Review article: Biomedical intelligence
Vol. 155 No. 7 (2025)
Caffeine, nicotine, cannabis, and psilocybin: Pharmacology, toxicology, and potential therapeutic uses of four naturally occurring psychoactive substances
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Cite this as:
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Swiss Med Wkly. 2025;155:4346
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Published
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01.07.2025
Summary
Psychoactive substances are compounds that can influence perception, consciousness, cognition, and emotions. The psychoactive substances caffeine, nicotine, cannabis, and psilocybin all originate from natural sources and can be used without complex processing or synthesis. Their natural availability has contributed to a long-standing history of human use and cultural significance. Caffeine and nicotine are freely available and commonly used as everyday stimulants, whereas psilocybin is more strictly regulated and cannabis has been legalised in some countries and regions. Some of these substances have been intensively studied, and their pharmacological and toxicological properties are well known, but ongoing research continues to investigate their therapeutic use for specific diseases and disorders. This narrative review aims to provide an overview of the pharmacology and toxicology of these four naturally occurring psychoactive substances, including a summary of the currently available evidence on their therapeutic potential, health benefits, and associated risks.
References
- World Health Organization (WHO). Drugs (psychoactive). Available from: https://www.who.int/health-topics/drugs-psychoactive#tab=tab_1
- Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, et al. Cannabinoids for medical use: A systematic review and meta-analysis. JAMA. 2015 Jun;313(24):2456–73. doi: https://doi.org/10.1001/jama.2015.6358
- Goodwin GM, Croal M, Feifel D, Kelly JR, Marwood L, Mistry S, et al. Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication. Neuropsychopharmacology. 2023 Sep;48(10):1492–9. doi: https://doi.org/10.1038/s41386-023-01648-7
- Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016 Dec;30(12):1165–80. doi: https://doi.org/10.1177/0269881116675512
- Fisone G, Borgkvist A, Usiello A. Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci. 2004 Apr;61(7-8):857–72. doi: https://doi.org/10.1007/s00018-003-3269-3
- Willson C. The clinical toxicology of caffeine: A review and case study. Toxicol Rep. 2018 Nov;5:1140–52. doi: https://doi.org/10.1016/j.toxrep.2018.11.002
- Nelson LS, Lewin NA, Howland MA, Hoffmann RS, Goldfrank LR, Flomenbaum NE, editors. Goldfrank’s Toxicologic Emergencies. 9th ed. New York: McGraw Hill Medical; 2011.
- Jamieson RW. The essence of commodification: caffeine dependencies in the early modern world. J Soc Hist. 2001;35(2):269–94. doi: https://doi.org/10.1353/jsh.2001.0125
- Olson KR. Poisoning & Drug Overdose. By the faculty, staff and associates of the California Poison Control System. 4th ed. New York: McGrawHill; 2004.
- Davis JM, Zhao Z, Stock HS, Mehl KA, Buggy J, Hand GA. Central nervous system effects of caffeine and adenosine on fatigue. Am J Physiol Regul Integr Comp Physiol. 2003 Feb;284(2):R399–404. doi: https://doi.org/10.1152/ajpregu.00386.2002
- Caffeine content of popular drinks. Available from: https://www.math.utah.edu/~yplee/fun/caffeine.html
- Davies S, Lee T, Ramsey J, Dargan PI, Wood DM. Risk of caffeine toxicity associated with the use of ‘legal highs’ (novel psychoactive substances). Eur J Clin Pharmacol. 2012 Apr;68(4):435–9. doi: https://doi.org/10.1007/s00228-011-1144-y
- Aranda JV, Cook CE, Gorman W, Collinge JM, Loughnan PM, Outerbridge EW, et al. Pharmacokinetic profile of caffeine in the premature newborn infant with apnea. J Pediatr. 1979 Apr;94(4):663–8. doi: https://doi.org/10.1016/S0022-3476(79)80047-5
- Aguilar-Navarro M, Muñoz G, Salinero JJ, Muñoz-Guerra J, Fernández-Álvarez M, Plata MD, et al. Urine caffeine concentration in doping control samples from 2004 to 2015. Nutrients. 2019 Jan;11(2):286. doi: https://doi.org/10.3390/nu11020286
- Stavchansky S, Combs A, Sagraves R, Delgado M, Joshi A. Pharmacokinetics of caffeine in breast milk and plasma after single oral administration of caffeine to lactating mothers. Biopharm Drug Dispos. 1988;9(3):285–99. doi: https://doi.org/10.1002/bod.2510090307
- Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000 Jul;343(2):118–26. doi: https://doi.org/10.1056/NEJM200007133430208
- Brent RL, Christian MS, Diener RM. Evaluation of the reproductive and developmental risks of caffeine. Birth Defects Res B Dev Reprod Toxicol. 2011 Apr;92(2):152–87. doi: https://doi.org/10.1002/bdrb.20288
- Knutti R, Rothweiler H, Schlatter C. Effect of pregnancy on the pharmacokinetics of caffeine. Eur J Clin Pharmacol. 1981;21(2):121–6. doi: https://doi.org/10.1007/BF00637512
- Schmidt M, Farna H, Kurcova I, Zakharov S, Fric M, Waldauf P, et al. Succesfull treatment of supralethal caffeine overdose with a combination of lipid infusion and dialysis. Am J Emerg Med. 2015;33(5):738 e5-7. doi: https://doi.org/10.1016/j.ajem.2014.11.002
- Tajima Y. Coffee-induced Hypokalaemia. Clin Med Insights Case Rep. 2010;3:9–13. doi: https://doi.org/10.4137/CCRep.S4329
- Bradberry SM, Vale JA. Disturbances of potassium homeostasis in poisoning. J Toxicol Clin Toxicol. 1995;33(4):295–310. doi: https://doi.org/10.3109/15563659509028915
- Wallukat G. The beta-adrenergic receptors. Herz. 2002 Nov;27(7):683–90. doi: https://doi.org/10.1007/s00059-002-2434-z
- Echeverri D, Montes FR, Cabrera M, Galán A, Prieto A. Caffeine’s vascular mechanisms of action. Int J Vasc Med. 2010;2010:834060. doi: https://doi.org/10.1155/2010/834060
- Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet. 2000 Aug;39(2):127–53. doi: https://doi.org/10.2165/00003088-200039020-00004
- Sharp DS, Benowitz NL. Pharmacoepidemiology of the effect of caffeine on blood pressure. Clin Pharmacol Ther. 1990 Jan;47(1):57–60. doi: https://doi.org/10.1038/clpt.1990.8
- Caldeira D, Martins C, Alves LB, Pereira H, Ferreira JJ, Costa J. Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies. Heart. 2013 Oct;99(19):1383–9. doi: https://doi.org/10.1136/heartjnl-2013-303950
- Frost L, Vestergaard P. Caffeine and risk of atrial fibrillation or flutter: the Danish Diet, Cancer, and Health Study. Am J Clin Nutr. 2005 Mar;81(3):578–82. doi: https://doi.org/10.1093/ajcn/81.3.578
- Wilson RE, Kado HS, Samson R, Miller AB. A case of caffeine-induced coronary artery vasospasm of a 17-year-old male. Cardiovasc Toxicol. 2012 Jun;12(2):175–9. doi: https://doi.org/10.1007/s12012-011-9152-9
- Forman J, Aizer A, Young CR. Myocardial infarction resulting from caffeine overdose in an anorectic woman. Ann Emerg Med. 1997 Jan;29(1):178–80. doi: https://doi.org/10.1016/S0196-0644(97)70326-3
