Learning to Use Psychedelic Agents With Undefined Protocols


Learning to use a psychedelic agent can be challenging when the protocols are not defined. Here’s how a psychiatrist got started.




Learning a completely new skill outside of a training program can be challenging and I found that to be the case with learning to do ketamine-assisted psychotherapy (KAP).

Ketamine is a dissociative anesthetic that was approved for use in 1970. It has been used off-label to treat psychiatric conditions. Ketamine is not technically a psychedelic—it affects different neurotransmitters than lysergic acid diethylamide (LSD), psilocybin, and 3,4-methylenedioxymethamphetamine (MDMA).

However, in sub-anesthetic doses, it allows individuals to enter a non-ordinary state of consciousness, similar to the states induced by the classic psychedelics.

For some, it works as an antidepressant even when conventional antidepressants have failed. Ketamine is legal, it induces short journeys that last approximately an hour, and patients do not need to stop their serotonergic antidepressants to take ketamine.

Intranasal esketamine (Spravato) is the only form of ketamine that has approval from the US Food and Drug Administration for the treatment of depression. Patients may get intravenous infusions of ketamine off-label, and this has a defined protocol: Ketamine is given at a dose of 0.5mg/kg infused over 40 minutes, 2 or 3 times a week, for a total of 6 doses. With ketamine infusions, and with esketamine, the goal is the antidepressant effect—any dissociative or psychedelic effects are considered unwanted adverse effects.

KAP, on the other hand, is often done using either sublingual (SL) or intramuscular (IM) ketamine, and there is no standard protocol for dosing or for the number of treatments. It may be used in low doses to facilitate talk therapy or in higher doses to induce a dissociative state or “journey.” There are companies that mail ketamine to patients for use during telehealth appointments, and there are prescribers who will prescribe for home use on an indefinite basis.

Bioavailability with sublingual dosing is approximately 25% and patients may be instructed to spit out their saliva (with the dissolved drug) after anywhere from 7 to 20 minutes. The bioavailability of IM dosing is roughly 93% and the medication takes effect all at once very soon after injection.

The administration of ketamine has not been standardized, nor has the psychotherapy that is done to go along with it. Science intertwines with art and experience, and this lack of standard protocol is deemed “the wild west” of using ketamine.

In a study of KAP conducted at 3 outpatient clinics, using a variety of doses, both SL and IM administration, and including home use, Dore, et al,1 looked at the effects of KAP on depression and anxiety scales for patients with a variety of diagnoses. They found that KAP was effective, especially for older patients and for those who started out with more symptoms. Drozdz, et al,2 did a review of 17 published studies with 603 participants and concluded that psychotherapy may improve and prolong outcomes.

In KAP, there are some important elements that differentiate the psychotherapy from that used in traditional office settings. There is at least 1 session before ketamine administration that is devoted to preparation, and sessions after for “integration.” Patients set an “intention”3 for the ketamine experience—something they wish to get out of the session.

The content of the psychedelic experience is assumed to have significance. It is not viewed as an unwanted adverse effect or as a product of drug-induced delirium, so the work of integration involves helping patients make sense of the material within the context of their lives.

There is a structure and a trajectory to the therapy, and an appealing aspects of psychedelic medicine is that it happens quickly, and not over years. Some therapists use very low doses of ketamine and will work with the patient in a disinhibited state for exploration of past events with some ability to distance from trauma.

Ketamine and other psychedelics provide a period of neuroplasticity,4 a time when old patterns and ruminations can be unlearned while new ones can be laid down. These chemicals have been used in the treatment of depression, anxiety, posttraumatic stress disorder, obsessive-compulsive disorder, negative ruminations, and compulsive behaviors, including addictions. Trans-diagnostic treatments can be tricky—they have been known to over-promise.

There is a lot to like about this idea of KAP and I was drawn in. I found myself on unfamiliar terrain without a role model or mentor and I needed to design a learning path for myself. I started by listening to podcasts and watching YouTube presentations, and I found IMHU.org,5 which had a free KAP introductory training lecture. I quickly discovered that although I am interested in treatments for psychiatric illness, KAP branches into spirituality and mysticism that in a way does not fit my purview from mainstream psychiatry. More on this later.

