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Ketamine vs. Psilocybin for Therapy: Insights into Efficacy, Administration, and Side Effects

janvier 26, 2025

comparing ketamine vs psilocybin for therapy in Canada

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.

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 psychothérapie assistée par la psilocybine 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 psychothérapie assistée par la psilocybine 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

KétaminePsilocybineMDMA
Also Known AsSpecial K, Horse Tranquilizer, Spravato, KetShrooms, Magic Truffles, Magic MushroomsMolly, Ecstasy, X
Drug ClassDissociative anestheticTryptamine psychedelicEmpathogen,
Entactogen
, Stimulant
LegalityLegal in the US, Canada, and several other countries.Not widely legalized outside of research settings.Only legal to use in research settings
Route of AdministrationIM injection, IV infusion, by mouth, nasallyBy mouthBy mouth, nasally
Journey Onset0-10 minutes (IM/IV)30 minutes – 1 hour30-45 minutes (by mouth)
Journey LengthAbout 40 minutes (IM)4-6 hours3-6 hours
Made FromSynthetic manufacturingPsilocybin-containing mushrooms and trufflesSynthetic manufacturing
Hypothesized Method of ActionAffects the neurotransmitters glutamate and GABA, increases neuroplasticityMimics the neurotransmitter serotonin, increases neuroplasticityAffects the neurotransmitters dopamine, serotonin, and norepinephrine.
UsesKetamine 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. 

A propos de l'auteur

Dr. Mario Nucci

Dr. Mario Nucci MD CCFP est un médecin de famille agréé qui se passionne pour la santé mentale et le développement de nouvelles thérapies. Il est activement engagé dans la recherche avec un poste de professeur associé à l'École de médecine du Nord de l'Ontario et des collaborations de recherche avec l'Université d'Ottawa, l'Université de Calgary, l'Université Lakehead, l'Université Concordia et l'Université de l'île de Vancouver.

Le Dr Nucci est le fondateur du Bay and Algoma Health Centre en 2019, une clinique de médecine sans rendez-vous et de toxicomanie. Il a fondé le Canadian Centre for Psychedelic Healing en 2019, qui opère maintenant sous le nom de Field Trip Health, offrant des soins de santé mentale de pointe dans les régions de l'Atlantique.  TorontoMontréalVancouverOttawaHamiltonKitchener-WaterlooThunder BaySault Ste. Marieet à domicile.

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