Psilocybin therapy

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Psilocybin-containing mushrooms Gymnopilus purpuratus in New Zealand.jpg
Psilocybin-containing mushrooms

Psilocybin therapy is the use of psilocybin (the psychoactive ingredient in psilocybin mushrooms) in treating a range of mental health conditions, such as depression, anxiety, addictions, [1] obsessive compulsive disorder (OCD), and psychosis. [2] It is one of several forms of psychedelic therapy under study. Psilocybin was popularized as a psychedelic recreational drug in the 1970s and was classified as a Schedule I drug by the DEA. Research on psilocybin as a medical treatment was restricted until the 1990s because of the sociocultural fear of dependence on this drug. As of 2022, psilocybin is the most commonly researched psychedelic due to its safety and low potential for abuse and dependence. [2] Clinical trials are being conducted at universities and there is evidence confirming the use of psilocybin in the treatment of depression, post-traumatic stress disorder (PTSD) and end of life anxiety. [3]

Contents

History

The first historical record of psilocybin use dates back to Mesoamerica. A Codex known as the "Yuta Tnoho" or "Vindobonensis Mexicanus I" that belonged to the Mixtec culture in the 1500s BCE depicted religious and medicinal ritual ingestion of psilocybin-containing mushrooms. [4] [5] Fungi were a prominent feature in Mixtec cultures, with over 5,000 different names of common edible mushrooms known across Mexican languages. [5]

Despite colonists efforts to eradicate these ceremonies, ritualistic consumption of psilocybe mushrooms continues into modern spiritual and medicinal practice [6] . The hallucinations produced by the psilocybin induces a trance-like state that is believed to allow the soul to disconnect from the body, resulting in healing and spiritual enlightenment. [4]

Traditional psilocybin use was typically achieved through the consumption of dried or fresh psilocybin containing mushrooms. [6] However, in 1959, Albert Hofmann, a Swiss chemist, became the first person to extract pure psilocybin from the mushroom Psilocybe mexicana . Sandoz, the company that employed Hofmann, then began to sell the active compound to clinicians as an aid in psychedelic psychotherapy. [7]

Albert Hofmann's discovery of psilocybin played a pivotal role in catalyzing the Psychedelic Era, a cultural phenomenon that unfolded during the 1960s and 1970s. This era witnessed significant societal, musical, and artistic transformations, many of which were heavily influenced by the use of psychedelic substances, including psilocybin. At this time though, there was very little known about psychedelics and their long-term effects

In August 1960, Timothy Leary conducted a self-experiment using psilocybin mushrooms. After trying pure, extracted psilocybin, he and Dr. Richard Alpert tested whether it could help reduce recidivism rate and constitute an effective psychotherapy aid. In 1963, Leary and Alpert were suspended from their jobs at Harvard University, due to irresponsible and dangerous experimentation with psilocybin mushrooms. [8] Psilocybin research in the United States ended in 1970 when the use and possession of psilocybin mushrooms became illegal. [9] [10]

In 2018–19, the United States Food and Drug Administration (FDA) granted breakthrough therapy designation to facilitate further research for psilocybin in the possible treatment of depressive disorders. [11]

Neuroscience and Pharmacology

"Your brain on psilocybin" Your brain on psilocybin.jpg
"Your brain on psilocybin"

Psilocybin is the main psychoactive compound in the mushroom genus Psilocybe. Psilocybin (O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine) and its active metabolite psilocin (4-hydroxy-N,N-dimethyltryptamine) are part of a group of tryptamine/indolamine hallucinogens that are related to serotonin.

Psilocybin is a prodrug for psilocin, meaning that psilocybin is de-phosphorylated in the GI tract of the body into psilocin so it can cross the blood-brain barrier. Psilocyn is a selective agonist of the 5HT receptors, specifically 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, and 5-HT2C. [12] Although to a lesser extent, psilocin also bonds to dopamine-3 receptors, which may aid in treating substance use disorders. [2]

Nausea, vomiting, muscle weakness, and lack of coordination are some of the physical side effects. Hallucinations and an inability to distinguish fiction from reality are among the psychological effects of psilocybin use. Panic attacks and psychotic-like episodes are also possible, especially if a high amount is consumed. [13]

Chemical compound of psilocin Psilocin.svg
Chemical compound of psilocin
Chemical compound of psilocybin Psilocybin, Kekule, skeletal formula of canonical psilocybin.svg
Chemical compound of psilocybin

Further, psilocin has some effect on the amygdala and hypothalamus that aids in circadian rhythm regulation. [2]

