Ketamine vs Psychedelics Like Psilocybin Magic Mushrooms
Key Takeaways
Ketamine
Robust and rapid antidepressant effects, anti-suicidal effects
Unsure about long-term improvements
Good for someone seeking immediate relief from depression and anxiety
Psilocybin
Powerful insights and changes across psychological, physical, and spiritual healing
Sustained mental health improvements at 6 month and 12 month follow ups
Good for “steady” individuals seeking pivotal mental health changes and personal growth
People seeking “psychedelic therapy” may find that the term can be used to describe therapeutic work with classic psychedelics, like psilocybin magic mushrooms, or non-classics like ketamine.
Research shows that both psilocybin and ketamine, in the context of therapy, can have benefits for mental health.
These compounds have similarities and unique differences, which might make one a better fit than the other.
In the following sections, we'll cover ketamine and psilocybin, their therapeutic benefits, and how they can help those who seek psychedelic therapy.
What is Ketamine?
Ketamine is a synthesized compound that was first used in 1962 as an anesthetic for field surgeries during the Vietnam War.
They classified it as a “dissociative anesthetic”, which meant the recipient felt a sense of detachment from their environment and even their sense of self.
And while ketamine can be used in surgeries, it functions as a psychedelic at low to medium dose levels and is the most accessible psychedelic medicine in the U.S. today.
Clinical researchers have found ketamine effective at treating depression, anxiety, social anxiety, treatment resistant depression, and PTSD. [1] [2] [3]
How Does Ketamine Work?
Ketamine affects the glutamine levels in the brain. There are two putative therapeutic effects from this:
Increased neural communication, which leads to the rapid onset of antidepressant effects.
Increased synaptic plasticity, which can improve the brain's ability to change in response to stimuli.
Clinicians have noted ketamine's effects since the mid 60s and have used it to treat depression, anxiety, post traumatic stress disorder, suicidal ideation, and for chronic pain management.
How Ketamine Therapy Works
One of the main advantages to ketamine is that it is the only psychedelic prescribable in America today. It’s approved off-label to treat anxiety and depression.
The classic psychedelics, like psilocybin mushrooms and LSD, remain federally illegal Schedule I substances.
Most ketamine clinics or prescription companies work in two steps:
They evaluate your mental health and physical health to ensure safety.
They prescribe you ketamine for in-clinic or at-home use.
This treatment usually lacks therapeutic support, even though it’s marketed as ketamine “therapy”.
However, you can work with a therapist or coach on your own to support you during ketamine treatment.
Our process at Pivot works like this:
We connect you with a doctor or NP who can prescribe ketamine
We help you prepare for the experience, reviewing your intentions for healing.
You complete the ketamine treatment, either in a clinic or at home.
After your treatment, we help you process your emotions and meaningful insights.
We draw from our training in ketamine assisted psychotherapy (KAP) to help clients move beyond their mental health challenges and towards a renewed sense of self.
What Is Psilocybin?
For those unsure, you pronounce it “Sil-Oh-Sigh-Bin”.
When people use the word "psychedelics" to describe medicinal compounds, they're oftentimes referring to psilocybin (found in magic mushrooms), lysergic acid diethylamide (known as "LSD), or MDMA (commonly knowns as "ecstasy").
For the purposes of this article, we will primarily focus on psilocybin containing magic mushrooms.
As mentioned, psilocybin remains federally illegal, but there are states like Oregon and Colorado and cities like Santa Cruz, CA and Oakland, CA where it is decriminalized.
Psilocybin is a naturally occurring compound found in over 200 types of fungi around the world. Indigenous cultures in the Americas used these plant medicines (though they are technically fungi) for centuries as rites of passage and spiritual ceremonis.
The Swiss Chemist Albert Hoffman first synthesized psilocybin in 1958 (he's also the scientist who discovered LSD). It was studied along with other psychedelics throughout the 20th century, until the Nixon administration made several compounds, like psilocybin, illegal.
Psilocybin converts into psilocyin which attaches to and activates the serotonin 5-hydroxytryptamine 2A receptor (5HT2A). This leads to altered perceptions and cognitive processes.
The effects of psilocybin also include increased neural connectivity and neuroplasticity.
