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Psilocybin: Safety, Side Effects & Intriguing Research

Written by Ana Aleksic, MSc (Pharmacy) | Last updated:
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Psilocybin is a naturally occurring psychedelic substance produced by psilocybin mushrooms, also called ‘magic’ mushrooms. With the modern revival of psychedelic research, psilocybin is being investigated for its potential to help people overcome depression and anxiety. Read on to learn about the history of its use and the intriguing current research.

What is Psilocybin?

Mysterious Psychedelic

Psilocybin (chemically known as 4-phosphoryloxy-N, N-dimethyltryptamine) is a classic psychedelic that belongs to the group of hallucinogenic tryptamines. But the story about psilocybin indigenous use and modern research over the past century is anything but classic [1].

Over 100 species of hallucinogenic “magic” mushrooms contain psilocybin (including Psilocybe, Conocybe, and Paneolus). These mushrooms grow in different parts of the world and have been used ritually for at least 3000 years [2, 1].

Despite the recent renaissance in psychedelic research, there is a lot of controversy surrounding psilocybin use, legal status, and its potential therapeutic effects. Not many people know the whole story behind the traditional use of psilocybin-containing mushrooms, nor about the efforts that produced our current state of knowledge about it.

Psilocybin is a natural psychedelic found in psilocybin mushrooms, also called “magic” mushrooms. Modern research is catching up with their age-old traditional use, surrounded by mystery and controversy.

The Story Of Magic Mushrooms


The first use of hallucinogenic mushrooms dates back about 3,000 years to Mexico. They are still used by native people in some areas for religious ceremonies and healing, although the local communities encountered many struggles in the past.

Shortly after the European conquest of these territories, magic mushrooms were banned for the first time in the early 17th century [2, 3, 4].

A couple of centuries passed before these mushrooms gained the attention of Western scientists and doctors for the first time. Robert Wasson, an American ethnomycologist, popularized these mushrooms in the 50s after returning from an expedition to Mexico where he participated in an indigenous Mazatec religious ritual.

He was one of the first Westerners to participate in such a ritual. He published an article in the Life magazine called “Seeking The Magic Mushroom” in which he described his experience [5].

The article became extremely popular, especially in the counterculture movement of the time, and led many people to travel Mexico seeking to experience the same. But this only brought devastation and unwanted attention from foreigners and police to the local community.

Luckily, it also brought some attention from the scientific community. Psilocybin was first isolated, identified, and synthesized by Albert Hofmann, the “father of LSD”, in the late 50s (from P. mexicana). He later summarized his thoughts about psychedelics, including LSD and psilocybin, in the book “LSD – My Problem Child” [6, 7].

Native Americans have used magic mushrooms in religious and healing rituals for ages. They got introduced into western science in the 50s.

The 60s and 70s

In the 60s, psilocybin research boomed with over 1,000 studies published. It was used in both experimental research and psychotherapy [8].

Some scientists thought that psychedelics like psilocybin modeled “madness” and schizophrenia. Others were investigating its effects on creativity, cognition, and mystical experiences. Many key figures, including Timothy Leary, the British writer Aldous Huxley, and even Allen Ginsberg were involved in these experiments.

It didn’t take long for psilocybin to become popular among the general public as a recreational drug. The name of the band “The Doors” was inspired by Aldous Huxley’s book “The Doors of Perception”, in which he describes his own theories and experiences with psychedelics.

As recreational use got out of hand, psilocybin and other psychedelics were soon banned in the 70s and classified as Schedule I drugs (the same class as heroin). This group of drugs contains substances considered to be the most dangerous for human health and with the highest potential for abuse [6].

Psychedelic research became marginalized, funding was cut, and all human experiments came to a halt [1].

Psilocybin research and recreational use boomed in the 60s. It was banned and classified as a Schedule I drug in the 70s, which halted psychedelic research.

Modern Revival

In the late 1990s, scientists started looking into psilocybin once again. Psychedelics research was revived, and the number of scientific publications is now increasing every day [6].

Although psilocybin remains classified as a Schedule I drug (and is therefore illegal to use and very difficult to study), scientists have become intrigued by its therapeutic potential [6, 1].

