Sarah Brown
Psilocybin, a substance found in certain species of mushrooms, has been consumed by humans for thousands of years, with the first European record of its use dating back to the 16th century. Also known as magic mushrooms, these fungi contain the psychoactive compounds psilocybin and psilocin, which induce hallucinations and alter consciousness. Psilocybin's effects are primarily mediated by its active metabolite, psilocin, which shares structural similarities with serotonin, an endogenous monoamine neurotransmitter involved in various cognitive functions. While psilocybin has been designated as a controlled substance due to its potential for abuse, it has also garnered scientific interest for its therapeutic potential in treating brain disorders, including depression, OCD, and addiction.
| Characteristics | Values |
|---|---|
| Neurotransmitters affected by psilocybin | Serotonin, 5-HT2A serotonin receptors, glutamate |
| Neurotransmitters chemically similar to psilocybin | Psilocin, serotonin |
| Effects | Hallucinations, altered perception, emotion, cognition, ego dissolution, reduced brain activity and connectivity, therapeutic effects on depression, anxiety, OCD, addiction, and cluster headaches |
| History of use | Used by indigenous cultures for millennia, first recorded by a Spanish priest in the 16th century, isolated by Hoffman in the 1950s, designated as a controlled substance in the US in 1968 |
| Legality | Illegal under US federal law, but decriminalized in some states and cities |
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What You'll Learn
Psilocybin is a serotonergic psychedelic
Psilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), is a naturally occurring tryptamine alkaloid and investigational drug found in more than 200 species of mushrooms, with hallucinogenic and serotonergic effects. It is a serotonergic psychedelic that acts as a prodrug of psilocin, the active form of the drug.
Psilocybin is structurally related to serotonin, a monoamine neurotransmitter that is a derivative of the amino acid tryptophan. Psilocin is a close analogue of serotonin and acts as a non-selective agonist of the serotonin receptors, including behaving as a partial agonist of the serotonin 5-HT2A receptor. It shows high affinity for most of the serotonin receptors, with the notable exception of the serotonin 5-HT3 receptor. Psilocybin's psychedelic effects are mediated specifically by agonism of the serotonin 5-HT2A receptor.
The psychedelic effects of psilocybin are believed to emerge through stimulation of serotonin 2A receptors (5-HT2ARs) by psilocybin's active metabolite, psilocin. Psilocybin intake results in dose-related 5-HT2AR occupancies, and both psilocin plasma levels and 5-HT2AR occupancy are closely associated with the subjective intensity of the psychedelic experience. Psilocybin's hallucinogenic effects and serotonin 5-HT2A receptor occupancy in humans have been found to have a significant relationship.
Psilocybin's psychedelic effects can be blocked by serotonin 5-HT2A receptor antagonists such as ketanserin and risperidone in humans. Activation of serotonin 5-HT2A receptors in layer V of the medial prefrontal cortex (mPFC) and subsequent glutamate release in this area have been specifically linked to the hallucinogenic effects of psilocybin and other serotonergic psychedelics. Serotonin 5-HT1A receptor activation appears to inhibit the hallucinogenic effects of psilocybin and other psychedelics.
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Psilocybin affects multiple neurotransmitters
Psilocybin is a naturally occurring substituted tryptamine found in certain species of mushrooms. It is structurally related to serotonin, a monoamine neurotransmitter. Psilocybin is metabolized into psilocin, which is a close analogue of serotonin and acts as a non-selective agonist of serotonin receptors.
Psilocybin has been shown to affect multiple neurotransmitters in the brain, including serotonin (5-HT), glutamate, GABA, and dopamine (DA). It has a high affinity for multiple neurotransmitter receptors, particularly the 5-HT2A serotonin receptor. By activating these receptors, psilocybin can modulate activity on excitatory pyramidal and inhibitory GABA-ergic neurons, leading to diminished brain activity and connectivity.
The activation of 5-HT2A serotonin receptors by psilocybin is believed to be responsible for its psychedelic effects. Inhibitory neuronal activity can also be augmented by psilocybin, influencing both excitatory and inhibitory neuronal circuits. This mixture of actions may contribute to the complex pharmacological effects of psilocybin and other hallucinogens.
Research has shown that psilocybin increases extracellular levels of glutamate in the frontal cortex, which may be linked to its therapeutic effects. This increase in glutamate levels has been associated with "ego dissolution," a dissolving of the subjective boundaries between the self and the wider world. Higher levels of glutamate in certain brain regions have been linked to unpleasant aspects of ego dissolution, such as a loss of control over thoughts and anxiety.
Additionally, psilocybin has been found to increase dopamine and GABA levels in the frontal cortex, further demonstrating its impact on multiple neurotransmitter systems. The exact mechanisms of psilocybin's effects are still being studied, but its ability to influence various neurotransmitters highlights the complexity of its actions in the brain.
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Psilocybin's effects on the brain
Psilocybin is a naturally occurring substituted tryptamine found in certain species of mushrooms. It is structurally related to serotonin, a monoamine neurotransmitter. Psilocybin is metabolized into psilocin, which activates neurotransmitter receptors and modulates neuronal activity. Psilocybin's effects on the brain are complex and not yet fully understood, but research suggests that it interacts with serotonin receptors and alters brain connectivity, leading to potential therapeutic benefits.
Psilocybin acts as a prodrug, meaning it is biologically inactive until it is converted by the body into psilocin, its active form. Psilocin is a close analogue of serotonin and acts as an agonist of serotonin receptors, particularly the 5-HT2A receptor. This interaction with serotonin receptors is believed to be primarily responsible for psilocybin's psychedelic effects.
