Ketamine- or psilocybin-assisted psychedelic therapy: A review of differences, upsides and challenges

Psychedelic shapes and colors create abstract pattern.

By Pamela Peters (Learn more about how I support people interested in the transformative benefits of Ketamine-assisted psychotherapy here.)

I get this question a lot, “Which type of psychedelic assisted therapy is best for me—psilocybin or Ketamine?” I work from the assumption that only you know what is best for you. With that in mind, I have written here about what I see as the main differences, benefits and challenges between ketamine assisted and psilocybin assisted therapy. This way you can learn more and make your own decision.

I will assume you have some idea of what ketamine assisted psychotherapy (KAP) and psilocybin assisted psychotherapy (PAP) look like, so I won’t go into detail here about the importance of set, setting, and relationship with your guide, or my considerations for indigenous lineage. Instead I will focus here on the more clinical differences between the two types of psychedelic assisted therapy. To learn more about each therapy, look at the Psychedelic Support website’s substance guides.

I am not a medical practitioner so I will not be discussing the drug interactions or medical diagnoses that could causes issues with these medicines. You should discuss these issues with a psychedelic-aware physician or nurse practitioner.

Ketamine

Overview

Here I discuss the sublingual use of a psychedelic dose of ketamine (100mg-700mg) in a therapeutic setting with an experienced and trained therapist. To learn more about what this process looks like, visit my Ketamine Assisted Psychotherapy page or read my blog about what a ketamine journey might feel like.

Brain stuff

I won’t get too deep here into what ketamine does in our brains. Much of how it works is still being discovered (i.e. it’s a mystery). We do know that ketamine increases brain derived neurotrophic factor (BDNR) which is essential in ketamine’s role in decreasing depression.  BDNF encourages new brain cells to grow as well as the creation of new connections between brain cells. In other words, ketamine assisted therapy might help your brain grow and connect new brain cells. When integrating after KAP sessions we can take advantage of these new connections to create long-lasting healthy habits.  

Research

Most recent ketamine research revolves around: treatment resistant depression, suicidal ideation, post-traumatic stress disorder (PTSD), substance us disorders, and chronic pain. Since ketamine has been legalized and in use as an anesthetic since 1970, new research is not as widespread as with psilocybin.

What it feels like

A ketamine journey has three phases which sequence seamlessly for the participant. When the medicine is first swished in someone’s mouth for the first 15-20 minutes, they may feel some anxiety with the idea of losing control or the uncertainty of a new experience. At 5-10 minutes the person usually begins to feel warmth suffuse their body and a slight veil over their thoughts. Some describe it as a pleasant and warm hug.

As the medicine enters the blood stream from about minutes 20 to 75, the person may experience the unconscious mind which can be difficult to put into words. Usually during this phase people do not speak much. Participants may describe feeling distant, egoless, floaty, strange, and even like they have experienced death. Often someone will have a very realistic memory or flashback to their past. When this is a traumatic event, the participant has the opportunity to feel and understand the event from a safe distance, without the defenses they might have in their non-altered state.

The last phase is the ramp back down to baseline which can last from minute 75 to around 180. People feel softened, very relaxed, and peaceful. This is when I have time to engage with my client about what they’ve experienced—what their unconscious mind would like their conscious mind to know. This is a good time for me to ask a client any questions we may have collaborated about beforehand.

What ketamine assisted psychotherapy (KAP) is best for

The following are some official mental health diagnoses and other conditions that benefit the most from KAP: PTSD and trauma, mild to moderate depression, seasonal affective disorder (SAD), grief, and transformational movement toward connection. Participants often describe transcendental or spiritual events which move participants from feeling stuck to being more in flow.

Benefits of ketamine-assisted therapy

Following are just some of the benefits of ketamine-assisted therapy in comparison to psilocybin. To learn more about the benefits, visit my specialty page.

Duration: As opposed to psilocybin, a ketamine session is usually 2 to 3 hours. This can reasonably take up to a half day out of your everyday life. This shorter (than psilocybin) session length is beneficial because you’ll be paying for less of a therapist’s time. In addition, if the experience becomes uncomfortable, you’ll be out of the experience within the hour—as opposed to a much longer period of potential discomfort with psilocybin.

