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 about ketamine vs psilocybin for therapy? 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 vs 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.
Are there legal differences between ketamine and psilocybin?
Is Ketamine a Controlled Substance?
Ketamine is in fact an opioid, and 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 glutamate levels, giving it the ability to rapidly reduce suicidality and depression symptoms. 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.
Ketamine vs. Psilocybin for Therapy: Do both 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 on Ketamine Therapy vs. Psilocybin therapy
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.
Ketamine & Psilocybin At a Glance
| Ketamine | Psilocybin | MDMA | |
| Also Known As | Special K, Horse Tranquilizer, Spravato, Ket | Shrooms, Magic Truffles, Magic Mushrooms | Molly, Ecstasy, X |
| Drug Class | Dissociative anesthetic | Tryptamine psychedelic | Empathogen, Entactogen, Stimulant |
| Legality | Legal in the US, Canada, and several other countries. | Not widely legalized outside of research settings. | Only legal to use in research settings |
| Route of Administration | IM injection, IV infusion, by mouth, nasally | By mouth | By mouth, nasally |
| Journey Onset | 0-10 minutes (IM/IV) | 30 minutes – 1 hour | 30-45 minutes (by mouth) |
| Journey Length | About 40 minutes (IM) | 4-6 hours | 3-6 hours |
| Made From | Synthetic manufacturing | Psilocybin-containing mushrooms and truffles | Synthetic manufacturing |
| Hypothesized Method of Action | Affects the neurotransmitters glutamate and GABA, increases neuroplasticity | Mimics the neurotransmitter serotonin, increases neuroplasticity | Affects the neurotransmitters dopamine, serotonin, and norepinephrine. |
| Uses | Ketamine has mostly been studied to reduce suicidality and symptoms of depression, however clinical usage has found it to be effective also against anxiety and trauma disorders. | Research shows that psilocybin may be effective at treating addiction, depression, and reducing death anxiety. Psilocybin has also historically been used in spiritual contexts across the globe. | Research with MDMA has principally looked at its ability to treat psychological trauma and improve relational functioning. |
About the Author
Dr. Mario Nucci MD CCFP is a licensed Family Physician with a passion for mental health and the development of new therapies. He is actively engaged in research with a faculty associate professorship at Northern Ontario School of Medicine, and research collaborations with the University of Ottawa, University of Calgary, Lakehead University, Concordia University and Vancouver Island University.
Dr. Nucci is the founder of Bay and Algoma Health Centre in 2019, a walk-in and addiction medicine clinic. He founded the Canadian Centre for Psychedelic Healing in 2019, now operating as Field Trip Health, providing cutting edge mental health care in Toronto, Montreal, Vancouver, Ottawa, Hamilton, Kitchener-Waterloo, Thunder Bay, Sault Ste. Marie, and at-home.
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