By: Kevin E.G. Perry

After being diagnosed with clinical depression as a teenager, Warren Gumpel spent years swallowing handfuls of antidepressants that would often leave him feeling “catatonic”. Then, during a severe depressive episode five years ago, Gumpel turned to a New York clinic offering a relatively new form of depression treatment: ketamine infusion therapy. The results were immediate, and transformative.

“The SSRI mixtures I was taking would just suppress my emotions,” says Gumpel, speaking over Zoom from his home in Florida. “But ketamine expands your consciousness and even grows grey matter in your brain. It’s the most incredible way to deal with things that you didn’t know were in your subconscious, things that affect the decisions you make every day.”

Gumpel felt so liberated by his experience with ketamine that he became a vocal advocate for the treatment, encouraging friends and family members who were dealing with depression to try it for themselves. Together with his business partner, Mike ‘Zappy’ Zapolin, Gumpel founded The Ketamine Fund, a non-profit that has donated over 400 treatments to military veterans. Their next venture is KetaMD, an online ketamine clinic set to open this year which they hope will help widen access to the treatment by allowing it to be prescribed over a video call.

Still best known as a party drug, ketamine’s reputation as a new type of antidepressant has grown steadily in recent years. It was first synthesised in 1962 by Calvin L Stevens, a chemist in Detroit who was trying to develop a more manageable alternative to PCP to use as an anaesthetic. By 1970 it had been approved by the FDA and was being given to American soldiers fighting in Vietnam, where it proved revolutionary as, unlike other anaesthetics, it barely affects the respiratory system. That meant medics could operate on the battlefield without breathing machines. Still more remarkably, anecdotal reports began to emerge that even soldiers who’d had their limbs blown off were less likely to experience post-traumatic stress if they’d been given ketamine. By the 90s, studies of soldiers returning from the Gulf War showed that using ketamine greatly reduced the prevalence of PTSD, spurring curiosity about its potential for therapeutic use.

Subsequent research at the Yale School of Medicine set the standard for today’s ketamine infusion therapy. As Gumpel explains, this means patients typically receive a 45-minute intravenous or intramuscular ketamine infusion six times over the course of two to three weeks. They then return for a further infusion ‘top-up’ once they feel their symptoms return, with the aim that over time these top-ups are needed less and less frequently. Between 2015 and 2018, the number of American clinics offering this sort of treatment jumped from 60 to over 300.

Part of this boom in popularity is because, unlike traditional antidepressants which take weeks to start having an effect, ketamine has been shown to alleviate symptoms of depression within hours of receiving the first infusion – even for patients like Gumpel, who have ‘treatment-resistant’ depression. He describes the experience of receiving a ketamine infusion in psychedelic terms: “Commonly I see a fabric that doesn’t allow me to see where I end and somebody else begins. There’s no distinction between me and another person, or even me and the furniture. It’s all just one big connected thing, and there’s something very comforting about that. It feels like the whole universe is within (reach) to you, and yet you also feel like a speck of dust at the same time. You feel like nothing and everything at once. It’s so liberating.”

The experience that patients have during the infusion is key to the success of ketamine treatments. Exactly why the drug is so effective in fighting depression remains something of a mystery, although it’s thought to be due to the multiple ways in which the drug affects brain function. Firstly, ketamine is an NMDA inhibitor, which acts as a painkiller and gives the drug its dissociative effect. Secondly, it has been shown to encourage the regrowth of neurons and synapses in the brain, which is significant as a reduction in neurons and synapses is closely associated with depression. Thirdly, ketamine acts on an area of the brain called the lateral habenula, the region which mediates negative emotions. Dysfunction in the lateral habenula is linked to depression, schizophrenia and drug-induced psychoses, but this can be reversed by ketamine infusion therapy. “It’s not just one thing,” says Dr Joseph Rosado, a Florida-based physician who is advising KetaMD. “It’s a combination of things, and that’s what makes it such a novel treatment in therapy.”

Ketamine infusions are usually only available in a doctor’s office or other clinical setting, but KetaMD’s aim is to offer ‘at-home’ treatments. Patients will speak to a doctor during an online TeleMed consultation, and then once ketamine lozenges have been mailed out each infusion session will be guided by a nurse using the same technology. This is only possible because of new guidelines brought in as a response to the coronavirus pandemic. “During this health emergency there’s been an exception to The Ryan Haight Act, which is a federal law that essentially doesn’t allow controlled substances to be prescribed through virtual meetings,” explains Dustin Robinson, KetaMD’s legal advisor. “During corona, doctors have been allowed to prescribe controlled substances remotely.”

Both Gumpel and Zapolin say they see widening access to ketamine therapy as a important tool in dealing with America’s epidemic of suicide, addiction and depression – something which has only worsened during the pandemic. Statistics from the CDC published last summer stated that one in four young adults between the ages of 18 and 24 had considered suicide in the past month due to the pandemic. “We’re trying to get to the millennial audience who are hurting in a big way out there,” says Zapolin. “What I love about ketamine is that it’s not just for treatment-resistant depression. It’s for people who have PTSD, which is pretty much everyone right now. If you’ve lived through coronavirus, you have PTSD. It’s important we open this up and make it the first stop in mental health instead of the last stop after nothing else has worked.”

Zapolin believes that ketamine therapy will soon become mainstream – and argues that it could even challenge the big pharma companies who have a clear profit incentive to keep patients on a steady diet of antidepressants year after year. “What’s exciting is that, as big and powerful as pharma is, what’s bigger and more powerful is the insurance industry,” he says. “The insurance companies don’t want to keep paying for all these expensive medications. Ketamine is very cost-effective, so I think eventually when they have the data they’re going to tell the pharma companies, ‘Hey, sorry, we’re not paying for your stuff anymore.’”

In the UK, research into ketamine therapy for patients with treatment-resistant depression has been spearheaded by Dr Rupert McShane, a consultant psychiatrist at Oxford Health and researcher in Oxford University’s Department of Psychiatry. He has been carrying out studies at the Oxford Health NHS Foundation Trust since 2014, and is cautiously optimistic that ketamine could indeed prove to be a useful treatment for a variety of other conditions. “There is already some data to support its use in treating PTSD, bipolar, eating disorders, substance misuse and social anxiety, but not enough to support widespread use,” he says. “Getting enough data is so expensive, and the barriers to use so low, that it is inevitable ketamine will be used outside treatment-resistant depression before we have enough data to be sure. This creates a real risk of overuse, stigma and backlash. The only way to manage this risk, given where we are, is transparent, detailed monitoring of use outside clinical trials.” As for whether this sort of therapy will become easier to access in Britain, he adds: “The NHS will rightly be cautious, but I do think it likely that ketamine will eventually become a mainstream treatment.”

For Gumpel, the day that ketamine becomes as easy to access as traditional antidepressants can’t come soon enough – and he says potential patients shouldn’t be put off by the drug’s hard-partying reputation. “The ‘Special K’ association is there, but we have to remember ketamine is very widely used and very safe – it’s on the World Health Organisation’s list of the most essential medications in the world,” he points out. “I’d love to see a paradigm shift right now when we need it the most. I want more people to be able to get ketamine, and I really want more people to get ketamine before they get stuck on Prozac.”

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