Abstract
This chapter aims to address the question of whether there is a clinically relevant difference between natural and synthetic psilocybin. Examining the history of when psilocybin was first researched in the late 1950s revealed that both synthetic and natural compounds were explored but lost momentum with the declaration of the war on drugs in 1971. The past few years have shown a significant rise of research interest in psilocybin in the mental health field. Due to the current regulations and market capitalization, the industry relies on an investment strategy aligned with the traditional pharmaceutical model. Interestingly, there is a long history of popular natural medicines being produced by pharmaceutical companies, and a number of natural products are currently being used in mental health. Research on natural psilocybin, including the phenomenon of the entourage effect, as well as the factors and considerations for future research on natural and synthetic psilocybin, are discussed. Comparing the natural psilocybin molecule to the synthetic psilocybin molecule should be fundamentally similar. Still, the active pharmaceutical ingredient (API) differs from other ingredients in the whole mushroom, and natural extracts may have synergistic effects.
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Abbreviations
- 5-HT2a:
-
5-Hydroxytryptamine (serotonin) 2a receptor
- API:
-
Active pharmaceutical ingredient
- ATAI:
-
atai Life Sciences
- CAGR:
-
Compound annual growth rate
- CMPS:
-
Compass Pathways
- CYBN:
-
Cybin
- DEA:
-
United States Drug Enforcement Administration
- FDA:
-
Food and Drug Administration
- FTRP:
-
Field Trip Health
- LSD:
-
Lysergic acid diethylamide
- MAPS:
-
Multidisciplinary Association for Psychedelic Studies
- NASDAQ:
-
National Association of Securities Dealers Automated Quotations
- NIH:
-
National Institutes of Health
- NUMI:
-
Numinus Wellness
- NYU:
-
New York University
- PAT:
-
Psychedelic-assisted therapies
- PTSD:
-
Post-traumatic stress disorder
- SPRAVATO:
-
Esketamine nasal spray
- TSXV:
-
Toronto Stock Exchange Venture
- UCLA:
-
University of California, Los Angeles
- UCSF:
-
University of California, San Francisco
- USD:
-
United States dollar
- USFDA:
-
United States Food and Drug Administration
References
ACS (1999) Discovery and development of penicillin [Online]. Am Chem Soc. https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenicillin.html. Accessed 12 Dec 2021
Akers BP, Ruiz JF, Piper A, Ruck CAP (2011) A prehistoric mural in Spain depicting neurotropic psilocybe mushrooms? Econ Bot 65(2):121–128. https://doi.org/10.1007/s12231-011-9152-5
Attele AS, Xie JT, Yuan CS (2000) Treatment of insomnia: an alternative approach. Altern Med Rev 5(3):249–259
Augustyn A (2016) War on drugs: U.S. history [Online]. https://www.britannica.com/topic/war-on-drugs. Accessed 30 Nov 2021
Barnes MP (2006) Sativex: clinical efficacy and tolerability in the treatment of symptoms of multiple sclerosis and neuropathic pain. Expert Opin Pharmacother 7(5):607–615. https://doi.org/10.1517/14656566.7.5.607
Bauer BE (2019) The entourage effect in magic mushrooms. Psychedelic Sci Rev [Online]. https://psychedelicreview.com/the-entourage-effect-in-magic-mushrooms/. Accessed 02 Dec 2021
Bauer BE (2020) Catching up with the psychedelic entourage effect-part 1: how we got here. Psychedelic Sci Rev [Online]. https://psychedelicreview.com/the-entourage-effect-in-magic-mushrooms/. Accessed 02 Dec 2021
