Psilocin

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Summary sheet: Psilocin
Not to be confused with Psilocybin Mushrooms.
Psilocin
Molecular structure of 4-HO-DMT
Psilocin.svg
Chemical Nomenclature
Common names Psilocin, Psilocine, Psilocyn, Psilotsin, 4-HO-DMT, 4-OH-DMT
Substitutive name 4-hydroxy-N,N-dimethyltryptamine
Systematic name 3-[2-(dimethylamino)ethyl]-1H-indol-4-ol
Class Membership
Psychoactive class Psychedelic
Chemical class Tryptamine
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.



Oral
Dosage
Threshold 5 - 10 mg
Light 10 - 15 mg
Common 15 - 25 mg
Strong 25 - 40 mg
Heavy 40 mg +
Duration
Total 4 - 6 hours
Onset 20 - 45 minutes
Peak 2 - 3 hours
Offset 1.5 - 2 hours
After effects 4 - 24 hours









DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

4-Hydroxy-N,N-dimethyltryptamine (commonly known as Psilocin, Psilocine, Psilocyn, Psilotsin, or abbreviated as 4-HO-DMT and 4-OH-DMT) is a naturally-occurring psychedelic substance of the tryptamine chemical class that produces what are now typically considered to be "classical psychedelic" effects (i.e. those associated with LSD, Mescaline, Psilocybin and DMT) when administered. It is known as the primary psychoactive constituent in certain species of psilocybin-containing mushrooms, and as a closely related structural analog of the powerful visionary entheogen DMT (also known as N,N-dimethyltryptamine), which it shares many core subjective features with.

Psilocin and its phosphorylated inactive precursor (i.e. prodrug) psilocybin were first isolated and named in 1958 by Swiss chemist Albert Hofmann. Hofmann obtained the chemicals from laboratory-grown specimens of the entheogenic mushroom Psilocybe mexicana before proceeding to find their synthetic routes.[1] Psilocin's psychoactivity is thought to emerge from the close structural similarities that it shares on a molecular level with serotonin (5-hydroxy-trypamine), which enables it to interact with a wide range of serotonin receptor sites distributed throughout the brain and central nervous system that are integral for sensory input processing and higher-order cognitive processes.[citation needed] It is believed to exert most of its characteristic psychedelic activity by binding to serotonin-2A or 5-HT-2A receptors with an atypically high degree of selectivity[citation needed] (please see this page for more information).

Notably, while psilocin naturally co-occurs with psilocybin in significant amounts of most psychedelic or psilocybin-containing mushrooms, it is only ever rarely encountered in its isolated synthetic form. Those who have had the opportunity to experiment with synthetic psilocin powder have reported it to be a powerful, visionary substituted tryptamine with a deep, all-encompassing headspace, immersive visuals with high-level geometry, and a rapid challenging come up that is both reportedly more lucid and anxiety-provoking than orally ingested psilocybin mushrooms; this may make the experience overly intense for those who are not well versed with psychedelics.

As with psychedelics in general, psilocin is not considered to be addictive by the research and medical community.[2] Nevertheless, unpredictable adverse reactions such as anxiety, paranoia, delusions and psychotic breaks can still always occur, particularly among those predisposed to psychiatric disorders.[3] While these negative reactions or "bad trips" can often be attributed to factors like the inexperience or improper preparation of the user's set and setting, they have been known to happen spontaneously among even the most experienced of users as well. This is why despite its scientifically-backed reputation for possessing negligible toxicity,[4] it is still highly advised to approach this potent, unpredictable, hallucinogenic substance with the proper amount of precaution and harm reduction practices if one chooses to use it.

Chemistry

Psilocin, or 4-HO-DMT, is an organic indole alkaloid molecule of the tryptamine class of chemicals. Tryptamines share a core structure comprised of a bicyclic indole heterocycle attached at R3 to an amino group via an ethyl side chain. 4-HO-DMT is substituted at R4 of its indole heterocycle with an hydroxyl (-OH) functional group; it also contains two methyl groups CH3- bound to the terminal amine RN of the ethyl side chain. This makes psilocin the 4-hydroxy structural analog of DMT, and dephosphorylated analog of psilocybin.

Psilocin can be obtained by dephosphorylation of natural psilocybin under strongly acidic or under alkaline conditions via hydrolysis,[citation needed] which is how it becomes metabolically active in the human body as well.[citation needed]

In terms of its physical properties, 4-HO-DMT is relatively unstable in solution due to its phenolic hydroxy (-OH) group. In the presence of oxygen it readily forms bluish and dark black degradation products.[citation needed] For this reason it is recommended to store it in optimal chemical storage conditions (i.e. cool, dry, away from light) to avoid excessive degradation.

