Made popular for its use as a club drug — under the moniker “Special K” — and for its use in anesthesia, ketamine may now have antidepressant effects, according to one study, but without the added side effects posed by prescription drugs.

Testing Ketamine On Depression Patients

Based out of Michael E. Debakey VA Medical Center and Baylor College of Medicine in Houston, the study was the largest ever to examine ketamine’s effects on depression. While the researchers concede the 73-person trial still comprises only a small body of research into ketamine, the findings suggest alternative futures for treating depression without the use of prescription antidepressants. The team found 64 percent of people found relief within 24 hours of receiving the drug.

“Generally, we saw some type of improvement within a four-hour period [with ketamine],” said lead researcher Sanjay J. Mathew, M.D., a psychiatrist at the Debakey VA Center. “Then our primary outcome was looking at 24-hour outcomes where we found about two-thirds of patients with pretty severely refractory illnesses had a significant response on the depression scales.”

Ketamine works by blocking pain receptors and preventing the uptake of glutamate, an inhibitory neurotransmitter many scientists believe is most responsible for normal brain function. While typically used to anesthetize patients, both human and animal, ketamine’s ability to induce hallucinations and dissociative states in stronger doses gave researchers concern in selecting members for their trial.

Participants first had to have undergone three different traditional medicines, in addition to not having a history of a psychotic illness or bipolar disorder, alcohol or substance abuse in the previous two years, unstable medical illnesses, serious and imminent suicidal or homicidal risk, or various other medical issues.

The study was particularly noteworthy not only for its size, but also for its split among two locations, a trait the researchers believe eliminates geographical bias. Across patient background and location, results pointed toward successful effects through low-dosage (40 minutes via intravenous drip) ketamine administration.

“A big surprise was there were subgroups of patients who remained well, depression-free, and never relapsed in the five week observation period,” Mathew added. “And this is all off antidepressants.”

The Effects Of Taking Ketamine

Patients reported a range of experiences while receiving the drug, spanning feelings of “lightness” to deeper dissociative states — the latter appearing in 17 percent of subjects. Mathew classified the dissociate state as a feeling of unrealness — a detachment from reality and a diminished sense of time. What wasn’t experienced, the researchers highlighted, was a euphoric feeling. The drug did not cause giddy feelings, as many hallucinatory drugs can. It merely deducted the depressive ones.

“If they’re describing depression as this big weight that’s keeping them down and preventing them from living, then there’s a sense of being released from that weight. So it’s a very different feeling than euphoria,” Mathew said. “It’s more of a removal of something bad than the induction of something ecstatic. Our sense about it is it’s not a euphoric or happy pill, it’s taking away pain.”

The team speculates ketamine’s effects work because of the inhibition of glutamate in the brain. Roughly 80 percent of all neurons contain the transmitter, so when one receptor closes, researchers believe others open. This leads to neuroplasticity and greater connections in areas that otherwise lie dormant — a cascade of new associations, Mathew said, that influences the neural shaping process.

Where It’s Headed

These studies are still in their early stages, so no clinical practice is on the horizon. Overall, ketamine studies make up a small percentage of research into depression, so any findings on the drug must first be verified by larger samples with fewer constraints, Mathew said. However, the drug’s speedy effects should not be understated; whereas antidepressants require a four- to six-week timeline, ketamine needed a fraction of the time.

“I don’t think there will ever be a perfect pharmaceutical for something as complex as depression where there are multiple factors at play,” Mathew said. “But what this drug does is it works on a fundamental different system than the unusual antidepressant medications we have on the market. Ketamine may be fast tracking this process [to] within a few hours.”