
This article is for educational purposes only. Field Trip Health does not provide psilocybin- or MDMA-assisted psychotherapy. These substances remain controlled in Canada and are not approved for therapeutic use. The information below summarizes publicly available research and legal distinctions to help readers understand the evolving field of psychedelic-assisted psychotherapy.
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 therapeutic experience is unique, a few key distinctions between these medicines can be made. Here we explore what research has revealed about ketamine and psilocybin, while noting that only ketamine is legally available in Canada for therapeutic use.
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 a dissociative anesthetic that has been used safely for decades in hospitals and emergency medicine. In recent years, it has been prescribed off-label under medical supervision for treatment-resistant depression and related conditions.
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 focused on depression, suicidality, and certain anxiety-related conditions. Psilocybin research has examined its potential role in depression, addiction, and end-of-life distress, but it remains investigational. Both compounds are being explored for their possible impact on mental health, though only ketamine is currently approved for clinical use in Canada. They are both being investigated and 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. As interest in psychedelic research grows, both ketamine and psilocybin are important areas of study.
Current evidence supports ketamine-assisted psychotherapy as a safe, legal, and effective treatment when delivered under professional supervision. Psilocybin therapy remains investigational and is not legally available in Canada outside authorized clinical trials. If you are exploring mental health treatment options, speak with a licensed provider about approved and evidence-based therapies available today.
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. | Available only in authorized research settings. | Available only in authorized 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. |
Ketamine & Psilocybin Therapies are available across Canada, including in Montreal, Ottawa, Toronto, Hamilton, Sault Ste Marie, Thunder Bay, Hamilton, Kitchener-Waterloo, and even at-home.
Field Trip Health Toronto offers additional alternative treatments for treatment-resistant depression, anxiety, PTSD, and other mental health disorders such as Stellate Ganglion Block therapy, Neurofeedback therapy, and repetitive Transcranial Magnetic Stimulation (rTMS)
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.