What Are the Effects of Psilocybin Therapy for Depression?

In This Article:


Integrating science and spirituality is like mixing oil and water since these two subjects are generally thought to be on two immiscible, polar-opposite ends of a spectrum.

Nonetheless, a growing number of scientists in the biohacking community are looking into a mysterious substance rooted deeply in the indigenous culture and has been used for spiritual, medicinal, and religious purposes for thousands of years – psilocybin.

This article aims to review the latest findings on psilocybin, how it is effective as a treatment option for depression, and whether it will be available as a standard pharmaceutical in conjunction with traditional therapies in psychiatry.

RELATED: The Rise of Psychedelic Medicine | What We Know So Far


What is Psilocybin Therapy?

Understanding Psilocybin and Psilocybin Mushroom

Psilocybin is a psychoactive and hallucinogenic compound derived from certain types of mushrooms, known as psilocybin mushrooms or often colloquially referred to as “magic mushrooms” or “shrooms.”

Psilocybin mushrooms are a group of fungi that contain psilocybin. Some examples of psilocybin mushrooms include:

  1. Psilocybe cubensis (Stropharia cubensis)
  2. Psilocybe caerulescens (Landslide Mushroom)
  3. Psilocybe mexicana (Teonanacatl or Pajaritos)
  4. Psilocybe caerulipes (Blue Foot Mushroom)
  5. Psilocybe stuntzii (Blue Ringer Mushroom)
Examples of psilocybin-producing mushrooms
Examples of psilocybin-producing mushrooms


The History of Psilocybin Therapy

Researchers first began studying psilocybin in the 1950s, particularly when chemist Albert Hofmann isolated psilocybin and identified it as the active compound in psychoactive mushrooms in 1958. Even then, psilocybin was a promising therapeutic drug for several mental health conditions.

However, psilocybin was banned during the 1970s, resulting in tremendous difficulties among scientists continuing research on the substance. Psilocybin was then classified as a Schedule I substance, meaning the compound had a high potential for abuse and was forbidden from medical and clinical use.

It was not until several decades later that Dr. Roland Griffiths from Johns Hopkins University restarted psilocybin research in 1999, allowing the once Schedule I substance to be reclassified and legally studied among healthy volunteers.


Historical timeline of psychedelic substances
Historical timeline of psychedelic substances


Psilocybin Therapy in Today’s Psychiatry

Since the restart, the progress in psilocybin and psilocybin therapy research has been significant and promising enough to attract a wider group of scientists and potentially become a branch of mainstream science.

Today, many psychiatrists, psychologists, and scientists consider psilocybin therapy a promising, near-standard treatment option to complement traditional therapies in treating mental health conditions.

So, what exactly is psilocybin therapy?

Psilocybin therapy, also known as “shroom therapy,” involves ingestion of psilocybin in a certain way, either through oral consumption, liquid administration, or fume inhalation. Psilocybin use induces psychological effects that are thought to contribute to the treatment of depression and provide a complementary strategy to conventional therapies.

RELATED: Psychedelics Research and Psilocybin Therapy


How Does Psilocybin Therapy Work for Depression?


After ingestion, psilocybin is rapidly metabolized to psilocin, the primary, active substance that causes psychological effects on the user. Psilocybin is therefore considered a “prodrug” (an inactive substance that can be converted into an active one) to psilocin.

According to a study by the MDPI, some possible mechanisms of action by which psilocybin produces antidepressant effects include:


Psilocybin Deactivates or Normalizes the Hyperactivity of the Brain

The medial prefrontal cortex frequently exhibits hyperactivity during depressive disorders. Psilocybin may work as an antidepressant by deactivating or normalizing the medial prefrontal cortex’s typical level of hyperactivity.


Psilocybin Modulates the Brain Regions Responsible for Emotion-processing

Psilocybin’s antidepressant effects are mediated by its ability to modulate certain brain areas, particularly the amygdala. The amygdala, located deep within the brain’s temporal lobes, is responsible for sensory and emotional responses.


