Ketamine has been an essential medicine since 1970 when it was originally approved as an anesthetic for people in severe distress. However, within the last few years, ketamine’s off-label use as a treatment for mood disorders and chronic pain has become much more common.
Today, ketamine therapy refers to subanesthetic doses of ketamine to treat depression, chronic pain, and related comorbidities and symptoms. Beyond this high-level description, ketamine therapy varies widely. This is because we are in the early stages of defining this treatment. And like with any relatively new therapy, there may be numerous ways to achieve outcomes which balance safety, efficacy, and cost.
For example, a quick survey of how ketamine therapy is practiced today would show different routes of administration, doses, session frequencies, durations, settings, modalities, tools, safety precautions, and adjunctive therapies—to say nothing of provider backgrounds! While some may be critical of this variability, I believe it can be celebrated.
As long as there are competent regulatory agencies, licensing boards, industry associations, and transparent journalism, there will be safeguards to protect the public. Meanwhile, licensed healthcare professionals with different skills, backgrounds, and resources should be encouraged to contribute to this dynamic field. With greater participation, it will take less time to learn which approaches result in better patient outcomes at lower costs.
If you are a health care professional who is new to ketamine therapy, I can empathize with you. Last year, I began to focus on ketamine therapy when I opened Innerbloom in San Luis Obispo. Even though I have personally treated hundreds of patients, I am still learning about new techniques, alarming headlines, and truly awesome patient outcomes all the time. Change is constant.
If you seek better patient outcomes, you must keep an open mind. Therefore, with the exception of the three tenets below, I will not advocate for anything specific in this two-part post. Rather, I will attempt to summarize what has shaped ketamine therapy recently. My hope is to encourage greater participation by making it easier to understand how we got here. Since it’s the end of the year, I will also speculate about ten ways in which ketamine therapy may evolve. My aim is to spark thoughtful debates among those who will guide the practice in the years to come.
After nearly 800 ketamine therapy infusions at Innerbloom and, before that, administering ketamine to my patients for over 12 years as a trauma surgeon, I am confident in the following:
Researchers began to study then replicate the antidepressant effects of ketamine in the 2000s. Not long after and using similar methods, clinicians from coast to coast began to apply the lessons from this research on patients suffering with mood disorders like depression. What was once an experimental therapy would soon become much more widespread.
For example, a popular treatment protocol that may be traced back to early research involves administering a series of intravenous or IV ketamine infusions over the course of four weeks or longer. Depending on each patient’s medical history and treatment response, doses may start at 0.5 milligrams of ketamine hydrochloride per kilogram of bodyweight. In order to reach a psychedelic conscious state, where many believe ketamine’s antidepressant effects are strongest, some patients may tolerate larger doses with subsequent infusions. Also, many providers incorporate psychotherapy within a day or two of each infusion, during what is known as a critical period, as a way to help people integrate the powerful psychedelic experience into their thoughts and behaviors.
In a move that surprised some, the Food and Drug Administration or FDA approved a molecular variant of ketamine—but importantly, one that could be patented—called esketamine in March 2019 that was marketed under the brand name Spravato with a nasal spray route of administration. Soon, pharmaceuticals, researchers, and medical practitioners wondered alike: If esketamine was approved for Treatment Resistant Depression or TRD, might its antecedent, racemic ketamine, also be safe and effective for similar indications? Short answer: Yes.
Compelling new research into ketamine’s antidepressant effects was funded and published. In large part due to tireless work by Rick Doblin and the Multidisciplinary Association for Psychedelic Studies or MAPS, hundreds of millions of dollars began pouring into the burgeoning psychedelics industry, which includes ketamine therapy. And within a few years, hundreds of medical practices started to offer ketamine therapy across the country. Based on anecdotal but powerful evidence, people started to notice.
I frequently see local news stories from across the US about the opening of a new ketamine clinic. From Pittsburgh, Kansas City, Las Vegas, and even here in San Luis Obispo, many news teams are sharing stories about patients who have found relief from ketamine therapy, oftentimes, after years of pain and suffering. Also contributing to this positive feedback loop: Ketamine therapy has been featured extensively by journalists who describe mostly positive experiences. For example:
It’s not just the blogosphere. Ketamine therapy is trending among podcasters too. Listeners may have first heard about ketamine therapy during a 30-minute episode of the popular science podcast, Science Vs, before they listened to the nearly 4-hour conversation with John Krystal MD, considered by many to be one of the most important ketamine researchers, on The Tim Ferris Show in 2022.
As people increasingly turn to social media for information, more celebrities and influencers will promote psychedelic therapy, including ketamine therapy, online in short video format. Drug manufacturers (who are already subject to advertising regulations for prescription medications) and others who with negative perceptions of psychedelics will put more pressure on the FDA and the Federal Trade Commission to regulate this content.
With ubiquitous shelter-in-place orders during the pandemic, a new way to offer ketamine therapy also grew online. Emphasizing convenience and taking advantage of an exception to the Ryan Haight Act of 2008 (granted during the pandemic and continuing through at least November 2024), these new companies advertise ketamine therapy for less out-of-pocket cost compared with ketamine clinics with physical locations.
How? Online platforms don’t actually provide ketamine therapy. Rather, they pay prescribers to review patient medical histories, and if appropriate, send prescriptions to mail order compounding pharmacies. In turn, compounding pharmacies manufacture and send ketamine troches (oral dissolving tablets or lozenges) directly to patients for self-administration. Invariably, patients must agree to strict medication instructions and virtual therapist sessions in order to continue their at-home ketamine therapy.
These companies are undoubtedly helping answer the question of how to increase access to ketamine therapy, even if some have argued that they prioritize convenience and affordability over quality of care.
