Therapeutic potential of magic mushrooms

Mushrooms of the Psilocybe genus, known as magic mushrooms or shrooms, have a rich history of use in religious ceremonies in Central and South America, as well as other cultures around the world. Because of their hallucinogenic and psychedelic effects, although illegal, magic mushrooms are still popular for recreational consumption today. In recent decades, many studies of the therapeutic potential of their main active ingredient – psilocybin – have been ongoing.

Psilocybin

Psilocybin is the main molecule responsible for the hallucinogenic effects of Psilocybe mushrooms. It is a derivative of tryptamine, and due to the phosphate in its structure, it does not cross the blood-brain barrier and acts as a prodrug. In first-pass metabolism in the liver, it is converted into its active form- psilocin. As such, psilocin is much more lipophilic, it passes the blood-brain barrier and achieves its effects there.

Due to its structural similarity to serotonin, psilocin agonistically and selectively binds to serotonergic 5-HT_2A receptors on postsynaptic neurons. In this way, it leads to typical psychoactive and hallucinogenic effects, but also numerous other ones. By binding to 5-HT_2A receptors, psilocin stimulates the release of glutamate in the prefrontal cortex, which improves cognitive function. Also, activation of the 5-HT_2A receptor regulates the release of dopamine in the striatum responsible for the feeling of reward.

In addition to acting on the serotonergic system, psilocin has the ability to activate the brain-derived neurotrophic factor, BDNF. By binding to receptors, BDNF stimulates gene transcription and activation of NMDA and AMPA receptors in the prefrontal cortex. These changes are responsible for increased neural plasticity, regeneration and neurogenesis.

Therapeutic potentials

Addictions

Psilocybin shows promising results in research for the treatment of various types of addiction. It was discovered that in people addicted to alcohol there is a reduced activity of glutamate signaling pathways from the medial prefrontal cortex to the nucleus accumbens. This leads to an increased desire for alcohol and the creation of addiction. Psilocin stimulates the activity of the glutamate signaling pathway, reduces the need for alcohol and stimulates cognitive functions. Currently, it shows the best results in the treatment of alcohol and nicotine addiction, and the impact on addiction to cocaine, methamphetamine and opioids is also being investigated.

Major depressive disorder

Research indicates the great potential of psilocybin in the treatment of major depressive disorder. By activating 5-HT_2A receptors, psilocin causes an increased release of dopamine from the striatum, which regulates the defective reward signaling pathway in depressed patients with suicidal ideation. In addition, through the already mentioned action via BDNF, it promotes neural plasticity and connection between neurons, which is significantly reduced in depression.

Oncological patients

Cancer patients often develop mood disorders such as depression and anxiety. Conventional therapy with antidepressants and anxiolytics in many cases does not lead to significant results, and alternative therapy is used more and more. Clinical research has shown a significant improvement in the emotional state of patients on psilocybin therapy. It is believed that psilocybin, according to the aforementioned mechanisms, changes perception and promotes more positive thinking in these patients.

Safety?

Psilocybin is a psychotropic with a low potential for addiction. Despite this, it was included on the List of Drugs, Psychotropic Substances, Plants from Which Drugs Can Be Obtained and Substances That Can Be Used to Make Drugs in Croatia on the basis of the Law on the Prevention of Drug Abuse, in accordance with the UN Convention on Psychotropic Substances from 1971. Therefore, psilocybin is considered a drug with a high risk of abuse and is, for that reason, poorly accepted in medicine.

When used uncontrolled, for recreational purposes, psilocybin can lead to an unwanted emotional and physical experience called a “bad trip“. It is characterized by altered visual perception, fear, lack of coordination, depersonalization and derealization, panic attacks and paranoia. Short-term psychosis and other symptoms similar to those in patients with schizophrenia may also occur. In addition, there are physical side effects such as nausea, vomiting, headache, mydriasis and drowsiness.

Future

Current research shows promising results for the use of psilocybin in the treatment of severe disorders such as addictions, depression and anxiety in oncology patients. There are still many questions regarding the activity of psilocybin, and more research is required to determine its safe use.