Recently, the FDA approved a clinical trial of psilocybin for treatment-resistant depression, which will be conducted in 2019. It will be the largest ever clinical trial of “psychoactive care” – the combination of psilocybin and psychological support.

It’s possible that psilocybin may be approved for depression or other conditions in the future, but it’s still too early and uncertain to say.

The late 90s brought a revival of psilocybin scientific research and interest. Large clinical trials to investigate its therapeutic and antidepressant effects are on the way.

Mechanism of Action

As a classic psychedelic, psilocybin causes hallucinogenic effects by activating specific serotonin receptors: 5-HT2A. It also slightly activates dopamine pathways in the brain and the sympathetic, fight-or-flight system in higher doses [1, 6, 9].

Psilocybin probably achieves long-lasting effects on the brain and its plasticity by changing gene expression, a result of activating 5-HT2A receptors [10].

Ego Dissolution

The key to understanding its mechanism may lie in parts of the brain it affects.

In brain imaging studies in 15 healthy volunteers, psilocybin decreased connectivity in the brain’s default mode network. This system is activated when a person is thinking about oneself, the past, and the future. Meditation also reduces activity in this system [11, 12, 1].

What’s common to both meditation and psychedelic experience is the focus on immediate experience as a dissolution of the sense of self or “ego.”

In the brain imaging study, psilocybin led to so-called “unrestrained cognition.” This resembles the sudden opening of a “valve” that otherwise keeps normal consciousness in check to a more fluid, hyperconnected state [13].

Aldous Huxley first envisioned this valve as something that restricts consciousness but is necessary to maintain biological functions and a sense of self in everyday life. Experiences that occasionally loosen it open up the doors of perception, according to him.

Aldous Huxley Valve "cerebral reducing valve", taken from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853825/

This is also what some refer to as a “resetting” of the brain by psilocybin, which may be necessary for its therapeutic effects. It may explain why the effects of psilocybin persist long after a single use, since brain networks may continue to rearrange themselves after the experience [1].

Psilocybin induces hallucinations via serotonin 5-HT2A receptors. It “rewires” the brain, dissolves the sense of self or ego, and alters perception and consciousness.

Sensory Changes

In another brain imaging study with 7 volunteers, psilocybin (0.25 mg/kg, oral) intensified emotions and sensory perception, caused difficulty concentrating, dreaminess, and a loss of ego boundaries [14].

The sensory changes ranged from illusions to complex scenery hallucinations. Most of them also experienced heightened mood or euphoria. The effects peaked after 30-40 minutes, started to decline after 2 hours, and completely subsided after about 6 hours.

Altered State of Consciousness

Some think psilocybin is very useful for understanding the very nature of human consciousness. In a study of 8 healthy people, psilocybin was given at different doses – from very low (45 μg/kg) to high (315 μg/kg). With higher doses, psilocybin induced a more intense consciousness shift, marked by [15]:

  • Oceanic boundlessness, euphoria, and depersonalization
  • Ego dissolution, which may provoke anxiety
  • Visual hallucinations and synesthesia (mixing of the senses)
  • Dreaminess and reduced alertness

The blurring of the boundaries between self and environment was generally experienced as “touching” or “unifying with a higher reality”. Medium and high doses caused hallucinations, while the lower doses only caused some changes in perception. Only one person in the high-dose group experienced anxiety [15].

Psilocybin triggers sensory changes and intensifies emotions. Higher doses can cause ego dissolution, full-blown hallucinations, and the sense of oneness with the universe.

Psilocybin Content in Mushrooms

Psilocybin content in dried mushrooms varies from 0.2-1% [2].

In research, pure psilocybin pills or intravenous injections are given. Recreationally, people take psilocybin by eating raw or dried hallucinogenic mushrooms, alone or mixed into beverages.


In clinical studies, the effective oral dose was 10-30 mg/70kg or 0.045-0.429 mg/kg, and 1-2 mg per adult intravenously. The minimal dose for psychedelic effects was 15 mg orally. And when it comes to the current research, safety guidelines state that high oral doses of psilocybin are >25 mg [6].


If taken orally, psilocybin converts to psilocin, its active form, in the liver. Psilocin then enters the bloodstream and reaches the brain [16].

How Long Do the Effects Last?