Psilocybin Interacts With or Alters the Default-mode Network (DMN)

Another way psilocybin might exert its antidepressant properties is through interaction with or alteration of the default-mode network (DMN). For example, some of the regions of the brain involved in emotional thinking may negatively affect the DMN in depression, causing resting cognition to be taken over by negative feelings.


Psilocybin Increases Dopamine, a Neurotransmitter Responsible for Emotion Regulation

The last possible mechanism may be the ability of psilocybin to increase dopamine, a neurotransmitter in charge of controlling emotions and even a person’s physical well-being.

RELATED: 4 Genius Ways to Biohacking Your Brain


Evidence for Psilocybin Therapy as the Treatment of Depression

Research by the Journal of Psychopharmacology

According to a study on the effects of psilocybin on depression and anxiety in 51 cancer patients, high doses of the drug resulted in significant, positive changes in both clinician- and patient-rated indicators. These changes include reduced depressed mood and anxiety and the fear of death, as well as increases in optimism, quality of life, and life meaning.

At the 6-month follow-up, these changes had persisted, with over 80% of subjects still displaying significant improvement in anxiety and depressive mood.


Research by Springer Psychopharmacology

The efficacy of psilocybin therapy for depression is backed by another study, in which 20 patients with severe treatment-resistant depression were assigned to two oral doses of psilocybin. The study found that psilocybin treatment improved depression after six months, with no patients seeking conventional antidepressant treatment within five weeks of psilocybin.

The study also implies that psilocybin may protect against depression to a comparable extent to the daily use of antidepressants.


Research by JAMA Psychiatry

One of the most recent studies published in 2020 has also found that psilocybin-assisted therapy is effective among patients with major depressive disorder. Specifically, findings suggest that psilocybin can help treat the condition in 24 participants after two sessions.


Decrease in depression scores (GRID-HAMD) at week 1 and week 4
Decrease in depression scores (GRID-HAMD) at week 1 and week 4


Is Psilocybin Therapy Safe, Addictive, or Legal?

Psilocybin Therapy Safety

Psilocybin therapy is still in the infancy of experimental research, and the data collected from all the relevant trials remain insufficient to conclude if it is entirely safe. Still, research by The Lancet Medical Journal shows that mushrooms are surprisingly much less harmful than other recreational drugs and substances, like alcohol or tobacco.


Drugs and substances ordered by their overall harm scores
Drugs and substances ordered by their overall harm scores

However, the statistics above do not mean that psilocybin is risk-free. Initial trials on the substance have shown that users may experience some physical and mental side effects in case of abuse. As a result, scientists refer to psilocybin abuse as a “bad trip.”

Possible physical side effects of psilocybin therapy include:

  • Drowsiness and headaches
  • Nausea and vomiting
  • Altered visual perception or euphoria
  • Muscle weakness or relaxation
  • Lack of coordination or concentration


Possible mental side effects of psilocybin therapy include:

  • Disoriented sense of time, place, and reality
  • Prolonged or intense auditory and visual hallucinations
  • Inability to discern fantasy from reality (psychosis)
  • Panic reactions or heightened anxiety
  • Extreme anxiety to the point of delusion and irrationality (paranoia)


If there are any, a “bad trip” due to psilocybin side effects is typically treated with benzodiazepines.


Psilocybin Therapy Addiction Issue

Psilocybin is not addictive. It is difficult to overuse psilocybin since the more frequently it is taken, the milder the effects are. This lessened reaction is because psilocybin causes short-term increases in tolerance in users. Therefore, psilocybin therapy does not lead to physical dependence or addiction.

The Registry of Toxic Effects of Chemical Substances (RTECS) has confirmed that psilocybin has almost no effects on public health, criminal impact, and very low acute and chronic toxicity. Therefore, there is currently no established value for a lethal dose at either the recreational or medical levels in humans.