- Khan S, Babu K, Sidhu R, Niemi M. Caffeine intoxication treated with hemodialysis. Semin Dial. 2023;36(5):414–8. doi: https://doi.org/10.1111/sdi.13169
- Rapuri PB, Gallagher JC, Kinyamu HK, Ryschon KL. Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. Am J Clin Nutr. 2001 Nov;74(5):694–700. doi: https://doi.org/10.1093/ajcn/74.5.694
- Korpelainen R, Korpelainen J, Heikkinen J, Väänänen K, Keinänen-Kiukaanniemi S. Lifestyle factors are associated with osteoporosis in lean women but not in normal and overweight women: a population-based cohort study of 1222 women. Osteoporos Int. 2003 Jan;14(1):34–43. doi: https://doi.org/10.1007/s00198-002-1319-6
- Griffiths RR, Woodson PP. Caffeine physical dependence: a review of human and laboratory animal studies. Psychopharmacology (Berl). 1988;94(4):437–51. doi: https://doi.org/10.1007/BF00212836
- Martín I, López-Vílchez MA, Mur A, García-Algar O, Rossi S, Marchei E, et al. Neonatal withdrawal syndrome after chronic maternal drinking of mate. Ther Drug Monit. 2007 Feb;29(1):127–9. doi: https://doi.org/10.1097/FTD.0b013e31803257ed
- McGowan JD, Altman RE, Kanto WP Jr. Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine. South Med J. 1988 Sep;81(9):1092–4. doi: https://doi.org/10.1097/00007611-198809000-00006
- Bernstein GA, Carroll ME, Crosby RD, Perwien AR, Go FS, Benowitz NL. Caffeine effects on learning, performance, and anxiety in normal school-age children. J Am Acad Child Adolesc Psychiatry. 1994;33(3):407–15. doi: https://doi.org/10.1097/00004583-199403000-00016
- Bernstein GA, Carroll ME, Dean NW, Crosby RD, Perwien AR, Benowitz NL. Caffeine withdrawal in normal school-age children. J Am Acad Child Adolesc Psychiatry. 1998 Aug;37(8):858–65. doi: https://doi.org/10.1097/00004583-199808000-00016
- Higdon JV, Frei B. Coffee and health: a review of recent human research. Crit Rev Food Sci Nutr. 2006;46(2):101–23. doi: https://doi.org/10.1080/10408390500400009
- Benowitz NL, Hall SM, Modin G. Persistent increase in caffeine concentrations in people who stop smoking. BMJ. 1989 Apr;298(6680):1075–6. doi: https://doi.org/10.1136/bmj.298.6680.1075
- Benvenga S, Bartolone L, Pappalardo MA, Russo A, Lapa D, Giorgianni G, et al. Altered intestinal absorption of L-thyroxine caused by coffee. Thyroid. 2008 Mar;18(3):293–301. doi: https://doi.org/10.1089/thy.2007.0222
- Gertz BJ, Holland SD, Kline WF, Matuszewski BK, Freeman A, Quan H, et al. Studies of the oral bioavailability of alendronate. Clin Pharmacol Ther. 1995 Sep;58(3):288–98. doi: https://doi.org/10.1016/0009-9236(95)90245-7
- Bushra R, Aslam N, Khan AY. Food-drug interactions. Oman Med J. 2011 Mar;26(2):77–83. doi: https://doi.org/10.5001/omj.2011.21
- Abu-Shaweesh JM, Martin RJ. Neonatal apnea: what’s new? Pediatr Pulmonol. 2008 Oct;43(10):937–44. doi: https://doi.org/10.1002/ppul.20832
- Diener HC, Gold M, Hagen M. Use of a fixed combination of acetylsalicylic acid, acetaminophen and caffeine compared with acetaminophen alone in episodic tension-type headache: meta-analysis of four randomized, double-blind, placebo-controlled, crossover studies. J Headache Pain. 2014 Nov;15(1):76. doi: https://doi.org/10.1186/1129-2377-15-76
- Franke AG, Koller G, Krause D, Proebstl L, Kamp F, Pogarell O, et al. Just “like coffee” or neuroenhancement by stimulants? Front Public Health. 2021 Jun;9:640154. doi: https://doi.org/10.3389/fpubh.2021.640154
- Antal A, Luber B, Brem AK, Bikson M, Brunoni AR, Cohen Kadosh R, et al. Non-invasive brain stimulation and neuroenhancement. Clin Neurophysiol Pract. 2022 May;7:146–65. doi: https://doi.org/10.1016/j.cnp.2022.05.002
- Chen Y, Sun X, Lin Y, Zhang Z, Gao Y, Wu IX. Non-genetic risk factors for Parkinson’s disease: An Overview of 46 Systematic Reviews. J Parkinsons Dis. 2021;11(3):919–35. doi: https://doi.org/10.3233/JPD-202521
- Hernán MA, Takkouche B, Caamaño-Isorna F, Gestal-Otero JJ. A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson’s disease. Ann Neurol. 2002 Sep;52(3):276–84. doi: https://doi.org/10.1002/ana.10277
- Belvisi D, Pellicciari R, Fabbrini A, Costanzo M, Ressa G, Pietracupa S, et al. Relationship between risk and protective factors and clinical features of Parkinson’s disease. Parkinsonism Relat Disord. 2022 May;98:80–5. doi: https://doi.org/10.1016/j.parkreldis.2022.04.017
- Chen JF, Eltzschig HK, Fredholm BB. Adenosine receptors as drug targets—what are the challenges? Nat Rev Drug Discov. 2013 Apr;12(4):265–86. doi: https://doi.org/10.1038/nrd3955
- Abbott RD, Ross GW, White LR, Sanderson WT, Burchfiel CM, Kashon M, et al. Environmental, life-style, and physical precursors of clinical Parkinson’s disease: recent findings from the Honolulu-Asia Aging Study. J Neurol. 2003 Oct;250(0 Suppl 3):III30–9. 10.1007/s00415-003-1306-7
- Ascherio A, Chen H, Schwarzschild MA, Zhang SM, Colditz GA, Speizer FE. Caffeine, postmenopausal estrogen, and risk of Parkinson’s disease. Neurology. 2003 Mar;60(5):790–5. doi: https://doi.org/10.1212/01.WNL.0000046523.05125.87
- Ascherio A, Weisskopf MG, O’Reilly EJ, McCullough ML, Calle EE, Rodriguez C, et al. Coffee consumption, gender, and Parkinson’s disease mortality in the cancer prevention study II cohort: the modifying effects of estrogen. Am J Epidemiol. 2004 Nov;160(10):977–84. doi: https://doi.org/10.1093/aje/kwh312
- Barranco Quintana JL, Allam MF, Serrano Del Castillo A, Fernández-Crehuet Navajas R. Alzheimer’s disease and coffee: a quantitative review. Neurol Res. 2007 Jan;29(1):91–5. doi: https://doi.org/10.1179/174313206X152546
- Huxley R, Lee CM, Barzi F, Timmermeister L, Czernichow S, Perkovic V, et al. Coffee, decaffeinated coffee, and tea consumption in relation to incident type 2 diabetes mellitus: a systematic review with meta-analysis. Arch Intern Med. 2009 Dec;169(22):2053–63. doi: https://doi.org/10.1001/archinternmed.2009.439
- Liu F, Wang X, Wu G, Chen L, Hu P, Ren H, et al. Coffee consumption decreases risks for hepatic fibrosis and cirrhosis: a meta-analysis. PLoS One. 2015 Nov;10(11):e0142457. doi: https://doi.org/10.1371/journal.pone.0142457
- Steppuhn A, Gase K, Krock B, Halitschke R, Baldwin IT. Nicotine’s defensive function in nature. PLoS Biol. 2004 Aug;2(8):E217. doi: https://doi.org/10.1371/journal.pbio.0020217
- Jordt SE. Synthetic nicotine has arrived. Tob Control. 2023 Apr;32 e1:e113–7. doi: https://doi.org/10.1136/tobaccocontrol-2021-056626
- Zettler PJ, Hemmerich N, Berman ML. Closing the regulatory gap for synthetic nicotine products. Boston Coll Law Rev. 2018;59(6):1933–82.
- Stephenson J. FDA gains power to regulate synthetic nicotine in e-cigarettes. JAMA Health Forum. 2022 Apr;3(4):e221140. doi: https://doi.org/10.1001/jamahealthforum.2022.1140
- Duren M, Atella L, Welding K, Kennedy RD. Nicotine pouches: a summary of regulatory approaches across 67 countries. Tob Control. 2023 Feb 7:tc-2022-057734.
