1. Psilocin By: XXXX

2. What is it? What is it? Natural compound found in psychedelic mushrooms. Molecular formula: C 12 H 16 N 2 O Molecular weight: 204.27 g/mol “Magic mushrooms,” “shrooms,” “Shroomies” Considered a substituted tryptamine alkaloid.

3. Facts: Found in over 190 separate mushroom species, and grows in every continent across the globe. - Psilocybe cubensis Affects the neurotransmitter serotonin in the brain. Two main forms: - Phosphorylated: psilocybin - Dephosphorylated: psilocin

4. History Recorded to have been used as far back as 9000 B.C. in indigenous cultures - African, Mayan, Aztecs Used by Indian tribes in Mexico and Peru during ceremonies/ rituals as ways to speak to their gods. - teonanacatl (“flesh of the gods”) Spanish conquest and Catholicism banned its use.

5. History In 1955, mycologists, R. Gordon Wasson took part of a ceremony with Psilocybe mexicana. Albert Hoffman in 1959 extracted the compound from 100 grams of the Mexican mushrooms. Roger Dean, David Vaughan, Steve Jobs, Francis Crick, known for using these psychedelic mushrooms.

6. History In 1971, United Nations declared psilocybin as Schedule I drug under an amendment to the Controlled Substances Act called Psychotropic Substances Act Illegal in many countries today, however there is a lot of vagueness about the laws and some exceptions.

7. Biological Activity Similar to the neurotransmitter serotonin, so disrupts intracellular signaling pathways in brain. - Serotonin 5HT2 receptors Does not affect dopamine receptors directly like LSD does. Serotonin psilocin psilocybin

8. Biological Activity Mushroom is normally ingested dried, cooked, or even frozen. Effects start 10-20minutes after ingestion and can last up to 6 hours. After dephosphorylation, psilocin accumulates in liver, kidneys, and brain. - Monoamine oxidase breaks down psilocin into metabolites that circulate blood plasma.

9. Common effects -Visual acuity - Time distortion -Conceptual thinking, -Closed eye hallucination -Delusions -Connectivity of thought

10. Disruptions in the Brain The serotonin receptors in the prefrontal cortex and their interaction with psilocin causes intracellular changes in the connectivity patterns Psilocin also disrupts the regulation of sensory input that occurs from thalamus to the cortex in the brain enhancing colors, appearances of after images, distorted scenery.

11. Bad effects: Phenylethylamine in mushroom causes some adverse physiological effects in the person: - Dizziness - Nausea - Weakness - Dilated pupils - Tachycardia - Swaeting - Abdominal pain

12. Effects continued 65% is excreted in urine within 24 hours. 10-20% will remain in system for up to 7 days, can be detected in Urine or blood. There are no long term effects, and tolerance builds up almost immediately after ingestion.

13. Biosynthesis Similarities to serotonin and tryptophan was a key element to figuring it out. In 1968, Stig Agurell & Lars Nilsson proposed a biosynthesis

14. Chemical Synthesis In 2003, Osamu Shirota, Wataru Hakamata, and Yukihiro Goda, proposed a synthesis. 1. 4-hydroxyindole gets acetylated to protect OH group 2. Two acylation-amidation to produce glyoxalylamide 3. This gets reduced by LiAlH 4 producing 85% yield of psilocin.

15. Chemical Synthesis Nicholas gathergood and Peter J. Scammells proposed these chemical synthesis Protected N-tert-butoxycarbonyl-2-iodo-3-methoxyaniline and a properly substituted silyl acetylene combine to form hydroxytryptamine by using a palladium catalysts. Finally protected group is removed yielding psilocin.

16. Current Day Use Serotonergic systems as treatment for depression and anxiety disorders. Using Psilocin and other psychedelics is something they are trying. The developed tolerance to repeated administration might possibly reduce dependency. - No need for daily use.

17. Current Day use In 2014, researchers David Baumeister, Georgina Barnes, Giovanni Giaroli and Derek Tracy, did a study on pharmacodynamics of these potential drugs. Results showed positive therapeutic results. FDA will not allow this.

18. References Agurell, S. T. I. G., & Nilsson, J. L. G. BiosynActa Chem. Scand, 1968. 22(4). Baumeister, D., Barnes, G., Giaroli, G., & Tracy, D. Therapeutic advances in psychopharmacology, 2014. 2045125314527985. Beug, Michael W., and Jeremy Bigwood. "Psilocybin and psilocin levels in twenty species from seven genera of wild mushrooms in the Pacific Northwest, USA." Journal of ethnopharmacology 5, no. 3 [ online] 1982, 271-285. http://www.sciencedirect.com/science/article/pii/0378874182900137 (accessed February 11, 2015) http://www.sciencedirect.com/science/article/pii/0378874182900137 End of Game [Online] 2012, http://endofthegame.net/2012/05/09/psychedelic- mushrooms-and-you/ (accessed April 2, 2015).http://endofthegame.net/2012/05/09/psychedelic- mushrooms-and-you/ Gathergood, N., & Scammells, P. J.Organic letters, 2003. 5(6), 921-923 Hendricks, P. S., Thorne, C. B., Clark, C. B., Coombs, D. W., & Johnson, M. W. Journal of Psychopharmacology, 2015. 0269881114565653. Hofmann, A., Heim, R., Brack, A., Kobel, H., Frey, A., Ott, H.,... & Troxler, F. Helvetica Chimica Acta, 1959. 42(5), pp 1557-1572.

19. References Horita, A., & Weber, L. J. Toxicology and Applied Pharmacology, 1962. 4(6), 730-737 Kalberer, F., Kreis, W., & Rutschmann, J. The fate of psilocin in the rat. Biochemical pharmacology, [online] 1962, 11(4), 261-269. http://www.sciencedirect.com/science/article/pii/0006295262900503. http://www.sciencedirect.com/science/article/pii/0006295262900503 Kysilka, R., & Wurst, M. Planta medica. 1990. 56(3), 327-328. National Center for Biotechnology Information. PubChem Compound Database; 2005 CID=4980, http://pubchem.ncbi.nlm.nih.gov/compound/4980 (accessed Mar. 30, 2015). Psilocin and psilocybin. Encyclopædia Britannica [Online]; s. v., edited July 16, 2014 http://www.britannica.com/EBchecked/topic/481419/psilocin-and- psilocybin. (accessed February 04 2015). http://www.britannica.com/EBchecked/topic/481419/psilocin-and- psilocybin Sargent, Paul [Online] 2011, http://gategetos.com/neurogenesis-serotonin-11125.html (accessed April 1, 2015)http://gategetos.com/neurogenesis-serotonin-11125.html Scifinder Scholar, version 2015; Drug Testing and Analysis: Albuquerque, NM, 2012; 2012:957800 (psilocin and psilocibyn) Shirota, O., Hakamata, W., & Goda, Y. Journal of natural products. 2003 66(6), 885-887.