The effects peak after 1-2 hours and last for 4-6 hours after oral use. All the effects wear off after 6-8 hours, even after high psilocybin doses, according to several studies in healthy volunteers [14, 15].

Dry mushrooms contain 0.1-1% of psilocybin. The effective dose is 10-30 mg/70kg, and the effects last for 4-6 hours. The liver converts psilocybin into active psilocin.

Types of Psychedelic Mushrooms

There are over 100 species of psychedelic mushrooms, but the best-known ones are [6, 1]:

  • Psilocybe azurescens (highest psilocybin content)
  • Psilocybe bohemica (second highest psilocybin content)
  • Conocbe cyanopus
  • Copelandia cyanescens
  • Panaeolus africanus
  • Panaeolus subbalteus
  • Inocybe aeruginascens
  • Psilocybe cubensis
  • Psilocybe cyanescens
  • Psilocybe mexicana
  • Psilocybe semilanceata
  • Psilocybe tampanensis

Psilocybin vs LSD or Mescaline

In terms of psychedelic effects, psilocybin is:

  • 45 times less potent than a similar weight of LSD, and
  • 66 times more potent than a similar weight of mescaline

The effects of LSD last much longer, though, sometimes up to 15 hours [17].

What Has Psilocybin Been Studied For?

Note: psilocybin is a Schedule I illegal substance which has not been approved by the FDA for any purpose. We strongly recommend against taking psilocybin for any reason.

1) Treatment-Resistant Depression

In the first clinical study of psilocybin in 12 people with treatment-resistant depression, psilocybin greatly reduced depressive symptoms for up to 3 months after the initial experience. It was given in a supportive setting, at an increasing dose (10-25 mg). It also improved anxiety and the ability to feel pleasure [18].

In another trial, psilocybin improved symptoms in 15 people with treatment-resistant depression. Just one week after the session, they were less pessimistic and their mood improved. Overall, psilocybin along with psychological support enabled them to gain a more positive and accurate outlook on life [19].

Encouraged by these findings, larger clinical trials of psilocybin in people with treatment-resistant depression are underway.

Psilocybin improved treatment-resistant depression in two small clinical studies. Larger trials to verify this effect are underway.

2) Cancer and Terminal Illness

Anxiety in people with life-threatening diseases is often overlooked, although it’s linked to poor mental health and clinical outcomes. Psilocybin can help these people by drastically changing their outlook on life for the better. Finding meaning may transform despair into a positive self-exploration [4, 20].

Given in a safe and supportive environment, psilocybin sessions can help people regain a sense of meaning, lessen death anxiety, and improve mood [21, 22, 23].

In a trial of 12 people with advanced cancer, a modest dose of psilocybin improved mood two weeks later, which was sustained for 6 months. It also reduced anxiety for 3 months after the treatment. None experienced anxiety from psilocybin or a “bad trip” [21].

In 51 cancer patients with depression, high-dose psilocybin (20-30 mg) reduced depression, anxiety, and fear of death while increasing the quality of life and optimism. These changes were sustained even after 6 months. Psilocybin increased well-being by changing attitudes toward life, relationships, and spirituality [22].

A single psilocybin dose reduced anxiety and depression quickly and long-term in a trial of 29 people with cancer. It reduced hopelessness, improved spiritual wellbeing, and increased quality of life. Most patients continued to improve even after 7 months [24].

In patients with cancer and terminal illness, psilocybin may combat anxiety, depression, and fear of death. According to some researchers, it may change life attitude, improve well-being, and increase spirituality.

3) May Improve Obsessive-Compulsive Disorder (OCD)

Psilocybin reduced OCD symptoms in one trial of 9 people. Each person received 4 different psilocybin doses one week apart. The dose didn’t turn out to matter in this study, as everyone experienced improvements – both from microdoses (25 μg/kg) and high doses (300 μg/kg) [25].

It also reduced OCD symptoms in mice [26].

4) May Help with Addictions

Scientists realized the potential of psychedelics, including psilocybin, for treating addiction back in the 50s. They realized that insightful effects they produced may encourage sobriety. That’s when the term “psychedelic,” was coined, meaning “mind-manifesting” [1].

Psilocybin is emerging again as an option for overcoming tobacco and alcohol addiction, as well as substance abuse disorders.