Psilocybin Therapy Legitimacy

The legitimacy of psilocybin, psilocybin mushrooms and psilocybin therapy may vary in states, regions, and countries. On this account, it is best to research by yourself to see if they are legally available in your area.


What Can You Expect About Psilocybin Therapy?

Is Psilocybin Therapy for You?

Psilocybin therapy is typically for people with mental health conditions like depression that conventional treatments cannot treat. If you have the following issues and have tried and failed with other approaches, you should consider psilocybin therapy:

  • Depression and anxiety due to chronic and life-threatening illnesses
  • Treatment-resistant, severe, and debilitating depression and anxiety
  • Chronic post-traumatic stress disorder (PTSD)
  • Overcoming drug addiction and smoking cessation


According to research, psilocybin therapy may also offer some extra, long-term benefits if implemented appropriately at the correct dosage and duration:

  • Reduced frequency and severity of depression
  • Higher chance of remission of depression
  • Improved mood and quality of life
  • Positive changes in personality
  • Enhanced feelings of connectedness
  • Pro-environmental behavior
  • Decreased violent and criminal behavior
  • Reduced suicidal thought


What is the Right Dosage for Psilocybin Therapy?

Scientific Study Experiment with Psilocybin, a derivative from Magic Mushrooms-ss-What is the Right Dosage for Psilocybin Therapy

The amount of psilocybin in mushrooms that should be taken for psilocybin therapy depends on the mushrooms’ psilocybin content, which differs significantly between and within the same species. According to research:

  • The usual dosage of a common psilocybin mushroom, like Psilocybe cubensis, ranges from 1.0 to 2.5 g of the dried weight.
  • Dosage ranging from 2.5 to 5.0 g of dried mushroom is a strong dose.
  • Dosage above 5 g is regarded as a heavy dose and is referred to as a “heroic dose.”


Remember that the dosages above refer to the amount of dried psilocybin-producing mushroom material, not the amount of psilocybin content.


What Happens During a Psilocybin Therapy Session?

A typical session of psilocybin therapy is conducted by having the patient talk to and familiarize with the therapist in a visually and audibly pleasing environment. The purpose of the initial stage of the session is for the therapist to gain the patients’ trust, which may help reduce the side effects afterward.

The patient will then ingest a capsule containing psilocybin, then be subjected to complete resting under a tranquil and supervised condition until the effects of psilocybin arise. During the resting phase, the patient shifts their attention inward to be isolated from reality and avoid interruption due to side effects like anxiety or fear.

The psychological effects of psilocybin therapy typically appear around 30-60 minutes after ingestion. However, the results are subjective, and the time psilocybin takes to “kick in” may vary considerably among users. From here on, the patient goes on a psychoactive and hallucinogenic “journey” under the facilitation of their therapist.


How Long Will the Effects of Psilocybin Therapy Last?

The psychoactive and hallucinogenic effects of psilocybin therapy are relatively short-lasting, typically 3-6 hours, depending on the patient’s age, physical and mental health, and prior exposure to the substance. Anecdotally, the effects subside by the end of the therapy. However, the memories of the therapy experiences may remain for a longer time.

RELATED: The Science of Psilocybin and Its Use to Relieve Suffering


Recent Findings in Psilocybin Therapy for Depression

Psilocybin and Mindfulness Meditation Might Be Complementary When Combined

According to a recent review by the Frontiers, mindfulness meditation and psilocybin produce similar beneficial effects on mood and neuroplasticity.

Maladaptive plasticity in the neurons may lead to the persistence of depressive symptoms. Therefore, correcting neuroplasticity, on top of improving mood, may aid in the remission of the mental illness.

The review suggests that mindfulness meditation and psilocybin, when used in combination, could exert complementary effects by intensifying or prolonging mutual positive outcomes, such as facilitating psilocybin-induced peak experiences.


Psilocybin-assisted Treatment is Effective for Up to 12 Months

Until now, psilocybin-assisted therapy has shown dramatic, positive effects on depression. However, little is known about long-term results.

