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The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act
Open accessAbstract
This review assesses the abuse potential of medically-administered psilocybin, following the structure of the 8 factors of the US Controlled Substances Act (CSA). Research suggests the potential safety and efficacy of psilocybin in treating cancer-related psychiatric distress and substance use disorders, setting the occasion for this review. A more extensive assessment of abuse potential according to an 8-factor analysis would eventually be required to guide appropriate schedule placement. Psilocybin, like other 5-HT2A agonist classic psychedelics, has limited reinforcing effects, supporting marginal, transient non-human self-administration. Nonetheless, mushrooms with variable psilocybin content are used illicitly, with a few lifetime use occasions being normative among users. Potential harms include dangerous behavior in unprepared, unsupervised users, and exacerbation of mental illness in those with or predisposed to psychotic disorders. However, scope of use and associated harms are low compared to prototypical abused drugs, and the medical model addresses these concerns with dose control, patient screening, preparation and follow-up, and session supervision in a medical facility. CONCLUSIONS: (1) psilocybin has an abuse potential appropriate for CSA scheduling if approved as medicine; (2) psilocybin can provide therapeutic benefits that may support the development of an approvable New Drug Application (NDA) but further studies are required which this review describes; (3) adverse effects of medical psilocybin are manageable when administered according to risk management approaches; and (4) although further study is required, this review suggests that placement in Schedule IV may be appropriate if a psilocybin-containing medicine is approved. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'.
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“are not associated with addiction [9, 11, 12]”
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“Hence, despite psilocybin being classified as a drug of abuse, the US Drug Enforcement Administration (DEA) does not include it among the drugs that can cause dependence and/or addiction. 45”
From The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges (2024) · cites this paper as [45]
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“Psilocybin is a serotonin 5-HT2A receptor agonist with very low abuse potential (11)”
From Psilocybin-assisted psychotherapy for methamphetamine dependence: a case report involving daily methamphetamine use (2024) · cites this paper as [11]
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“Psilocybin-assisted psychotherapy (PAT) also appears to be safe and potentially efficacious for substance use disorders, based on early trials for nicotine and alcohol use disorders [14,15], with little evidence of harmful use in the community [16].”
From Psilocybin‐assisted psychotherapy for methamphetamine use disorder: A pilot open‐label safety and feasibility study. (2025) · cites this paper as [16]
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“the use of a single dose of either LSD or psilocybin in a controlled clinical setting can considerably improve the quality of life of patients in parallel with relatively few side effects and a low prevalence of abuse”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Johnson, Griffiths, Hendricks, & Henningfield, 2018
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Self-citationHaertzen, C. A., Hill, H. E., & Belleville, R. E. (1963) · Psychopharmacology · doi:10.1007/bf02584088 · Cited by 172 · cited 1×
“Studies of LSD and psilocybin contributed to the development of this questionnaire and a broader understanding of abuse (Haertzen and Hickey,1987; Haertzen et al., 1963; Hill et al., 1963).”
Garcia‐Romeu, A., Davis, A. K., Erowid, E., Erowid, F., Griffiths, R. R., & Johnson, M. W. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00955 · Cited by 171
Self-citationTerry, C. E., & Pellens, M. (1928) · Medical Entomology and Zoology · Cited by 171
Hill, H. E., Haertzen, C. A., Wolbach, A. B., & Miner, E. J. (1963) · Psychopharmacologia · doi:10.1007/bf02584089 · Cited by 159 · cited 2×
“frequently self-administer the substance; it was often referred to as the “dysphoria” scale (Hill et al., 1963; Jasinski et al., 1984).”
Historical and cultural aspects of man's relationship with addictive drugs
Crocq, M. (2007) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2007.9.4/macrocq · Cited by 152 · cited 1×
“By way of contrast, alcohol, cocaine, opioids, and tobacco also have histories of use dating thousands of years, but these substances were recognized as addicting and harmful to the lives of many users for centuries (Corti, 1931; Crocq, 2007; Lewin, 1998; Rush, 1808; Terry and Pellens, 1970).”
