Psilocin: An Annotated Bibliography

What is Psilocin?

Introduction 

Psilocin is the active metabolite of the prodrug psilocybin. A prodrug is a biologically inactive compound which can be metabolized in the body to produce a drug. Both psilocin and psilocybin are naturally found in mushrooms of certain species referred to as “magic mushrooms” or “shrooms”. Psilocybin-containing mushrooms are often consumed for their hallucinogenic effects caused by psilocybin rapidly dephosphorylating to psilocin in the body. Historically, psilocybin has been used to initiate altered states of consciousness during religious practices. In recent years, FDA-approved clinical trials have been investigating the potential of psilocybin-assisted therapies in treating depression, anxiety, and some addictions. Potential medical benefits aside, recreational use of psilocybin mushrooms for their psychedelic effects is widely perceived as safe, but a “bad trip” may include unpleasant hallucinations, anxiety, paranoia, or panic. Other adverse reactions may include agitation, vomiting, diarrhea, muscle weakness, and seizures.  

Available Testing

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Urine

Hair

Fingernail

Additional Information on Psilocin Testing

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—2010

A critical review of reports of endogenous psychedelic N,N-dimethyltryptamines in humans: 1955-2010 

Barker SA, McIlhenny EH, Strassman R. A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955-2010. Drug Test Anal. 2012 Jul-Aug;4(7-8):617-35.
DOI: 10.1002/dta.422. Epub 2012 Feb 28. PMID: 22371425. 

Abstract: 

Three indole alkaloids that possess differing degrees of psychotropic/psychedelic activity have been reported as endogenous substances in humans; N,N-dimethyltryptamine (DMT), 5-hydroxy-DMT (bufotenine, HDMT), and 5-methoxy-DMT (MDMT). We have undertaken a critical review of 69 published studies reporting the detection or detection and quantitation of these compounds in human body fluids. In reviewing this literature, we address the methods applied and the criteria used in the determination of the presence of DMT, MDMT, and HDMT. The review provides a historical perspective of the research conducted from 1955 to 2010, summarizing the findings for the individual compounds in blood, urine, and/or cerebrospinal fluid. A critique of the data is offered that addresses the strengths and weaknesses of the methods and approaches to date. The review also discusses the shortcomings of the existing data in light of more recent findings and how these may be overcome. Suggestions for the future directions of endogenous psychedelics research are offered.

Implications of the Study: 

Bufotenine (HDMT) is a structural isomer of psilocin, so it is not surprising that both may be abused for their similar psychoactive effects. Bufotenine can be found in the venom of some toads, but there have also been reports of endogenous bufotenine detected in human specimens. This review took a critical look at 69 published studies reporting the detection of three endogenous tryptamines, including bufotenine, from 1955 to 2010. The most recent methods using LC-MS/MS detection and stringent confirmation criteria have confirmed that bufotenine can be found in human blood and urine. However, the early studies used less specific techniques and weaker confirmation criteria, so they likely overestimated the frequency and concentrations in which it is present in human body fluids. It is difficult to compare the concentrations of endogenous bufotenine found in each study because there was a wide variety of methods and units used to report the findings. In addition, only 7 of the 51 studies examining bufotenine in urine included a hydrolysis step. From these studies, we know that about 50% of total bufotenine is excreted as a glucuronide conjugate. Therefore, many of the studies did not determine the total amount of bufotenine. Some studies examined dietary influences on detection of bufotenine in urine, but no dietary sources were found.

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—2013

Determination of psilocin, bufotenine, LSD and its metabolites in serum, plasma and urine by SPE-LC-MS/MS 

Martin R, Schürenkamp J, Gasse A, Pfeiffer H, Köhler H. Determination of psilocin, bufotenine, LSD and its metabolites in serum, plasma and urine by SPE-LC-MS/MS. Int J Legal Med. 2013 May;127(3):593-601.
DOI: 10.1007/s00414-012-0796-1. Epub 2012 Nov 27. PMID: 23183899. 

