Ketamine’s abuse potential: 5 Questions for psychiatrist Jennifer Swainson

Swainson discusses what we know about ketamine's abuse potential.

Amid the rise of therapeutic psychedelics, ketamine, too, has become more popular. Because doctors can legally prescribe it in the U.S, posh clinics and online start-ups have begun offering ketamine therapy. Some argue that ketamine should not be considered a psychedelic; the drug acts on different receptors than “classic psychedelics” like psilocybin, but at high doses, it can produce hallucinations. Ketamine has been widely available for use as an anesthetic for decades, but now, clinicians are prescribing smaller doses of the medication as a treatment for depression, PTSD, and addiction.

But over the last few months, ketamine has been in the news not for treating addiction, but for being a drug of abuse. When actor Matthew Perry died, a large amount of ketamine was found in his system, and federal officials have charged five people, including two doctors, alleging they illegally provided the drugs to Perry. The Drug Enforcement Administrator’s head Anne Milgram appeared on the CBS News program Face the Nation, comparing the current landscape of ketamine diversion and abuse to the opioid epidemic. 

To better understand the drug’s abuse potential, The Microdose spoke with Jennifer Swainson, a practicing psychiatrist at the Misericordia Community Hospital in Edmonton, who has published research about ketamine’s abuse potential, and has treated patients in her clinic with ketamine for nearly a decade. 

How would you describe the abuse potential of ketamine?

Ketamine can certainly be abused. There are different levels of drug use, though: there's substance misuse and abuse, and then there's a full blown addiction where there is a physiological dependence. Ketamine is abused in many parts of the world, particularly in Asia as a club drug. Abuse in North America is quite low, from what we know, but certainly the potential is there. The drug can produce dissociative effects, but not everyone likes that effect. But for some people, it is very pleasant, and any time someone has a pleasant psychological experience with a substance, there is a risk that they're going to want to use it again. 

The risk for a physical dependence on ketamine is lower than some other substances, like, for example, alcohol. Someone would have to be using very large amounts of ketamine on a very regular basis to develop physical dependence. At the doses used to treat depression, physical dependence doesn't develop, but there is still a risk of psychological dependence.

With ketamine abuse in the news, what do you think people should know about the drug? 

In the case of Matthew Perry’s death, it’s important to note that it was not due to his therapeutic ketamine infusions at antidepressant doses. Perry was a known substance abuser of other substances, and he sought out extra ketamine; he was using a lot of ketamine. At the time of his death, he had anesthetic levels of ketamine in his system. That's very different from when we are treating people in a clinical setting.

If you think about a drug like Tylenol, we commonly take it for things like a headache. But consider that in large doses, it can be extremely toxic. 

In a paper you published in 2022, you and your co-authors reviewed 65 studies to understand ketamine’s abuse potential. What did you learn? 

What was interesting was that in clinical trials of ketamine as an antidepressant, none of them mentioned abuse potential. When we actually looked at the studies, there was no actual measure of abuse potential. The absence of any reports of concern has led to the idea that there is no concern. When you look at the literature, the preclinical data — data with studies on non-human animals — does suggest that there may be a risk of abuse. Clinically, we just don't know, because it hasn't been measured significantly. That’s partly because there is no easy way to measure it; there are no scales that are typically put into studies. 

So using FDA suggestions about measuring drug liking and craving, we developed a short scale to use with our patients. We used it to survey patients that were using sublingual and intranasal ketamine, and we found that there were some patients that really liked the effects and did have some craving. But when they reported any desire to use more of the substance than what was prescribed, it was typically because they thought more ketamine would help their mood symptoms more. These are small studies, but we haven’t really seen the clinical population wanting to use more ketamine for the purpose of getting high or its psychological effects. 

That study was published two years ago. Has there been more data measuring drug liking or craving, or is the state of research more or less the same as it was?

We're in a similar place. We're currently in the process of putting together a real world study on ketamine, where we did survey drug liking and craving, but I really haven't seen many other groups looking at this significantly. This is the direction we're seeing for other psychedelics as well. When you look at the MAPS studies for MDMA, they looked at abuse potential by reports of adverse events. But that’s different from actively seeking out information and questioning participants about drug liking and craving. 

When you’re administering treatment to your patients, you’re using ketamine in a medical setting. Over the last few years, there have been more companies using a mail-order model, where people receive doses and self-administer ketamine at home. What are your thoughts on this practice?

It’s controversial, and I know the U.S. Food and Drug Administration has warned against it. But my take on it is a little bit different, especially being in Canada. Our ketamine program is part of a public health care system, and it easily reaches capacity. In our program, we do a series of eight treatments of intravenous ketamine, done twice a week over four weeks. Depending on their response, we might extend that by a couple of treatments, or drop down to a weekly or every couple of weeks schedule as we transition them to a sublingual or intranasal ketamine, if we think they’ll need maintenance treatments. And most patients who have a good response to ketamine do need some form of maintenance treatment, but it's just not sustainable for them to keep coming back in a public system for repeated treatment. 

That's where it could make sense for patients to use a sublingual or intranasal ketamine at home. It can be a very good option that increases access, but only when it's the right patient and right situation. Of course, I don’t think mail order ketamine for anybody who wants it is a good idea. But when prescribed appropriately, I would consider ketamine use no different than prescribing other psychiatric drugs like benzodiazepines or stimulants. 

It’s really important for people to receive a psychiatric assessment and follow up, and not to self-medicate. Just because there is some evidence it can be a useful medication doesn't mean that it should be obtained illicitly and used without the supervision of a physician. 

This interview has been edited and condensed for clarity and length.