Psilocybin has been shown to diminish brain activity and connectivity, particularly in the default mode network (DMN). The DMN is associated with internal thoughts, self-reflection, and a person's sense of time, space, and self. Psilocybin reduces synchronization within the DMN and between the DMN and other brain networks, such as the hippocampus. This desynchronization may contribute to the altered perceptions, sensory experiences, and sense of self commonly associated with psilocybin ingestion.
Research has also found that psilocybin increases glutamate signalling and glucose metabolism while decreasing the power of electrophysiological signals and hemodynamic fluctuations. These effects suggest that psilocybin alters the brain's energy dynamics and neuronal communication. Additionally, psilocybin may induce synaptogenesis in certain brain regions, which could be key to its potential antidepressant effects.
The therapeutic potential of psilocybin is a growing area of interest. Preliminary research suggests that it may be effective in treating mental health conditions such as depression, anxiety, and post-traumatic stress disorder (PTSD). The U.S. Food and Drug Administration has designated psilocybin as a potential "breakthrough therapy" for severe depression. However, it is important to note that psilocybin should be used under controlled conditions due to the risk of adverse effects, and ongoing research is necessary to fully understand its impact on the brain.
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Psilocybin's therapeutic potential
Psilocybin, the main psychoactive component of "magic mushrooms", has been utilised for thousands of years in mushroom-worshipping ceremonies in old-world cultures. It is a naturally occurring psychedelic compound found in certain mushrooms that allows it to penetrate the central nervous system.
Psilocybin has garnered attention for its high therapeutic potential in psychiatry and mental health treatment. Its unique mechanism of action, primarily involving 5-HT2A receptors, differs significantly from conventional antidepressants, suggesting a potential for distinct and possibly superior therapeutic effects. It is structurally related to serotonin, a monoamine neurotransmitter. Psilocybin is transformed into psilocin by dephosphorylation mediated via phosphatase enzymes. Psilocin is chemically related to serotonin and acts as a non-selective agonist of the serotonin receptors, including behaving as a partial agonist of the serotonin 5-HT2A receptor.
Psilocybin has been effectively decriminalised in a few states and cities in the US in the past few years, and a movement has begun to test it as a potential treatment for depression, anxiety, and other psychiatric conditions. In 2018, the US Food and Drug Administration designated psilocybin as a potential "breakthrough therapy" for severe depression.
Research has shown that psilocybin reduces the reactivity of the amygdala to negative stimuli, correlating with an increase in positive mood states among participants. This suggests its potential therapeutic application in the treatment of mood and depression, where emotional processing is often impaired. It is also being explored as a treatment for tobacco addiction.
The therapeutic applications of psilocybin have been explored in a diverse range of clinical studies, confirming the potential of psilocybin-assisted therapy as a promising adjunct to psychotherapy.
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Psilocybin's adverse effects
Psilocybin, the active ingredient in psychedelic mushrooms, has a range of adverse effects on the human body and mind. While it is considered to have a low level of toxicity, it can still cause unpleasant and, in some cases, dangerous side effects.
Psilocybin is a serotonergic psychedelic, which acts as a prodrug of psilocin, its active form. Psilocin is chemically related to serotonin, a monoamine neurotransmitter, and acts as an agonist of serotonin receptors, including the serotonin 5-HT2A receptor. Psilocybin's psychedelic effects are believed to be due to its activation of these serotonin receptors.
The adverse effects of psilocybin can be wide-ranging and vary between individuals. The substance can cause distorted perceptions of reality, including hallucinations, and altered senses of sight, sound, and time. Psilocybin may also induce intense emotions, ranging from euphoria and bliss to fear, terror, and anxiety. Physical side effects can include increased heart rate, high blood pressure, nausea, vomiting, and headache. In some cases, psilocybin can lead to extreme anxiety, paranoia, panic, or even short-term psychosis, known as a "bad trip."
Higher doses of psilocybin are associated with an increased risk of negative experiences, and pre-existing mental health conditions may also elevate this risk. The substance can cause psychological distress, which may persist even after the acute effects have worn off. However, it is important to note that the side effects of psilocybin are typically mild to moderate and often resolve with time.
While psilocybin has a low potential for causing fatal events, it can still lead to unpredictable and potentially dangerous behaviour, which may result in injuries. Additionally, there is a risk of misidentifying mushrooms, as dried hallucinogenic mushrooms may contain other substances, and some mushrooms are toxic.
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Frequently asked questions
Psilocybin mushrooms, also known as "magic mushrooms", are hallucinogenic fungi that contain the compounds psilocybin and psilocin.
Yes, psilocybin and psilocin are both similar in structure to serotonin (5-HT), an endogenous monoamine neurotransmitter.
Psilocybin and psilocin activate serotonin 5-HT2A receptors in the brain, which are thought to be their main target. This activation decreases brain "connectivity" and allows the brain to transition between different activity states more easily.
Psilocybin mushrooms can induce an altered state of consciousness, similar to acute psychosis, with hallucinations, loss of ego boundaries, and alterations in perception, cognition, and time perception. They have been studied for their therapeutic potential in treating brain disorders and conditions such as depression, OCD, addiction, and cluster headaches.
Psilocybin mushrooms can have adverse effects, including "bad trips" or panic reactions, which may lead to anxiety, confusion, agitation, or disorientation. They are also contraindicated for pregnant or breastfeeding women due to insufficient research. Additionally, they are illegal in many places due to their classification as Schedule I controlled substances.