Abstract: 

A validated method for the simultaneous determination of psilocin, bufotenine, lysergic acid diethylamide and its metabolites in serum, plasma and urine using liquid chromatography-electrospray ionization/tandem mass spectrometry was developed. During the solid-phase extraction procedure with polymeric mixed-mode cation exchange columns, the unstable analytes were protected by ascorbic acid, drying with nitrogen and exclusion of light. The limits of detection and quantitation for all analytes were low. Recovery was ≥86 % for all analytes and no significant matrix effects were observed. Interday and intraday imprecisions at different concentrations ranged from 1.1 to 8.2 % relative standard deviation, bias was within ±5.3 %. Processed samples were stable in the autosampler for at least 2 days. Furthermore, freeze/thaw and long-term stability were investigated. The method was successfully applied to authentic serum and urine samples.

Implications of the Study: 

This study is important because it validated an LC-MS/MS method for the detection and quantification of psilocin, bufotenine, and LSD in serum, plasma, and urine and then applied it to authentic specimens from six suspected drug users. Of the six cases, five included a urine specimen that was tested for total psilocin and total bufotenine. Bufotenine was detected in three of the five cases at concentrations of 1.0, 1.3, and 2.5 ng/mL. While it cannot be known conclusively based on the source of the specimens, the authors assume that these are endogenous levels of total bufotenine. This is significant because earlier reports of endogenous bufotenine have been criticized for using non-specific techniques and for not taking into account both free bufotenine and bufotenine present in the glucuronide form. In two of the cases, total psilocin was detected at 1.5 and 4.3 ng/mL. These specimens were collected 1.5 days and 16 hours after suspected use, respectively. The latter case included a paired serum specimen in which only a trace of psilocin could be detected. In all urine samples that were positive for bufotenine or psilocin, the total amount of analyte was much higher than the free one. This is consistent with other findings in the literature and further demonstrates the importance of including a hydrolysis step in the analysis. In addition, it is important to be able to distinguish between bufotenine and psilocin to prevent false-positive results of either.

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—2014

Synthesis, hydrolysis and stability of psilocin glucuronide 

Martin R, Schürenkamp J, Pfeiffer H, Lehr M, Köhler H. Synthesis, hydrolysis and stability of psilocin glucuronide. Forensic Sci Int. 2014 Apr;237:1-6.
DOI: 10.1016/j.forsciint.2014.01.006. Epub 2014 Jan 15. PMID: 24513688. 

Abstract:  

A two-step synthesis of psilocin glucuronide (PCG), the main metabolite of psilocin, with methyl 2,3,4-tri-O-isobutyryl-1-O-trichloroacetimidoyl-α-d-glucopyranuronate is reported. With the synthesized PCG, hydrolysis conditions in serum and urine were optimized. Escherichia coli proved to be a better enzyme source for β-glucuronidase than Helix pomatia. It was essential to add ascorbic acid to serum samples to protect psilocin during incubation. Furthermore the stability of PCG and psilocin was compared as stability data are the basis for forensic interpretation of measurements. PCG showed a greater long-term stability after six months in deep frozen serum and urine samples than psilocin. The short-term stability of PCG for one week in whole blood at room temperature and in deep frozen samples was also better than that of psilocin. Therefore, PCG can be considered to be more stable than the labile psilocin and should always be included if psilocin is analyzed in samples.

Implications of the Study: 

This was one of the first papers to present a synthesis of psilocin-glucuronide, the main urinary metabolite of psilocin, which was not commercially available at the time of the study. Synthesizing the compound allowed hydrolysis and stability studies to be carried out in order to determine the best method to analyze toxicological specimens if there is suspicion of psilocybin mushroom consumption. The study found that, at two different concentrations, both free psilocin and psilocin-glucuronide were stable in serum and urine after three freeze/thaw cycles and after six weeks of storage at -20C. After six months of storage at -20C, free psilocin was considered unstable in both serum and urine, but psilocin-glucuronide was stable even after six months in both matrices. Psilocin-glucuronide was also more stable than free psilocin after a week at room temperature. The short-term stabilities of the two compounds were similar when stored at refrigerator temperature (4C) for a week. Since psilocin-glucuronide is clearly more stable than free psilocin, enzymatic hydrolysis extends the detection window of psilocin so that magic mushroom consumption may be proven.