It is not addictive itself, has low toxicity, and is safe when used in a controlled environment. Psilocybin works differently than the drugs currently used to fight addiction since a single session can trigger long-term changes in behavior and thinking [1, 27].

Alcohol Dependence

In 10 people with alcohol dependence, psilocybin increased abstinence from alcohol long-term with no adverse effects. Psilocybin was accompanied by a 3-month motivational therapy. The benefits persisted for 6 months after the initial sessions [28].

Smoking cessation

Psilocybin helped 12 out of 15 cigarette smokers quit in one clinical trial, without side effects. They received both moderate (20 mg/70 kg) and high (30 mg/70 kg) doses over the 15-week cessation period. Six months later, 12 of them completely quit smoking. Such a success rate (80%) is much higher than any other therapy [29].

Interestingly, more intense mystical-type psilocybin experiences were linked to a greater reduction in craving after 6 months in this study.

Insightful experiences with psilocybin may encourage sobriety and help with addictions. It showed promising results for alcohol dependence and smoking cessation, but more trials are needed to confirm this effect.

5) Mystical Experiences

In many of the studies above, mystical experiences elicited by psilocybin induced other psychological and health benefits.

For example, the cancer patients who had a more intense mystical experience had greater improvements in mood and wellbeing. Similarly, people with alcohol dependence were more likely to maintain sobriety if they had a strong mystical experience from psilocybin [1].

This suggests a shift from the current medical framework to the one in which psychological experiences may have more wide-ranging benefits than previously thought [1].

Some scientists think the feeling of profound awe and overcoming a limited sense of self is what drives the long-term psychological benefits of psilocybin [30, 31].

In one study, 30 religious or spiritual people who never took psychedelics before underwent 8-hour psilocybin sessions (30mg/70kg). After two months, they rated the psilocybin experience as one of great personal meaning and spiritual significance [32].

At the 14-month follow up, almost 70% of them rated the psilocybin experience as being among the five most meaningful and spiritually significant experiences of their lives; 64% indicated that it increased well-being or life satisfaction [33].

By inducing mystical experiences, psilocybin may provide a range of psychological benefits. Many users experienced a positive shift in life perception, wellbeing, and spirituality, but larger trials will be required to confirm this effect.

6) May Help with PTSD

In traumatized mice, psilocybin reduced fear. These mice developed PTSD symptoms from being exposed to sound-signaling electroshocks. Lower doses of psilocybin helped mice transcend the fear even better than high doses [34].

In this study, psilocybin also increased neurogenesis, the growth, and repair of brain cells in the hippocampus, a brain center for emotions, mood, and memory. If neurogenesis is blocked in mice, fear intensifies. In imaging studies, people with PTSD had smaller hippocampi [34, 35, 36].

Psilocybin may be able to increase neurogenesis in the hippocampus and help people with PTSD, much like successful psychological treatment does [37, 38].

Psilocybin may help overcome PTSD, but the available evidence is limited to animal studies.

7) May Boost Neurogenesis

Neurogenesis is not important only for PTSD. Growing your brain may also help with mental health, cognition, and brain injuries.

Psilocybin could increase neurogenesis in traumatized mice. Other similar psychedelics increased both neurogenesis and new brain connections – synapses – in animal and cellular studies [34].

Psilocin and similar psychedelics also increased the branching of brain cells and their plasticity, both of which are crucial for mental health and cognition [39].

According to animal and cell studies, psilocybin may boost the birth of new brain cells, which is crucial for mood, cognition, and overall brain health.

8) Increases Positive Emotions and Mood

In 17 healthy people, psilocybin increased positive emotions and enhanced mood. When the participants were shown pictures of people, their attention shifted to see the positive and disregard negative emotions and facial features [40].

It boosted mood in another study of 25 healthy volunteers [41].

Its effects on mood could be important both for healthy people and those with mental health problems. People with depression and anxiety have an overactive amygdala, which triggers negative mood [42].

In smaller clinical trials, people receiving psilocybin experienced more positive emotions and were in a better mood.

9) Induces a Dream-Like State

Medium and high-dose psilocybin induced a dream-like state in eight healthy volunteers. Similar effects are known from other studies as well [43, 44].