More companies offering at-home ketamine therapy like Mindbloom will merge or acquire competitors (or collaborators like in the case with Nue Life) in order to grow and access better technology. Some will join forces with online therapy matchmakers like BetterHelp. Soon after, at least one will successfully commercialize autonomous virtual therapy. Instead of meeting with a licensed human therapist, patients will interact with a computer program called a large language model or LLM which will be the first technology to be licensed by regulators to provide psychotherapy.
Like with artificial intelligence, advancements in healthcare can lead to temporary setbacks. We may remember the state of ketamine therapy in early 2023 as a time when ambition briefly outpaced reality: Field Trip Health & Wellness expands, contracts, then disappears.
In February, Toronto-based Field Trip started trading in the US on a stock exchange known for early-stage and developing companies called the OTCQB. Later that month, Field Trip issued a press release which signaled financial trouble for the fast-growing company. And just one week later, Field Trip announced that it would close its locations in Chicago, DC, Seattle, and San Diego. This past summer, Field Trip’s remaining US locations were purchased by Stella, a behavioral health provider which specializes in post-traumatic stress disorder or PTSD.
As if on cue, Ketamine Wellness Centers, once a leading provider of ketamine treatments for depression and other chronic conditions, abruptly ceased operations across its locations in nine states last March. The unexpected closure affected staff and patients, some of whom were stranded in the middle of their treatments. Shortly after, patients posted about the closing on Reddit, describing a conflict between the founders and their parent company, Delic Corporation. Later in April, the Green Market Report reported on a possible acquisition of the company by Peter MD, an online men’s health clinic.
What explains these unexpected closures? Some suggested that they expanded too quickly while others cite insufficient capital. Regardless of what happened in early 2023, most industry watchers would agree these closures were a momentary reversal and that psychedelic therapy will continue to grow for decades to come.
Like their online counterparts, ketamine clinics will invest in new ways to grow amidst increasing competition. Many will attempt group therapy and retreats. Most will expand their offerings as MDMA, psilocybin, and other psychedelic therapies become better understood and—importantly—legal. Others will incorporate technology like immersive sound and virtual reality to conjure different cognitive states in their patients before, during, and after their ketamine therapy. We will also see a few regional ketamine therapy leaders expand nationwide by acquiring or managing services for independently-owned and operated clinics like we’ve seen with hospitals in towns across the country.
In June, enough people to make up a small town (up from 3,000 at the last conference in 2017) converged in Denver for Psychedelic Science 2023. The landmark gathering was hosted by MAPS and was the fourth time that people from around the world gathered for this conference to discuss the latest developments in psychedelic science, medicine, business, and therapy.
While the agenda covered psychedelics like psilocybin, MDMA, 5-meo-DMT, and ibogaine, ketamine received lots of attention, likely because it’s currently the only legal psychedelic therapy. Roaming the vast Colorado Convention Center between presentations, it seemed like every third practitioner I met was working with (or planning to work with) ketamine therapy. Some highlights included:
Psychedelic Science 2023 was notable for its size and celebrity, given that many of the topics involved substances with no currently accepted medical use and a high potential for abuse according to your average member of Congress.
The FDA and Drug Enforcement Agency or DEA will clear the way for ketamine to be joined by specific formulations of MDMA and psilocybin for legal but controlled therapeutic use. Further on the horizon, universities, drug makers, logistics companies, providers, and regulators will come together and set standards for the controlled manufacture, transport, and administration of a growing number of psychoactive substances. In other words, psychedelics will remain illegal by default, except when contained within a secure supply chain by those who can demonstrate ongoing compliance with standards.
In March, the Board of a non-profit called the American Society of Ketamine Physicians, Psychotherapists, and Practitioners or ASKP3 sent an email to its members. In it, they reaffirmed their commitment to transparency, collaboration, education, and advocacy. Because I had just joined in 2022, I assumed that I was lacking some historical context. To a newer member like me, I had come to look forward to ASKP3’s communications, webinars, and events like its annual conference.
ASKP3 hosted its two-day annual conference on December 8-9 near where I completed my residency: Austin, Texas. In addition to learning about some of the latest findings and methods from those advancing the practice of therapeutic ketamine for non-anesthetic indications, I was hoping to hear how Sandhya Prashad MD, ASKP3 President and Founding Member, is driving the adoption of standards of practice for ketamine therapy. While the non-profit’s leadership introduced a new faculty of experts alongside its ambitious three-pronged approach to 2024, it seemed like the event was overshadowed at times by a rift in leadership earlier this year.
ASKP3—or an emerging industry association—will establish a certification for ketamine therapy providers. The certification will demonstrate adherence to quality-of-care standards for ketamine therapy. It will help protect the industry from unscrupulous providers. Eventually, the certifying organization will collaborate with other psychedelic therapy associations to establish a treatment registry (as Gerard Sanacora PhD MD has suggested) along with compelling incentives for providers to participate and share data. A database like this would greatly improve ketamine therapy research, access, and patient outcomes.
Next week, I will post the second half of this post on the evolution of ketamine therapy with five more predictions.
About the Author
Dr. Ray Rivas, a former general and trauma surgeon with over a decade of experience utilizing ketamine, became a ketamine therapy specialist to treat mental health and pain after witnessing its profound impact on his hospital trauma patients and his own mental health. As the founder and medical director of Innerbloom Ketamine Therapy in San Luis Obispo, California, Dr. Rivas applies his extensive medical expertise to provide safe, evidence-based ketamine treatments for mood disorders, including depression, anxiety, PTSD, and chronic pain. His passion lies in helping patients find relief and rediscover hope through personalized, compassionate care.
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