It's probably not the first place you'd go to find relief from severe clinical depression, but the psychedelic party drug ketamine has revealed itself to be something of a 'miracle drug', performing far more quickly and effectively than traditional antidepressants and mood stabilisers.
Where current treatments take weeks to work - and then might not work at all, depending on the patient - ketamine has been shown to treat the symptoms of depression within hours.
"It's not subtle. It's really obvious if it's going to be effective," Enrique Abreu, a Portland-based doctor who began treating depressed patients with ketamine in 2012, told The Washington Post. "And the response rate is unbelievable. This drug is 75 percent effective, which means that three-quarters of my patients do well. Nothing in medicine has those kind of numbers."
Also known as Special K, ketamine first came on the scene as an hallucinogenic club drug in the 1960s, but has since been embraced by emergency rooms as a quick and easy anaesthetic. It's used as an anaesthetic for children with broken bones, during emergency surgery in war zones, and is often given to patients in burn centres as a sedative.
But over the past decade, the drug's enormous potential in the treatment of mental health issues has become a focus for researchers and psychiatrists trying to come up with a solution to severe depression where currently available medications have failed.
"Since 2006, dozens of studies have reported that it can also reverse the kind of severe depression that traditional antidepressants often don't touch," Sara Solovitch reports for The Washington Post. "Experts are calling it the most significant advance in mental health in more than half a century."
Why is a new treatment option for depression so exciting? Put simply, for many people with severe depression, the drugs available to them - known as selective serotonin reuptake inhibitors (SSRIs) - pretty much suck. Not only do they take three to eight weeks to actually have an effect, but once you make it through those months of waiting, there's no guarantee they'll actually work for you.
As we reported back in July, SSRIs are believed to work by limiting the reabsorption of serotonin into the brain's presynaptic cell, and this readjustment of serotonin levels appears to help the brain cells send and receive chemical messages more effectively, which can boost a person's mood.
But every SSRI has a different chemical make-up, and it's basically a case of trial-and-error to see which ones will benefit or mess with your unique brain chemistry. And on top of not being super effective for many people, SSRIs are also known to cause a range of negative side effects, such as nausea, dizziness, drowsiness, insomnia, weight gain, and reduced sexual desire or erectile dysfunction.
Clearly, there has to be a better way.
Academic medical centres across the US are now increasingly opting to treat their patients with ketamine, including Yale University, the University of California at San Diego, the Mayo Clinic, and the Cleveland Clinic. The drug is administered by a single intravenous infusion at doses less than those used in anaesthesia, which is thought to prevent addictions from developing.
Patients who've had no choice but to keep trawling through the various types of SSRIs for years to see if one fits - while having to deal with the debilitating effects of having untreated depression - are finally seeing results, sometimes as quickly as within 2 hours of taking the drug.
"There is a significant number of people who don't respond to antidepressants, and we've had nothing to offer them other than cognitive behaviour therapy, electroshock therapy and transcranial stimulation," L. Alison McInnes, a psychiatrist from the Kaiser Permanente clinic in California, told Solovitch.
Just yesterday, researchers from Vanderbilt University Medical Centre published the results of a study where mice with alcoholism had their depressive-like withdrawal symptoms reversed when treated with ketamine.
So why does ketamine work so well? Scientists aren't actually sure, but a 2010 study published in Science suggests that by blocking proteins called NMDA receptors, the drug prompts the brain to increase the production of synaptic signalling proteins in the prefrontal cortex - a region thought to regulate complex cognitive, emotional, and behavioural functioning.
In doing this, it appears to be not only promoting the growth of new synapses, which leads to greater connectivity in the brain, but it's also switching certain connections on and off, and for whatever reason, this has a rapid anti-depressive effect. SSRIs, on the other hand, target the serotonin and noradrenalin systems in the brain.
The drug isn't perfect by any means - some patients find the hallucinations it causes to be uncomfortable, and the cost isn't regulated, which means it can get very expensive depending on where you get it. It's also not a 'cure' - time between doses varies between person to person, but in order to treat the symptoms of severe depression, you need to keep taking it, just like traditional anti-depressants.
That said, the fact that it's bringing relief to many people who are resistant to SSRIs is really exciting, and with so much support for the drug as a mental health aid in the medical community right now, we're only going to get a better understanding of its potential.
Editors's note: It has been brought to our attention that despite many positive first-hand accounts from treatment-resistant depression patients, and the researchers and doctors who work with them, some researchers are in opposition of ketamine being touted as a treatment for depression.
While there have been many studies conducted on the antidepressant effects of ketamine, and positive accounts from patients who have found no success from traditional drugs, criticism has been squared at the limited sample sizes of these studies and the strength of the evidence - most notably, this 2015 review.
"Nearly all ketamine studies had short-term follow-ups," Keith Harris from the University of Queensland, Australia told ScienceAlert. "Very few tested even modestly long-term affects on substance abuse and other possible effects."
As with many experimental drug treatments with conflicting statements for and against their merits, it will take many years to figure out the true value of ketamine in this space.
What we do know is patients with few alternatives have benefitted from it, and research institutions are investing a lot of time and money into figuring out its potential, and we'll update you with more information as it's made known.