Pharmacology

Further information: Serotonergic psychedelic
Skeletal formula of the psilocybin molecule.
The diagram above demonstrates the neural connections associated with sobriety in comparison to being under the influence of psilocybin as demonstrated through the use of MRI scans. The width of the links is proportional to their weight and the size of the nodes is proportional to their strength. Note that the proportion of heavy links between communities is much higher (and very different) in the psilocybin group, suggesting greater integration[5]

Psilocin's psychedelic effects are believed to come from its binding efficacy at the 5-HT2A receptor as a partial agonist. Unlike LSD, this compound has no significant effect on dopamine receptors and only affects the noradrenergic system at very high dosages.[6] However, the role of these interactions and how they result in the psychedelic experience continues to remain elusive.

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include injury or death.

Physical effects
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Visual effects
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Cognitive effects
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Multi-sensory effects
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Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

Additional experience reports can be found here:

Combinations

  • Cannabis - When used in conjunction with cannabis, both the visual and cognitive effects of psilocin can be intensified and extended with extreme efficiency. This should be used with extreme caution, especially if one is not experienced with psychedelics. This interaction can also amplify the anxiety, confusion and psychotomimetic producing aspects of cannabis significantly. The THC and psilocin synergy is unique in that the severity of its mind-altering qualities can greatly depend on when during the trip the cannabis is taken, as psilocin experiences are often considered to have less continuity than many other commonly used psychedelics.
  • Dissociatives - When used in combination with dissociatives, the geometry, euphoria, dissociation and hallucinatory effects are often greatly enhanced. Dissociative-induced holes, spaces, and voids while under the influence of psilocin can result in significantly more vivid visuals than dissociatives alone present, along with more intense internal hallucinations, confusion, nausea, delusions and chances of a psychotic reaction.
  • MDMA - When used in conjunction with MDMA, the physical and cognitive effects of MDMA are amplified. The visual, physical and cognitive effects of psilocin are also intensified with an overwhelming euphoric bliss manifested through uniquely pleasurable body highs and headspaces, and uniquely colorful, intricate and majestic visuals. The synergy between these substances is unpredictable, and it is best to start with lower dosages than one would take for both substances individually.
  • Alcohol - This interaction is not typically recommended due to alcohol’s ability to cause dehydration, depression, nausea and thought disorganization which can negatively affect a trip if taken in high dosages. This combination is however reasonably safe in low doses and when used responsibly, this can often take the edge off a trip as well as dull its psychedelic effects in a fashion somewhat similar to benzodiazepines, it is, however, more stressful on the body. With psilocybin mushrooms in particular it is often recommended that the user wait until the come down before they indulge in the consumption of alcohol due to the sometimes already nauseating and lumbering physical effects of mushrooms, especially within the first 2 - 3 hours of the trip. With pure psilocin these physical effects can appear to be less intense but are still generally not recommended due to the infamously unpredictable and purportedly even perilous nature of the psilocin and ethanol synergy. It also is worth noting that experiencing psilocybin/psilocin while feeling the after effects of alcohol can present substantially negative psychological reactions and a significant risk for bad trips that is uniquely higher with psilocin than it is with other common psychedelics.
  • Benzodiazepines - When used in combination with benzodiazepines, benzodiazepines can, depending on the dosage, slightly to completely reduce the intensity of the cognitive, physical and visual effects of a psilocin trip. They can be very efficient at largely stopping or mitigating a bad trip at the cost of amnesia and reduced trip intensity. Caution is advised when acquiring them for this purpose, however, due to the very high addiction potential that benzodiazepines possess.