These effects are believed to be what makes these medicines so therapeutic. Psilocybin seems to increase the capacity for people to think and feel differently, often with a fresh perspective or the feeling of a mental reset.
In clinical research settings, psilocybin assisted therapy has proved effective for major depressive disorder, end-of-life anxiety, and addiction, including alcohol use. [4] [5] [6] [7] [8]
How Psychedelic Therapy Works
Often we get asked two questions about psychedelic therapy:
Is it effective?
How does it work?
The efficacy of psychedelics depends upon the mindset of the individual who uses them and the setting within which the psychedelic experience occurs.
Additionally, both clinical and Indigenous traditions alike have a strong focus on an emotionally and socially supportive process to increase positive effects. Here is a general breakdown of the approach used:
Preparation: Time to prepare mentally, physically, emotionally, or spiritually for the psychedelic experience
Journey: The actual day of the psychedelic experience, which lasts around 6 hours.
Integration: Aftercare following the psychedelic experience to solidify psychedelic insights and newfound wellbeing into daily life
Both ketamine and psilocybin could be used in this psychedelic-assisted therapy framework.
Key factors for therapeutic psychedelic use are set (mindset) and setting (environment):
Set: One's mindset, beliefs, attitude, and intentions heading into a psychedelic experience. This is believed to largely shape the journey, including what comes up for the client.
Setting: The physical and social environment within which the psychedelic experience takes place. A therapeutic setting typically involves a safe, peaceful location, a comfortable space for the client to journey, and the support of an experienced, compassionate guide.
Ketamine vs Psilocybin Mushrooms Comparison
Both ketamine and psilocybin have a great deal to offer for healing. While there are some shared psychedelic properties of these substances, there are key differences, some unique advantages and disadvantages.
We've broken down the pros and cons of each type of psychedelic medicine (without AI) into a dropdown chart:
-
Ketamine
Rapid onset of action
Dissociation, feeling of detachment
Altered perception of reality
Psilocybin
Gradual onset of action
Enhanced emotional release and introspection
Altered perception and cognition in high doses
-
Ketamine
Effective for treatment-resistant depression and anxiety, including social anxiety
Rapid reduction in mental health symptoms
Potential benefits in chronic pain and PTSD
Psilocybin
Promising results in treatment-resistant depression
Reduction in existential anxiety, particularly in terminal illnesses
Potential in treating addiction (e.g., alcohol, tobacco)
-
Ketamine
Some risk with overuse and dependency
Should be administered under medical supervision
Low risk of overdose in controlled settings
Psilocybin
Low potential for abuse
Generally safe in controlled, therapeutic settings
Low toxicity and physical risk in appropriate doses
-
Ketamine
Affects prefrontal cortex, glutamine receptors
Increased heart rate and blood pressure
Nausea and/or disorientation in some cases
Psilocybin
Affects prefrontal cortex, serotonin receptors
Potential for nausea and dizziness
Changes in heart rate and blood pressure
Sensory enhancement
-
Ketamine
Legal for medical use in anesthesia and some mental health treatments
Controlled substance, illegal without a prescription
Psilocybin
Currently illegal in most countries for personal use
Legal under research settings and decriminalized in some places for medical research and therapy
-
Ketamine
Short-acting; effects typically last 1-3 hours
Requires repeated sessions for sustained benefits
Psilocybin
Longer-lasting; effects last several hours (around 6)
May require fewer sessions for therapeutic benefits
-
Ketamine
Ketamine infusion via intravenous (IV) or intramuscular (IM) injection
Nasal spray formulations
Oral rapidly dissolving tablets
Psilocybin
Orally consumed, usually in capsule form or dried mushrooms)
Orally drank, typically crushed dried mushrooms brewed into a tea with hot water and lemon
-
Ketamine
Minimal at most ketamine clinics and companies
Some therapists and integration coaches (like us at Pivot) provide support before, during, and after ketamine sessions
Psilocybin
Minimal at group events and retreats
Psychedelic guides provide support before, during, and after
Ketamine and Depression Symptoms
This is a story of how Mark received ketamine treatment.
Mark is a veteran, who underwent ketamine treatment for depression and related PTSD.
He had been in talk therapy and saw several psychiatrists through the VA. He tried several types of antidepressant medications, but never felt like they helped much.