In fact, there is a lot of similarity between the psychedelic state and the dreaming state, such as [45]:

  • An altered state of perception
  • Mental imagery
  • Emotion activation
  • Fear memory extinction.

They are closest to lucid dreaming, a mixed state of dreaming and waking consciousness.

Some scientists think that out-of-body experiences are triggered by similar pathways in the body that psilocybin and other psychedelics act on [46].

Psilocybin may induce dream-like states with altered perception, emotions, and memories. These effects could tell us a lot about dreaming and altered states of consciousness.

10) May Increase Creativity

Psilocybin and other psychedelics can increase certain measures of creativity, such as [47]:

  • Cognitive flexibility
  • Divergent thinking
  • Making more associations
  • A unique use of language and words
  • Intense mental imagery
  • Finding meaning in music or other stimuli

Back in the 60s, scientists discovered similarities between the traits of creative people and the psychedelic experience. More research is needed to see if psilocybin could be a creative nootropic since the older studies are not up to the standard of modern-day ones [47, 48].

Psilocybin and psychedelic experiences may stimulate creativity, but newer well-designed trials should confirm this effect.

11) May Alter Cognition

Although psilocybin has profound effects on perception, it doesn’t alter mental control much. In several human studies, it slowed down reactions but didn’t reduce memory accuracy. It also reduced focused attention and made concentrating more difficult [49].

In a study of 20 hallucinogen users, psilocybin did not cause cognitive impairment. It did alter working memory, though, especially in high doses (30 mg/70 kg) [50].

Psilocybin may slow down reactions and alter working memory. Based on what little research is available, its effects on cognition are mixed and require further study

12) Psychedelic Psychotherapy

Initial studies in the 50s gave birth to “psychedelic psychotherapy,” a concept that’s being researched again.

Most of the mentioned studies in this article have shown the benefits of psilocybin only in combination with psychotherapy. Psilocybin administered without psychological support and a supportive environment may have limited benefits and, in rare cases, even worsen someone’s condition [51].

Music and Psychotherapy

Psilocybin could be used with specific types of music to support meaning-making, emotional response, mental imagery in a psychotherapeutic environment. Music may play an important role in facilitating the benefits of psychedelic therapy, but more research is needed [52].

Psychotherapy and support are essential parts of psilocybin treatment. A combination with music therapy may be particularly beneficial, but more research is needed.

13) May Reduce Criminal Behavior

In prison experiments in the 60s, psilocybin with psychotherapy reduced criminal behavior. The prisoners were not offered support after release from prison, though, nor properly followed up. Whether psilocybin could reduce crime rates or not remains unknown until new studies look into it [53].

14) May Reduce Inflammation

In animals, low doses of psychedelics reduced inflammation. Substances similar to psilocybin are being explored as anti-inflammatory drugs [54].

15) May Reduce Cluster Headaches

Cluster headaches are short but extremely painful. Some people turn to psilocybin to alleviate the pain and reduce attacks [55].

In one interview, 22 out of 26 psilocybin users with cluster headaches reported improvements and half of them experienced complete remission [56].


Micro-dosing has become increasingly popular over the years, spreading over internet communities and media.

Everyone from students to businessmen is reporting that psychedelic micro-dosing improves their concentration and problem-solving skills. Others are claiming it helps them with everyday functioning. But no clinical studies have investigated this phenomenon.

One study recruited 21 people who experimented with micro-dosing. They reported improved mood, cognition, and creativity. Most considered that the beneficial effects helped them counteract anxiety and depression. Some found psychedelic micro-dosing challenging and worthless [57].

“Microdoses” are typically considered anything that is 10-20 times less than the full dose, which amounts to about 0.1–0.3 g of Psilocybe cubensis mushrooms. In the above study, microdoses didn’t alter perception or functioning. A quarter of a full dose (mini-dose) wasn’t compatible with work and everyday activities [57].

Experienced users micro-dosed for a couple of weeks or months, one to three times per week, and then stopped for a period of time. Some reported dosing on a daily basis [57].

A very low dose (0.014-0.043 mg/kg)of psilocybin was enough to improve mood in a study of 51 cancer patients [1].

Psilocybin microdosing (taking 10-20 times lower doses) is popular among recreational users. It supposedly boosts cognition and creativity without altering consciousness, but studies on this purported effect are extremely limited.