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—2014

Ultra-high-pressure liquid chromatography tandem mass spectrometry determination of hallucinogenic drugs in hair of psychedelic plants and mushrooms consumers 

Pichini S, Marchei E, García-Algar O, Gomez A, Di Giovannandrea R, Pacifici R. Ultra-high-pressure liquid chromatography tandem mass spectrometry determination of hallucinogenic drugs in hair of psychedelic plants and mushrooms consumers. J Pharm Biomed Anal. 2014 Nov;100:284-289.
DOI: 10.1016/j.jpba.2014.08.006. Epub 2014 Aug 10. PMID: 25171488. 

Abstract: 

A procedure based on ultra-high-pressure liquid chromatography tandem mass spectrometry has been developed for the determination of mescaline, N,N-dimethyltryptamine, psilocin, psilocybin, salvinorin A in hair of consumers of psychedelic vegetal material such peyote or trichocereus cacti, psilocybe mushrooms, Salvia divinorum or psychedelic beverage ayahuasca. After hair washing with methyl alcohol and diethyl ether and subsequent addition of mescaline-d9 and 3,4-methylenedioxypropylamphetamine as internal standards, hair samples were treated with 250 μl VMA-T M3 reagent for 1 h at 100 °C. After cooling, 100 μl M3 extract were diluted with 400 μl water and a volume of 10 μl was injected into chromatographic system. Chromatographic separation was achieved at ambient temperature using a reverse-phase column and a linear gradient elution with two solvents: 0.3% formic acid in acetonitrile and 5 mM ammonium formate pH 3. The mass spectrometer was operated in positive ion mode, using multiple reaction monitoring via positive electrospray ionization.

The method was linear from the limit of quantification (0.03–0.05 ng/mg depending on analyte under investigation) to 10 ng/mg hair, with an intra- and inter-assay imprecision and inaccuracy always less than 15% and an analytical recovery between 79.6% and 97.4%, depending on the considered analyte. Using the validated method, mescaline was found in concentration range of 0.08–0.13 ng/mg in hair of peyote smokers, 3.2 ng salvinorin A per mg hair were determined in hair from a S. divinorum smoker, 5.6 ng N,N-dimethyltryptamine per mg hair from an ayahuasca user and finally 0.8 ng psilocybin per ng hair of a psilocybe consumer.

Implications of the study: 

A validated method for the detection of hallucinogenic drugs, including psilocybin and psilocin, was used to test an authentic hair specimen from a psilocybin consumer. It was found that the hair contained a psilocybin concentration of 0.8 ng/mg. Psilocin was not detected. These results demonstrate that psilocybin may be detected in human hair specimen following the consumption of psilocybin.

What makes this method different from other published methods for the detection of psilocybin and/or psilocin in hair specimen is that the sample preparation included a chemical digestion of the hair with a 1hr incubation at 100°C. The other published methods use mechanical means of breaking down the matrix, either by cutting or by pulverization in a ball mill. It is worth noting that psilocin is known to be a very unstable compound. It may be possible that psilocin was not detected in the hair of this consumer due to its degradation during the high temperature incubation step.

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—2015

Analysis of Psilocin, Bufotenine, and LSD in Hair  

Martin R, Schürenkamp J, Gasse A, Pfeiffer H, Köhler H. Analysis of psilocin, bufotenine and LSD in hair. J Anal Toxicol. 2015 Mar;39(2):126-9.
DOI: 10.1093/jat/bku141. Epub 2014 Dec 23. PMID: 25540060. 

Abstract: 

A method for the simultaneous extraction of the hallucinogens psilocin, bufotenine, lysergic acid diethylamide (LSD) as well as iso-LSD, nor-LSD and O-H-LSD from hair with hydrochloride acid and methanol is presented. Clean-up of the hair extracts is performed with solid phase extraction using a mixed-mode cation exchanger. Extracts are measured with liquid chromatography coupled with electrospray tandem mass spectrometry. The method was successfully validated according to the guidelines of the ‘Society of Toxicological and Forensic Chemistry’ (GTFCh). To obtain reference material hair was soaked in a solution of the analytes in dimethyl sulfoxide/methanol to allow incorporation into the hair. These fortified hair samples were used for method development and can be employed as quality controls.