Baystreet (2021) The functional mushroom market could hand you a $62 billion opportunity [Online]. https://www.baystreet.ca/stockstowatch/9666/The-Functional-Mushroom-Market-Could-Hand-You-a-62-Billion-Opportunity. Accessed 01 Dec 2021
Beliveau V, Ganz M, Feng L et al (2017) A high-resolution in vivo atlas of the human brain’s serotonin system. J Neurosci 37(1):120–128. https://doi.org/10.1523/jneurosci.2830-16.2016
Beutler JA (2009) Natural products as a foundation for drug discovery. Curr Protoc Pharmacol 46:9.11.11–19.11.21. https://doi.org/10.1002/0471141755.ph0911s46
Blei F, Dörner S, Fricke J et al (2020) Simultaneous production of psilocybin and a cocktail of β-carboline monoamine oxidase inhibitors in "magic" mushrooms. Chemistry 26(3):729–734. https://doi.org/10.1002/chem.201904363
Bloch MH, Hannestad J (2012) Omega-3 fatty acids for the treatment of depression: systematic review and meta-analysis. Mol Psychiatry 17(12):1272–1282. https://doi.org/10.1038/mp.2011.100
Canal CE (2018) Serotonergic psychedelics: experimental approaches for assessing mechanisms of action. Handb Exp Pharmacol 252:227–260. https://doi.org/10.1007/164_2018_107
Darbinyan V, Aslanyan G, Amroyan E et al (2007) Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nord J Psychiatry 61(5):343–348. https://doi.org/10.1080/08039480701643290
de Veen BT, Schellekens AF, Verheij MM, Homberg JR (2017) Psilocybin for treating substance use disorders? Expert Rev Neurother 17(2):203–212. https://doi.org/10.1080/14737175.2016.1220834
Fleming A (2001) On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. 1929. BullWorld Health Organ 79(8):780–790
Fusar-Poli P, Borgwardt S (2008) Albert Hofmann, the father of lsd (1906–2008). Neuropsychobiology 58(1):53–54. https://doi.org/10.1159/000157779
GarcÃa-Gutiérrez MS, Navarrete F, Gasparyan A et al (2020) Cannabidiol: a potential new alternative for the treatment of anxiety, depression, and psychotic disorders. Biomol Ther 10(11). https://doi.org/10.3390/biom10111575
Gartz J (1989) Biotransformation of tryptamine in fruiting mycelia of Psilocybe cubensis. Planta Med 55(3):249–250
Gates M, Tschudi G (1956) The synthesis of morphine. J Am Chem Soc 78(7):1380–1393
Geiger HA, Wurst MG, Daniels RN (2018) DARK classics in chemical neuroscience: psilocybin. ACS Chem Neurosci 9(10):2438–2447. https://doi.org/10.1021/acschemneuro.8b00186
Giacoppo S, Bramanti P, Mazzon E (2017) Sativex in the management of multiple sclerosis-related spasticity: an overview of the last decade of clinical evaluation. Mult Scler Relat Disord 17:22–31. https://doi.org/10.1016/j.msard.2017.06.015
Grimm O, Kraehenmann R, Preller K, Seifritz E, Vollenweider F (2018) Psilocybin modulates functional connectivity of the amygdala during emotional face discrimination. Eur Neuropsychopharmacol 28:691–700
Halberstadt AL, Geyer MA (2011) Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology 61(3):364–381. https://doi.org/10.1016/j.neuropharm.2011.01.017
Hofmann A, Heim R, Brack A, Kobel H (1958) Psilocybin, a psychotropic substance from the Mexican mushroom Psilocybe mexicana Heim. Experientia 14(3):107–109. https://doi.org/10.1007/bf02159243
Hofmann A, Troxler F (1963) Esters of indoles. USA Patent 3075992A, 29 January 1963
Hoge JF (1951) The Durham–Humphrey Bill. Food Drug Cosmetic Law J 6 (2):135–141