5-HT receptors and reward-related behaviour: A review
Hayes, D. J., & Greenshaw, A. J. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.03.005 · Cited by 151 · cited 1×
“neu suggest a need for additional studies to better understand the mechanisms of action of psilocybin and other psychedelic substances and how these may contribute to their apparent low overall abuse potential (Baker, 2017; Hayes and Greenshaw, 2011).”
Henningfield, J. E., Fant, R. V., & Wang, D. W. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4813-4 · Cited by 151 · cited 1×
“Thus, if an NDA for a psilocybin product is submitted to the FDA and approved, then the CSA would require its rescheduling, and schedule placement would be determined by evaluation of its overall abuse potential (Drug Enforcement Administration, 2017a; Henningfield et al., 2017; U.S. Food and Drug Administration, 2017…”
Self-citationStrassman, R. J. (2000) · UNM’s Digital Repository (University of New Mexico) · Cited by 151
Psilocybin links binocular rivalry switch rate to attention and subjective arousal levels in humans
Carter, O. L., Hasler, F., Pettigrew, J. D., Wallis, G. M., Liu, G. B., & Vollenweider, F. X. (2007) · Psychopharmacology · doi:10.1007/s00213-007-0930-9 · Cited by 146 · cited 1×
“neu reductions in arousal/vigilance (Carter et al., 2007), and attentional impairment (Carter et al.”
Kohn, B., & Hofmann, A. (1981) · The Antioch Review · doi:10.2307/4638477 · Cited by 146
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Comparison of the reactions induced by psilocybin and LSD-25 in man
Isbell, H. (1959) · Psychopharmacology · doi:10.1007/bf00408109 · Cited by 140 · cited 4×
“Its binding to and agonist effects at 5-HT2A serotonin receptors are associated with dilation of the pupils (mydriasis), reduced threshold for knee reflex, and commonly increased heartrate and blood pressure, and feelings of nausea (Isbell, 1959a; b).”
InfluentialThe Psychedelic Explorer's Guide: Safe, Therapeutic, and Sacred Journeys
Fadiman, J. (2011) · Cited by 138
Cross tolerance between LSD and psilocybin
Isbell, H., Wolbach, A. B., Wikler, A., & Miner, E. J. (1961) · Psychopharmacologia · doi:10.1007/bf00407974 · Cited by 137
The Use of LSD in Psychotherapy and Alcoholism
Blaine, G. B. (1968) · Psychosomatic Medicine · doi:10.1097/00006842-196807000-00014 · Cited by 135
Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers
Johnson, M. W., Sewell, R. A., & Griffiths, R. R. (2011) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2011.10.029 · Cited by 132 · cited 1×
“In addition, it is possible that the often undesirable effects of high doses of psilocybin (Griffiths et al., 2011; Johnson et al., 2012), combined with large variability in the psilocybin-content of mushrooms (Bigwood and Beug, 1982) may lead many users to be cautious about dosing.”
Self-citationBelleville, R. E., Fraser, H. F., Isbell, H., LOGAN, C. R., & Wikler, A. (1956) · PubMed · Cited by 126
Opioids: Similarity between evaluations of subjective effects and animal self‐administration results
Griffiths, R. R., & Balster, R. L. (1979) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt1979255part1611 · Cited by 125
Self-citationComparison of psilocin with psilocybin, mescaline and LSD-25
Wolbach, A. B., Miner, E. J., & Isbell, H. (1962) · Psychopharmacology · doi:10.1007/bf00412109 · Cited by 123
Dennis, R. W. G., Wasson, V. P., & Wasson, R. G. (1957) · Kew Bulletin · doi:10.2307/4113701 · Cited by 122
Increased activation of indirect semantic associations under psilocybin
Spitzer, M., Thimm, M., Hermle, L., Holzmann-Erens, P., Kovar, K., Heimann, H., Gouzoulis‐Mayfrank, E., Kischka, U., & Schneider, F. W. (1996) · Biological Psychiatry · doi:10.1016/0006-3223(95)00418-1 · Cited by 115
Psilocybin, psychological distress, and suicidality
Hendricks, P. S., Johnson, M. W., & Griffiths, R. R. (2015) · Journal of Psychopharmacology · doi:10.1177/0269881115598338 · Cited by 114
Self-citationStudies on Lysergic Acid Diethylamide (LSD-25)
Isbell, H. (1956) · A M A Archives of Neurology & Psychiatry · doi:10.1001/archneurpsyc.1956.02330290012002 · Cited by 112
Testing for abuse liability of drugs in humans
Fischman, M. W., & Mello, N. K. (1989) · Cited by 111
Indoleamine Hallucinogens in Cluster Headache: Results of the Clusterbusters Medication Use Survey
Schindler, E. A. D., Gottschalk, C. H., Weil, M. J., Shapiro, R. E., Wright, D. A., & Sewell, R. A. (2015) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2015.1107664 · Cited by 110 · cited 1×
“, 2015), obsessive-compulsive disorder (Schindler et al., 2015), and cluster headaches (Matsushima et al.”