Implications of the study: 

This is one of the first published methods for analyzing psilocin or bufotenine in hair. At the time, it was unknown if these substances could be detected in hair after consumption. A lack of authentic positive hair specimens creates challenges during method development. Extraction efficiency cannot be determined accurately from spiked material. This paper provided a method of artificially incorporating psilocin into hair specimen so that common techniques in hair testing could be evaluated for the analysis of these unstable analytes. For example, the fortified hair sample was used to determine that extraction efficiency improved with increased sonication times. Other papers warn against the use of sonication, stating a loss of signal for thermally-unstable psilocin (Kintz et al., Shi et al.). In these papers, it is unclear how this conclusion was determined. To protect the analytes from degradation, protection from light and the use of ascorbic acid was noted.

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—2017

Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance 

Dinis-Oliveira, R. J. (2017). Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance. Drug Metabolism Reviews, 49(1), 84–91.
DOI: 10.1080/03602532.2016.1278228 

Abstract: 

Psilocybin and psilocin are controlled substances in many countries. These are the two main hallucinogenic compounds of the “magic mushrooms” and both act as agonists or partial agonists at 5-hydroxytryptamine (5-HT)2A subtype receptors. During the last few years, psilocybin and psilocin have gained therapeutic relevance but considerable physiological variability between individuals that can influence dose-response and toxicological profile has been reported. This review aims to discuss metabolism of psilocybin and psilocin, by presenting all major and minor psychoactive metabolites. Psilocybin is primarily a pro-drug that is dephosphorylated by alkaline phosphatase to active metabolite psilocin. This last is then further metabolized, psilocin-O-glucuronide being the main urinary metabolite with clinical and forensic relevance in diagnosis.

Implications of the Study: 

The purpose of this manuscript was to present all of the available metabolic data regarding psilocybin and psilocin from electronic journal articles and books. Equimolar amounts of psilocybin and psilocin evoke qualitatively and quantitatively similar psychotropic effects in humans, so psilocybin is referred to as a prodrug, and it should be understood that psilocin is responsible for the drug’s effects. A controlled study in humans showed that within 24 hours, less than 5% of the applied dose of psilocybin was excreted in urine as free psilocin. Later studies showed that the major metabolite of psilocin in urine is psilocin-glucuronide (approximately 80%). This is important because the glucuronide metabolite is more stable than the notoriously labile free psilocin. Therefore, enzymatic hydrolysis extends the detection window for psilocin in urine samples. Psilocin is further metabolized to its minor metabolites by liver monoamine oxidase (MAO), so users may simultaneously take MAO-inhibitors to intensify the hallucinogenic effects of psilocin.  

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—2020

UHPLC-MS/MS method for simultaneously detecting 16 tryptamines and their metabolites in human hair and applications to real forensics cases 

Shi Y, Wang R, Yuan S, Qiang H, Shen M, Shen B, Drummer OH, Yu Z, Zhao Y, Xiang P. UHPLC-MS/MS method for simultaneously detecting 16 tryptamines and their metabolites in human hair and applications to real forensics cases. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Nov 30;1159:122392.
DOI: 10.1016/j.jchromb.2020.122392. Epub 2020 Oct 16. PMID: 33126071.  

Abstract: 

Tryptamines are hallucinogenic substances many of which have appeared recently as novel psychoactive substances (NPS). Herein, we describe the establishment of a rapid UHPLC-MS/MS quantitative method for the targeted screening of 16 tryptamines of abuse in hair. Twenty milligram pieces of hair were pulverized below 4 °C in 0.5 mL of deionized water containing 0.1% formic acid and an internal standard (2 ng/mL psilocin-d10 and psilocybin-d4). After subsequent centrifugation, 5 μL of the supernatant was injected into a LC-MS/MS system fitted with a Waters Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm). The column was gradient eluted at 0.3 mL/min with mobile phases composed of 20 mmol/L ammonium acetate, 5% acetonitrile, and 0.1% formic acid in water (solvent A) and acetonitrile (solvent B). Limits of detection ranged between 0.1 and 20 pg/mg, with limits of quantitation ranging from 3 to 50 pg/mg. The calibration curves for all analytes were linear (r > 0.992). Accuracies varied between 91% and 114%, with intraday precision RSDs < 14% and interday precision RSDs of between 1.3% and 14%. The recoveries of all tryptamines were in the 85-115% range, with the matrix effect ranging from 95% to 112%. The validated method was successfully used to analyse 191 hair samples from suspected tryptamine users, 77 of which were 5-MeO-DiPT-positive, while the 16 tryptamines and their metabolites were not detected in the remaining 114 hair samples. 5-MeO-DiPT and its 5-MeO-NiPT, 5-OH-DiPT, and 4-OH-DiPT metabolites were concurrently detected in 34 hair samples. 5-MeO-DiPT, as the parent drug, was the parent substance found in the hair samples.