Research

Use of psilocybin for treating depression is under preliminary research. [14]

Safety

In the United States, psilocybin and other psychedelic drugs have been heavily criminalized since the 1960s, classified as a Schedule I substance under the federal Controlled Substances Act (Schedule I is defined as a substance having substantial potential for abuse, absence of adequate safety evidence, and no currently accepted clinical uses for therapy). [15] Prior to the 1960s, psychedelics were not considered "hard drugs," and were studied extensively for their immense medicinal potential for treating psychiatric disorders; the criminalization of psychedelics via their classification as Schedule I substances is inconsistent with over 70 years of scientific and medical research and was contrary to all available evidence at the time. [16] According to the largest controlled clinical study of psilocybin to date at King's College London, volunteers who received doses of psilocybin experienced no serious adverse side effects, experiencing some changes in mood and perception but no negative effects on cognitive or emotional functioning. [17]

An important area of concern is identifying appropriate candidates for psilocybin therapy. In patients with depression, it will be important to consider psychological, social, and biological factors. These factors may predispose them to negative reactions to the substance and result in adverse events. Research into the effects of psilocybin on those experiencing suicidality varies. While some research found that psilocybin therapy could be destabilizing and upsetting to these patients, other studies found psilocybin treatment resulted in reduced suicidal behavior and thoughts. [14]

According to the Controlled Substances Act, psilocybin is classified as a Schedule I drug. Heroin and LSD are examples of Schedule I substances, which have a high potential for misuse and have no accepted medical use in the US. [18]

While the use and possession of psilocybin in the United States is still illegal under federal law, [19] several U.S. cities and a few states have decriminalized its use.

In Australia, authorized psychiatrists can prescribe psilocybin for treatment-resistant depression. [20]

They are currently petitions being made advocating for general considerations to sponsors developing psychedelic drugs for treatment of medical conditions (e.g., psychiatric disorders, substance use disorders). [21] For psychedelic drugs that are Schedule I controlled substances, activities associated with IND (Investigational New Drug) must comply with the applicable Drug Enforcement Administration (DEA) regulations for research, manufacturing, importation/exportation, handling, and storage. [21]

Related Research Articles

<span class="mw-page-title-main">Psilocybin</span> Chemical compound found in some species of mushrooms

Psilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), and formerly sold under the brand name Indocybin, is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi. Psilocybin is itself biologically inactive but is quickly converted by the body to psilocin, which has mind-altering effects similar, in some aspects, to those of other classical psychedelics. Effects include euphoria, visual and mental hallucinations, changes in perception, a distorted sense of time, and perceived spiritual experiences. It can also cause adverse reactions such as nausea and panic attacks.

<span class="mw-page-title-main">Psychedelic drug</span> Hallucinogenic class of psychoactive drug

Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states and a perceived "expansion of consciousness". Also referred to as classic hallucinogens or serotonergic hallucinogens, the term psychedelic is sometimes used more broadly to include various types of hallucinogens, such as those which are atypical or adjacent to psychedelia like salvia and MDMA, respectively.

<i>Psilocybe cubensis</i> Species of fungus

Psilocybe cubensis, commonly known as the magic mushroom, shroom, golden halo, golden teacher, cube, or gold cap, is a species of psilocybin mushroom of moderate potency whose principal active compounds are psilocybin and psilocin. It belongs to the fungus family Hymenogastraceae and was previously known as Stropharia cubensis. It is the best-known psilocybin mushroom due to its wide distribution and ease of cultivation.

<span class="mw-page-title-main">Psilocybin mushroom</span> Mushrooms containing psychoactive indole alkaloids

Psilocybin mushrooms, commonly known as magic mushrooms,shrooms, or broadly as hallucinogenic mushrooms, are a polyphyletic informal group of fungi that contain psilocybin, which turns into psilocin upon ingestion. The most potent species are members of genus Psilocybe, such as P. azurescens, P. semilanceata, and P. cyanescens, but psilocybin has also been isolated from approximately a dozen other genera, including Panaeolus, Inocybe, Pluteus, Gymnopilus, and Pholiotina.

<i>Psilocybe</i> Genus of fungi

Psilocybe is a genus of gilled mushrooms, growing worldwide, in the family Hymenogastraceae. Many species contain the psychedelic compounds psilocybin and psilocin.