- Berman ML, Zettler PJ, Jordt SE. Synthetic nicotine: science, global legal landscape, and regulatory considerations. World Health Organ Tech Rep Ser. 2023;1047:35–60.
- Cheetham AG, Plunkett S, Campbell P, Hilldrup J, Coffa BG, Gilliland S 3rd, et al. Analysis and differentiation of tobacco-derived and synthetic nicotine products: addressing an urgent regulatory issue. PLoS One. 2022 Apr;17(4):e0267049. doi: https://doi.org/10.1371/journal.pone.0267049
- Perfetti TA, Ashraf-Khorassani M, Coleman WM 3rd, Dube MF. Qualitative and quantitative analyses of the enantiomers of nicotine and related alkaloids employing chiral supercritical fluid chromatography in commercial nicotine samples and in e-cigarette products. Contrib Tob Nicotine Res. 2023 Aug;32(3):77–89. doi: https://doi.org/10.2478/cttr-2023-0010
- Benowitz NL, Hukkanen J, Jacob P 3rd. Nicotine chemistry, metabolism, kinetics and biomarkers. Handb Exp Pharmacol. 2009;192:29–60. doi: https://doi.org/10.1007/978-3-540-69248-5_2
- Tanner JA, Zhu AZ, Claw KG, Prasad B, Korchina V, Hu J, et al. Novel CYP2A6 diplotypes identified through next-generation sequencing are associated with in-vitro and in-vivo nicotine metabolism. Pharmacogenet Genomics. 2018 Jan;28(1):7–16. doi: https://doi.org/10.1097/FPC.0000000000000317
- Hukkanen J, Jacob P 3rd, Benowitz NL. Metabolism and disposition kinetics of nicotine. Pharmacol Rev. 2005 Mar;57(1):79–115. doi: https://doi.org/10.1124/pr.57.1.3
- Pérez-Stable EJ, Herrera B, Jacob P 3rd, Benowitz NL. Nicotine metabolism and intake in black and white smokers. JAMA. 1998 Jul;280(2):152–6. doi: https://doi.org/10.1001/jama.280.2.152
- Benowitz NL, Pérez-Stable EJ, Herrera B, Jacob P 3rd. Slower metabolism and reduced intake of nicotine from cigarette smoking in Chinese-Americans. J Natl Cancer Inst. 2002 Jan;94(2):108–15. doi: https://doi.org/10.1093/jnci/94.2.108
- Benowitz NL, Lessov-Schlaggar CN, Swan GE, Jacob P 3rd. Female sex and oral contraceptive use accelerate nicotine metabolism. Clin Pharmacol Ther. 2006 May;79(5):480–8. doi: https://doi.org/10.1016/j.clpt.2006.01.008
- Rebagliato M, Bolúmar F, Florey CV, Jarvis MJ, Pérez-Hoyos S, Hernández-Aguado I, et al. Variations in cotinine levels in smokers during and after pregnancy. Am J Obstet Gynecol. 1998 Mar;178(3):568–71. doi: https://doi.org/10.1016/S0002-9378(98)70440-5
- Selby P, Hackman R, Kapur B, Klein J, Koren G. Heavily smoking women who cannot quit in pregnancy: evidence of pharmacokinetic predisposition. Ther Drug Monit. 2001 Jun;23(3):189–91. doi: https://doi.org/10.1097/00007691-200106000-00001
- Molander L, Hansson A, Lunell E. Pharmacokinetics of nicotine in healthy elderly people. Clin Pharmacol Ther. 2001 Jan;69(1):57–65. doi: https://doi.org/10.1067/mcp.2001.113181
- Zacny JP, Stitzer ML. Cigarette brand-switching: effects on smoke exposure and smoking behavior. J Pharmacol Exp Ther. 1988 Aug;246(2):619–27. doi: https://doi.org/10.1016/S0022-3565(25)22128-0
- Dawkins LE, Kimber CF, Doig M, Feyerabend C, Corcoran O. Self-titration by experienced e-cigarette users: blood nicotine delivery and subjective effects. Psychopharmacology (Berl). 2016 Aug;233(15-16):2933–41. doi: https://doi.org/10.1007/s00213-016-4338-2
- Sofuoglu M, Herman AI, Nadim H, Jatlow P. Rapid nicotine clearance is associated with greater reward and heart rate increases from intravenous nicotine. Neuropsychopharmacology. 2012 May;37(6):1509–16. doi: https://doi.org/10.1038/npp.2011.336
- Papke RL. Merging old and new perspectives on nicotinic acetylcholine receptors. Biochem Pharmacol. 2014 May;89(1):1–11. doi: https://doi.org/10.1016/j.bcp.2014.01.029
- Wills L, Ables JL, Braunscheidel KM, Caligiuri SP, Elayouby KS, Fillinger C, et al. Neurobiological mechanisms of nicotine reward and aversion. Pharmacol Rev. 2022 Jan;74(1):271–310. doi: https://doi.org/10.1124/pharmrev.121.000299
- Fowler CD, Turner JR, Imad Damaj M. Molecular mechanisms associated with nicotine pharmacology and dependence. Handb Exp Pharmacol. 2020;258:373–93. doi: https://doi.org/10.1007/164_2019_252
- Hughes JR. Effects of abstinence from tobacco: valid symptoms and time course. Nicotine Tob Res. 2007 Mar;9(3):315–27. doi: https://doi.org/10.1080/14622200701188919
- Kerr DC, Owen LD, Capaldi DM. The timing of smoking onset, prolonged abstinence and relapse in men: a prospective study from ages 18 to 32 years. Addiction. 2011 Nov;106(11):2031–8. doi: https://doi.org/10.1111/j.1360-0443.2011.03500.x
- Jacob P 3rd, Benowitz NL, Copeland JR, Risner ME, Cone EJ. Disposition kinetics of nicotine and cotinine enantiomers in rabbits and beagle dogs. J Pharm Sci. 1988 May;77(5):396–400. doi: https://doi.org/10.1002/jps.2600770508
- Nwosu CG, Godin CS, Houdi AA, Damani LA, Crooks PA. Enantioselective metabolism during continuous administration of S-(-)- and R-(+)-nicotine isomers to guinea-pigs. J Pharm Pharmacol. 1988 Dec;40(12):862–9. doi: https://doi.org/10.1111/j.2042-7158.1988.tb06289.x
- Ikushima S, Muramatsu I, Sakakibara Y, Yokotani K, Fujiwara M. The effects of d-nicotine and l-isomer on nicotinic receptors. J Pharmacol Exp Ther. 1982 Aug;222(2):463–70. doi: https://doi.org/10.1016/S0022-3565(25)33223-4
- Fotedar S, Fotedar V. Green tobacco sickness: a brief review. Indian J Occup Environ Med. 2017;21(3):101–4. doi: https://doi.org/10.4103/ijoem.IJOEM_160_17
- Henstra C, Dekkers BG, Olgers TJ, Ter Maaten JC, Touw DJ. Managing intoxications with nicotine-containing e-liquids. Expert Opin Drug Metab Toxicol. 2022 Feb;18(2):115–21. doi: https://doi.org/10.1080/17425255.2022.2058930
- Maessen GC, Wijnhoven AM, Neijzen RL, Paulus MC, van Heel DA, Bomers BH, et al. Nicotine intoxication by e-cigarette liquids: a study of case reports and pathophysiology. Clin Toxicol (Phila). 2020 Jan;58(1):1–8. doi: https://doi.org/10.1080/15563650.2019.1636994
- Mayer B. How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. Arch Toxicol. 2014 Jan;88(1):5–7. doi: https://doi.org/10.1007/s00204-013-1127-0
- Alkam T, Nabeshima T. Molecular mechanisms for nicotine intoxication. Neurochem Int. 2019 May;125:117–26. doi: https://doi.org/10.1016/j.neuint.2019.02.006
- Connolly GN, Richter P, Aleguas A Jr, Pechacek TF, Stanfill SB, Alpert HR. Unintentional child poisonings through ingestion of conventional and novel tobacco products. Pediatrics. 2010 May;125(5):896–9. doi: https://doi.org/10.1542/peds.2009-2835