Implications of the study: 

This paper presents a method for the detection of tryptamines in hair, including both psilocin and psilocybin with limits of detection of 5 pg/mg. The procedure uses frozen pulverization for sample preparation and extraction of drugs, noting the unsuitability of ultrasonic techniques that may cause thermal degradation of unstable analytes. However, the authors do not note any experimentation to support this assumption.

The validated method was applied to 191 authentic hair specimens from suspected users in China. Psilocybin nor psilocin were identified in any of the specimens, although 77 specimens had positive results for another psychedelic drug known as “Foxy.”

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—2021

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 

Karolina E. Kolaczynska, Matthias E. Liechti, Urs Duthaler, 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, Journal of Chromatography B, Volume 1164, 2021, 122486, ISSN 1570-0232.
DOI: 10.1016/j.jchromb.2020.122486. 

Abstract: 

Psilocin is the active metabolite of psilocybin, a serotonergic psychedelic substance. It is used recreationally and investigated in substance-assisted psychotherapy. The pharmacokinetic properties of psilocin are only partially characterized. Therefore, we developed and validated a rapid LC-MS/MS method to quantify psilocin and its metabolite 4-hydroxyindole-3-acetic acid (4-HIAA) in human plasma.

Plasma samples were processed by protein precipitation using methanol. The injected sample was mixed with water in front of a C18 analytical column to increase retention of the analytes. Psilocin and 4-HIAA were detected by multiple reaction monitoring (MRM) in positive and negative electrospray ionisation mode, respectively.

An inter-assay accuracy of 100–109% and precision of ≤8.7% was recorded over three validation runs. The recovery was near to complete (≥94.7%) and importantly, consistent over different concentration levels and plasma batches (CV%: ≤4.1%). The plasma matrix caused negligible ion suppression and endogenous interferences could be separated from the analytes. Psilocin and 4-HIAA plasma samples could be thawed and refrozen for three cycles, kept at room temperature for 8 h or 1 month at − 20 ◦C without showing degradation (≤10%). The linear range (R ≥ 0.998) of the method covered plasma concentrations observed in humans following a common therapeutic oral dose of 25 mg psilocybin and was therefore able to assess the pharmacokinetics of psilocin and 4-HIAA. The LC-MS/MS method was convenient and reliable for measuring psilocin and 4-HIAA in plasma and will facilitate the clinical development of psilocybin.

Implications of the study: 

While this paper presents a validated LC-MS/MS method for the quantification of psilocin and 4-HIAA in human plasma, it also provides a thorough overview of the previously published methods for the quantification of psilocin, 4-HIAA, and/or psilocin-glucuronide in human plasma and urine from 1997 to 2017. A majority of the more recent methods employ LC-MS/MS instrumentation, but sample processing techniques vary. The method presented in this paper was used to analyze the pharmacokinetics of psilocin and 4-HIAA in three healthy individuals after an oral dose of 25 mg psilocybin. The result of this study agreed with previous reports stating that the majority of psilocin is conjugated by glucuronidation. This is important because it supports that accurate quantification techniques of psilocin in body fluids should include a hydrolysis step to free the psilocin from the glucuronide. Otherwise, it may go undetected.

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—2021

Sensitive quantitative analysis of psilocin and psilocybin in hair samples from suspected users and their distribution in seized hallucinogenic mushrooms 

Zhou, L., Xiang, P., Wen, D. et al. Sensitive quantitative analysis of psilocin and psilocybin in hair samples from suspected users and their distribution in seized hallucinogenic mushrooms. Forensic Toxicol 39, 464–473 (2021).
DOI: 10.1007/s11419-020-00566-3 

Abstract: 

