As mental health treatments continue to evolve, therapies harnessing psychedelic compounds are increasingly recognized for their potential, particularly in treating conditions like treatment-resistant depression. Among these, ketamine and psilocybin (often known as “magic mushrooms”) stand out, each operating under unique mechanisms, therapeutic principles, and clinical settings. At our ketamine infusion clinic in San Luis Obispo, we’re receiving more and more questions about psilocybin: Can I microdose while undergoing ketamine therapy? Which treatment is right for me?
While we cannot endorse the use of illegal substances, even with the growing body of research suggesting psilocybin's potential for relief from depression, we can outline key differences between ketamine and psilocybin. Here, we’ll examine critical distinctions between these two options, covering legality, mechanisms of action, safety, potential interactions with medications, and what a treatment session looks like for each. Understanding these aspects can empower individuals to make informed choices within safe, legally accessible treatments.
One of the primary distinctions between ketamine and psilocybin is legality. Ketamine, an FDA-approved anesthetic since the 1970s, has been safely repurposed for off-label use in treating depression, anxiety, and PTSD. Clinics across the U.S. and other countries can legally administer it, generally as an IV infusion or intramuscular injection, under medical supervision.
Psilocybin, however, is classified as a Schedule I controlled substance in the U.S., making it illegal outside of tightly controlled research trials or specialized therapy sessions in jurisdictions where it has been decriminalized or permitted for medical use. While significant clinical trials are ongoing, psilocybin is not yet approved for general clinical use, though several studies support its potential as a safe and effective treatment.
Ketamine primarily acts on NMDA (N-methyl-D-aspartate) receptors, modulating the brain's glutamate system. This action promotes neuroplasticity, the brain’s ability to adapt and create new connections, which can help people form healthier cognitive and emotional patterns. Its rapid-acting effects are often felt within hours of administration, making it especially effective for acute relief of depressive symptoms or suicidality.
Psilocybin interacts with serotonin receptors, particularly the 5-HT2A receptor, creating a profound impact on mood and perception. Psilocybin’s effects are often introspective and can lead to altered states of consciousness with high doses during a therapeutic “trip,” often described as being transformative. These sessions can provide profound insights that may help users reframe depression from a new perspective.
Safety is a critical consideration in psychedelic therapies. Both ketamine and psilocybin are generally safe when administered in clinical settings, though each comes with unique risks.
Ketamine has a well-established safety profile, particularly in medical settings where trained professionals can monitor its effects, which may include dissociation, elevated blood pressure, and, in rare cases, nausea. A typical ketamine infusion is 40 minutes to 1 hour long. Because ketamine's effects wear off quickly, patients usually completely recover within a few hours. Ketamine does not interact with respiratory function.
Psilocybin is non-toxic and not physically addictive, but its psychological effects require careful supervision. The hallucinogenic nature of high-dose psilocybin can sometimes lead to anxiety or challenging experiences, with particular concern for those with a history of schizophrenia personally or in their family. Clinical studies on psilocybin use protocols that include screening for potential risks and trained therapists to support patients through the experience, which generally lasts between 4 to 6 hours, depending on various factors such as the dose, individual physiology, and the particular mushroom strain. Nausea is a common side effect.
Note: Patients on antidepressants may need special considerations when exploring psychedelic treatments, especially with psilocybin.
Ketamine is often used alongside other antidepressant medications. Research indicates that ketamine can work effectively as an adjunct treatment to conventional antidepressants, enhancing or supplementing their effects without adverse interactions.
Psilocybin, however, can interact with SSRIs (selective serotonin reuptake inhibitors) and other types of antidepressants. SSRIs may dampen or neutralize psilocybin’s effects because both affect serotonin receptors, potentially reducing efficacy and increasing the risk of side effects. This interaction often necessitates that patients taper off antidepressants before psilocybin therapy, which must be done carefully under medical guidance.
The experience of undergoing ketamine versus psilocybin therapy is quite different. Each has distinct protocols for preparation, session structure, and follow-up.
Ketamine: Patients undergoing ketamine therapy typically begin with a preparation session led by a certified ketamine-assisted psychotherapist. This session is designed to set intentions, discuss expectations, and prepare patients for their first ketamine experience. During a typical ketamine session, patients are seated or reclined comfortably in a calm, supportive clinic environment, often with eye shades and a soothing music playlist curated to enhance the therapeutic experience.
The ketamine is administered via infusion or injection, with effects starting within minutes. Patients often experience mild dissociation or “floating” sensations, which can provide a detached perspective on their thoughts and feelings, facilitating new insights. Mild, dream-like hallucinations are common. Sessions usually last about 40 minutes to an hour, after which patients are monitored for recovery before leaving the clinic shortly after.
Following sessions, patients meet with a ketamine-trained psychotherapist for an integration appointment, a crucial part of the process. During integration, patients have the opportunity to process their experiences, explore new insights, and work on translating these into positive changes in thoughts, behaviors, and lifestyle. Integration sessions are essential for reinforcing the benefits of ketamine therapy, helping patients make meaningful and lasting improvements in their mental health.
Psilocybin: A psilocybin session is longer and more immersive. Sessions are generally conducted in a calm, therapeutic environment with a trained guide or therapist present throughout.
After taking psilocybin, patients feel the onset 1 to 2 hours after ingestion ,with a peak phase lasting around 4 to 6 hours. During the peak phase, visual and auditory hallucinations, mood changes, and altered thought patterns are most intense. Therapeutic support is essential to help patients navigate intense experiences or emotions that may arise. Much like ketamine therapy, patients often incorporate preparation and integration sessions with a trained therapist.
Both ketamine and psilocybin have shown promising results in clinical trials, but they differ in their effectiveness and the types of depression they best address.
Ketamine has been extensively studied and shown to provide rapid relief for individuals with treatment-resistant depression and suicidal ideation. Patients may feel significant mood improvement within hours to days. Some individuals require periodic booster sessions for sustained relief.
Psilocybin trials indicate that it can produce long-lasting changes in mood and mental health, sometimes from just a single high-dose session. For some, psilocybin’s antidepressant effects may last for months, though more research is needed to determine the optimal dosing and frequency of sessions.
Beyond high-dose sessions, psilocybin is also explored in microdosing, where small, sub-hallucinogenic doses are taken regularly to boost mood and cognition. While microdosing has become popular in some circles, its effects are largely anecdotal, and scientific evidence is limited. Unlike the profound shifts seen in full-dose psilocybin sessions, microdosing is commonly believed to subtly enhance focus, creativity, and emotional resilience without altering consciousness. However, the benefits and safety of microdosing are still under research, and it is not currently recognized as a clinical treatment for depression.
Ketamine and psilocybin offer unique approaches to treating depression. Ketamine provides rapid relief and can complement traditional antidepressants, making it an effective option for immediate support. Psilocybin therapy, while still awaiting broader legal approval, shows promising potential as research progresses. With greater accessibility, individuals may soon have the freedom to choose the treatment that aligns best with their needs and comfort. However, one crucial, but sometimes understated factor is the need for professional guidance to ensure safe, effective outcomes for those exploring ketamine infusions or psilocybin-assisted therapy.
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