Potential therapeutic applications

Antidepressant effects

While further research is needed to establish the utility of psilocybin and other psychedelics in treating depression, a pilot study has observed significantly decreased depression scores in terminal cancer patients six months after treatment with psilocybin.[8] An open-label study was carried out in 2016 in the UK to investigate the feasibility, safety and efficacy of psilocybin in treating patients with unipolar treatment-resistant depression with promising results; although the study was small and involved only twelve patients, seven of those patients met formal criteria for remission one week following psilocybin treatment and five of those were still in remission from their depression at three months.[9]

The mechanism behind this is not known as of yet, but researchers have suggested that psilocin's deactivation of the medial prefrontal cortex[10] (mPFC) may be relevant to its antidepressant effects, as the mPFC is known to be elevated in depression and normalized after effective treatment.[10] mPFC hyperactivity has been associated with trait rumination.[11] Another possible factor to psilocybin's potential against depression may be that depressed patients with high levels of dysfunctional attitudes were found to have low levels of 5-HT(2A) agonism.[12][13]

Toxicity and harm potential

Psilocin is non-addictive, is not known to cause brain damage, and has an extremely low toxicity relative to dose. Similar to other psychedelic drugs, there are relatively few physical side effects associated with acute psilocin exposure. Various studies have shown that in reasonable doses in a careful context, it presents little to no negative cognitive, psychiatric or toxic physical consequences.[citation needed]

Lethal dosage

The toxicity of psilocybin and psilocin is extremely low. In rats, the median lethal dose (LD50) of psilocybin when administered orally is 280 milligrams per kilogram (mg/kg). Psilocybin comprises approximately 1% of the weight of Psilocybe cubensis mushrooms and so nearly 1.7 kilograms (3.7 lb) of dried mushrooms or 17 kilograms (37 lb) of fresh mushrooms would be required for a 60 kilogram (130 lb) person to reach the 280 mg/kg LD50 value of rats. Based on the results of animal studies, the lethal dose of psilocybin has been extrapolated to be 6 grams, 1000 times greater than the effective dose of 6 milligrams.[citation needed]

Despite its lack of physical toxicity, however, it is still strongly recommended that one use harm reduction practices if choosing to use this substance.

Tolerance and addiction potential

Psilocin is not habit-forming and the desire to use it can actually decrease with use. It is most often self-regulating.

Tolerance to the effects of psilocin are built almost immediately after ingestion. After that, it takes about 3 days for the tolerance to be reduced to half and 7 days to be back at baseline (in the absence of further consumption). Psilocin presents cross-tolerance with all psychedelics, meaning that after the consumption of psilocin all psychedelics will have a reduced effect.

Legality

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This legality section is a stub.

As such, it may contain incomplete or wrong information. You can help by expanding it.

Psilocin is a Schedule I drug under the Convention on Psychotropic Substances, meaning the possession and sale of it (including psilocin and psilocybin-containing mushrooms) is prohibited in most countries.[14]

  • Brazil - Possession, production and sale is illegal as it is listed on Portaria SVS/MS nº 344[15], but mushrooms fall under religious use laws.
  • British Virgin Isles: The sale of mushrooms is illegal, but possession and consumption is legal.
  • Bulgaria: The sale of mushrooms is illegal, but possession and consumption is legal.
  • Belgium: Possession and sale of mushrooms have been illegal since 1988.
  • Canada: Psilocybin and psilocin are illegal to possess, obtain or produce without a prescription or license as they are Schedule III under the Controlled Drugs and Substances Act.[16]
  • Czech Republic: The distribution (including sale) of mushrooms is illegal, but consumption is legal. The possession of over 40 hallucinogenic caps is considered a crime if they contain more than 50mg of psilocin or the corresponding amount of psilocybin. The possession of more than 40g of hallucinogenic mycelium is considered a crime. If these limits are not exceeded, the act is considered a minor offence and a fine of up to 15 thousand CZK may be imposed.
  • Cyprus The possession, sale and consumption of mushrooms is illegal.
  • Denmark: The possession, growth, sale and consumption of mushrooms is illegal.
  • Finland: The possession, growth, sale and consumption of mushrooms is illegal.
  • Germany: The possession, growth, sale and consumption of mushrooms is illegal.
  • Greece: The possession, growth, sale and consumption of mushrooms is illegal.
  • Ireland: The possession, growth, sale and consumption of mushrooms is illegal.
  • Japan: The possession, growth, sale and consumption of mushrooms is illegal.
  • Latvia: Hallucinogenic mushrooms, psilocin and psilocibyn are Schedule I controlled substances.[17]
  • Mexico: The possession, growth, sale and consumption of mushrooms is illegal. Rules are relaxed regarding religious use however.
  • The Netherlands: The possession, growth, sale and consumption of mushrooms is illegal. However, due to a legal loophole, psilocybin truffles can be legally possessed, grown, sold and consumed.
  • New Zealand: Psilocybin is Class A.
  • Norway: Possession, growth, sale and consumption of mushrooms is illegal. Spores, even though not containing psilocybin, are also illegal.
  • Turkey: The possession, growth, sale and consumption of mushrooms is illegal.
  • UK: According to the 2005 Drugs Act, fresh and prepared psilocybin mushrooms are Class A.[18]
  • USA: Psilocybin and psilocin are illegal Schedule I drugs.[19]