Few drug interactions: Since ketamine does not impact serotonin receptors, clients do not need to stop taking SSRIs when doing KAP treatments. Since weaning off of SSRIs is a lengthy and challenging process which can cause physical and emotional distress (this may be what we are attempting to alleviate) continuing with SSRIs and KAP is a huge benefit.

Legality: When seeking KAP from an experienced therapist, you will obtain your own medicine legally from a compounding pharmacy. There is not the worry about the quality of medicine or the legality of obtaining it, as opposed to psilocybin.

Considerations/Cautions

Drug interactions: There can be drug interactions for which you would need to consult with a medical practitioner.

Contraindicative diagnoses: Some mental health conditions such as borderline personality disorder, bipolar 1, and schizoaffective disorder may be contraindicated for sublingual ketamine assisted therapy. Please consult a medical practitioner if you have a mental health diagnosis and are curious about ketamine.

Addiction: Ketamine, taken at high doses and frequently, has shown potential for addiction. This is not likely when using the doses and frequency that I work with my clients.

Medical diagnoses: Someone with hypertension or high blood pressure may not be a good candidate for KAP. A medical provider might prescribe a medication to be taken with the ketamine because blood pressure increases during a ketamine session.

GI issues: Like psilocybin, ketamine can cause nausea and vomiting in people who are prone to motion sickness. Again, a medical provider can prescribe a companion medicine to decrease the nausea.

Cystitis: Studies show that frequent and high doses of ketamine can lead to an uncomfortable and difficult-to-treat condition involving the bladder. My understanding is that this mostly is an issue with high and frequent recreational use.

Learn more about my ketamine assisted psychotherapy (KAP) offerings.  

Psilocybin

Overview

Here I am discussing the use of macro doses of psilocybin (1-4 grams dried mushroom) in a therapeutic one-on-one setting with a guide or clinician. I realize that there are many other methods of using psilocybin including ceremonial use and recreational use. These will not be discussed here.

Brain stuff

Psilocybin binds to serotonin receptors, which means that it acts similarly to selective serotonin reuptake inhibitor (SSRI) anti-depressants. This might be why it gives such a strong and long-lasting anti-depressant effect to users immediately after use. This is also why many practitioners do not recommend using SSRIs and psilocybin at the same time.

Research

Psilocybin is currently being researched by many big-name universities and pharmaceutical companies for its healing effects on substance use disorder, depression and anxiety, existential distress in palliative care/cancer diagnoses, headache disorders, obsessive compulsive disorder (OCD), anorexia, and body dysmorphic disorder, and more.

What it feels like

When under the influence of psilocybin you may have feelings of connectedness, expansiveness, distortions of space and time, mystical experiences, and feelings one-ness with the universe. You may also experience visual and auditory hallucinations, altered cognition, and extreme insightfulness.

Sometimes, even during the same medicine journey, you can also experience more challenging effects like light sensitivity, disorientation, frightening flashbacks, anxiety/panic, confusion and paranoia. Although these moments may prove challenging, they are also moments when you may gain clarity and insight that help you move forward in your healing journey. These more challenging effects are one of the best reasons to experience this medicine when with a trusted and experienced guide who can offer support when needed.  

What psilocybin is best for

Looking at evidence-based trials, psilocybin could be most useful for: depression and anxiety, obsessive compulsive symptoms, eating disorders, substance us disorders, and head ache disorders. Psilocybin has also been used by many people for spiritual and personal transformation. Psilocybin has been in the media frequently related to offering relief to veterans experiencing extreme treatment resistant PTSD.

Upsides

Safety: Physically extremely safe; currently there is no established psilocybin toxicity in humans. It also has the lowest addiction potential of any “street/recreational” substance.

Legality: Psilocybin will probably will be legalized and regulated within the next several years in the United States. It is already legal in many nations which allow psilocybin retreats for those currently seeking PAP.