- Obertova N, Navratil T, Zak I, Zakharov S. Acute exposures to e-cigarettes and heat-not-burn products reported to the Czech Toxicological Information Centre over a 7-year period (2012-2018). Basic Clin Pharmacol Toxicol. 2020 Jul;127(1):39–46. doi: https://doi.org/10.1111/bcpt.13393
- Franchitto N, Bloch J, Solal C, Pélissier F; French PCC Research Group. French PCCRG, Pelissier F. Self-poisoning by e-cigarette and e-liquids: national reports to French poison control centers from July 2019 to December 2020: VIGIlance and VAPE: the VIGIVAPE Study. Nicotine Tob Res. 2024 Feb;26(3):281–8. doi: https://doi.org/10.1093/ntr/ntad116
- Ferris Wayne G, Connolly GN. Application, function, and effects of menthol in cigarettes: a survey of tobacco industry documents. Nicotine Tob Res. 2004 Feb;6 Suppl 1:S43–54. 10.1080/14622203310001649513
- Fagan P, Pokhrel P, Herzog TA, Pagano IS, Franke AA, Clanton MS, et al. Nicotine metabolism in young adult daily menthol and nonmenthol smokers. Nicotine Tob Res. 2016 Apr;18(4):437–46. doi: https://doi.org/10.1093/ntr/ntv109
- Scientific Committee on Health. Opinion on additives used in tobacco products. Available from: https://health.ec.europa.eu/scientific-committees_en
- Anderson GD, Chan LN. Pharmacokinetic drug interactions with tobacco, cannabinoids and smoking cessation products. Clin Pharmacokinet. 2016 Nov;55(11):1353–68. doi: https://doi.org/10.1007/s40262-016-0400-9
- Zevin S, Benowitz NL. Drug interactions with tobacco smoking. An update. Clin Pharmacokinet. 1999 Jun;36(6):425–38. doi: https://doi.org/10.2165/00003088-199936060-00004
- Piper ME, Smith SS, Schlam TR, Fiore MC, Jorenby DE, Fraser D, et al. A randomized placebo-controlled clinical trial of 5 smoking cessation pharmacotherapies. Arch Gen Psychiatry. 2009 Nov;66(11):1253–62. doi: https://doi.org/10.1001/archgenpsychiatry.2009.142
- Henningfield JE, Keenan RM. Nicotine delivery kinetics and abuse liability. J Consult Clin Psychol. 1993 Oct;61(5):743–50. doi: https://doi.org/10.1037/0022-006X.61.5.743
- Etter JF. Addiction to the nicotine gum in never smokers. BMC Public Health. 2007 Jul;7(1):159. doi: https://doi.org/10.1186/1471-2458-7-159
- Hajek P, Phillips-Waller A, Przulj D, Pesola F, Myers Smith K, Bisal N, et al. A randomized trial of e-cigarettes versus nicotine-replacement therapy. N Engl J Med. 2019 Feb;380(7):629–37. doi: https://doi.org/10.1056/NEJMoa1808779
- Prochaska JJ, Benowitz NL. Current advances in research in treatment and recovery: nicotine addiction. Sci Adv. 2019 Oct;5(10):eaay9763. doi: https://doi.org/10.1126/sciadv.aay9763
- Lasser K, Boyd JW, Woolhandler S, Himmelstein DU, McCormick D, Bor DH. Smoking and mental illness: A population-based prevalence study. JAMA. 2000 Nov;284(20):2606–10. doi: https://doi.org/10.1001/jama.284.20.2606
- Sagud M, Mihaljevic Peles A, Pivac N. Smoking in schizophrenia: recent findings about an old problem. Curr Opin Psychiatry. 2019 Sep;32(5):402–8. doi: https://doi.org/10.1097/YCO.0000000000000529
- Adler LE, Olincy A, Waldo M, Harris JG, Griffith J, Stevens K, et al. Schizophrenia, sensory gating, and nicotinic receptors. Schizophr Bull. 1998;24(2):189–202. doi: https://doi.org/10.1093/oxfordjournals.schbul.a033320
- Fluharty M, Taylor AE, Grabski M, Munafò MR. The association of cigarette smoking with depression and anxiety: a systematic review. Nicotine Tob Res. 2017 Jan;19(1):3–13. doi: https://doi.org/10.1093/ntr/ntw140
- Li X, Li W, Liu G, Shen X, Tang Y. Association between cigarette smoking and Parkinson’s disease: A meta-analysis. Arch Gerontol Geriatr. 2015;61(3):510–6. doi: https://doi.org/10.1016/j.archger.2015.08.004
- Yang F, Pedersen NL, Ye W, Liu Z, Norberg M, Forsgren L, et al. Moist smokeless tobacco (Snus) use and risk of Parkinson’s disease. Int J Epidemiol. 2017 Jun;46(3):872–80.
- Ma C, Molsberry S, Li Y, Schwarzschild M, Ascherio A, Gao X. Dietary nicotine intake and risk of Parkinson disease: a prospective study. Am J Clin Nutr. 2020 Oct;112(4):1080–7. doi: https://doi.org/10.1093/ajcn/nqaa186
- Tanner CM, Goldman SM, Aston DA, Ottman R, Ellenberg J, Mayeux R, et al. Smoking and Parkinson’s disease in twins. Neurology. 2002 Feb;58(4):581–8. doi: https://doi.org/10.1212/WNL.58.4.581
- Villafane G, Thiriez C, Audureau E, Straczek C, Kerschen P, Cormier-Dequaire F, et al. High-dose transdermal nicotine in Parkinson’s disease patients: a randomized, open-label, blinded-endpoint evaluation phase 2 study. Eur J Neurol. 2018 Jan;25(1):120–7. doi: https://doi.org/10.1111/ene.13474
- Vieregge A, Sieberer M, Jacobs H, Hagenah JM, Vieregge P. Transdermal nicotine in PD: a randomized, double-blind, placebo-controlled study. Neurology. 2001 Sep;57(6):1032–5. doi: https://doi.org/10.1212/WNL.57.6.1032
- Clemens P, Baron JA, Coffey D, Reeves A. The short-term effect of nicotine chewing gum in patients with Parkinson’s disease. Psychopharmacology (Berl). 1995 Jan;117(2):253–6. doi: https://doi.org/10.1007/BF02245195
- Fratiglioni L, Wang HX. Smoking and Parkinson’s and Alzheimer’s disease: review of the epidemiological studies. Behav Brain Res. 2000 Aug;113(1-2):117–20. doi: https://doi.org/10.1016/S0166-4328(00)00206-0
- Cataldo JK, Prochaska JJ, Glantz SA. Cigarette smoking is a risk factor for Alzheimer’s Disease: an analysis controlling for tobacco industry affiliation. J Alzheimers Dis. 2010;19(2):465–80. doi: https://doi.org/10.3233/JAD-2010-1240
- Shim SB, Lee SH, Chae KR, Kim CK, Hwang DY, Kim BG, et al. Nicotine leads to improvements in behavioral impairment and an increase in the nicotine acetylcholine receptor in transgenic mice. Neurochem Res. 2008 Sep;33(9):1783–8. doi: https://doi.org/10.1007/s11064-008-9629-5
- Srivareerat M, Tran TT, Salim S, Aleisa AM, Alkadhi KA. Chronic nicotine restores normal Aβ levels and prevents short-term memory and E-LTP impairment in Aβ rat model of Alzheimer’s disease. Neurobiol Aging. 2011 May;32(5):834–44. doi: https://doi.org/10.1016/j.neurobiolaging.2009.04.015
- Howe MN, Price IR. Effects of transdermal nicotine on learning, memory, verbal fluency, concentration, and general health in a healthy sample at risk for dementia. Int Psychogeriatr. 2001 Dec;13(4):465–75. doi: https://doi.org/10.1017/S1041610201007888
- White HK, Levin ED. Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer’s disease. Psychopharmacology (Berl). 1999 Apr;143(2):158–65. doi: https://doi.org/10.1007/s002130050931