In this study, we developed a very sensitive method for quantitative analysis of psilocin and psilocybin in hair samples of magic mushroom consumers. The analyses were performed with pretreatments of samples, followed by ultra-high pressure liquid chromatography (LC) connected to a Q-Trap type tandem mass spectrometry (MS/MS). For LC, mobile phase (A) consisted of 0.1% formic acid in water, and mobile phase (B) was acetonitrile for gradient elution using a Acquity™ UPLC HSS T3 column. For MS/MS, electrospray ionization measurements in positive selected reaction monitoring mode were used. The calibration curves were linear from 5 to 500 pg/mg (r > 0.99) and no selectivity problems occurred. The limit of detection was 1 pg/mg, and the lower limit of quantitation was 5 pg/mg. The ranges of the matrix effects and recovery rates were 90.4–107% and 76.0–102%, respectively. The concentrations of psilocin in two authentic hair were 161 and 150 pg/mg, respectively, and psilocybin was not detected from both samples. This method was also used to analyze the distribution of psilocin and psilocybin in seven hallucinogenic mushrooms. To our knowledge, this is the first demonstration of psilocin concentrations in hair samples of hallucinogenic mushroom consumers, and also our method is most sensitive for quantitative analysis of psilocin and psilocybin in hair samples.

Implications of the study: 

This was the first report of psilocin detected in hair specimens. Psilocin concentrations of 161 pg/mg and 150 pg/mg were found in the specimens of two suspected users. The authors noted special care was taken to prevent psilocin’s degradation from light and heat exposure. They also noted the use of a basic pH solution during specimen preparation, which is consistent with other published methods. Psilocybin could not be detected in either specimen despite the limit of detection being as low as 1 pg/mg. The authors hypothesize this is due to the rapid metabolism of psilocybin to psilocin in the body. The detection of psilocin in urine and other conventional biological samples is known to be challenging due to its limited stability and therefore short detection window. Detection of psilocin in hair may be a more useful tool for determining the consumption of psilocybin.

Additionally, this validated method was applied to the canopies and stems of seized hallucinogenic mushrooms. The results show the psilocin content is higher than the psilocybin content. Previously published literature both supports and contradicts this finding. Regardless, there is agreement that both psilocin and psilocybin are present in hallucinogenic mushroom species, which may be of significance when attempting to interpret environmental exposure versus ingestion.

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—2021

Testing human hair after magic mushrooms abuse by LC-MS/MS: Pitfalls and limitations 

Kintz, Pascal & Raul, Jean-Sébastien & Ameline, Alice. (2021). Testing human hair after magic mushrooms abuse by LC-MS/MS: Pitfalls and limitations. Forensic Chemistry. 26. 100364.
DOI: 10.1016/j.forc.2021.100364. 

Abstract:  

Although it has been published during the last 15 years that hallucinogens derived from new psychoactive substances are increasingly abused, the old psychedelic agents are still used. Among these vegetal compounds, magic mushrooms are frequently mentioned. The major ingredient of the Psilocybe species is psilocybin, which is rapidly converted into psilocin in the human body. Therefore, psilocin represents the key target to document magic mushrooms abuse. The aim of the present work was to develop a specific method to identify psilocin in human hair by LC-MS/MS and review potential pitfalls. The method involves incubation of 10 mg of cut hair in 1 mL of acid methanol in presence of psilocin-d10 for 2 h at 4 °C. The chromatographic separation was performed using a reverse phase column HSS C18 with a gradient elution of 8 min. Linearity was verified from 1 to 200 pg/mg (r2 = 0.9994), after spiking blank hair with the corresponding amounts of psilocin. The limit of detection was estimated at 0.4 pg/mg. The precision was lower than 20 % and there was no interference with any extractable material present in hair. Psilocin was identified in the hair of a repetitive magic mushrooms consumer at 2.5 pg/mg (segment 0–1 cm), 4.4 pg/mg (segment 1–2 cm) and 5.4 pg/mg (segment 2–3 cm). Cold conditions during hair preparation and protection from the light were found mandatory to avoid psilocin degradation.

Implications of the Study: 

This published method for the detection of psilocin in hair involves cutting hair into fine pieces and extracting the drug with a solution of methanol and 1% formic acid and horizontal agitation at 4°C. The method was used to analyze three segments of a hair specimen from a repetitive magic mushrooms consumer. The three segments contained 2.5, 4.4, and 5.4 pg/mg psilocin. This is the second and most recent published report of psilocin detected in hair specimen.