<i>Psilocybe cyanescens</i> Species of fungus

Psilocybe cyanescens, commonly known as the wavy cap or potent psilocybe, is a species of potent psychedelic mushroom. The main compounds responsible for its psychedelic effects are psilocybin and psilocin. It belongs to the family Hymenogastraceae. A formal description of the species was published by Elsie Wakefield in 1946 in the Transactions of the British Mycological Society, based on a specimen she had recently collected at Kew Gardens. She had begun collecting the species as early as 1910. The mushroom is not generally regarded as being physically dangerous to adults. Since all the psychoactive compounds in P. cyanescens are water-soluble, the fruiting bodies can be rendered non-psychoactive through parboiling, allowing their culinary use. However, since most people find them overly bitter and they are too small to have great nutritive value, this is not frequently done.

Psychedelic therapy refers to the proposed use of psychedelic drugs, such as psilocybin, ayahuasca, LSD, psilocin, mescaline (peyote), DMT, 5-MeO-DMT,Ibogaine,MDMA, to treat mental disorders. As of 2021, psychedelic drugs are controlled substances in most countries and psychedelic therapy is not legally available outside clinical trials, with some exceptions.

<span class="mw-page-title-main">Psilocin</span> Chemical compound

Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin. Psilocin is a Schedule I drug under the Convention on Psychotropic Substances. Acting on the serotonin 5-HT2A receptors, psilocin's psychedelic effects are directly correlated with the drug's occupancy at these receptor sites. The subjective mind-altering effects of psilocin are highly variable and are said to resemble those of lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT).

<span class="mw-page-title-main">Psychedelic experience</span> Altered state of consciousness brought upon by the consumption of psychoactive substances

A psychedelic experience is a temporary altered state of consciousness induced by the consumption of a psychedelic substance. For example, an acid trip is a psychedelic experience brought on by the use of LSD, while a mushroom trip is a psychedelic experience brought on by the use of psilocybin. Psychedelic experiences feature alterations in normal perception such as visual distortions and a subjective loss of self-identity, sometimes interpreted as mystical experiences. Psychedelic experiences lack predictability, as they can range from being highly pleasurable to frightening. The outcome of a psychedelic experience is heavily influenced by the person's mood, personality, expectations, and environment.

<i>Psilocybe tampanensis</i> Psychedelic mushroom in the family Hymenogastraceae

Psilocybe tampanensis is a very rare psychedelic mushroom in the family Hymenogastraceae. Originally collected in the wild in a sandy meadow near Tampa, Florida, in 1977, the fungus would not be found in Florida again until 44 years later. The original Florida specimen was cloned, and descendants remain in wide circulation. The fruit bodies (mushrooms) produced by the fungus are yellowish-brown in color with convex to conic caps up to 2.4 cm (0.9 in) in diameter atop a thin stem up to 6 cm (2.4 in) long. Psilocybe tampanensis forms psychoactive truffle-like sclerotia that are known and sold under the nickname "philosopher's stones". The fruit bodies and sclerotia are consumed by some for recreational or entheogenic purposes. In nature, sclerotia are produced by the fungus as a rare form of protection from wildfires and other natural disasters.

<span class="mw-page-title-main">Ethocybin</span> Chemical compound

Ethocybin is a homologue of the mushroom alkaloid psilocybin, and a semi-synthetic psychedelic alkaloid of the tryptamine family. Effects of ethocybin are comparable to those of a shorter LSD or psilocybin trip, although intensity and duration vary depending on dosage, individual physiology, and set and setting.

<span class="mw-page-title-main">Stoned ape theory</span> Theory of cognitive development in early humans

The stoned ape theory is a controversial hypothesis first proposed by American ethnobotanist and mystic Terence McKenna in his 1992 book Food of the Gods. The idea claims that the transition from Homo erectus to Homo sapiens and the cognitive revolution was caused by the addition of psilocybin mushrooms, specifically the mushroom Psilocybe cubensis, into the human diet around 100,000 years ago. Using evidence largely based on studies from Roland L. Fischer et al. from the 1960s and 1970s, he attributed much of the mental strides made by humans during the cognitive revolution to the effects of psilocybin intake found by Fischer.

<i>Psilocybe zapotecorum</i> Species of fungus

Psilocybe zapotecorum is a psilocybin mushroom which has psilocybin and psilocin as main active compounds. It is in the section Zapotecorum.

<span class="mw-page-title-main">Drug policy of California</span> Overview of the drug policy of the U.S. state of California

Drug policy of California refers to the policy on various classes and kinds of drugs in the U.S. state of California. Cannabis possession has been legalized with the Adult Use of Marijuana Act, passed in November 2016, with recreational sales starting January of the next year. With respect to many controlled substances, terms such as illegal and prohibited do not include their authorized possession or sale as laid out by applicable laws.