Naturally occurring: Unlike ketamine, you can find psilocybin mushrooms growing in many parts of the world. People grow their own, which essentially gives them the power to obtain their own medicine. Again, growing and collecting psilocybin containing mushrooms is not legal in most of the United States yet. Colorado is one exception, which allows “growing, gifting and sharing” under the “personal use” section of the Colorado Natural Health Act.  

Considerations/Cautions

Duration: A session can take between six and eight hours. This requires you take more time out of your everyday life to have these experiences. If you use a guide or therapist you will be paying for a longer amount of time than with ketamine sessions. You may actually find the idea of taking a few days out of your everyday to be a benefit of this medicine as well. 

Quality/Potency/Consistency: Psilocybin quality and potency are never certain. Since psilocybin mushrooms are not regulated, you do not know exactly what you are getting. This is due to many factors such as age of mushroom, different mushroom strains/genetics, different amounts of psilocybin in each fruiting body, and other factors.

Accessibility: Medicine procurement may be your responsibility. I’d say that most psilocybin practitioners like to gift their clients the mushrooms so they can have some control over the quality of the medicine. Responsible practitioners will make certain the medicine is safe and from a reputable source. But, if you are the one who must procure it, keep the above quality considerations in mind. In addition, buying psilocybin mushrooms in most places in the United States is still illegal and a federal offense.

Contraindications: Psilocybin is not recommended for people with any past psychosis or mania. Other mental health diagnoses may also be made worse, or be contraindications for using psilocybin. This is where a good psilocybin guide/practitioner will refer you to a medical provider for evaluation and assessment. If you have a mental health diagnosis, work with your medical provider to determine if psilocybin is a good fit for you.

Affects with SSRIs: It may take more psilocybin (30%-50%) to have a significant journey when you are also taking selective serotonin reuptake inhibitors (SSRIs). Many psilocybin practitioners ask participants to wean off SSRIs prior to a psilocybin experience, which for some can be a long and difficult challenge.

GI issues: Psilocybin can cause nausea and vomiting at the onset of the medicine. This usually passes, but can be a distraction from the effects of the psilocybin in the moment.

Illegal: I know I said above that psilocybin will probably be legal in the U.S. soon. In fact some states, cities, and regions have already decriminalized psilocybin. However this is a reminder that it still is not legal or regulated except in Oregon (and soon Colorado).

Psychological impacts: Medicine journeys can sometimes be emotionally challenging which can have lasting effects. These can be reduced when you use psilocybin in an emotionally and physically safe setting with the guidance of someone with whom you have an established and secure relationship (guide, therapist, medical practitioner).

To learn more about psilocybin therapy visit Psychedelic Support website. Although I do not currently offer psilocybin therapy, you can learn more about my ketamine assisted psychotherapy offerings.

Both/And

All this said, I also think there is also space for both ketamine and psilocybin (taken at separate times) with individuals. Since both ketamine and psilocybin are beneficial for some of the same issues, it can make sense to begin with one or more ketamine sessions. After the person is familiar with the psychedelic space they can then transition to a longer and very different feeling psilocybin session. This is a particularly advantageous sequence when someone is a bit anxious about or never has tried any type of psychedelics. Since ketamine is shorter acting and has a warmer overall feel, it can be a good medicine for novices to start with. If this is successful and someone wants to explore further, psilocybin can be a good next step.

I wrote this article based on my own experiential understanding as well as actual experiences with both ketamine and psilocybin as a participant and a clinician. I have not written an academic article; nor is it medical advice. Please continue to do your own research to determine whether KAP or PAP could be right for you.

Some of the knowledge here I gleaned from my training with Dr. Craig Heacock. You can hear his psychiatric perspectives on the “Back From the Abyss” podcast episode dated 03/23/23, “Psychedelic assisted therapy: Ketamine vs MDMA vs Psilocybin.”

Read my blog to learn more about what a ketamine journey may feel like. If you’d like to book a consult with me regarding doing ketamine assisted psychotherapy with me, complete my contact form.

Pamela Peters

Pamela Peters is a trained relationship therapist who works with couples, folx in consensually non-monogamous (CNM) and polyamorous relationships. She also offers ketamine-assisted psychotherapy in her Denver, Colorado office.

https://www.pamelapeterstherapy.com
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