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