Psychedelics & Psilocybin Treatment For Depression

Is Psychedelics and Psilocybin treatment right for depression treatment? Telapsychiatry is here to guide you.

Many types of mushrooms, sometimes referred to as “magic mushrooms,” contain the hallucinogenic compound psilocybin. When consumed, this drug causes euphoric sensations and sensory hallucinations that linger for several hours. 

One of the most widespread mental illnesses is depression. According to data from the National Institute of Mental Health, 7.1% of all American adults reported having at least one depressive episode in the previous 12 months.[1]

Fortunately, conventional therapies like antidepressants and psychotherapy can be successful. However, a recent upsurge of interest in using psychedelics and psilocybin to treat mental diseases has found that drugs like psilocybin may be another helpful therapy for treating depression.

Psychedelics and Psilocybin Therapy

Psilocybin therapy, also known as psilocybin-assisted therapy, is a form of psychotherapy that makes use of a hallucinogenic substance, psychedelics, that is found naturally in a particular kind of mushroom.

History of Psilocybin and Psilocybin Treatment

While psilocybin and other psychedelics are increasingly being studied for their potential therapeutic applications, their use for religious and medicinal purposes is not new.

Psychedelic drugs have been in use for a long time in traditional medicine and spiritual ceremonies by many different cultures and religions.

The discovery of LSD in the 1940s sparked a significant deal of investigation into the potential benefits of psychedelic substances for mental health.

The idea of using psychedelic drugs for therapy may seem countercultural or fringe to many people. That is not the case. 

Highly reputable medical institutions like Johns Hopkins are researching and using psilocybin therapy. Even though psychedelic research and therapy were outlawed by the American government in 1970, John Hopkins University was the institution to get regulatory certification for the first time in 2000. [2] 

Johns Hopkins University published its initial study on the beneficial long-term effects of psilocybin use in a therapeutic study in 2006. Numerous scholarly articles and studies have since been published. [3]

Hopkins received a federal grant for psychedelic treatment research in 2021 when some states started decriminalizing it. Hopkins received this grant in conjunction with a federal initiative. Psilocybin is currently more legal due to legislation approved in more than a dozen states. 

It is crucial to remember that the decriminalization of the drug and its use has been based on its potential for therapeutic use. In most places where it is legal, people can only use it in specific settings. [4]

Research on Psychedelics and Psilocybin Therapy

Clinical trials have produced positive outcomes, and more studies are being done on using psilocybin-assisted therapy for depression.

According to a 2016 study, patients receiving cancer treatment who had psilocybin therapy experienced significantly less anxiety and depressive side effects.

Various additional advantages were associated with the treatment in addition to these outcomes. Psilocybin patients claimed to have more optimism and a higher overall quality of life. [5]

Some studies conducted by scientists at Johns Hopkins Medicine show that psilocybin therapy, a type of psychedelic, helped adults with major depressive disorder feel better for up to a month. 

The strong antidepressant effects of psilocybin-assisted therapy, when combined with supportive psychotherapy, may endure at least a year for certain patients. [6]

How Psychedelic-Assisted Therapy Session Work

You will take a small quantity of psilocybin under a professional’s guidance in a secure and comforting setting.

You will work with the therapist after the psychedelic session to help them integrate it. The objective is to assist the you in processing and giving meaning to their recent experiences.

Psychotherapy is an essential part of this process. A person’s psychedelic experience can be processed and made sense of in a way that may have long-term positive effects on their mental health when they work with a therapist.

In a study, researchers also discovered that subjects who received 25 mg doses of the psilocybin medication compared to those who received 1 mg dosage experienced fewer depressive symptoms three weeks after treatment. [7]

How Psychedelics and Psilocybin Work to Relieve Depression in the Brain

Despite several clinical studies demonstrating that psilocybin can effectively cure sadness, including despair and anxiety linked to cancer, little is understood about how psilocybin relieves depression in the brain.

Two recent studies, published in The New England Journal of Medicine and Nature Medicine, have clarified this perplexing process. 

Psilocybin is a hallucinogen that alters how the brain reacts to the neurotransmitter serotonin. Users experience an altered state of consciousness and sensation when it is broken down by the liver (into “psilocin”).