<span class="mw-page-title-main">Legal status of psilocybin mushrooms</span>

The legal status of unauthorised actions with psilocybin mushrooms varies worldwide. Psilocybin and psilocin are listed as Schedule I drugs under the United Nations 1971 Convention on Psychotropic Substances. Schedule I drugs are defined as drugs with a high potential for abuse or drugs that have no recognized medical uses. However, psilocybin mushrooms have had numerous medicinal and religious uses in dozens of cultures throughout history and have a significantly lower potential for abuse than other Schedule I drugs.

<span class="mw-page-title-main">Magic truffle</span> Hallucinogenic mushroom preparation

Magic truffles are the sclerotia of psilocybin mushrooms that are not technically the same as "mushrooms". They are masses of mycelium that contain the fruiting body which contains the hallucinogenic chemicals psilocybin and psilocin.

Psychoplastogens are a group of small molecule drugs that produce rapid and sustained effects on neuronal structure and function, intended to manifest therapeutic benefit after a single administration. Several existing psychoplastogens have been identified and their therapeutic effects demonstrated; several are presently at various stages of development as medications including ketamine, MDMA, scopolamine, and the serotonergic psychedelics, including LSD, psilocin, DMT, and 5-MeO-DMT. Compounds of this sort are being explored as therapeutics for a variety of brain disorders including depression, addiction, and PTSD. The ability to rapidly promote neuronal changes via mechanisms of neuroplasticity was recently discovered as the common therapeutic activity and mechanism of action.

Psychedelic treatments for trauma-related disorders are the use of psychedelic substances, either alone or used in conjunction with psychotherapy, to treat trauma-related disorders. Trauma-related disorders, such as post-traumatic stress disorder (PTSD), have a lifetime prevalence of around 8% in the US population. However, even though trauma-related disorders can hinder the everyday life of individuals with them, less than 50% of patients who meet criteria for PTSD diagnosis receive proper treatment. Psychotherapy is an effective treatment for trauma-related disorders. A meta-analysis of treatment outcomes has shown that 67% of patients who completed treatment for PTSD no longer met diagnostic criteria for PTSD. For those seeking evidence-based psychotherapy treatment, it is estimated that 22-24% will drop out of their treatment. In addition to psychotherapy, pharmacotherapy (medication) is an option for treating PTSD; however, research has found that pharmacotherapy is only effective for about 59% of patients. Although both forms of treatment are effective for many patients, high dropout rates of psychotherapy and treatment-resistant forms of PTSD have led to increased research in other possible forms of treatment. One such form is the use of psychedelics.

<small>L</small>-Tryptophan decarboxylase Enzyme

L-Tryptophan decarboxylase is an enzyme distinguished by the substrate L-tryptophan.