See also

External links

References

  1. Hofmann, A., Heim, R., Brack, A., Kobel, H., Frey, A., Ott, H., Petrzilka, Th. and Troxler, F. (1959), Psilocybin und Psilocin, zwei psychotrope Wirkstoffe aus mexikanischen Rauschpilzen. HCA, 42: 1557–1572. https://doi.org/10.1002/hlca.19590420518
  2. Lüscher, C., & Ungless, M. A. (2006). The Mechanistic Classification of Addictive Drugs, 3(11). https://doi.org/10.1371/journal.pmed.0030437
  3. Strassman, R. J. (1984). Adverse Reactions to Psychedelic Drugs: A Review of the Literature. The Journal of Nervous and Mental Disease, 172(10), 577-595. PMID: 6384428
  4. Nichols, D. E. (2016). "Psychedelics." Pharmacological Reviews, 68(2), 264-355. https://doi.org/10.1124/pr.115.011478
  5. Petri, G., Expert, P., Turkheimer, F., Nutt, D., Hellyer, P. J., & Vaccarino, F. (2014). Homological scaffolds of brain functional networks, 14–18. https://doi.org/10.1038/nrn2618
  6. Psilocybin Investigator’s Brochure | http://www.maps.org/research/psilo/psilo_ib.pdf
  7. Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P., & Griffiths, R. R. (2014). Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. Journal of Psychopharmacology, 28(11), 983-992. https://doi.org/10.1177/0269881114548296
  8. Grob, C. S., Danforth, A. L., Chopra, G. S., Hagerty, M., McKay, C. R., Halberstadt, A. L., & Greer, G. R. (2011). Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Archives of General Psychiatry, 68(1), 71-78. https://doi.org/10.1001/archgenpsychiatry.2010.116
  9. Carhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M., Erritzoe, D., Kaelen, M., ... & Taylor, D. (2016). Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry, 3(7), 619-627. https://doi.org/10.1016/S2215-0366(16)30065
  10. 10.0 10.1 Carhart-Harris, R. L., Erritzoe, D., Williams, T., Stone, J. M., Reed, L. J., Colasanti, A., ... & Hobden, P. (2012). Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proceedings of the National Academy of Sciences, 109(6), 2138-2143. https://doi.org/10.1073/pnas.1119598109
  11. Farb, N. A. S., Anderson, A. K., Bloch, R. T., & Segal, Z. V. (2011). Mood Linked Responses in Medial Prefrontal Cortex Predict Relapse in Patients with Recurrent Unipolar Depression. Biological Psychiatry, 70(4), 366–372. https://doi.org/10.1016/j.biopsych.2011.03.009
  12. Bhagwagar, Z., Hinz, R., Taylor, M., Fancy, S., Cowen, P., & Grasby, P. (2006). Increased 5-HT 2A receptor binding in euthymic, medication-free patients recovered from depression: a positron emission study with [11 C] MDL 100,907. American Journal of Psychiatry, 163(9), 1580-1587. http://dx.doi.org/10.1176/ajp.2006.163.9.1580
  13. Meyer, J. H., McMain, S., Kennedy, S. H., Korman, L., Brown, G. M., DaSilva, J. N., ... & Houle, S. (2003). Dysfunctional attitudes and 5-HT2 receptors during depression and self-harm. American Journal of Psychiatry, 160(1), 90-99. https://www.doi.org/10.1176/appi.ajp.160.1.90
  14. "Green list" (PDF). INCB. Retrieved 2017-10-11.
  15. http://portal.anvisa.gov.br/documents/10181/3115436/%281%29RDC_130_2016_.pdf/fc7ea407-3ff5-4fc1-bcfe-2f37504d28b7
  16. Controlled Drugs and Substances Act of Canada
  17. Noteikumi par Latvijā kontrolējamajām narkotiskajām vielām, psihotropajām vielām un prekursoriem (I saraksts) | http://likumi.lv/doc.php?id=121086
  18. Legislation - Drugs Act 2005| http://www.legislation.gov.uk/ukpga/2005/17/contents
  19. FDA - Controlled Substances Act| http://www.fda.gov/regulatoryinformation/legislation/ucm148726.htm