Is Ketamine An Opiate – The Analysis

About the Author Dr. Steven P. Levine is a board-certified psychiatrist internationally recognized for his contributions to advancements in mental health care. Though he is a psychiatrist who places great emphasis on the importance of psychotherapy, medication is often a necessary component of treatment, and he was dissatisfied with the relatively ineffective available options with burdensome side effects. Dr. Levine pioneered a protocol for the clinical use of ketamine infusions, has directly supervised many thousands of infusions and has helped establish similar programs across the country and around the world.

Is Ketamine an Opiate?

The answer is, “No, ketamine is not an opiate”, but this has been a question on many people’s minds lately.  In the midst of a national opiate abuse epidemic, a recent study published by Stanford University showed the rapid antidepressant effects of ketamine could be blunted by a medication that blocks an opiate receptor.  While some have interpreted this finding as contradictory to the leading glutamate hypothesis, it merely shows that this system needs to be functioning.

Nonetheless, we do know that ketamine has abuse potential, so how do we justify its use for treatment-resistant depression and anxiety disorders?  It helps to have some kind of standard in mind, such as, “What kind of treatment would I want my family member to have?” For me, it’s a matter of satisfying two voices in my head. (Yes, I’m a psychiatrist who hears voices.)

Breaking Comfort Barriers

One morning, as a first-year resident on an inpatient psychiatric unit, a more senior resident had been on call overnight and was asked to present the case of a patient she had admitted.  To even the least experienced member of this team, the story was a clear presentation of a patient who had been admitted in an acute manic state. When the resident finished her presentation, Dr. S turned to her and asked, “What do you want to do?”  Without missing a beat, she answered, “Start lithium.”

Lithium may be an “old-fashioned” medicine, but to this day, it remains the gold standard treatment for acute mania. That being said, when Dr. S responded, “You want to give the patient poison?” we were all taken aback.

I don’t know if Dr. S had come in that day intending to teach us a lesson, or if it was something about the resident’s confidence in recommending lithium that provoked him, but he didn’t actually disagree with her answer. Instead, he was pointing out that physicians should be very careful and thoughtful about doling out potentially harmful substances, even — or, perhaps, especially — when it seems like the obvious choice.

Marching forward with that voice in my head, I entered my final year of training as the chief resident for a longer-term, Monday-to-Friday outpatient day program serving the severely and persistently mentally ill. One day, I had a supervision meeting with Dr. M. When he recommended a certain medication for one of my patients, I balked because I still had Dr. S’s voice in my head and I didn’t want to give the patient poison.

When “First-line” Therapies Are Not Aggressive Enough…Ketamine

But then, Dr. M advised, “If you don’t have an adverse event once in a while, you are probably not being aggressive enough.” His essential point was that we were not out on the street pulling people into treatment; they were there because they had severe symptoms that interfered with their lives, and if our only aim was to “Do No Harm” (or avoid giving them poison), then we might not help them effectively.

Since my residency training, I have been hearing those two voices in my head almost every time I consider a treatment recommendation, and I try to satisfy those voices by finding the synthesis of their lessons. A shortcut that many physicians take is to strictly adhere to the FDA-approved uses of medications and procedures. Those physicians accept the possibly useful self-delusion that this type of regulation has already satisfied the balance of safety and acceptable risk.

However, the fact is that we’re constantly taking risks with patients’ safety. Therefore, if we are brave enough to acknowledge that any of our medicines can be poisonous, then we will be able to thoughtfully and selectively pick our poison in bolder and more creative ways that will most effectively address our patients’ suffering.

This brings us back to ketamine, a 56-year-old anesthetic that is now in widespread off-label use for psychiatric indications, representing the first novel mechanism in the fight against depression and suicide in decades.1 Mary Poppins once sang, “A spoonful of sugar helps the medicine go down.”  Most medicine does taste bad, but should it have to?  Many people enjoy the experience of having a ketamine infusion.  They find it to be a relaxing, insightful, or spiritual experience (others may find it frightening).

Because of this, there is some risk that people may use ketamine recreationally, which can lead to addiction and potential medical harm.  It is important that we do not disregard this risk, and to mitigate it by limiting access to controlled, medical settings with careful screening and psychiatric oversight. With proper care, the potential for addiction is quite low, and the benefits may be life-saving.

In the meantime, we must be careful not to conflate the science of the mechanism of ketamine with the politics of the opiate crisis or the biases of those with financial conflicts of interest.


  1. Mercer, SJ. et al. ‘The Drug of War’–a historical review of the use of Ketamine in military conflicts. ‘The Drug of War’–a historical review of the use of Ketamine in military conflicts. J R Nav Med Serv. 2009;95(3):145-50.