.

What Ketamine Does to the Brain

Ketamine is primarily an NMDA receptor antagonist — meaning it blocks N-methyl-D-aspartate receptors, which are glutamate receptors that play a central role in synaptic plasticity, memory formation, and the brain’s baseline excitatory tone. When ketamine blocks NMDA receptors, it produces a rapid cascade: glutamate accumulates in the synapse, AMPA receptors (a different glutamate receptor type) are activated, and the downstream result is a surge in BDNF — brain-derived neurotrophic factor — that promotes synaptogenesis, the growth of new synaptic connections.

In people with treatment-resistant depression, this synaptogenesis is thought to repair the cortical pruning and synaptic atrophy that chronic stress and depression produce over time. The antidepressant effect arrives within hours, not weeks. That speed — unprecedented in a field where standard antidepressants take four to six weeks to act — is why the psychiatry community took ketamine seriously despite its unconventional profile.

A 2026 study in the American Journal of Psychiatry added complexity to this picture. The randomized crossover trial found that ketamine’s effects on depressive symptoms are not purely glutamatergic. The drug also activates opioid receptors — specifically mu-opioid receptors, the same receptors targeted by opioids — and this opioidergic component appears to contribute meaningfully to the antidepressant effect. The interaction between ketamine’s glutamate blockade and its opioid receptor activity is still being characterized. What the study established is that the “ketamine works through glutamate” story is incomplete.

The opioid receptor finding matters for addiction medicine in a specific way. Ketamine’s abuse potential — which is real, documented in recreational users and in countries where it is widely available outside of clinical settings — may be partly opioidergic. The same reward circuitry that creates dependence on opioids, stimulants, and alcohol is being activated by a drug that the emerging clinic industry is positioning as fundamentally different from the substances it is meant to help treat.

The Dissociation Between Therapeutic Use and Dependence Risk

Ketamine use disorder is not theoretical. In clinical populations, it is rare. In recreational populations — particularly in parts of East and Southeast Asia where ketamine has been widely available as a club drug for decades — it is well-documented and serious. Chronic heavy ketamine use produces “k-hole” dissociation, urinary tract damage (ketamine-induced uropathy, which can progress to bladder loss), severe withdrawal, and persistent cognitive impairment.

The clinical dose used for depression treatment is lower than recreational doses. The supervised setting reduces but does not eliminate misuse risk. The population most likely to misuse ketamine — people with prior substance use disorders, people with trauma histories, people with severe and refractory depression — is substantially overlapping with the population being treated in ketamine clinics.

The clinical dose used for depression treatment is lower than recreational doses.

Dr. Nora Volkow, director of NIDA, wrote in 2024 that the expansion of ketamine treatment “is genuinely exciting and the efficacy data is real, but we are repeating the mistake of the opioid era in one specific way: scaling access faster than we’re studying the long-term risk profile in clinical populations.” Volkow’s concern is not that ketamine clinics should stop operating. It is that without systematic post-market surveillance — required reporting of adverse events, data collection on who develops dependence or tolerance, longitudinal follow-up of patients who undergo repeated ketamine infusions — the field is flying partially blind.

Johnson & Johnson’s ECHO study, which followed 570 patients across Europe and Israel using esketamine for up to 48 weeks, found that depressive symptoms continued to improve through the end of the follow-up period (-17.6 points by week 48) and that treatment effects were maintained for six months after discontinuation. These are encouraging findings. The ECHO study was also conducted with close clinical supervision, patient selection criteria, and monitoring protocols that are not uniformly present at the 1,500+ ketamine clinics operating across the U.S. without FDA oversight of their infusion protocols.

The Regulatory Patchwork

Here is the state of ketamine clinic oversight in the United States in 2026: the FDA has approved esketamine (Spravato) for two specific indications, with a REMS (Risk Evaluation and Mitigation Strategy) program requiring that it be administered in certified healthcare settings under observation. IV ketamine — the most common form used in clinics — has no FDA approval for any psychiatric indication. It is prescribed and administered entirely off-label, meaning the only regulatory oversight comes from state medical boards, DEA registration requirements, and facility-level accreditation standards that vary enormously.

Texas, in January 2026, became the first state to enact comprehensive regulations specifically for Psychotropic Ketamine Therapy (PKT) clinics. The rules require mandatory physician presence during administration, biennial clinic registration, adverse event logging, continuous patient monitoring, and limitation of treatment to three specific diagnoses: treatment-resistant depression, PTSD, and suicidal ideation. The physician ordering ketamine must complete mental health training or ketamine-specific coursework. Informed consent documentation is mandatory.

These are reasonable standards. They are also entirely absent in most other states.

California, New York, and Texas restrict corporate practice of medicine — meaning non-physician investors cannot own and operate ketamine clinics directly. Many other states impose no such restriction. The business model that emerged in the absence of these rules is familiar: private equity-backed clinic chains with a supervising physician on paper and a delivery model optimized for volume rather than clinical depth. Whether a person sitting in a ketamine infusion room in those states has the same level of supervision, screening, and follow-up as a person in a Texas or New York clinic is, at present, unknowable at the population level, because no one is collecting that data systematically.

What Harm Reduction Looks Like Here

For people who are considering or currently undergoing ketamine treatment, the evidence strongly supports its efficacy for treatment-resistant depression — particularly in the acute suicidal ideation indication, where the speed of effect is uniquely valuable. The concern is not whether it works. The concern is the conditions under which it is being delivered.

Questions worth asking before or during treatment: Does the clinic conduct psychiatric screening before initiating treatment and at each session? Is a physician (not just a nurse or technician) present during infusion? Is there a protocol for patients who show signs of increasing psychological dependence — wanting more frequent sessions, using recreational ketamine between appointments, escalating distress between doses? Is there a plan for what happens when the infusions stop?

Treatment-resistant depression is a serious illness and ketamine is a legitimate tool for treating it. The people sitting in ketamine infusion chairs in 2026 deserve the same thing that any patient receiving a powerful psychoactive drug deserves: a clinical setting with standards, a prescriber with training, and a system that will notice if the treatment is helping or beginning to harm.

Treatment-resistant depression is a serious illness and ketamine is a legitimate tool for treating it.

The clinic boom has outpaced the framework. Texas drew a line. The rest of the country is watching, or not watching, and the patients in the gap are the ones who pay if it goes wrong.