HIRSHFELD-FLORES, A. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.8.1448 · Cited by 109
Gable, R. S. (1993) · The American Journal of Drug and Alcohol Abuse · doi:10.3109/00952999309001618 · Cited by 108 · cited 3×
“For example, in a comparative overview of the dependence potential and acute toxicity of psychoactive substances, Gable concluded that psilocybin carried a lower risk of dependence than caffeine and among the lowest risks of death of all major substance abuse categories including cannabis (Gable, 1993).”
Psilocybin for treating substance use disorders?
de Veen, B. T. H., Schellekens, A., Verheij, M. M. M., & Homberg, J. R. (2016) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2016.1220834 · Cited by 108
Fantegrossi, W. E., Woods, J. H., & Winger, G. (2004) · Behavioural Pharmacology · doi:10.1097/00008877-200403000-00007 · Cited by 101 · cited 2×
“For example, Fantegrossi, Woods and Winger (Fantegrossi et al., 2004) evaluated the classic psychedelic compounds N,N-dimethyltryptamine (DMT), mescaline, and psilocybin in rhesus monkeys with histories of selfadministering 3,4-methylenedioxymethamphetamine (MDMA), a compound which is not a classic psychedelic but whi…”
Hendricks, P. S., Crawford, M. S., Cropsey, K. L., Copes, H., Sweat, N. W., Walsh, Z., & Pavela, G. (2017) · Journal of Psychopharmacology · doi:10.1177/0269881117735685 · Cited by 101
Self-citationA Prehistoric Mural in Spain Depicting Neurotropic Psilocybe Mushrooms?1
Akers, B. P., López, J. F. R., Piper, A., & Ruck, C. A. P. (2011) · Economic Botany · doi:10.1007/s12231-011-9152-5 · Cited by 97
Carter, L. P., Richards, B. D., Mintzer, M. Z., & Griffiths, R. R. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301146 · Cited by 96
Self-citationHendricks, P. S., Clark, C. B., Johnson, M. W., Fontaine, K. R., & Cropsey, K. L. (2014) · Journal of Psychopharmacology · doi:10.1177/0269881113513851 · Cited by 96
Self-citationTolerance and cross-tolerance among psychotomimetic drugs
Appel, J. B., & Freedman, D. X. (1968) · Psychopharmacology · doi:10.1007/bf00401404 · Cited by 96 · cited 2×
“No apparent physiological dependence as evidenced by withdrawal symptoms has been documented in humans (clinical observations) or animals (laboratory studies), although tolerance has been observed (Abramson et al., 1960; Appel and Freedman, 1968; Isbell et al., 1961).”
An analysis of some discriminative properties of d-amphetamine
Kuhn, D. M., Appel, J. B., & Greenberg, I. (1974) · Psychopharmacology · doi:10.1007/bf00421458 · Cited by 94 · cited 1×
“Similarly, another study found the psilocybin failed to substitute for amphetamine in rats trained to discriminate amphetamine from saline (Kuhn et al., 1974).”
Abuse liability assessment in human subjects
Jasinski, D. R., Johnson, R. E., & Henningfield, J. E. (1984) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(84)90415-2 · Cited by 87 · cited 4×
“LSD and psilocybin most reliably elevated scores on the LSD scale, but frequently also, at a certain dose and in some individuals, elevated scores on theMBG scale, but generally at a lesser magnitude than opioids and stimulants (Haertzen and Hickey, 1987; Jasinski and Henningfield, 1989; Jasinski et al., 1984).”
