Psilocybin is a naturally occurring psychedelic substance from ‘magic’ mushrooms with a wide range of psychoactive effects. With the modern revival of psychedelic research, it’s being investigated for helping people overcome depression and anxiety. Read on to learn about the intriguing history of its use and find out about all its known effects and side effects.

What is Psilocybin?

Psilocybin (chemically known as 4-phosphorryloxy-N, N-dimethyltryptamine) is a classical 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 [R].

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 [R, R].

Despite the recent psychedelic research renaissance, 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 all the efforts that got us to our current state of scientific knowledge about it.

If you’re just interested in the research and effects, skip to the Benefits and Effects of Psilocybin section of this article. But if you’re looking to dig deeper and understand the whole story, you may appreciate the current research efforts even more.

The Story Of Magic Mushrooms

Beginnings

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 [R, R, R].

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 [R].

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 in the late 50s (from P. mexicana). This was the same Hoffman that discovered LSD – better known as the “father of LSD”. He later summarized his thoughts about psychedelics, including LSD and psilocybin in the book “LSD – My Problem Child” [R+, R].

The 60s and 70s

In the 60s, psilocybin research boomed. Over 1,000 studies were published. It was used in both experimental research and psychotherapy [R].

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 extent psychedelics popularity is echoed in the fact that the name of the band 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. Psychedelic research became marginalized, funding was cut, and all human experiments came to a halt [R+, R].

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 [R+].

Although psilocybin remains classified as a Schedule I drug, its therapeutic potential is becoming hard to ignore. Researchers and authorities are also becoming aware of the importance of providing psychotherapy alongside psilocybin for safe and more efficient use with fewer side effects [R+, R].

And recently, the FDA approved a clinical trial of psilocybin for treatment-resistant depression, which will be conducted in 2019 (by COMPASS pathways). 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.

Mechanism of Action

As a classic psychedelic, psilocybin activates specific serotonin receptors called 5-HT2A [R]. This is what causes hallucinogenic effects. Psilocybin also slightly activates dopamine pathways in the brain and the sympathetic, fight-or-flight system in higher doses [R+, R].

Ego Dissolution

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

In a brain imaging studies in 15 healthy volunteers, psilocybin decreased connectivity in the brain’s default mode network. This system is active when a person is thinking about oneself, the past, the future, and during a kind of mind wandering. Meditation also reduces activity in this system. 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” [R, R, R].

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. 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 vast doors of perception, according to him [R].

Aldous Huxley Valve
Huxley’s “cerebral reducing valve”, taken from Link R. Swanson’s “Unifying Theories of Psychedelic Drug Effects”

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 [R].

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. 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 [R].

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 altered state of consciousness, marked by [R]:

  • Oceanic boundlessness, euphoria, and depersonalization
  • Ego Dissolution, which can potentially be anxiety-provoking
  • Visual hallucinations and synesthesia
  • 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. Psilocybin also slightly increased blood pressure [R].

Metabolism

If taken orally, Psilocybin needs to be converted to Psilocin, its active form, in the liver. Psilocin then enters the bloodstream and reaches the brain [R].

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 [R, R].

Psilocybin Content in Mushrooms

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

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.

Psilocybin Dosage

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 anything higher than 25 mg [R+].

Types of Psychedelic Mushrooms

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

  • 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 LSD, and
  • 66 times more potent than mescaline

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

Benefits and Effects of Psilocybin

1) Psilocybin Reduces Depression Long-term

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, first at a lower dose (10 mg) and one week later at a higher dose (25 mg). Psilocybin also improved anxiety and the ability to feel pleasure in life [R].

In another trial, psilocybin improved symptoms in 15 people with treatment-resistant depression. Just 1 week after the session, they were less pessimistic and their mood improved. Overall, psilocybin along with psychological support enables them to gain a more positive and accurate outlook on life [R].

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

2) Psilocybin Helps People with Cancer and Terminal Illness

The existential anxiety people with life-threatening diseases face is often overlooked, although it’s linked to poor mental health and clinical outcomes. The power of psilocybin to help people with advanced cancer and terminal illness lies exactly in its ability to drastically change their outlook on life for the better. Finding meaning may transform despair into a positive self-exploration [R, R].

Given in a safe and supportive environment, psilocybin sessions can help people regain a sense of meaning, lessen death anxiety, and improve mood long-term [R, R, R].

In a trial of 12 people with advanced cancer, a modest dose of psilocybin improved mood 2 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 [R].

And in another trial of 51 cancer patients with depression, high dose psilocybin (20-30 mg) reduced depressed mood, 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 [R].

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 [R].

Since psilocybin can improve mood and anxiety in people with life-threatening diseases, scientists think it may also help with chronic pain. No studies have investigated this yet, though [R].

3) Psilocybin Improves Obsessive-Compulsive Disorder

Psilocybin reduced obsessive-compulsive disorder (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 microg/kg) and high doses (300 microg/kg) [R].

It also reduced OCD symptoms in mice [R].

4) Psilocybin 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” [R].

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 [R, R].

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 4 were maintained 6 months after the initial sessions. The more intense the psilocybin experience was, the stronger it affected abstinence and reduced craving [R].

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 weeks cessation period. 6 months later, 12 of them completely quit smoking. Such a success rate (80%) is much higher than any other therapy [R].

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

5) Psilocybin and Mystical Experiences

In many of the studies above, mystical experiences elicited by psilocybin were linked to 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 [R].

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

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 [R, R].

In one study, 30 religious or spiritual people who never took psychedelics before underwent 8-hour psilocybin sessions (30mg/70kg). During the sessions, they were told to direct their attention inward and close their eyes. After 2 months, they rated the psilocybin experience as one of great personal meaning and spiritual significance. They even attributed sustained positive lifestyle changes to these sessions [R].