Mechanism of Action

Previous research using functional magnetic resonance imaging (fMRI) of the brain has demonstrated that psilocybin appears to decrease activity in the medial prefrontal cortex, an area of the brain that aids in regulating several cognitive functions, including attention, inhibitory control, habits, and memory. 

The substance also weakens the connections between this region and the posterior cingulate cortex, which is a region that may be involved in the control of memory and emotions.

The brain’s “default mode network” typically includes an effective link between these two brain regions. This network is active while we rest and concentrate internally, possibly daydreaming about the future, reflecting on the past, or thinking about other people or ourselves. 

Psilocybin may be freeing the internal “self” by lowering network activity; users claim to have an “open mind” and a better sense of their surroundings.

It is interesting that rumination, or feeling “stuck” in unpleasant ideas, especially ones about oneself, is a sign of sadness. Additionally, we are aware that patients who engage in more negative ruminating tend to exhibit increased activity in the default mode network as compared to other networks that are at rest, which results in a decrease in their ability to respond to their environment. 

The origin of this changed activity is yet unknown, and it is unclear whether people with an active default mode network are more prone to depression.

Most Recent Research on Psilocybin’s Mechanism

The most convincing proof of psilocybin’s mechanism of action comes from a double-blind, randomized controlled trial, which is the gold standard of clinical studies. This study was the first to compare a group of depressed people taking psilocybin to those taking the antidepressant medication escitalopram. The trial’s results were contrasted with other fMRI findings from a recent clinical trial and further analyzed using MRI brain scans.

One day following the initial psilocybin dose, fMRI measurements showed an overall increase in connection between the major brain networks, which is generally decreased in people with severe depression.

The default mode network was simultaneously made smaller while connectivity to other networks was more robust, supporting earlier, smaller experiments.

Some persons saw a more significant increase in connectedness than others after the dose. However, the investigations revealed that six months later, the symptoms improved most for those whose network connections had increased the most.

Six weeks into therapy, however, there was no difference in the connection between the default mode and other brain networks in the brains of escitalopram users. Escitalopram might result in modifications in the future. However given that psilocybin’s antidepressant impact kicks in quickly, it might be the best option for those who do not respond to currently available antidepressants. [8]

According to the study, psilocybin and escitalopram exert different effects on the brain’s “serotonergic 5-HT2A receptors,” with psilocybin having a more concentrated effect. These receptors, which are active in all networked brain regions, including the default mode network, are triggered by serotonin. We already know that psilocybin’s amount of binding to these receptors causes psychedelic effects. However, it is still unknown precisely how their activation affects network connectivity. [9]

Read About: How Diet Can Affect Mood, Cognition, And Sleep

What Issues Can Be Treated with Psilocybin Therapy

Numerous mental health issues, including addiction and depression, can be effectively treated using psychedelic therapy. While further study is required, experiments are currently being conducted to understand better the applicability and efficacy of certain psychedelic medications to treat particular illnesses.

Problems with Anxiety and Mood

Additionally, psilocybin and psilocybin-assisted therapy were linked to enhanced optimism, higher life satisfaction, and lower mortality fear. A six-month follow-up revealed improvements in almost 80% of subjects.[10]

Another study examined the impact of psychedelic use. LSD and psilocybin use reportedly improved participants’ moods and increased their sense of social connection. Additionally, they stated that these results persisted even after the medication ceased. [11]

Chronic Illness Patients

A single dose of psilocybin has been demonstrated to significantly lower the anxiety and depression of cancer patients facing a life-threatening illness. The effects persisted for over six months, with 60% to 80% of the group reporting relief in those symptoms. 

More than 80% of cancer patients continued to feel better over six months after receiving the single-dose medication, according to a different study. In addition to a decline in their despair, anxiety, and emotions of dread or hopelessness related to their illness, they also reported changes in their outlook on life, their moods, and their sense of spirituality. [12]

PTSD Patients

After a terrible experience, post-traumatic stress disorder symptoms can linger for years, interfering with all aspects of life. Positive outcomes are shown from studies on the use of psilocybin with people with PTSD. PTSD has also been investigated in relation to other psychedelics, including MDMA and ketamine. [13]

Things To Consider Before Taking Psychedelics and Psilocybin Therapy

It is crucial to get all the facts before considering psilocybin because it is a psychedelic chemical. Also, it should always be carried out in the presence of a trained professional therapist specializing in therapeutic application.