- Mahid SS, Minor KS, Soto RE, Hornung CA, Galandiuk S. Smoking and inflammatory bowel disease: a meta-analysis. Mayo Clin Proc. 2006 Nov;81(11):1462–71. doi: https://doi.org/10.4065/81.11.1462
- Tracey KJ. Reflex control of immunity. Nat Rev Immunol. 2009 Jun;9(6):418–28. doi: https://doi.org/10.1038/nri2566
- Mabley J, Gordon S, Pacher P. Nicotine exerts an anti-inflammatory effect in a murine model of acute lung injury. Inflammation. 2011 Aug;34(4):231–7. doi: https://doi.org/10.1007/s10753-010-9228-x
- Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L, et al. Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med. 2004 Nov;10(11):1216–21. doi: https://doi.org/10.1038/nm1124
- Cheng Z, Li-Sha G, Jing-Lin Z, Wen-Wu Z, Xue-Si C, Xing-Xing C, et al. Protective role of the cholinergic anti-inflammatory pathway in a mouse model of viral myocarditis. PLoS One. 2014 Nov;9(11):e112719. doi: https://doi.org/10.1371/journal.pone.0112719
- Sadis C, Teske G, Stokman G, Kubjak C, Claessen N, Moore F, et al. Nicotine protects kidney from renal ischemia/reperfusion injury through the cholinergic anti-inflammatory pathway. PLoS One. 2007 May;2(5):e469. doi: https://doi.org/10.1371/journal.pone.0000469
- Shi FD, Piao WH, Kuo YP, Campagnolo DI, Vollmer TL, Lukas RJ. Nicotinic attenuation of central nervous system inflammation and autoimmunity. J Immunol. 2009 Feb;182(3):1730–9. doi: https://doi.org/10.4049/jimmunol.182.3.1730
- Strzelak A, Ratajczak A, Adamiec A, Feleszko W. Tobacco smoke induces and alters immune responses in the lung triggering inflammation, allergy, asthma and other lung diseases: a mechanistic review. Int J Environ Res Public Health. 2018 May;15(5):1033. doi: https://doi.org/10.3390/ijerph15051033
- Ligresti A, De Petrocellis L, Di Marzo V. From phytocannabinoids to cannabinoid receptors and endocannabinoids: pleiotropic physiological and pathological roles through complex pharmacology. Physiol Rev. 2016 Oct;96(4):1593–659. doi: https://doi.org/10.1152/physrev.00002.2016
- Dos Reis Rosa Franco G, Smid S, Viegas C. Phytocannabinoids: general aspects and pharmacological potential in neurodegenerative diseases. Curr Neuropharmacol. 2021;19(4):449–64. doi: https://doi.org/10.2174/1570159X18666200720172624
- Aizpurua-Olaizola O, Soydaner U, Öztürk E, Schibano D, Simsir Y, Navarro P, et al. Evolution of the cannabinoid and terpene content during the growth of cannabis sativa plants from different chemotypes. J Nat Prod. 2016 Feb;79(2):324–31. doi: https://doi.org/10.1021/acs.jnatprod.5b00949
- Corroon J. Cannabinol and sleep: separating fact from fiction. Cannabis Cannabinoid Res. 2021 Oct;6(5):366–71. doi: https://doi.org/10.1089/can.2021.0006
- Foster BC, Abramovici H, Harris CS. Cannabis and cannabinoids: kinetics and interactions. Am J Med. 2019 Nov;132(11):1266–70. doi: https://doi.org/10.1016/j.amjmed.2019.05.017
- Reboussin BA, Wagoner KG, Sutfin EL, Suerken C, Ross JC, Egan KL, et al. Trends in marijuana edible consumption and perceptions of harm in a cohort of young adults. Drug Alcohol Depend. 2019 Dec;205:107660. doi: https://doi.org/10.1016/j.drugalcdep.2019.107660
- Syed YY, McKeage K, Scott LJ. Delta-9-tetrahydrocannabinol/cannabidiol (Sativex®): a review of its use in patients with moderate to severe spasticity due to multiple sclerosis. Drugs. 2014 Apr;74(5):563–78. doi: https://doi.org/10.1007/s40265-014-0197-5
- Sholler DJ, Schoene L, Spindle TR. Therapeutic efficacy of cannabidiol (CBD): a review of the evidence from clinical trials and human laboratory studies. Curr Addict Rep. 2020 Sep;7(3):405–12. doi: https://doi.org/10.1007/s40429-020-00326-8
- Lucas CJ, Galettis P, Schneider J. The pharmacokinetics and the pharmacodynamics of cannabinoids. Br J Clin Pharmacol. 2018 Nov;84(11):2477–82. doi: https://doi.org/10.1111/bcp.13710
- Lunn S, Diaz P, O’Hearn S, Cahill SP, Blake A, Narine K, et al. Human pharmacokinetic parameters of orally administered Δ(9)-tetrahydrocannabinol capsules are altered by fed versus fasted conditions and sex differences. Cannabis Cannabinoid Res. 2019 Dec;4(4):255–64. doi: https://doi.org/10.1089/can.2019.0037
- Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet. 2003;42(4):327–60. doi: https://doi.org/10.2165/00003088-200342040-00003
- Heuberger JA, Guan Z, Oyetayo OO, Klumpers L, Morrison PD, Beumer TL, et al. Population pharmacokinetic model of THC integrates oral, intravenous, and pulmonary dosing and characterizes short- and long-term pharmacokinetics. Clin Pharmacokinet. 2015 Feb;54(2):209–19. doi: https://doi.org/10.1007/s40262-014-0195-5
- Sharma P, Murthy P, Bharath MM. Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iran J Psychiatry. 2012;7(4):149–56.
- Lowe RH, Abraham TT, Darwin WD, Herning R, Cadet JL, Huestis MA. Extended urinary Delta9-tetrahydrocannabinol excretion in chronic cannabis users precludes use as a biomarker of new drug exposure. Drug Alcohol Depend. 2009 Nov;105(1-2):24–32. doi: https://doi.org/10.1016/j.drugalcdep.2009.05.027
- McPherson C. Up in smoke: the impacts of marijuana during pregnancy. Neonatal Netw. 2023 Jul;42(4):222–32. doi: https://doi.org/10.1891/NN-2022-0040
- Baker T, Datta P, Rewers-Felkins K, Thompson H, Kallem RR, Hale TW. Transfer of inhaled cannabis into human breast milk. Obstet Gynecol. 2018 May;131(5):783–8. doi: https://doi.org/10.1097/AOG.0000000000002575
- Babayeva M, Loewy ZG. Cannabis pharmacogenomics: a path to personalized medicine. Curr Issues Mol Biol. 2023 Apr;45(4):3479–514. doi: https://doi.org/10.3390/cimb45040228
- Hess C, Schoeder CT, Pillaiyar T, Madea B, Müller CE. Pharmacological evaluation of synthetic cannabinoids identified as constituents of spice. Forensic Toxicol. 2016;34(2):329–43. doi: https://doi.org/10.1007/s11419-016-0320-2
- Alipour A, Patel PB, Shabbir Z, Gabrielson S. Review of the many faces of synthetic cannabinoid toxicities. Ment Health Clin. 2019 Mar;9(2):93–9. doi: https://doi.org/10.9740/mhc.2019.03.093
- Peng J, Fan M, An C, Ni F, Huang W, Luo J. A narrative review of molecular mechanism and therapeutic effect of cannabidiol (CBD). Basic Clin Pharmacol Toxicol. 2022 Apr;130(4):439–56. doi: https://doi.org/10.1111/bcpt.13710
- Cohen K, Weinstein AM. Synthetic and non-synthetic cannabinoid drugs and their Adverse effects-a review from public health prospective. Front Public Health. 2018 Jun;6:162. doi: https://doi.org/10.3389/fpubh.2018.00162
- Schep LJ, Slaughter RJ, Glue P, Gee P. The clinical toxicology of cannabis. N Z Med J. 2020 Oct;133(1523):96–103.