InsightSLICE (2021) Herbal medicine market global sales are expected to reach US$ 550 Billion by 2030 [Online]. https://www.globenewswire.com/en/news-release/2021/02/16/2176036/0/en/Herbal-Medicine-Market-Global-Sales-Are-Expected-To-Reach-US-550-Billion-by-2030-as-stated-by-insightSLICE.html. Accessed 30 Nov 2021
Intelligence E (2020) Which trends offer opportunities or pose threats on the European natural ingredients for health products market? CBI [Online]. https://www.cbi.eu/market-information/natural-ingredients-health-products/trends. Accessed 12 Oct 2021
Jamshidi N, Cohen MM (2017) The clinical efficacy and safety of Tulsi in humans: a systematic review of the literature. Evid Based Complement Alternat Med 2017:9217567. https://doi.org/10.1155/2017/9217567
Janda K, Wojtkowska K, Jakubczyk K et al (2020) Passiflora incarnata in neuropsychiatric disorders-a systematic review. Nutrients 12(12). https://doi.org/10.3390/nu12123894
Kasper S (2013) An orally administered lavandula oil preparation (Silexan) for anxiety disorder and related conditions: an evidence based review. Int J Psychiatry Clin Pract 17(Suppl 1):15–22. https://doi.org/10.3109/13651501.2013.813555
Khuda-Bukhsh AR, Pathak S (2008) Homeopathic drug discovery: theory update and methodological aspect. Expert Opin Drug Discov 3(8):979–990. https://doi.org/10.1517/17460441.3.8.979
Kim DH (2012) Chemical diversity of Panax ginseng, Panax quinquifolium, and Panax notoginseng. J Ginseng Res 36(1):1–15. https://doi.org/10.5142/jgr.2012.36.1.1
Lockermann G (1951) Friedrich Wilhelm Serturner, the discoverer of morphine. J Chem Educ 28(5):277
Logan AC (2004) Omega-3 fatty acids and major depression: a primer for the mental health professional. Lipids Health Dis 3:25. https://doi.org/10.1186/1476-511x-3-25
Lopresti AL, Drummond PD (2014) Saffron (Crocus sativus) for depression: a systematic review of clinical studies and examination of underlying antidepressant mechanisms of action. Hum Psychopharmacol 29(6):517–527. https://doi.org/10.1002/hup.2434
Lord LD, Expert P, Atasoy S et al (2019) Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin. NeuroImage 199:127–142. https://doi.org/10.1016/j.neuroimage.2019.05.060
Lowe H, Toyang N, Steele B et al (2021) The therapeutic potential of psilocybin. Molecules 26(10). https://doi.org/10.3390/molecules26102948
Marais A, Adams B, Ringsmuth AK et al (2018) The future of quantum biology. J R Soc Interface 15(148):20180640. https://doi.org/10.1098/rsif.2018.0640
Markets RA (2021) Global psychedelic drugs market report 2020: market size is projected to reach $10.75 billion by 2027. Research and Markets [Online]. https://www.globenewswire.com/en/news-release/2021/03/18/2195240/28124/en/Global-Psychedelic-Drugs-Market-Report-2020-Market-Size-is-Projected-to-Reach-10-75-Billion-by-2027.html. Accessed 02 Dec 2021
Matsushima Y, Shirota O, Kikura-Hanajiri R, Goda Y, Eguchi F (2009) Effects of Psilocybe argentipes on marble-burying behavior in mice. Biosci Biotech Biochem 73(8):1866–1868. https://doi.org/10.1271/bbb.90095
Morales-GarcÃa JA, de la Fuente RM, Alonso-Gil S et al (2017) The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro. Sci Rep 7(1):5309. https://doi.org/10.1038/s41598-017-05407-9
Müller F, Liechti ME, Lang UE, Borgwardt S (2018) Advances and challenges in neuroimaging studies on the effects of serotonergic hallucinogens: contributions of the resting brain. Prog Brain Res 242:159–177. https://doi.org/10.1016/bs.pbr.2018.08.004
Nichols DE (2020) Psilocybin: from ancient magic to modern medicine. J Antibiot 73(10):679–686. https://doi.org/10.1038/s41429-020-0311-8
