With Denver recently legalizing psilocybin mushrooms, discussions of microdosing — using a tiny dose of a psychoactive drug that is too small to induce a “trip” — are on the rise. One of the most popular microdosing treatments being studied is using ketamine for treatment-resistant depression, i.e. depression with an inadequate response to two or more antidepressants of adequate dose and duration.

But does it work? Initial studies are mixed, and it must be cautioned that further inquiry is needed.

To find out why, let’s start with the basics: ketamine itself.

What is Ketamine?

Ketamine is a sedative, and until recently was commonly used in veterinary medicine to sedate horses and other large animals. Ketamine has historically been used to provide pain relief and sedation, and also to start and maintain anesthesia. In recreational settings it’s common as a club drug because it causes effects like delirium or a sense of disconnection from one’s body. A side-effect of its overuse is referred to as being stuck in a “K-hole.”

Other Possible Applications of Ketamine

Recently, some in Silicon Valley began promoting ketamine’s brain-boosting effects, and scientists caught wind of another possible application: a treatment for depression.

Researchers at the University of California, Davis began studying the drug, and found that there might actually be some truth behind the hype. Their study found that common psychedelics like ketamine, LSD, and MDMA actually change the structure of our brain’s neurons — something akin to tweaking the underlying circuits that can cause mental health disorders.

Research on Ketamine

“People have long assumed that psychedelics are capable of altering neuronal structure, but this is the first study that clearly and unambiguously supports that hypothesis,” said David Olson, an assistant professor in the university’s chemistry, biochemistry, and molecular medicine departments and the leader of the research team. “The rapid effects of ketamine on mood and plasticity are truly astounding.”

Ketamine’s club-drug party days may give it a bad rap, but very early research looks promising for those truly suffering from treatment-resistant depression — and entrepreneurs are naturally eager to cash in. The San Antonio-based Kalypso Wellness Centers offer $495 ketamine infusions, and the company’s success has been copied by a number of other clinics.

Caution on Ketamine hype

First, the clinics offering these services are often unlicensed and lack an on-site psychiatrist. They’re frequently prescribing off-label uses of ketamine that haven’t been rigorously studied. In addition to depression therapies, some advertise ketamine solutions for lupus- and cancer-related concerns.

It’s also important to note some of the common side effects of ketamine include dissociation and sedation, and there are specific subsets of patients for whom its use might be especially dangerous, including those with unstable or poorly controlled hypertension or with pre-existing aneurysmal vascular disorders.

But it’s clear that those who are suffering from treatment-resistant depression are clamoring for ketamine treatments, and the government is listening to those concerns. The benefits of the drug are so encouraging that the U.S. Food and Drug Association (FDA) recently approved a version of the drug for use as an “adjunctive therapy” for depression — meaning used in addition to the primary treatment method.

A New Option for Sufferers of Treatment-Resistant Depression

The new drug, Spravato — or esketamine, half of the ketamine molecule — has some interesting restrictions that likely arise from ketamine’s past as a club-kid. First, it’s a nasal spray, and patients must be taking another antidepressant to get a prescription. And you can’t simply drive to your favorite drug store to pick up your prescription. You’ll need to visit certified Spravato-dispensing clinics.

Spravato won’t be cheap, either: patients can expect to pay from $590 to $885 per dose, and many will require once- or twice-weekly treatment. That cost adds up fast — but if the drug successfully addresses treatment-resistant depression, it may be something that more are willing to explore.

And research says there may be reason for optimism. A double-blind, doubly randomized, delayed-start, placebo-controlled study of 126 adults showed some efficacy of Spravato in a longer-term maintenance-of-effect trial. According to a report from the FDA: “In one of the short-term studies, Spravato nasal spray demonstrated statistically significant effect compared to placebo on the severity of depression, and some effect was seen within two days. The two other short-term trials did not meet the pre-specified statistical tests for demonstrating effectiveness.”

Much more research on ketamine is needed, but early results are intriguing. But before exploring your own therapeutic regime, make sure to talk with both a licenced, qualified therapist as well as a doctor. They can help determine if your unique constellations of mental health needs would necessitate an intervention of this nature, and make sure you’re using the drug safely and appropriately.