InfluentialSelf-citationIsbell, H., & Jasinski, D. R. (1969) · Psychopharmacology · doi:10.1007/bf00403684 · Cited by 87 · cited 2×
“, 1961), but not to tetrahydrocannabinol (THC) indicating different mechanisms of action (Isbell and Jasinski, 1969).”
Addiction Research Center Inventory (ARCI): Measurement of Euphoria and Other Drug Effects
Haertzen, C. A., & Hickey, J. E. (1987) · Springer eBooks · doi:10.1007/978-1-4612-4812-5_24 · Cited by 86 · cited 1×
“LSD and psilocybin most reliably elevated scores on the LSD scale, but frequently also, at a certain dose and in some individuals, elevated scores on theMBG scale, but generally at a lesser magnitude than opioids and stimulants (Haertzen and Hickey, 1987; Jasinski and Henningfield, 1989; Jasinski et al., 1984).”
The association of psychedelic use and opioid use disorders among illicit users in the United States
Pisano, V. D., Putnam, N. P., Kramer, H. M., Franciotti, K., Halpern, J. H., & Holden, S. C. (2017) · Journal of Psychopharmacology · doi:10.1177/0269881117691453 · Cited by 86 · cited 1×
“60) among over 44,000 illicit opioid users who completed the NSDUH in years 2008 through 2013 (Pisano et al., 2017).”
Cunningham, K. A., & Appel, J. B. (1987) · Psychopharmacology · doi:10.1007/bf00690929 · Cited by 85 · cited 1×
“metabolite of psilocybin) and to LSD but not to mescaline, which is considered a classic psychedelic of the phenethylamine-based structural class rather than the tryptamine-based structural class of which psilocybin is a member (Cunningham and Appel, 1987; Koerner and Appel, 1982).”
Harms associated with psychoactive substances: findings of the UK National Drug Survey
Morgan, C. J. A., Muetzelfeldt, L., Muetzelfeldt, M., Nutt, D., & Curran, H. V. (2009) · Journal of Psychopharmacology · doi:10.1177/0269881109106915 · Cited by 80 · cited 2×
“A large survey of 1501 UK drug users (Morgan et al., 2010) assessed ratings of harms for the drugs previously examined by the UK drug experts in Nutt et al.”
ON THE NATURE OF ADDICTION AND HABITUATION*
Wikler, A. (1961) · British Journal of Addiction to Alcohol & Other Drugs · doi:10.1111/j.1360-0443.1961.tb05318.x · Cited by 79 · cited 2×
“At the same time theories of addiction and addiction liability assessment were evolving from the focus on physical dependence and withdrawal that had dominated the prior few decades of opioidfocused studies to a greater focus on the acute subjective and behavioral effects of drugs that contributed to their selfadminis…”
Psilocybin mushrooms of the world: an identification guide
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“More than 100 species of mushrooms, in the genus Psilocybe, contain psilocybin (Johnson and Griffiths, 2017; Stamets, 1996).”
InfluentialPsilocybin-induced stimulus control in the rat
Winter, J. C., Rice, K. C., Amorosi, D. J., & Rabin, R. A. (2007) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2007.06.003 · Cited by 75 · cited 2×
“Its agonist activity at the 5-hydroxytryptamine (HT)2A receptor appears to account partially for its behavioral effects, however, the mechanisms of action of its full range of effects have not been fully elucidated (Nichols, 2016; Winter et al., 2007).”
Regulation of human research with LSD in the United States (1949-1987)
Bonson, K. R. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4777-4 · Cited by 74 · cited 4×
“In those days this general approach was permitted for drugs that were not approved for therapeutic use (Bonson, 2018).”
InfluentialAbramson, H. A., Jarvik, M. E., Gorin, M. H., & Hirsch, M. W. (1956) · The Journal of Psychology · doi:10.1080/00223980.1956.9916206 · Cited by 72 · cited 1×
“However, physical dependence and withdrawal, which refer to adverse effects upon discontinuing repeated use of a drug, have not been documented (Abramson et al., 1956; Abramson and Rolo, 1965; Balestrieri, 1967; Isbell, 1959a; Isbell et al., 1961; Passie et al., 2002; Wolbach et al., 1962).”
