By the time she signed up for an experimental ketamine study, one young mother's obsessive compulsive disorder had forced her to give up her daughter for adoption. "When the baby was just a couple of days old it hit her like an injection of anxiety," Carolyn Rodriguez, assistant professor of psychiatry and behavioral sciences at Stanford University, tells me about her participant. "She was having difficulties even with changing the baby's diapers." Another participant suffering from contamination obsessions would brush his teeth compulsively, despite painful and bleeding gums. "Eventually he avoided brushing and dental hygiene altogether, and then ended up losing a fair amount of his teeth," Rodriguez says. Rather than being a "personality quirk," she emphasizes, OCD can be debilitating and even life threatening—one in seven adults with the condition will attempt suicide in their lifetime. Existing treatments—which include serotonin reuptake inhibitors (the group of medications that SSRIs belong to), cognitive behavioral therapy (CBT) and exposure and response prevention (ERP)—help in around 50 percent of cases. Rodriguez is two years into a five-year study of the effects of ketamine on OCD symptoms. So far, she has seen promising results. In 2013, she conducted the first randomized controlled study of intravenous ketamine infusions for OCD sufferers. Each patient got a 40-minute infusion at a dose of 0.5 mg per kg. Half of those given ketamine, rather than saline, still reported at least a 35 percent reduction in obsessive and compulsive symptoms (such as cleaning or checking rituals or uncontrollable taboo thoughts) after one week. "Patients said it was as if the weight of OCD had been lifted," she recalls. "People were really as surprised as I was." Ketamine acts far more rapidly than existing treatments, which can take months to have an effect and, in the case of talking therapy, require a lot of determination. One patient, a high school teacher, told Rodriguez the treatment was like a "vacation" from her condition.
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While SSRIs work on serotonin in the brain, ketamine acts on another neurotransmitter called glutamate. Though scientists don't know what type of imbalance in neurotransmitters cause OCD for sure, glutamate abnormalities have been linked with the condition. Rodriguez's research is pioneering in the scientific world but ketamine clinics across the US are already offering infusions as a treatment for OCD. These clinics primarily treat depression, PTSD and chronic pain, with OCD as a relatively recent addition which is taken up by a small proportion of patients. Ketamine isn't FDA-approved for these uses but, as it is legal as an anaesthetic, it can be administered off-label. Rodriguez is in two minds about the use of ketamine for OCD in the absence of the same body of research that backs ketamine as a treatment for depression. "I've seen it work and some patients really benefit from it," she says. "I think it's important for patients who are in dire straits—so, individuals who are suicidal, have tried every possible medication and just continue to suffer." But Rodriguez has concerns about the infusions' side effects, which can include nausea, vomiting and disassociation. She compares this floating feeling to getting "nitrous oxide at the dentist." The sensation does not match the intensity of a K-hole (or ketamine high), but participants aren't allowed to drive for 24 hours after having the treatment. Treatment center Ketamine Clinics of Los Angeles began administering the drug for OCD after patients who experienced obsessions and compulsions alongside other conditions found it worked on these symptoms too. Apart from Antarctica, the clinic has received visitors from every continent. "We were very gratified with the results," Steven L. Mandel, the center's president, tells me. "They can shake hands again, they can go to a public toilet without it being an hour's worth of rituals."
Outcomes for the clinic's OCD patients can vary widely, says Mandel, who has seen everything from patients totally relieved of symptoms, to "toned down" intrusive thoughts, to people who get little benefit at all. Mandel founded the clinic with his son Sam, who strongly doubts that ketamine causes longer term side effects. "Ketamine has been used all over the world for 50 years and people who received the first surgery and other applications for pain had much higher doses than we're using," he says. Of course, this early in research, there's no evidence proving this yet. Ryan*, a 24-year-old patient at treatment center Ketamine Health Centers Miami, suffers from a combination of PTSD, anxiety, depression and OCD and calls the treatment a "lifesaver." "Before the infusions I was not working at all. I tried to drive Uber but I would get obsessions while I drove that I was putting myself in a dangerous situation," he says. "The obsessions can take on so much importance that if I'm driving I'll focus on these thoughts instead of focusing on the road," he adds.
Since having ketamine infusions, alongside talking therapy, Ryan has secured a full-time job and feels optimistic about the possibility of recovery. "I have a long, long way to go but at least I'm making steps."
However, Christopher Pittenger, associate director of the Yale OCD research clinic, believes that in contrast with depression, ketamine's use for OCD "should be considered an experimental treatment, not an established one."
"I think it is premature to use ketamine broadly for the treatment of OCD," he tells me. "Ketamine is most appropriate in cases of OCD with severe comorbid depression, in which the depression is refractory to standard treatments and is causing substantial distress and/or is getting in the way of treatment for the OCD."
Pittenger—who is unaffiliated with Rodriguez's research—hopes to study whether repeated dosing of the drug increases its effectiveness for OCD and to build on a single-person trial his team conducted using an intranasal method of administering ketamine for OCD. He also intends to follow up another single-person study which trialled ketamine infusions and CBT in combination, in the hope of enhancing the drug's effects.
"We really encourage patients to also do talking therapy," Mandel says. "The renewal of hope enables them to pursue these longer term strategies that require more of a commitment."
Ryan agrees. "They just go hand-in-hand. If it wasn't for the infusions I wouldn't be strong enough to get over that hump." Rodriguez has studied the effects of giving patients a ketamine infusion followed by a course of exposure and response prevention, a kind of CBT where patients confront the fears associated with their obsessions. There was a 50 percent response rate among participants in her ketamine-only study after one week—with talking therapy and ketamine, it was 63 percent after two weeks. "These are all tools in a clinician's toolbox," she explains. "They can be used to enhance each other." Her next move will be to use ketamine's "bio-signature" to find a drug which acts similarly on the glutamate pathway to reduce OCD symptoms but without the same side effects. Ideally, she says, this would be a pill that patients could take in their own homes. "I don't want to paint the picture that ketamine is the ultimate," she tells me. "I hope within my lifetime I can identify a series of medications for folks. Obviously, no drug is one-size-fits-all, so we need lots of different kinds of strategies to target this pathway."
For Obsessive Compulsive Disorder information and support, visit the International OCD Foundation's website
*Name has been changed
Correction: A previous version of this story states there was a 50 percent response rate among participants in her ketamine-only study after one week—with talking therapy and ketamine, it was 53 percent after two weeks. The correct percentage after two weeks was 63.
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