- Choi NG, Marti CN, DiNitto DM, Baker SD. Cannabis and synthetic cannabinoid poison control center cases among adults aged 50+, 2009-2019. Clin Toxicol (Phila). 2021 Apr;59(4):334–42. doi: https://doi.org/10.1080/15563650.2020.1806296
- Rock KL, Englund A, Morley S, Rice K, Copeland CS. Can cannabis kill? Characteristics of deaths following cannabis use in England (1998-2020). J Psychopharmacol. 2022 Dec;36(12):1362–70. doi: https://doi.org/10.1177/02698811221115760
- Levinsohn EA, Hill KP. Clinical uses of cannabis and cannabinoids in the United States. J Neurol Sci. 2020 Apr;411:116717. doi: https://doi.org/10.1016/j.jns.2020.116717
- Benowitz NL. Managing cannabis use in patients with cardiovascular disease. Can J Cardiol. 2019 Feb;35(2):138–41. doi: https://doi.org/10.1016/j.cjca.2018.12.033
- McCartney D, Arkell TR, Irwin C, McGregor IS. Determining the magnitude and duration of acute Δ9-tetrahydrocannabinol (Δ9-THC)-induced driving and cognitive impairment: A systematic and meta-analytic review. Neurosci Biobehav Rev. 2021 Jul;126:175–93. doi: https://doi.org/10.1016/j.neubiorev.2021.01.003
- American Psychiatric Association D-TF. Diagnostic and statistical manual of mental disorders: DSM-5. 5th ed. American Psychiatric Publishing, Inc.; 2013.
- Haney M, Evins AE. Does cannabis cause, exacerbate or ameliorate psychiatric disorders? An oversimplified debate discussed. Neuropsychopharmacology. 2016 Jan;41(2):393–401. doi: https://doi.org/10.1038/npp.2015.251
- DeVuono MV, Parker LA. Cannabinoid hyperemesis syndrome: a review of potential mechanisms. Cannabis Cannabinoid Res. 2020 Jun;5(2):132–44. doi: https://doi.org/10.1089/can.2019.0059
- Badowski S, Smith G. Cannabis use during pregnancy and postpartum. Can Fam Physician. 2020 Feb;66(2):98–103.
- Gobbi G, Atkin T, Zytynski T, Wang S, Askari S, Boruff J, et al. Association of cannabis use in adolescence and risk of depression, anxiety, and suicidality in young adulthood: a systematic review and meta-analysis. JAMA Psychiatry. 2019 Apr;76(4):426–34. doi: https://doi.org/10.1001/jamapsychiatry.2018.4500
- Volkow ND, Compton WM, Weiss SR. Adverse health effects of marijuana use. N Engl J Med. 2014 Aug;371(9):879.
- Di Forti M, Sallis H, Allegri F, Trotta A, Ferraro L, Stilo SA, et al. Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users. Schizophr Bull. 2014 Nov;40(6):1509–17. doi: https://doi.org/10.1093/schbul/sbt181
- Lopera V, Rodríguez A, Amariles P. Clinical relevance of drug interactions with cannabis: a systematic review. J Clin Med. 2022 Feb;11(5):1154. doi: https://doi.org/10.3390/jcm11051154
- Hsu A, Painter NA. Probable interaction between warfarin and inhaled and oral administration of cannabis. J Pharm Pract. 2020 Dec;33(6):915–8. doi: https://doi.org/10.1177/0897190019854958
- Damkier P, Lassen D, Christensen MM, Madsen KG, Hellfritzsch M, Pottegård A. Interaction between warfarin and cannabis. Basic Clin Pharmacol Toxicol. 2019 Jan;124(1):28–31. doi: https://doi.org/10.1111/bcpt.13152
- Yamreudeewong W, Wong HK, Brausch LM, Pulley KR. Probable interaction between warfarin and marijuana smoking. Ann Pharmacother. 2009 Jul;43(7):1347–53. doi: https://doi.org/10.1345/aph.1M064
- Vierke C, Marxen B, Boettcher M, Hiemke C, Havemann-Reinecke U. Buprenorphine-cannabis interaction in patients undergoing opioid maintenance therapy. Eur Arch Psychiatry Clin Neurosci. 2021 Aug;271(5):847–56. doi: https://doi.org/10.1007/s00406-019-01091-0
- Stott C, White L, Wright S, Wilbraham D, Guy G. A Phase I, open-label, randomized, crossover study in three parallel groups to evaluate the effect of Rifampicin, Ketoconazole, and Omeprazole on the pharmacokinetics of THC/CBD oromucosal spray in healthy volunteers. Springerplus. 2013 May;2(1):236. doi: https://doi.org/10.1186/2193-1801-2-236
- Stockings E, Zagic D, Campbell G, Weier M, Hall WD, Nielsen S, et al. Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence. J Neurol Neurosurg Psychiatry. 2018 Jul;89(7):741–53. doi: https://doi.org/10.1136/jnnp-2017-317168
- Silva GD, Del Guerra FB, de Oliveira Lelis M, Pinto LF. Cannabidiol in the treatment of epilepsy: a focused review of evidence and gaps. Front Neurol. 2020 Oct;11:531939. doi: https://doi.org/10.3389/fneur.2020.531939
- Stockings E, Campbell G, Hall WD, Nielsen S, Zagic D, Rahman R, et al. Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: a systematic review and meta-analysis of controlled and observational studies. Pain. 2018 Oct;159(10):1932–54. doi: https://doi.org/10.1097/j.pain.0000000000001293
- McDonagh MS, Morasco BJ, Wagner J, Ahmed AY, Fu R, Kansagara D, et al. Cannabis-based products for chronic pain: a systematic review. Ann Intern Med. 2022 Aug;175(8):1143–53. doi: https://doi.org/10.7326/M21-4520
- Leweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW, Hoyer C, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012 Mar;2(3):e94. doi: https://doi.org/10.1038/tp.2012.15
- Mandolini GM, Lazzaretti M, Pigoni A, Oldani L, Delvecchio G, Brambilla P. Pharmacological properties of cannabidiol in the treatment of psychiatric disorders: a critical overview. Epidemiol Psychiatr Sci. 2018 Aug;27(4):327–35. doi: https://doi.org/10.1017/S2045796018000239
- Nichols DE. Psilocybin: from ancient magic to modern medicine. J Antibiot (Tokyo). 2020 Oct;73(10):679–86. doi: https://doi.org/10.1038/s41429-020-0311-8
- Van Court RC, Wiseman MS, Meyer KW, Ballhorn DJ, Amses KR, Slot JC, et al. Diversity, biology, and history of psilocybin-containing fungi: suggestions for research and technological development. Fungal Biol. 2022 Apr;126(4):308–19. doi: https://doi.org/10.1016/j.funbio.2022.01.003
- Hofmann A, Heim R, Brack A, Kobel H. [Psilocybin, a psychotropic substance from the Mexican mushroom Psilicybe mexicana Heim]. Experientia. 1958 Mar;14(3):107–9. doi: https://doi.org/10.1007/BF02159243
- Matzopoulos R, Morlock R, Morlock A, Lerer B, Lerer L. Psychedelic mushrooms in the USA: knowledge, patterns of use, and association with health outcomes. Front Psychiatry. 2022 Jan;12:780696. doi: https://doi.org/10.3389/fpsyt.2021.780696
- Keyes KM, Patrick ME. Hallucinogen use among young adults ages 19-30 in the United States: changes from 2018 to 2021. Addiction. 2023 Dec;118(12):2449–54. doi: https://doi.org/10.1111/add.16259
- Lowe H, Toyang N, Steele B, Valentine H, Grant J, Ali A, et al. The therapeutic potential of psilocybin. Molecules. 2021 May;26(10):2948. doi: https://doi.org/10.3390/molecules26102948
- van Amsterdam J, Opperhuizen A, van den Brink W. Harm potential of magic mushroom use: a review. Regul Toxicol Pharmacol. 2011 Apr;59(3):423–9. doi: https://doi.org/10.1016/j.yrtph.2011.01.006
- MacCallum CA, Lo LA, Pistawka CA, Deol JK. Therapeutic use of psilocybin: practical considerations for dosing and administration. Front Psychiatry. 2022 Dec;13:1040217. doi: https://doi.org/10.3389/fpsyt.2022.1040217
- Kamata T, Nishikawa M, Katagi M, Tsuchihashi H. Liquid chromatography-mass spectrometric and liquid chromatography-tandem mass spectrometric determination of hallucinogenic indoles psilocin and psilocybin in “magic mushroom” samples. J. Forensic. J Forensic Sci. 2005;50(2):JFS2004276–5. 10.1520/JFS2004276
