When Dr. Steven Mandel and his son, Sam Mandel, started using ketamine to treat mental health, they were among the first in Los Angeles to launch a business based on off-label use of the drug. It was 2014, and ketamine had been an FDA- approved anesthesia since its invention, in 1962, but it wasn’t until the late 1990s that researchers had begun testing it as a psychiatric treatment.
And even amid widespread, positive results, the drug remained in the domain of anesthesia departments and raves, where it became (and remains) a popular party drug. That, says Sam Mandel, is partly because the drug is so cheap to make – one estimate puts it at $1 per dose – and because the patent expired in 2002. Without financial incentive, some contend, the American medical establishment, broadly speaking, hasn’t been motivated to develop it for this additional use. So far just one company, Janssen Pharmaceuticals, created and patented their own version, esketamine, which is administered as a nasal spray.
But ketamine, which must be administered intravenously, has remained regulatory fair game in a gray area of off-label use, while still technically an FDA-approved drug. That allowed the Mandels to open their doors and build what’s now a staff of 17 at their practice, Ketamine Clinics Los Angeles.
Sam Mandel worked as an actor before starting the business with his father, a practicing anesthesiologist who had studied psychology as well. Having seen the painful impact of depression among friends and family, the younger Mandel was enthusiastic about ketamine’s possibilities, and convinced his father to launch a business dedicated to helping people with the drug, and to see what the father-son team could do together. Now, nine years later, they’re among the vanguard of psychedelic mental health treatment in an increasingly crowded field of providers.
He spoke with Terra about building the business, the ketamine landscape, and its challenges and opportunities. Our interview has been edited and condensed for clarity.
TERRA: There’s been a boom in ketamine use for mental health treatment in recent years. Why is that?
SAM MANDEL: It’s definitely increased exponentially in the last several years. When Spravato, or esketamine, was FDA approved it really added a lot of attention to IV ketamine because you really can’t talk about Spravato or esketamine without talking about ketamine. Big pharma was pretty active in disinformation campaigns against IV ketamine because it really threatened the less effective high-margin drugs they made and there was no one advocating for ketamine because it’s so cheap and the patent is up.
And especially even today…with depression being the leading cause of disability in the United States, and the mental health issues with veterans and veteran suicides increased exposure there. People are desperate and literally dying for new solutions. And so other psychedelic medicines like psilocybin, MDMA, etc have also started to gain a lot of attention. Institutions weren’t even allowed to do research with them until very recently. You know, that has really opened up a lot of possibilities. I mean, MDMA is most likely going to be approved next year in the second quarter, which is huge. You know, Rick Doblin at MAPS spent his whole entire life working on that one.
TERRA: What led you to start the Ketamine Clinics Los Angeles?
SAM MANDEL: Dr. Mandel’s background is as a psychologist who then became an anesthesiologist and spent his career working with ketamine. The early research on this drug that he was an expert with, indicating it was a really effective elevator of mood – even in treatment-resistant – cases was really exciting. And my background in mental health since I was young and personal connection to friends and family who have struggled and committed suicide. We were both really invested in a new solution that would work and agreed, let’s try this, let’s offer it to some people, without any idea just how much it would really grow and what it would become. I had said, let’s do this together. I think he was like ‘okay, cool,’ but I really just kind of took it to the moon and am still working on that.
TERRA: Why did you choose to administer IV ketamine, versus lozenges or esketamine nasal spray?
SAM MANDEL: Most psychiatrists are using Spravato or IM intramuscular injection or sublingual lozenges for ease of use.
However, IV is the gold standard. It is the safest and most efficacious and it is what more than 90% of the research is based on. So it always makes us cringe a little bit when I’ve been at dinner with psychiatrists who have just point blank said, ‘Yeah, we do Spravato because it’s easier,’ or ‘we do an IM injection because it’s just easier.’ Easy is not a good reason to choose a particular modality or route of administration for a patient.
I’m not putting any of those people down. I have friends and colleagues who are using those other ROAs [routes of administration] and I know patients who have had good results with them. It’s not to say they’re bad. But there are some important nuances and distinctions between them.
TERRA: Given the incredible increase in the number of companies that sell various ketamine treatments, what are some of your biggest business challenges?
SAM MANDEL: When we started, we kept saying, ‘We wish more people were doing this.’ We have patients flying in from all over the world and all over the country. Australia, Italy, France, New York, you name it. And in some ways, it was nice to be sought out as the guys to go to. But we also felt sad that people should have to undergo such a burden in time and money and energy just to get this treatment, and really wanted it to be more widespread. We still say, people don’t have to come to us, but they have to at least know that this exists and it’s an option.
But now we’re really concerned about quality of care. It’s like, be careful what you wish for. It’s great that there’s a lot more people doing it, but we wish that there were more good providers doing it in what we consider the right way.
TERRA: What are some of your concerns, specifically?
SAM MANDEL: As far as tranches and that kind of mail order model, a lot of these people will say, ‘We’re increasing access. It’s cheaper.’ I don’t want to criticize mail order company Mindbloom specifically, but I’ll say generally for that part of this field, we don’t feel like it’s very good care, sending people such mind-altering medicine in the mail. Most of these companies have very little-to-no screening of whom they choose to send to. There’s very little-to-no monitoring or supervision during the medicine session. And it comes with a lot of risks. Again, lozenges can help people but they’re generally for use as an extender of the benefit they might get from IV – they’re not a stand alone treatment. They’re not as robust and don’t really pull people out of the dumps. Sending people this medicine in an unsupervised setting we feel is not very good.
Ketamine is a pretty safe medicine, but it can cause problems. It can increase blood pressure, it can cause other psychiatric challenges for people in response to it.
TERRA: How does treatment work at your clinic?
SAM MANDEL: We have 17 employees, including a psychiatrist, a psychiatric nurse practitioner, a physician’s assistant, a nursing team, and an admin team. We do that to have a really intensive care model and to give really individualized care. Each patient gets lots of time and attention when they’re in the clinic or talking to us.
Our nursing team helps people prepare for the experience. We’re monitoring them with hospital grade monitoring equipment, so their blood pressure, pulse and EKG, we have eyes and ears on them at the end of the entire time. We can support them in not only being safe but comfortable with infusions. Afterward, we can recap with them a little bit about their experience, encourage them to have talk therapy, and follow up with them. There’s a lot that goes into the care outside of just giving the medicine.
In addition to marketing, we get referrals from psychiatrists, therapists, even OBGYNs because of postpartum depression, plus other specialists who will refer patients to us.
TERRA: What’s next for the clinic, especially as the ketamine landscape grows and changes?
SAM MANDEL: As far as where the industry is going, it’s important to expand and have other offerings, as well to meet all the patient’s needs, instead of us just having to send them down down the street to someone else because they need to talk about Paxil or whatever it might be. Other psychedelic medicines are exciting and…we’re enthusiastic about bringing them into the practice once they’re available. That’s going to really shift the business model a lot. You know, still TBD what that really will look like in terms of the requirements and the amount of time and space and credentials necessary, plus the insurance that it will require. It’s a pretty significant shift as a business.
Also, ketamine works 83% of the time in our clinic, which is great, but that still leaves 17% of patients who don’t really benefit. And instead of saying sorry, and maybe you want to go look at X,Y and Z, we can say, ‘why don’t we try TMS [transcranial magnetic stimulation] here? You know, why don’t we see what’s going on with your medications here? So that’s really enhancing the quality of the care that we can provide.
Learn more about the Ketamine Clinics Los Angeles here.