There is agreement with other published literature that protection from light is essential to prevent degradation of psilocin. A significant loss of chromatographic response was also observed after hair pulverization in a ball mill and ultrasonic incubation, so the final extraction procedure did not include these two techniques that are often used in hair testing.

The authors chose to focus on detecting psilocin because psilocybin was not observed in preliminary tests with an authentic hair specimen from a known magic mushroom user. Other published literature has also proposed psilocin is the target substance in hair to document repetitive psilocybin use.

The authors acknowledge the challenge of interpreting test results for psilocin in hair due to a lack of literature. In this case, psilocin was detected in three different 1 cm segments of hair, so one can interpret these findings as repetitive exposures to magic mushrooms. However, like other hair drug testing, inferences cannot be made about time, dose, or frequency.

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—2022

Psilocybin as a Treatment for Psychiatric Illness: A Meta-Analysis 

Irizarry R, Winczura A, Dimassi O, Dhillon N, Minhas A, Larice J. Psilocybin as a Treatment for Psychiatric Illness: A Meta-Analysis. Cureus. 2022 Nov 22;14(11):e31796.
DOI: 10.7759/cureus.31796. PMID: 36569662; PMCID: PMC9779908. 

Abstract: 

Psilocybin is an emerging potential therapy for the treatment of psychiatric illnesses. Microdosing has been shown to result in an overall improvement in patients with anxiety, depression, obsessive-compulsive disorder, post-traumatic stress disorder, and substance abuse. This meta-analysis explores and compiles prior research to make further inferences regarding psilocybin and its use for the treatment of psychiatric illness along with its safety and efficacy.

Database searches were conducted to identify peer-reviewed randomized controlled trials and clinical trials mentioning psilocybin use and psychiatric illness. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram was created and analysis was run on the nine articles that met all established inclusion criteria. An event is defined as a participant who showed improvement, in a quantitative method, from baseline after the use of psilocybin. Another analysis was done using depression severity (Quick Inventory of Depressive Symptomatology 16-Item Self Report, QIDS-SR16) at baseline and after the use of psilocybin.

Analyses of the original data and the nine articles showed a great deal of heterogeneity with an I2 value of 73.68%, suggesting that the studies in this meta-analysis cannot be considered to be studies of the same population. The Q value of 30.4 was higher than 15.507, which is the critical value for eight degrees of freedom found in a chi-square distribution. This Q value showed a high degree of variation and lacked significance. The second meta-run on QIDS-SR16 scores from three studies showed a Q value of 1.16 which was lower than 5.991, the critical value for two degrees of freedom found in a chi-square distribution. The I2 statistic for this second meta-analysis was -73% which can be equated to zero. This indicated that the data were homogeneous or that there was no observed heterogeneity. Due to low heterogeneity, the fixed-effects model was used. Based on this meta-analysis, psilocybin seems to show symptom improvement in some psychiatric illnesses. The effectiveness of psilocybin microdosing and the use of psilocybin, in general, need to be studied further to determine the efficacy and safety of potential applications in psychiatry.

Implications of the study: 

There has been a resurgence of interest in the therapeutic potential of psilocybin, particularly for use as an alternative treatment for anxiety, depression, OCD, PTSD, and substance abuse. This meta-analysis compiled data from nine different peer-reviewed randomized controlled trials and clinical trials from the last ten years. All nine studies used objective measures to assess the progress of subjects after treatment, and all studies used scales that are considered highly valid in the psychiatric community. These studies were used to evaluate the effect of psilocybin on psychiatric illness symptom reduction in patients diagnosed with schizophrenia, PTSD, depression, generalized anxiety disorder, and/or substance abuse. Overall, treatment with psilocybin has been shown to be safe and efficacious. Compared to some traditional treatments for mental illness, psilocybin offers decreased adverse effects, decreased dependency, and minimal usage. However, the results may not be generalizable to the general population. Future research should compare psilocybin treatment to the gold-standard treatments and should have several treatment groups at different doses and dosing schedules. Research could also be strengthened by studying participants with varying levels of symptom severity over a longer period of time. It is important to note that many studies used psilocybin in addition to psychotherapy, so it is unclear if symptom reduction are due to psilocybin alone or if they are due to the combination of psilocybin and psychotherapy. Overall, psilocybin does show potential in becoming a safe and effective treatment for mental illness, but further studies are needed to assess the long-term efficacy among a more diverse population.

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