- Andersson C, Kristinsson J, Gry J. Occurrence and use of hallucinogenic mushrooms containing psilocybin alkaloids. Nordic Council of Ministers; 2009.ISBN: 978-92-893-1836-5. doi: https://doi.org/10.6027/tn2008-606
- Beug MW, Bigwood J. Psilocybin and psilocin levels in twenty species from seven genera of wild mushrooms in the Pacific Northwest, U.S.A. J Ethnopharmacol. 1982 May;5(3):271–85. doi: https://doi.org/10.1016/0378-8741(82)90013-7
- Christiansen AL, Rasmussen KE, Høiland K. The content of Psilocybin in Norwegian Psilocybe semilanceata. Planta Med. 1981 Jul;42(7):229–35. doi: https://doi.org/10.1055/s-2007-971632
- Dinis-Oliveira RJ. Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance. Drug Metab Rev. 2017 Feb;49(1):84–91. doi: https://doi.org/10.1080/03602532.2016.1278228
- Hasler F, Bourquin D, Brenneisen R, Bär T, Vollenweider FX. Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man. Pharm Acta Helv. 1997 Jun;72(3):175–84. doi: https://doi.org/10.1016/S0031-6865(97)00014-9
- Kolaczynska KE, Liechti ME, Duthaler U. Development and validation of an LC-MS/MS method for the bioanalysis of psilocybin’s main metabolites, psilocin and 4-hydroxyindole-3-acetic acid, in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Feb;1164:122486. doi: https://doi.org/10.1016/j.jchromb.2020.122486
- Horita A, Weber LJ. The enzymic dephosphorylation and oxidation of psilocybin and psilocin by mammalian tissue homogenates. Biochem Pharmacol. 1961 Jul;7(1):47–54. doi: https://doi.org/10.1016/0006-2952(61)90124-1
- Holze F, Becker AM, Kolaczynska KE, Duthaler U, Liechti ME. Pharmacokinetics and pharmacodynamics of oral psilocybin administration in healthy participants. Clin Pharmacol Ther. 2023 Apr;113(4):822–31. doi: https://doi.org/10.1002/cpt.2821
- Kalberer F, Kreis W, Rutschmann J. The fate of psilocin in the rat. Biochem Pharmacol. 1962;11(4-5):261–9. doi: https://doi.org/10.1016/0006-2952(62)90050-3
- Rickli A, Moning OD, Hoener MC, Liechti ME. Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. Eur Neuropsychopharmacol. 2016 Aug;26(8):1327–37. doi: https://doi.org/10.1016/j.euroneuro.2016.05.001
- Manevski N, Kurkela M, Höglund C, Mauriala T, Court MH, Yli-Kauhaluoma J, et al. Glucuronidation of psilocin and 4-hydroxyindole by the human UDP-glucuronosyltransferases. Drug Metab Dispos. 2010 Mar;38(3):386–95. doi: https://doi.org/10.1124/dmd.109.031138
- Hasler F, Bourquin D, Brenneisen R, Vollenweider FX. Renal excretion profiles of psilocin following oral administration of psilocybin: a controlled study in man. J Pharm Biomed Anal. 2002 Sep;30(2):331–9. doi: https://doi.org/10.1016/S0731-7085(02)00278-9
- Grieshaber AF, Moore KA, Levine B. The detection of psilocin in human urine. J Forensic Sci. 2001 May;46(3):627–30. doi: https://doi.org/10.1520/JFS15014J
- Thomann J, Kolaczynska KE, Stoeckmann OV, Rudin D, Vizeli P, Hoener MC, et al. In vitro and in vivo metabolism of psilocybin’s active metabolite psilocin. Front Pharmacol. 2024 Apr;15:1391689. 10.3389/fphar.2024.1391689
- Passie T, Seifert J, Schneider U, Emrich HM. The pharmacology of psilocybin. Addict Biol. 2002 Oct;7(4):357–64. doi: https://doi.org/10.1080/1355621021000005937
- Brown RT, Nicholas CR, Cozzi NV, Gassman MC, Cooper KM, Muller D, et al. Pharmacokinetics of escalating doses of oral psilocybin in healthy adults. Clin Pharmacokinet. 2017 Dec;56(12):1543–54. doi: https://doi.org/10.1007/s40262-017-0540-6
- Holze F, Ley L, Müller F, Becker AM, Straumann I, Vizeli P, et al. Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects. Neuropsychopharmacology. 2022 May;47(6):1180–7. doi: https://doi.org/10.1038/s41386-022-01297-2
- Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Bäbler A, Vogel H, Hell D. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport. 1998 Dec;9(17):3897–902. doi: https://doi.org/10.1097/00001756-199812010-00024
- Nichols DE. Hallucinogens. Pharmacol Ther. 2004 Feb;101(2):131–81. doi: https://doi.org/10.1016/j.pharmthera.2003.11.002
- Hasler F, Grimberg U, Benz MA, Huber T, Vollenweider FX. Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose-effect study. Psychopharmacology (Berl). 2004 Mar;172(2):145–56. doi: https://doi.org/10.1007/s00213-003-1640-6
- Liechti ME, Holze F. Dosing Psychedelics and MDMA. Curr Top Behav Neurosci. 2022;56:3–21. doi: https://doi.org/10.1007/7854_2021_270
- Ley L, Holze F, Arikci D, Becker AM, Straumann I, Klaiber A, et al. Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants. Neuropsychopharmacology. 2023 Oct;48(11):1659–67. doi: https://doi.org/10.1038/s41386-023-01607-2
- Johnson M, Richards W, Griffiths R. Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008 Aug;22(6):603–20. doi: https://doi.org/10.1177/0269881108093587
- Straumann I, Holze F, Becker AM, Ley L, Halter N, Liechti ME. Safety pharmacology of acute psilocybin administration in healthy participants. Neurosci Appl. 2024;3:104060. doi: https://doi.org/10.1016/j.nsa.2024.104060
- Johnson MW, Griffiths RR, Hendricks PS, Henningfield JE. The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act. Neuropharmacology. 2018 Nov;142:143–66. doi: https://doi.org/10.1016/j.neuropharm.2018.05.012
- Cerletti A. Etude Pharmacologique de la Psilocybine. In: Heim R, Wasson RG, editors. Les champignons hallucinogenes du mexique. Paris: Museum de historie naturelle. 1958. p. 268-71. Available from: https://sciencepress.mnhn.fr/sites/default/files/articles/pdf/archives_du_museum_serie_7_tome_6_-_les_champignons_hallucinogenes_du_mexique_-_etudes_ethnologiques_taxinomiques_biologiques_physiologiques_et_chimiques_-_med.pdf
- Kaminski D, Reinert JP. The tolerability and safety of psilocybin in psychiatric and substance-dependence conditions: a systematic review. Ann Pharmacother. 2024 Aug;58(8):811–26. doi: https://doi.org/10.1177/10600280231205645
- Becker AM, Holze F, Grandinetti T, Klaiber A, Toedtli VE, Kolaczynska KE, et al. Acute effects of psilocybin after escitalopram or placebo pretreatment in a randomized, double-blind, placebo-controlled, crossover study in healthy subjects. Clin Pharmacol Ther. 2022 Apr;111(4):886–95. doi: https://doi.org/10.1002/cpt.2487
- Dahmane E, Hutson PR, Gobburu JV. Exposure-response analysis to assess the concentration-QTc relationship of psilocybin/psilocin. Clin Pharmacol Drug Dev. 2021 Jan;10(1):78–85. doi: https://doi.org/10.1002/cpdd.796
- Rouaud A, Calder AE, Hasler G. Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: comparison to known cardiotoxins. J Psychopharmacol. 2024 Mar;38(3):217–24. doi: https://doi.org/10.1177/02698811231225609
- Tagen M, Mantuani D, van Heerden L, Holstein A, Klumpers LE, Knowles R. The risk of chronic psychedelic and MDMA microdosing for valvular heart disease. J Psychopharmacol. 2023 Sep;37(9):876–90. doi: https://doi.org/10.1177/02698811231190865
- Barber G, Nemeroff CB, Siegel S. A case of prolonged mania, psychosis, and severe depression after psilocybin use: implications of increased psychedelic drug availability. Am J Psychiatry. 2022 Dec;179(12):892–6. doi: https://doi.org/10.1176/appi.ajp.22010073
- Hermle L, Ruchsow M, Täschner KL. [Hallucinogen Persisting Perception Disorder (HPPD) and Flashback Phenomena – Differential Diagnosis and Explanation Models]. Fortschr Neurol Psychiatr. 2015 Sep;83(9):506–15.