References

  1. ↑ Van Court, R.C.; Wiseman, M.S.; Meyer, K.W.; Ballhorn, D.J.; Amses, K.R.; Slot, J.C.; Dentinger, B.T.M.; Garibay-Orijel, R.; Uehling, J.K. (April 2022). "Diversity, biology, and history of psilocybin-containing fungi: Suggestions for research and technological development". Fungal Biology. 126 (4): 308–319. Bibcode:2022FunB..126..308V. doi: 10.1016/j.funbio.2022.01.003 . PMID   35314062.
  2. 1 2 3 4 Geiger, Haden A.; Wurst, Madeline G.; Daniels, R. Nathan (2018-10-17). "DARK Classics in Chemical Neuroscience: Psilocybin". ACS Chemical Neuroscience. 9 (10): 2438–2447. doi:10.1021/acschemneuro.8b00186. ISSN   1948-7193. PMID   29956917. S2CID   49591766.
  3. ↑ Marks, Mason; Cohen, Glen (October 4, 2021). "Psychedelic therapy: A roadmap for wider acceptance and utilization". Nature Medicine. 27 (10): 1669–1671. doi: 10.1038/s41591-021-01530-3 . PMID   34608331. S2CID   238355863.
  4. 1 2 Van Court, R.C.; Wiseman, M.S.; Meyer, K.W.; Ballhorn, D.J.; Amses, K.R.; Slot, J.C.; Dentinger, B.T.M.; Garibay-Orijel, R.; Uehling, J.K. (April 2022). "Diversity, biology, and history of psilocybin-containing fungi: Suggestions for research and technological development". Fungal Biology. 126 (4): 308–319. Bibcode:2022FunB..126..308V. doi: 10.1016/j.funbio.2022.01.003 . PMID   35314062.
  5. 1 2 Hernández-Santiago, Faustino; Martínez-Reyes, Magdalena; Pérez-Moreno, Jesús; Mata, Gerardo; Hernández-Santiago, Faustino; Martínez-Reyes, Magdalena; Pérez-Moreno, Jesús; Mata, Gerardo (00/2017). "Pictographic representation of the first dawn and its association with entheogenic mushrooms in a 16th century Mixtec Mesoamerican Codex". Revista mexicana de micología. 46: 19–28. ISSN   0187-3180.{{cite journal}}: Check date values in: |date= (help)
  6. 1 2 Van Court, R. C.; Wiseman, M. S.; Meyer, K. W.; Ballhorn, D. J.; Amses, K. R.; Slot, J. C.; Dentinger, B. T. M.; Garibay-Orijel, R.; Uehling, J. K. (2022-04-01). "Diversity, biology, and history of psilocybin-containing fungi: Suggestions for research and technological development". Fungal Biology. 126 (4): 308–319. doi:10.1016/j.funbio.2022.01.003. ISSN   1878-6146.
  7. ↑ Daniel, Jeremy; Haberman, Margaret (2018-03-23). "Clinical potential of psilocybin as a treatment for mental health conditions". The Mental Health Clinician. 7 (1): 24–28. doi:10.9740/mhc.2017.01.024. ISSN   2168-9709. PMC   6007659 . PMID   29955494.
  8. ↑ "When Did Psilocybin Mushrooms First Appear In Human Culture?". The Third Wave. 2016-07-27. Retrieved 2018-05-15.
  9. ↑ "Psilocybin" (PDF). Drug Enforcement Agency, US Department of Justice. 1 April 2020. Retrieved 24 March 2021.
  10. ↑ Daniel, Jeremy; Haberman, Margaret (2018-03-23). "Clinical potential of psilocybin as a treatment for mental health conditions". The Mental Health Clinician. 7 (1): 24–28. doi:10.9740/mhc.2017.01.024. ISSN   2168-9709. PMC   6007659 . PMID   29955494.
  11. ↑ "FDA grants Breakthrough Therapy Designation to Usona Institute's psilocybin program for major depressive disorder". www.businesswire.com. 2019-11-22. Retrieved 2019-11-25.
  12. ↑ Jann, Michael W (March 9, 2021). "Psilocybin Revisited: The Science Behind the Drug and Its Surprising Therapeutic Potential". Psychiatric Times. 38 (3).
  13. ↑ "Psilocybin - Alcohol and Drug Foundation". adf.org.au. Retrieved 2023-12-06.
  14. 1 2 Haikazian, Sipan; Chen-Li, David C. J.; Johnson, Danica E.; Fancy, Farhan; Levinta, Anastasia; Husain, M. Ishrat; Mansur, Rodrigo B.; McIntyre, Roger S.; Rosenblat, Joshua D. (2023-11-01). "Psilocybin-assisted therapy for depression: A systematic review and meta-analysis". Psychiatry Research. 329: 115531. doi:10.1016/j.psychres.2023.115531. ISSN   0165-1781.
  15. ↑ "Psilocybin (magic mushrooms)". Drugs.com. 2021. Retrieved 24 March 2021.
  16. ↑ Sproul, Conrad (2021). ""Don't Kill My Buzz, Man!" - Explaining the Criminalization of Psychedelic Drugs". Oregon Undergraduate Research Journal. 19 (1): 1–53. doi: 10.5399/uo/ourj.19.1.2 . S2CID   237845545.
  17. ↑ "Magic mushroom compound psilocybin found safe for consumption in largest ever controlled study". The Independent. 2019-12-18. Retrieved 2022-08-24.
  18. ↑ "Psilocybin Fast Facts". www.justice.gov. Retrieved 2023-12-06.
  19. ↑ "Psilocybin Fast Facts". www.justice.gov.
  20. ↑ Shepherd, Tory (2023-02-03). "Australia to allow prescription of MDMA and psilocybin for treatment-resistant mental illnesses". The Guardian. ISSN   0261-3077 . Retrieved 2023-10-26.
  21. 1 2 Research, Center for Drug Evaluation and (2023-06-26). "Psychedelic Drugs: Considerations for Clinical Investigations". www.fda.gov. Retrieved 2023-12-06.
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