Ketamine vs. Psilocybin for Therapy

February 9, 2023

Nue Life

Nue Life
This article was medically reviewed by Kristen Davis, PA-C.

Top Points:

  • Ketamine and psilocybin are two forms of psychedelic medicine being studied for medicinal benefits.
  • Ketamine has been shown to be efficacious as a treatment method for depression and anxiety, and is FDA-approved for use in a clinical setting.
  • Research is ongoing to further establish psilocybin’s efficacy and safety.

Psychedelic medicine is an ever-growing field. Interest in the therapeutic potential of psychedelics is continuing to grow as more and more clinical trials consistently yield positive results.

Two psychedelic drugs making a splash in the psychiatry world as therapeutic treatments for certain mental health conditions are ketamine and psilocybin. Ongoing research on these psychedelic compounds includes their use for the treatment of depression, specifically treatment-resistant depression and major depressive disorder (MDD). Because of this, the ongoing discussion surrounding ketamine vs psilocybin for depression and other forms of treatment continues to develop alongside the research associated with both.

While they do share some similarities, these two psychedelic therapies differ in major ways. In this article, we will explore the differences between these psychedelics and their potential uses when paired alongside psychotherapy.

Can Psychedelics Really Help?

In considering psilocybin vs ketamine, it’s important to discuss how the impact of psychedelics began in the first place. Many people believe that psychedelics are a modern invention – a product of the 1960s. While the 1960s certainly put many psychedelic drugs on the map, the history of psychedelics goes much further back — centuries back, in fact.

Plants with psychedelic properties have been used for thousands of years in many non-Western cultures as sacramental tools. In addition to being used for religious ceremonies and spiritual journeys, they were also used to relieve pain and heal wounds.

The first psychedelic research to hit the laboratories came in 1938 with Albert Hofmann’s synthesis of lysergic acid diethylamide (LSD). Timothy Leary, the American psychologist, also studied the effects of psilocybin and LSD for therapeutic purposes whilst at Harvard. However, studies into the therapeutic and medicinal uses of psychedelics came to a halt as drug laws became a reality.

Today, as we see a resurgence in psychedelics for therapeutic use, more and more psychedelics are being studied as treatments for a myriad of mental health disorders.

Ketamine and psilocybin are far from the only two psychedelics being researched for their therapeutic purposes. Common psychedelic drugs that are being considered in the psychiatric space include:

  • LSD
  • Mescaline
  • DMT
  • Psilocybin
  • MDMA
  • Ketamine
  • Ibogaine

What are psychedelics?

But what are psychedelics, exactly? In short, psychedelics are substances that produce psychoactive experiences and changes in consciousness. Other effects can include changes in cognitive function, changes in perceptions, and changes in overall mood. Psilocybin and ketamine have a lot to take into account when considering their other uses, but understanding the basics is a good start.

These substances are often referred to as hallucinogens. Many people who use psychedelic drugs claim to have mystical and insightful experiences and say they induce a realistic, dream-like state. Hallucinogenic side effects include changes in sensory input, such as taste, touch, sound, and sight.

The various effects and overall psychedelic experience will differ depending on the type of psychedelic, but some of the most common effects include:

  • Changes in mood
  • Feelings of euphoria
  • Changes in time perception
  • Increased heart rate
  • Visual and auditory hallucinations
  • Heightened senses
  • Expanded consciousness

So, can psychedelics really help boost mental health? The short answer is yes. For example, several studies have shown ketamine’s efficacy in reducing depressive symptoms, especially those with treatment-resistant depression and major depression.

This makes ketamine a great alternative to typical antidepressant medications, like SSRIs, which end up being ineffective for 30% of people diagnosed with depression. Other psychedelics have shown promising effects, too, especially when it comes to other mental health conditions like PTSD.

What Is Ketamine?

Getting further into the psilocybin vs ketamine dialogue, let’s break down what ketamine is first. The history of ketamine goes back more than 50 years to its introduction into clinical practice. The first published study on ketamine came out in 1966, examining the efficacy of ketamine as a dissociative anesthetic in high doses.  

According to the initial preclinical studies, ketamine had the ability to produce pain relief with an altered state of consciousness. These effects were of limited duration and safe for repeated administration.

In 1970, ketamine was approved by the Food and Drug Administration (FDA) for human use. Since its FDA approval decades ago, ketamine has made a name for itself as being one of the first anesthetic drugs to provide adequate sedation without compromising respiratory function in patients.

While ketamine is often lumped in with other psychedelic medicines because it shares some hallucinogenic properties with other psychedelics, it’s better described as a dissociative drug rather than a hallucinogen.

Ketamine is a Schedule III drug, maintaining its FDA approval for use as a dissociative anesthetic. This status also allows it to be prescribed off-label for therapeutic use to treat depression.