I started to canvas the local ketamine landscape in Baltimore. One name led to another, and I was introduced to David Mathai, MD, a fellow at the Hopkins Center for Psychedelic & Consciousness Research,who had prior experience with KAP. Although he had only been in Baltimore for a year, Mathai knew who was treating patients with KAP in the Baltimore-Washington region. 

He introduced me to others and had my name added to a tri-state psychedelic listserv. He also sent me some journal articles, including the paper by Dore, et al,1 on outpatient KAP and another that he co-authored,6 and he suggested that I read The Ketamine Papers: Science, Therapy, and Transformation by Wolfson and Hartilius.

“KAP has come to mean many things, depending on who you ask,” Mathai said. “There are many theories and ways of combining ketamine and psychotherapy, including models where there is neither deliberate intention-setting nor therapeutic value assigned to the subjective drug experience.”

Each person I spoke with led me to someone else, and my network broadened quickly. Soon I was on the Big Tent Ketamine listserv, a national email group with nearly 3500 members. As with all listservs, there is a lot of banter! Still, I learned a great deal about the many aspects of ketamine and I had a network of experienced people to go to with questions.

Still, I did not feel ready to prescribe ketamine and decided I needed to take an onsite course. I found a course offered by the Psychedelic Research and Training Institute (PRATI)7 in Colorado. Looking ahead, I blocked out time for the 4-day session offered in August. Mathai was the first of several individuals to warn me that getting into the PRATI class is difficult. Another physician likened it to getting Rolling Stones tickets.

The more people I spoke with, the more I realized how little ketamine and KAP were being used in Baltimore. I spoke with Brian Lerner, MD, who worked at a ketamine infusion clinic until it closed in 2020.

“Ketamine is very safe when administered and monitored in the appropriate setting,” Lerner said. “I gave roughly 3500 infusions, and no one had any major problems. Some people get nauseous, some vomit, and much less common was significant discomfort with the dissociative experience.” He said he felt it was very helpful for some patients, but not for everyone. 

I sat poised at my keyboard at 11 AM Eastern Time (9 AM Mountain Time) on a Monday in May, ready to type in my information and hit “submit.” My registration for the PRATI training course went through. I was both happy and relieved. I called my daughter in Colorado and was excited to let her know I would be visiting her before the course started.

“It’s a cult,” my daughter informed me, with distress, when I told her where I would be going. PRATI uses facilities that are a part of an intentional community.

“I’m not going to a cult,” I said. “I’m going to a ketamine training course. I know people who have gone; they say the food is good and everyone came home.”

In the spirit of a true millennial, my daughter still objected. She did not want me to support the organization where the training was being held. My husband joked with her about sending an extraction team.

“You’re going to learn to use it. You’re not taking it, right?” she asked.

Well, more on that later.

Dr Miller is a clinical psychiatrist and writer in Baltimore. She is on the faculty at the Johns Hopkins School of Medicine.

Note: In these commentaries, Miller will discuss her experiences and thoughts as she explores issues associated with ketamine-assisted psychotherapy.


1. Dore J, Turnipseed B, Dwyer S, et al. Ketamine assisted psychotherapy (KAP): patients demographics, clinical data and outcomes in three large practices administering ketamine with psychotherapy. J Psychoactive Drugs. 2019;51(2):189-198.

2. Drozdz SJ, Goel A, McGarr MW, et al. Ketamine assisted psychotherapy: a systematic narrative review of the literatureJ Pain Res. 2022;15:1691-1706.

3. Brown E, Tersavich C. Your complete guide to setting intentions. Mindbloom. October 12, 2021. Accessed April 15, 2024. https://www.mindbloom.com/blog/your-complete-guide-to-setting-intentions

4. Wu H, Savalia NK, Kwan AC. Ketamine for a boost of neural plasticity: how, but also when? Biol Psychiatry. 2021;89(11):1030-1032.

5. Ketamine-assisted psychotherapy. Integrative Mental Health Diversity. Accessed April 15, 2024. https://courses.imhu.org/courses/ketamine-assisted-psychotherapy

6. Mathai DS, Mora V, Garcia-Romeu A. Toward synergies of ketamine and psychotherapy. Front Psychol. 2022;13.

7. Our mission. Psychedelic Research and Training Institute. Accessed April 15, 2024. https://pratigroup.org/

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