The latest study by the Journal of Psychopharmacology found that psilocybin therapy may offer antidepressant benefits lasting at least 12 months. Specifically, 24 participants received two doses of psilocybin with supportive psychotherapy. After their second dose at week 8, the participants were followed through 12 months post-treatment.

Indeed, at month 12, depression scores (GRID-HAMD) remain relatively low and equivalent to the prior months. This data suggests that psilocybin can be used within a much longer duration than what has been demonstrated in the previous studies, offering more possibility of potent and prolonged efficacy of the treatment.


Decrease in depression scores (GRID-HAMD) over time from baseline through the 12-month follow-up
Decrease in depression scores (GRID-HAMD) over time from baseline through the 12-month follow-up


Bottom Line: Psilocybin or Antidepressants for Treating Depression?

Given the potential efficacy of psilocybin therapy in multiple studies, one central question around this emerging approach is: could it be more effective than the traditional, established treatment for depression?

According to a 2021 trial by the New England Journal of Medicine, there is no significant difference in antidepressant effects between psilocybin and escitalopram, an antidepressant belonging to the selective serotonin reuptake inhibitor (SSRI) class.

That said, larger-scaled and longer trials are needed to compare psilocybin with other established antidepressants. Until then, scientists will have been able to conclude whether psilocybin therapy alone is adequate to the point that no different complementary approaches are necessary during the treatment for depression.


There is no significant difference between psilocybin and escitalopram in treating depression
There is no significant difference between psilocybin and escitalopram in treating depression

In conclusion, access to psilocybin may be difficult, primarily if you are based in a particular region where this substance has not been legalized. While more research is under investigation, do not hesitate to start the therapy. Contact us for more information about psilocybin therapy if you need an approach to improving your mental health.



Nutt, D., King, L., Phillips, L. (2010). Drug Harms in the UK: a Multi-criterion Decision Analysis. The Lancet.

Griffiths, R., Johnson, M., Carducci, M. et al. (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.

Carhart-Harris, R., Bolstridge, M., Day, C. et al. (2018). Psilocybin With Psychological Support for Treatment-resistant Depression: Six-month Follow-up. Springer Nature.

Carhart-Harris, R., Bolstridge, M., Day, C. et al. (2018). Psilocybin With Psychological Support for Treatment-resistant Depression: Six-month Follow-up. Springer Psychopharmacology.

Albert, P. (2019). Adult Neuroplasticity: A New “Cure” for Major Depression. Journal of Psychiatry and Neuroscience.

Heuschkel, K., Kuypers, K. (2020). Depression, Mindfulness, and Psilocybin: Possible Complementary Effects of Mindfulness Meditation and Psilocybin in the Treatment of Depression. Frontiers in Psychiatry.

Davis, A., Barrett, F., May, D. et al. (2020). Effects of Psilocybin-assisted Therapy on Major Depressive Disorder. JAMA Psychiatry.

Lowe, H., Toyang, N., Steele, B. et al. (2021). The Therapeutic Potential of Psilocybin. The Multidisciplinary Digital Publishing Institute.

Carhart-Harris, R., Giribaldi, B., Watts, R. et al. (2021). Trial of Psilocybin Versus Escitalopram for Depression. New England Journal of Medicine.

Gukasyan, N., Davis, A., Barrett, F. et al. (2022). Efficacy and Safety of Psilocybin-assisted Treatment for Major Depressive Disorder: Prospective 12-month Follow-up. Journal of Psychopharmacology.


If you have questions about psilocybin therapy or any health problems discussed here, connect with us and learn more. 

At Peak Human, our team of healthcare professionals is dedicated to helping you reach your ‘peak’ health with a custom whole-person approach. Using the most cutting-edge, science-backed biohacking and aesthetic tools, technologies, and treatments available today, we help you achieve the highest physical/cognitive performance state, leading to an improved overall quality of life.

For questions or to book an appointment, don’t hesitate to contact us. Get personalized support and insight from expert physicians.


5/5 - (1 vote)

Leave a Reply

Your email address will not be published.