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Ketamine vs Psilocybin for Mental Health

Interest in psychedelics for therapy is growing, and people have questions. How do different psychedelic substances like ketamine, esketamine, “shrooms,” ibogaine, and MDMA compare? What is legal, and what is not? What is it like to trip?

While every journey is unique, a few key distinctions between medicines can be made. Here we will explore the therapeutic uses of ketamine and psilocybin (aka “shrooms”), but stay tuned for other articles on more medicines.

What Distinguishes Ketamine from Psilocybin

Ketamine and psilocybin are different types of drugs

Ketamine is a dissociative anesthetic with psychedelic properties, while psilocybin is a tryptamine psychedelic. This means that while the two medicines both have the potential to produce feelings of connection, insights, and mystical experiences, the way in which they go about doing so is different.

There are legal differences between ketamine and psilocybin

Ketamine has been used as a legal anesthetic in operating rooms, emergency departments, and battlefields for several decades. Since the 2010s, clinics have been using it off-label as a legal psychedelic for mental health treatment. 

Psilocybin, on the other hand, was outlawed for general use in the United States in 1970 with the Controlled Substances Act; Canada promptly followed suit in 1975 with their own Controlled Drugs and Substances Act (CDSA).

Ketamine and psilocybin have different histories

Ketamine was developed in 1962 by chemist Calvin L. Stevens. Its original purpose was to be a safer option than other anesthesia options of that time. It has since been studied for a wider range of applications including as a catalyst for therapy.

Psilocin, the precursor to psilocybin, occurs naturally in certain fungi worldwide. Once ingested, psilocin is converted into psychoactive psilocybin in the body. While its availability in nature has lended well to ceremonial use throughout history, getting a precise dose from natural sources can be challenging. 

Ketamine and psilocybin are taken in different ways

Ketamine can be administered in a number of different ways such as IM injection, IV infusion, intranasally, and orally. Psilocybin is typically consumed orally.

Psilocybin journeys are longer than ketamine journeys

A ketamine journey is substantially shorter than most psilocybin trips. While ketamine journeys average about 40 minutes, a person who has ingested psilocybin will likely feel the effects for 3-5 hours. Similarly, ketamine’s effects usually onset in under 10 minutes, while psilocybin can take up to an hour to take effect.

Ketamine and psilocybin have different effects on the body and mind

We are still learning about how psychedelics affect humans’ body and mind, however we do know a few things about how these medicines interact with key chemicals in the brain. For example, ketamine seems to work mostly on a person’s GABA and glutamate levels, giving it the ability to rapidly reduce suicidality. In contrast, psilocybin appears to work by mimicking serotonin, a neurotransmitter that is often targeted by antidepressant medications.

How Ketamine and Psilocybin are Similar

Both ketamine and psilocybin produce a psychedelic trip

One paper by Vollenweirder and Kometer (2010) comparing the two saw that psilocybin journeys produced slightly more visual alterations and imagery, while ketamine journeys often included a slightly greater sense of unity. Nevertheless, both ketamine and psilocybin can produce mystical, insight-giving, and transcendental experiences which may include visuals, physical sensations, messages, or other perceptual changes during the peak of the trip.

Both ketamine and psilocybin have positive mental health benefits

Research on ketamine has generally focused mostly on depression and suicidality; psilocybin–depression and end-of-life care. However, both ketamine and psilocybin have demonstrated antidepressant and anxiolytic (anti-anxiety) effects. They are both also used to treat trauma-related disorders, chronic pain, and substance use disorders.

There are potential side effects to both ketamine and psilocybin 

Ketamine- and psilocybin-assisted psychotherapy have similar risks and side effects such as blood pressure and heart rate changes, which may make them not appropriate treatments for certain individuals with chronic, unmanaged heart health conditions.

Bottom Line

As interest in psychedelic therapy grows, ketamine- and psilocybin-assisted psychotherapy are leading the way. Research has demonstrated that both may be effective at relieving difficult to treat mental health symptoms. That said, there are key differences in medicine legality, function, and experience that affect outcomes and accessibility. To learn more about which is right for you, we recommend that you consult a trained psychedelic provider.

Willow & Leaf does not endorse the use of substances that are not yet legalized.

About the Author

Image of Jordan Dobrowski, LCSW: white woman in mid twenties with a nose ring

Jordan Dobrowski is a Licensed Clinical Social Worker and Certified Psychedelic-Assisted Therapy Provider with experience providing psychotherapy to youth and adults in both English and Spanish. She received her Master’s in Social Work with certificates in Trauma-Informed Care and Culturally Responsive Mental Healthcare for Immigrant Families from the University of Chicago in 2018. She currently teaches with Naropa University and the Integrative Psychiatry Institute in their psychedelic clinical training programs. She is the founder of Willow & Leaf Counseling, and the executive director for Kaleidoscope Psychedelics — an organization working to improve psychedelic therapy access for BIPOC, queer, and neurodivergent folks in Chicago.

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