Ketamine also differs from other psychedelics when it comes to the neuroscience of how it works on our physiology. As an NMDA antagonist, ketamine blocks NMDA glutamate receptors, causing a spike in glutamate. This surge in glutamate helps activate your brain’s AMPA receptors while inducing brain-derived neurotrophic factors. These are important factors for neuronal survival, healing, growth, and plasticity.

How Does Ketamine Help in Therapy?

Between psilocybin and ketamine, it’s important to understand how each assists in mental health treatment. The therapeutic benefits of ketamine are extraordinary when it comes to its use as a therapeutic alternative for treatment-resistant depression. In fact, many placebo-controlled studies have shown that ketamine can be an effective treatment for reducing symptoms of depression, anxiety, and post-traumatic stress disorder (PTSD).

Currently, ketamine treatments can include a single dose of ketamine infusion through an IV, through an intramuscular injection,through nasal sprays (like esketamine), troches or sublingual tablets.

Ketamine treatment can be paired with psychotherapy for optimum results. In fact, thanks to the neuroplastic effects mentioned above, ketamine treatment can help individuals be more receptive and open to their therapy program.

What Is Psilocybin?

Psilocybin, along with psilocin, is a psychedelic compound found in certain mushrooms that grow in tropical and subtropical regions of the Americas. In traditional use, people often consume these mushrooms raw, dried, or even brewed into tea to drink.

But, magic mushrooms, as they are colloquially known, are also making waves for their therapeutic potential for treating treatment-resistant depression, anxiety, obsessive-compulsive disorder (OCD), addiction, and other mental health conditions. The majority of current research is focused on single administration or using a single dose of psilocybin for treatment-resistant depression.

Psilocybin has been shown to cause alterations in brain waves. More specifically, psilocybin can affect the neurons and neural circuits associated with emotional processing and introspection. This area of the brain is known as the prefrontal cortex.

Some studies have shown low-dose psilocybin’s ability to increase synaptic density and decrease 5-HT2a receptor density. In simple terms, this can cause antidepressant effects and alter dopamine release, which is a neurotransmitter responsible for feeling pleasure, satisfaction, and motivation. So, when it comes down to ketamine vs psilocybin, how do mushrooms provide therapeutic benefits?

How Does Psilocybin Help in Therapy?

Knowing how ketamine and psilocybin both help with therapy is important to determine if either is right for you. When people undergo psilocybin treatment, the effects of psilocybin typically last for about four to eight hours. Psilocybin therapy can cause relaxing feelings similar to cannabis. Also, as a hallucinogenic drug, psilocybin can induce introspective revelations and visual hallucinations.

Since psilocybin therapy is said to help flatten the brain’s neural landscape, it can help those with depression to open up and allow new thoughts, insights, and perspectives to emerge. This can be significant for those undergoing behavioral therapy, where developing new thought patterns are crucial.

When it comes right down to comparing psilocybin vs ketamine, which might better benefit you from a personal standpoint?

Which Is Best for You — Ketamine or Psilocybin?

So, which is best for you? Well, at the end of the day, that question can be as complex as the person asking it. Both ketamine and psilocybin have shown promising results as pharmacological alternatives for treating mental health conditions like depression and other mood disorders, but ketamine stands out.

Ketamine’s track record in a clinical and healthcare setting, combined with a long list of efficacy studies, makes it tough to beat when it comes to being a therapeutic alternative for depression.

The Bottom Line

Ketamine and psilocybin are two psychedelic-classified drugs that are becoming more and more popular in psychedelic medicine as therapeutic alternatives to antidepressants for treating mental health conditions like depression.

Both treatments can be used alongside psychotherapies to help unlock insights and help open the door to therapy demands. But ketamine’s proven track record outshines psilocybin when it comes to the relief of treatment-resistant depression, anxiety, and PTSD.

You can get started by scheduling your free evaluation with Nue Life today. From there, we’ll discuss how our programs work and help answer any questions you may have about ketamine treatments.

Treatment at Nue Life

Nue Life believes in holistic treatment, which means that what happens before and after your ketamine experience is equally as important as the experience itself. We want to ensure you have meaningful takeaways from your experiences and help you establish positive new neural pathways.

To ensure that you are reaping the full benefits of your ketamine treatment, we offer preparation sessions for you and your sitter. To help you take advantage of your new neuroplasticity, our programs include group integration sessions, and one-on-one health coaching. We are here to help map out the mind and body connections in your brain and help you discover and process the insights that lead to true healing.


Study Shows How Ketamine Reverses Depression—and How its Benefits Could Be Extended | Newsroom | Weill Cornell Medicine

Treatment-resistant depression: therapeutic trends, challenges, and future directions | National Institute of Health

Ketamine: 50 Years of Modulating the Mind | PMC

Ketamine: NMDA Receptors and Beyond | PMC

The Therapeutic Potential of Psilocybin | NIH

Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression | NEJM

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