Oreja-Guevara C (2012) Clinical efficacy and effectiveness of Sativex, a combined cannabinoid medicine, in multiple sclerosis-related spasticity. Expert Rev Neurother 12(4 Suppl):3–8. https://doi.org/10.1586/ern.12.11
Powell M (2015) Medicinal mushrooms - a clinical guide. Mycology Press, Bamboo Publishing Ltd, Sussex
GrandView Research (2021) Pharmaceutical manufacturing market size, share & trends analysis report (2021–2028) [Online]. https://www.grandviewresearch.com/industry-analysis/pharmaceutical-manufacturing-market. Accessed 12 Jan 2022
Ribas RMG, Oliveira DCL, Silva PC et al (2021) (2021) the different roles of Griffonia simplicifolia in the treatment of depression: a narrative review. Int J Complement Alt Med 14(3):167–172. https://doi.org/10.15406/ijcam.2021.14.00553
Sarris J, Kavanagh DJ, Byrne G et al (2009) The kava anxiety depression spectrum study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum. Psychopharmacol (Berl) 205(3):399–407. https://doi.org/10.1007/s00213-009-1549-9
Saville MW, Lietzau J, Pluda JM et al (1995) Treatment of HIV-associated Kaposi’s sarcoma with paclitaxel. Lancet 346(8966):26–28. https://doi.org/10.1016/s0140-6736(95)92654-2
Siff S (2018) R. Gordon Wasson and the publicity campaign to introduce magic mushrooms to mid-century America. Revue française d’études américaines 156(3):91–104
Singh N, Bhalla M, de Jager P, Gilca M (2011) An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med 8(5 Suppl):208–213. https://doi.org/10.4314/ajtcam.v8i5S.9
Smith T MF, Eckl V, Morton Reynolds C (2021) Herbal supplement sales in u.s. increase by record-breaking 17.3% in 2020 [Online]. https://www.herbalgram.org/news/press-releases/2021/record-breaking-us-herbal-supplement-sales-increase-in-2020/. Accessed 8 Sept 2021
Srivastava JK, Shankar E, Gupta S (2010) Chamomile: a herbal medicine of the past with bright future. Mol Med Rep 3(6):895–901. https://doi.org/10.3892/mmr.2010.377
Tagliazucchi E, Carhart-Harris R, Leech R, Nutt D, Chialvo DR (2014) Enhanced repertoire of brain dynamical states during the psychedelic experience. Hum Brain Mapp 35(11):5442–5456. https://doi.org/10.1002/hbm.22562
Usona Institute (2021) [Online]. https://usonaclinicaltrials.org/major-depressive-disorder-psilocybin-clinical-trial-psil201. Accessed 30 Nov 2021
Vargas AS, LuÃs Â, Barroso M, Gallardo E, Pereira L (2020) Psilocybin as a new approach to treat depression and anxiety in the context of life-threatening diseases-a systematic review and meta-analysis of clinical trials. Biomedicine 8(9). https://doi.org/10.3390/biomedicines8090331
Whiskey E, Werneke U, Taylor D (2001) A systematic review and meta-analysis of Hypericum perforatum in depression: a comprehensive clinical review. Int Clin Psychopharmacol 16(5):239–252. https://doi.org/10.1097/00004850-200109000-00001
Zhuk O, Jasicka-Misiak I, Poliwoda A et al (2015) Research on acute toxicity and the behavioral effects of methanolic extract from psilocybin mushrooms and psilocin in mice. Toxins (Basel) 7(4):1018–1029. https://doi.org/10.3390/toxins7041018
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Ali, A., Gifford, ME., Lowe, H., Gordon, L., Grant, J. (2023). Natural vs. Synthetic Psilocybin: The Same or Completely Different?. In: Agrawal, D.C., Dhanasekaran, M. (eds) Mushrooms with Therapeutic Potentials. Springer, Singapore. https://doi.org/10.1007/978-981-19-9550-7_18
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