It Could Trigger Uncomfortable Emotions

Even if the therapy delivers a positive effect, it might not be a fully joyful experience. Because of this, it must be led by someone who can support you if things change.

Possibility of Addiction Exists With Psychedelics and Psilocybin

Psilocybin is not typically considered an addictive substance, although people with substance abuse issues can nevertheless feel drawn to use it again outside of a clinical setting.

It is advisable to have a lengthy conversation with your practitioner about this as it is a complicated matter because the drug has been studied to treat specific substance use disorders.

Patients with Heart Issues Need to be Cautious

There have been some concerns that psilocybin might contribute to specific cardiac problems; however, there is not any conclusive proof of this. Consult your doctor before considering using it if you have cardiac or other difficulties.

Risks Associated with Psychedelics and Psilocybin Therapy

Additionally, it is critical to understand that psilocybin is typically considered harmless, but it can potentially result in negative consequences like delusions, drowsiness,  headaches, nausea, nervousness, panic, paranoia, and psychosis. 

There is a possibility of having a “poor trip” when psilocybin generates psychedelic experiences. A person could feel extreme levels of fear and anxiety during this event. It may also result in frightful paranoid, delusional, and hallucinogenic experiences.

It is vital to only experiment with psilocybin for depression under the guidance of a mental health expert since, even if it is impossible to avoid a poor trip, being in a soothing setting with a supportive person can be beneficial.

For those who have previously gone through maniacal or psychotic episodes, psilocybin may be risky. This is why those who suffer from certain mental health illnesses, such as schizophrenia or bipolar disorder, should not try psilocybin-assisted therapy.

Final Words

Recent studies on psychedelics and psilocybin have demonstrated that the use of the drug has significant positive impacts on mental health. Additionally, a higher percentage of people receiving psilocybin therapy displayed a favorable clinical response. The setting in which psilocybin is consumed significantly impacts its effectiveness. 

This indicates that using it as self-medication is not a good idea. Additionally, people for psychedelics and psilocybin-assisted therapy were carefully chosen based on their histories to reduce the risk of psychosis and other side effects.

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  1. NIMH » Major Depression. (n.d.). NIMH. Retrieved November 20, 2022, from 
  2. Hall, W. (2021, October 21). Why was early therapeutic research on psychedelic drugs abandoned? Cambridge University Press. Retrieved November 20, 2022, from 
  3. (Publications — Center for Psychedelic & Consciousness Research, n.d.) 
  4. (Johns Hopkins Medicine Receives First Federal Grant for Psychedelic Treatment Research in 50 Years, 2021)
  5. Ross, S., & Bossis, A. (2016, November 30). Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Sage Journals. Retrieved November 20, 2022, from 
  6. (Psilocybin Treatment for Major Depression Effective for Up to a Year for Most Patients, Study Shows, 2022)
  7. Pelc, C., Guildford, A., & Washington, N. (2022, November 8). Magic mushrooms: Single dose may relieve treatment-resistant depression symptoms. Medical News Today. Retrieved November 20, 2022, from 
  8. Harris, R. C., & Giribaldi, B. (2021, April 15). Trial of Psilocybin versus Escitalopram for Depression. The New England Journal of Medicine. Retrieved November 20, 2022, from 
  9. Madsen, M. K., Fisher, P. M., & Burmister, D. (2019, January 26). Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Retrieved November 20, 2022, from  
  10. Griffiths, R. R., & Johnson, M. W. (2016, November 30). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer. … – Sage Journals. Retrieved November 20, 2022, from 
  11. Forstmann, M. (2019, October 24). Transformative experience and social connectedness mediate the mood-enhancing effects of psychedelic use in naturalistic settings. PNAS. Retrieved November 20, 2022, from 
  12. Ross, S., & Schmidt, B. L. L. (2016, November 30). Sage Journals. Retrieved November 20, 2022, from
  13. Cherry, K. (2021, September 26). Psychedelic Therapy: Definition, Types, Techniques, and Efficacy. Verywell Mind. Retrieved November 20, 2022, from
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