Mark’s mental health issues escalated after a separation, and he sought some new forms of support.
Mark had read some books on psychedelics and therapy, and felt inspired when a friend of his talked about their experience with ketamine for depression. He got in touch with a prescribing physician who could assist.
Mark felt reassured that his ketamine treatment was prescribed by a doctor, essentially giving him the "okay" to safely work with this medicine.
Over the course of two months, Mark went through six ketamine sessions, and it brought him a great sense of relief.
After just the first session, he felt better. Mark said it felt like "a weight was lifted from (his) shoulders".
Through ketamine sessions and the support of his therapist, Mark felt a sense of relief again. While it didn’t eliminate his mental health challenges, it seemed to lessen or shrink their weight on Mark’s life. Mark was able to return to work, hobbies, and time with family without feeling over-saddened by the past.
Ketamine was a great tool for Mark, because he could access it via the medical system and it had fast-acting potential for quick results.
Psilocybin For Mental Health and Wellness
In another case, we worked with a client named Sara who wanted to sit with psilocybin.
Sara learned about the healing power of psychedelics through the psychedelic documentaries How to Change Your Mind and Fantastic Fungi.
In these films, she saw how plant medicines like psilocybin magic mushrooms could help "reset" the mind.
She was new to psychedelics, but wanted to explore microdosing and a large-dose psychedelic experience as ways to help her get "unstuck."
Sara worked with her psychedelic guide in preparation to explore the layers of her inner world that she wanted to work on.
Her therapeutic experience with the psychedelic brought up her relationship with her mother, a challenging breakup, feelings of self-worth, and a sense of purpose.
Sara's psilocybin journey had its ups and downs, moments of joy and emotional intensity. But she worked through the challenge with the help of her guide and found these moments to be powerful in their healing.
After the journey, Sara felt a tremendous sense of gratitude for life and a strong sense of joy.
She continued to work with her guide through Psychedelic Integration Therapy and she started microdosing as a way to tap into psychedelic insights.
Getting Started with Ketamine or Psilocybin Therapy
Paired with therapeutic support, psilocybin and ketamine can be extremely effective for working through mental health conditions and life challenges.
There are a variety of factors to consider when getting started, ranging from legality to long-term therapeutic benefits.
The Pivot team is happy to offer guidance to anyone curious about psilocybin, ketamine, psychedelic therapy, or microdosing. You can meet with us for a complimentary consultation to learn more.
References
Albott, C. S., Lim, K. O., Forbes, M. K., Erbes, C., Tye, S. J., Grabowski, J. G., Thuras, P., Batres-Y-Carr, T. M., Wels, J., & Shiroma, P. R. (2018). Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression. The Journal of clinical psychiatry, 79(3), 17m11634. https://doi.org/10.4088/JCP.17m11634
Yavi, M., Lee, H., Henter, I.D. et al. Ketamine treatment for depression: a review. Discov Ment Health 2, 9 (2022). https://doi.org/10.1007/s44192-022-00012-3
Taylor, J., Landeros-Weisenberger, A., Coughlin, C. et al. Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial. Neuropsychopharmacol. 43, 325–333 (2018). https://doi.org/10.1038/npp.2017.194
Watts, R., Day, C., Krzanowski, J., Nutt, D., & Carhart-Harris, R. (2017). Patients’ Accounts of Increased “Connectedness” and “Acceptance” After Psilocybin for Treatment-Resistant Depression. Journal of Humanistic Psychology, 57(5), 520-564. https://doi.org/10.1177/0022167817709585
Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., Cosimano, M. P., & Klinedinst, M. A. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of psychopharmacology (Oxford, England), 30(12), 1181–1197. https://doi.org/10.1177/0269881116675513
Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology. 2016;30(12):1165-1180. doi:10.1177/0269881116675512
Bogenschutz MP, Ross S, Bhatt S, et al. Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2022;79(10):953–962. doi:10.1001/jamapsychiatry.2022.2096
Johnson, M. W., Garcia-Romeu, A., & Griffiths, R. R. (2017). Long-term follow-up of psilocybin-facilitated smoking cessation. The American journal of drug and alcohol abuse, 43(1), 55–60. doi:10.3109/00952990.2016.1170135