- Carter OL, Burr DC, Pettigrew JD, Wallis GM, Hasler F, Vollenweider FX. Using psilocybin to investigate the relationship between attention, working memory, and the serotonin 1A and 2A receptors. J Cogn Neurosci. 2005 Oct;17(10):1497–508. doi: https://doi.org/10.1162/089892905774597191
- Carter OL, Hasler F, Pettigrew JD, Wallis GM, Liu GB, Vollenweider FX. Psilocybin links binocular rivalry switch rate to attention and subjective arousal levels in humans. Psychopharmacology (Berl). 2007 Dec;195(3):415–24. doi: https://doi.org/10.1007/s00213-007-0930-9
- Quednow BB, Kometer M, Geyer MA, Vollenweider FX. Psilocybin-induced deficits in automatic and controlled inhibition are attenuated by ketanserin in healthy human volunteers. Neuropsychopharmacology. 2012 Feb;37(3):630–40. doi: https://doi.org/10.1038/npp.2011.228
- Becker AM, Klaiber A, Holze F, Istampoulouoglou I, Duthaler U, Varghese N, et al. Ketanserin reverses the acute response to LSD in a randomized, double-blind, placebo-controlled, crossover study in healthy subjects. Int J Neuropsychopharmacol. 2023 Feb;26(2):97–106. doi: https://doi.org/10.1093/ijnp/pyac075
- Van Went GF. Mutagenicity testing of 3 hallucinogens: LSD, psilocybin and delta 9-THC, using the micronucleus test. Experientia. 1978 Mar;34(3):324–5. doi: https://doi.org/10.1007/BF01923013
- Law FC, Poon G, Chui YC, He SX. 14C-Psilocin tissue distribution in pregnant rats after intravenous administration. Funct Food Health Dis. 2014;4(6):232–46. doi: https://doi.org/10.31989/ffhd.v4i6.9
- Nayak SM, Gukasyan N, Barrett FS, Erowid E, Erowid F, Griffiths RR. Classic psychedelic coadministration with lithium, but not lamotrigine, is associated with seizures: an analysis of online psychedelic experience reports. Pharmacopsychiatry. 2021 Sep;54(5):240–5. doi: https://doi.org/10.1055/a-1524-2794
- Sarparast A, Thomas K, Malcolm B, Stauffer CS. Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review. Psychopharmacology (Berl). 2022 Jun;239(6):1945–76. doi: https://doi.org/10.1007/s00213-022-06083-y
- Halman A, Kong G, Sarris J, Perkins D. Drug-drug interactions involving classic psychedelics: A systematic review. J Psychopharmacol. 2024 Jan;38(1):3–18. doi: https://doi.org/10.1177/02698811231211219
- Strassman RJ. Human hallucinogen interactions with drugs affecting serotonergic neurotransmission. Neuropsychopharmacology. 1992 Nov;7(3):241–3.
- Bonson KR, Buckholtz JW, Murphy DL. Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans. Neuropsychopharmacology. 1996 Jun;14(6):425–36. doi: https://doi.org/10.1016/0893-133X(95)00145-4
- Bonson KR, Murphy DL. Alterations in responses to LSD in humans associated with chronic administration of tricyclic antidepressants, monoamine oxidase inhibitors or lithium. Behav Brain Res. 1996;73(1-2):229–33. doi: https://doi.org/10.1016/0166-4328(96)00102-7
- Barbut Siva J, Barba T, Kettner H, Kuc J, Nutt DJ, Carhart-Harris R, et al. Interactions between classic psychedelics and serotonergic antidepressants: effects on the acute psychedelic subjective experience, well-being and depressive symptoms from a prospective survey study. J Psychopharmacol. 2024 Feb;38(2):145–55. doi: https://doi.org/10.1177/02698811231224217
- Gukasyan N, Griffiths RR, Yaden DB, Antoine DG 2nd, Nayak SM. Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use. J Psychopharmacol. 2023 Jul;37(7):707–16. doi: https://doi.org/10.1177/02698811231179910
- Keeler MH. Chlorpromazine antogonism of psilocybin effect. Int J Neuropsychiatry. 1967;3(1):66–71.
- Pokorny T, Preller KH, Kraehenmann R, Vollenweider FX. Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience. Eur Neuropsychopharmacol. 2016 Apr;26(4):756–66. doi: https://doi.org/10.1016/j.euroneuro.2016.01.005
- Carhart-Harris R, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, Murphy R, et al. Trial of psilocybin versus escitalopram for depression. N Engl J Med. 2021 Apr;384(15):1402–11. doi: https://doi.org/10.1056/NEJMoa2032994
- Grob CS, Danforth AL, Chopra GS, Hagerty M, McKay CR, Halberstadt AL, et al. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry. 2011 Jan;68(1):71–8. doi: https://doi.org/10.1001/archgenpsychiatry.2010.116
- Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016 Dec;30(12):1181–97. doi: https://doi.org/10.1177/0269881116675513
- Peck SK, Shao S, Gruen T, Yang K, Babakanian A, Trim J, et al. Psilocybin therapy for females with anorexia nervosa: a phase 1, open-label feasibility study. Nat Med. 2023 Aug;29(8):1947–53. doi: https://doi.org/10.1038/s41591-023-02455-9
- Khan AJ, Bradley E, O’Donovan A, Woolley J. Psilocybin for trauma-related disorders. Curr Top Behav Neurosci. 2022;56:319–32. doi: https://doi.org/10.1007/7854_2022_366
- Bogenschutz MP, Ross S, Bhatt S, Baron T, Forcehimes AA, Laska E, et al. Percentage of heavy drinking days following psilocybin-assisted psychotherapy vs placebo in the treatment of adult patients with alcohol use disorder: a randomized clinical trial. JAMA Psychiatry. 2022 Oct;79(10):953–62. doi: https://doi.org/10.1001/jamapsychiatry.2022.2096
- Johnson MW, Garcia-Romeu A, Cosimano MP, Griffiths RR. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J Psychopharmacol. 2014 Nov;28(11):983–92. doi: https://doi.org/10.1177/0269881114548296
- Schindler EA, Sewell RA, Gottschalk CH, Luddy C, Flynn LT, Lindsey H, et al. Exploratory controlled study of the migraine-suppressing effects of psilocybin. Neurotherapeutics. 2021 Jan;18(1):534–43. doi: https://doi.org/10.1007/s13311-020-00962-y
- Schindler EA, Sewell RA, Gottschalk CH, Luddy C, Flynn LT, Zhu Y, et al. Exploratory investigation of a patient-informed low-dose psilocybin pulse regimen in the suppression of cluster headache: results from a randomized, double-blind, placebo-controlled trial. Headache. 2022 Nov;62(10):1383–94. doi: https://doi.org/10.1111/head.14420
- Heal DJ, Smith SL, Belouin SJ, Henningfield JE. Psychedelics: threshold of a therapeutic revolution. Neuropharmacology. 2023 Sep;236:109610. doi: https://doi.org/10.1016/j.neuropharm.2023.109610