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

6) Psilocybin May Help with PTSD

The potential of psilocybin to help people with PTSD is still limited to animal studies.

In mice, psilocybin reduced fear in traumatized mice. These mice developed PTSD symptoms from being exposed to a sound signaling electroshocks. Much like people with PTSD, they would start to react just to the sound, even without the electroshocks. Lower doses of psilocybin helped mice transcend the fear even better than high doses [R].

In this study, Psilocybin also increased neurogenesis, the growth and repair of brain cells in the hippocampus. The hippocampus is a brain region especially important for emotion, mood, and memory. If neurogenesis is blocked in mice, fear intensifies. In imaging studies, people with PTSD had smaller hippocampi [R, R, R].

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

7) Psilocybin and Neurogenesis

Neurogenesis is not important only for PTSD. Growing your brain may also help with depression, anxiety, cognition, heal from brain injury, and promote overall brain health.

Psilocybin could increase neurogenesis in traumatized mice. But other similar psychedelics also increased both neurogenesis and new brain connections – synapses – in animal and cellular studies [R].

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

8) Psilocybin Increases Positive Emotions

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 [R].

In brain imaging study of 25 healthy volunteers, Psilocybin enhanced mood by decreasing the reactivity of amygdala to negative stimuli. This way, psilocybin increased positive mood processing [R].

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 moods [R].

9) Psilocybin Induces a Dream-like State

Medium and high dose psilocybin induced a dream-like state in one study of 8 healthy volunteers. Similar effects are known from other studies as well [R, R].

In fact, there is a lot of similarity between the psychedelic state and the dreaming state. The similarities include an altered state of perception, self and body, mental imagery, emotion activation, and fear memory extinction. They are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness [R].

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

More psilocybin research could potentially tell us a lot about dreaming and how the brain works during altered states of consciousness.

10) Psilocybin May Increase Creativity

Psilocybin and other psychedelics can increase certain measures of creativity, such as cognitive flexibility, divergent thinking, making more associations, unique use of language and words, intense mental imagery, and finding meaning in music or other stimuli [R].

Back in the 60s, scientists discovered similarities between the traits of creative people and the psychological 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 [R, R].

11) Psilocybin Alters Cognition

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

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) [R]

12) Psychedelic Psychotherapy with Psilocybin

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 very rare cases, even worsen someone’s condition [R].

Music and Psilocybin Psychotherapy

Psilocybin could be used alongside specific types of music to support meaning-making, emotional response, and guide mental imagery in a psychotherapeutic environment. Music may play an important role in facilitating beneficial outcomes of psychedelic therapy, but more research is needed [R].

13) Psilocybin May Reduce Criminal Behavior

In prison experiments in the 60s, psilocybin with psychotherapy reduced criminal behavior short-term. The prisoners were not offered support after release from prison, though, nor properly followed up. So whether psilocybin could reduce crime rates or not is unknown, at least until new studies look into the possibility [R].

14) Psilocybin Microdosing

Microdosing has become increasingly popular over the years, spreading over internet communities and media. Everyone from students to businessmen is reporting that psychedelic microdosing 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 experiment with microdosing. They reported improved mood, cognition, and creativity. Most considered that the beneficial effects helped them counteract anxiety and depression. Some found psychedelic microdosing challenging and didn’t consider it worth continuing [R].

“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 noticeably. A quarter of a full dose (regarded as a mini-dose rather than a microdose) wasn’t compatible with work and everyday activities [R].

Experienced users microdosed 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 [R].

In many clinical trials, low doses of psilocybin only caused mild changes in perception and no hallucinations. A very low dose (0.014-0.043 mg/kg) was enough to improve mood in a study of 51 cancer patients [R].

15) Psilocybin May Reduce Inflammation

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

16) Psilocybin May Reduce Cluster Headaches

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

When 53 people with cluster headaches who had used psilocybin or LSD were interviewed, 22 out of 26 psilocybin users reported improvements, and half of them that the headaches went away completely [R].

Dangers and Side Effects of Psilocybin

Clinical Trials

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

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

In one trial of 18 people, the following happened [R]:

  • 39% experienced extreme fear, fear of insanity or felt trapped at some time during the session. This happened to 6 of 7 people in the high dose group (30 mg/70 kg) and only to one in the lower dose (20 mg/70 kg).
  • 44% reported delusions or paranoid thinking sometime during the session. This occurred to 7 of 8 people in the high dose group, and only to 1 in the low dose.

Ultimately, nobody rated the overall experience as having decreased her or his sense of well-being or life satisfaction.

Other adverse effects that occurred during sessions in clinical studies include  [R, R]:

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

Recreational Use

When it comes to recreational use, several hospital reviews and clinical trials found that magic mushrooms can cause [R, R, R, R, R, R]:

  • Unease, accompanied by anxiety, agitation, and panic reactions
  • An altered sense of time, place, and recognition, and depersonalization, which can trigger anxiety or paranoia if in an unsafe environment
  • Rarely, high blood pressure or an increased heart rate
  • Nausea/vomiting, muscles pain, fever
  • Mydriasis, a 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 that 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 “hallucinogen persisting perception disorder” [R, R].

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 [R, R].

In some analyses, LSD and amphetamines could trigger schizophrenia in genetically-prone people. But no studies have shown that psilocybin causes or triggers psychosis or schizophrenia in any way [R].

However, the majority of clinical trials excluded people with psychosis or schizophrenia. That means that we simply don’t know how psilocybin could affect people with schizophrenia. Experiences usually considered positive during psilocybin sessions are a source of serious mental struggles for people with psychosis.

Gene expression

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

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.

About the Author

Ana Aleksic - MS (PHARMACY) - Writer at Selfhacked

Ana Aleksic, MSc (Pharmacy)

MS (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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