Psilocybin Side Effects

Clinical Trials

Given in a supportive, controlled, psychotherapeutic environment, psilocybin does not cause any serious adverse effects [1, 43].

Higher doses of psilocybin are more likely to cause anxiety or fear due to feelings of ego dissolution or lack of control [1].

In one trial of 18 people, higher doses caused the following [58]:

  • 39% experienced extreme fear, fear of insanity or felt trapped
  • 44% reported delusions or paranoid thinking

Ultimately, nobody reported a decrease of wellbeing or life satisfaction from the overall experience.

Other adverse effects that occurred in clinical studies include [1, 43]:

  • Dizziness
  • A slight increase in blood pressure or heart rate
  • Unusual body sensations
  • Mood changes
  • Fatigue and yawning

Psilocybin was safe in a supportive, controlled environment. It may cause dizziness, fatigue, and mood changes. High doses may cause anxiety, extreme fear, and delusions.

Recreational Use

When it comes to recreational use, several hospital reviews and clinical trials found that magic mushrooms can cause [59, 60, 61, 62, 63, 64]:

  • Unease, accompanied by anxiety, agitation, and panic reactions
  • An altered sense of time, place, and recognition, and depersonalization
  • Rarely, high blood pressure or an increased heart rate
  • Nausea/vomiting, muscle pain, fever
  • Widening of eye pupils

No deaths or serious damage has been linked to psilocybin-containing mushrooms to date. Serious damage or disease was only linked to cases of people who consumed poisonous mushrooms under the belief they are psilocybin-containing varieties. Other times, psilocybin was combined with various other substances of abuse.

Rarely, psychedelic effects, flashbacks, delusions, and cognitive changes continue long after recreational use for unknown reasons. This is called the hallucinogen persisting perception disorder (HPPD) [65, 66].

Recreational use of psilocybin may cause anxiety, panic attacks, and depersonalization. It may cause persisting hallucinations in rare cases.

People with Schizophrenia or Psychosis

In some milder ways, psilocybin mimics schizophrenia in healthy individuals. This refers to the hallucination, changes in perception, and delusions that can be ascribed to psilocybin [67, 68].

LSD and amphetamines might trigger schizophrenia in genetically-prone people, but no studies have shown that psilocybin causes or triggers psychosis or schizophrenia in any way [69].

However, the majority of clinical trials excluded people with psychosis or schizophrenia. That means we don’t know how psilocybin could affect people with schizophrenia.

Some effects of psilocybin may resemble schizophrenia, but there isn’t enough evidence to determine the risk of long-term psychosis or similar side effects.

Limitations and Caveats

Although the research about the therapeutic potential of psilocybin is growing, psilocybin remains classified as a Schedule I drug. Until more research emerges or regulations change, psilocybin use outside of a research/medical environment is not considered safe.


Psilocybin is a natural psychedelic from ‘magic’ mushrooms, which have an age-old history of ritual use among Native Americans. After the initial “boom” in the 60s, psychedelics were banned and the research stalled, only to be revived in the late 90s.

The psychedelic effects of psilocybin stem from the activation of serotonin receptors, 5-HT2A. It induces sensory and emotional changes and dissolves the sense of self. In higher doses, it causes hallucinations, dream-like states, and altered consciousness.

Insightful and mystical experiences with psilocybin may help with depression, anxiety and fear of death, OCD, and addictions. They may improve creativity, wellbeing, life attitude, and spirituality. The effective dose is 10-30 mg for a 70-kg adult, while micro-doses (10-20 times lower) are popular among some recreational users.

Psychotherapy and support amplify the benefits of psilocybin and lower the risk of side effects such as anxiety, panic attacks, and depersonalization. Some users may experience dizziness, nausea, sensory changes, and fatigue. Until we know more about its safety, recreational use of psilocybin is not recommended.

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About the Author

Ana Aleksic

Ana Aleksic

MSc (Pharmacy)
Ana received her MS in Pharmacy from the University of Belgrade.
Ana has many years of experience in clinical research and health advising. She loves communicating science and empowering people to achieve their optimal health. Ana spent years working with patients who suffer from various mental health issues and chronic health problems. She is a strong advocate of integrating scientific knowledge and holistic medicine.

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