LSD before Leary: Sidney Cohen's Critique of 1950s Psychedelic Drug Research
Novak, S. (1997) · Isis · doi:10.1086/383628 · Cited by 71 · cited 2×
“…in 1965, and led Sandoz to discontinue manufacturing and marketing Please cite this article in press as: Johnson, M.W., et al., The abuse potent Substances Act, Neuropharmacology (2018), https://doi.org/10.1016/j.neu of Indocybin® in 1966 (Belouin and Henningfield, 2018; Bonson, 2018; Novak, 1997).”
InfluentialHuman Abuse Liability Assessment by Measurement of Subjective and Physiological Effects
Jasinski, D. R., & Henningfield, J. E. (1989) · PsycEXTRA Dataset · doi:10.1037/e496492006-008 · Cited by 71 · cited 2×
“LSD and psilocybin most reliably elevated scores on the LSD scale, but frequently also, at a certain dose and in some individuals, elevated scores on theMBG scale, but generally at a lesser magnitude than opioids and stimulants (Haertzen and Hickey, 1987; Jasinski and Henningfield, 1989; Jasinski et al., 1984).”
Self-citationMonitoring risk: Post marketing surveillance and signal detection
Dart, R. C. (2009) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2009.08.011 · Cited by 69 · cited 2×
“…and storage, and d) a post-marketing surveillance plan to provide the FDAwith timely and comprehensive communication of unintended consequences (Blanchette et al., 2015; Brandenburg et al., 2017; Dart, 2009; Dasgupta and Schnoll, 2009; U.S. Food and Drug Administration, 2015; Wu and Juhaeri, 2016).”
Illegal Drugs Laws: Clearing a 50-Year-Old Obstacle to Research
Nutt, D. (2015) · PLoS Biology · doi:10.1371/journal.pbio.1002047 · Cited by 67 · cited 3×
“As discussed elsewhere in this journal issue and in other publications (Nutt, 2015; Nutt et al., 2013; Scientific American Editors, 2014; Sinha, 2001; Spillane, 2004; Woodworth, 2011), legal restrictions have greatly constrained research; however, research did not altogether Please cite this…”
Walsh, Z., Hendricks, P. S., Smith, S. D., Kosson, D. S., Thiessen, M. S., Lucas, P., & Swogger, M. T. (2016) · Journal of Psychopharmacology · doi:10.1177/0269881116642538 · Cited by 67
Self-citationMiniature Mushroom Stones from Guatemala
de Borhegyi, S. F. (1961) · American Antiquity · doi:10.2307/278737 · Cited by 63 · cited 2×
“…Spain (Akers et al., 2011) 4000 BCE-900 CE e Mushroom stones and other artifacts from cultures throughout the Americas, including Mayan (de Borhegyi, 1961; Lowy, 1971; Schultes, 1969; Schultes et al., 2001; Truttman, 2012) 1600 e Spanish colonizers documented religious mushroom use by…”
An Analysis of the Function of Drugs in the Stimulus Control of Operant Behavior
Harris, R. T., & Balster, R. L. (1971) · Springer eBooks · doi:10.1007/978-1-4757-0788-5_7 · Cited by 61 · cited 1×
“For example, Harris and Balster compared psilocybin to amphetamine in a rodent model for assessing behavioral and discriminative effects (Harris and Balster, 1971).”
Can psychedelic compounds play a part in drug dependence therapy?
Sessa, B., & Johnson, M. W. (2015) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.114.148031 · Cited by 58 · cited 1×
“Data important in understanding the safety, mechanisms of action, and potential future indications for psilocybin-assisted treatment have included the treatment of substance use disorders (Bogenschutz et al., 2015; Garcia-Romeu et al., 2014; Johnson et al., 2012, 2014, 2017; Johnson and Griffiths, 2017; Nichols et al.…”
Self-citationExperienced Drug Users Assess the Relative Harms and Benefits of Drugs: A Web-Based Survey
Carhart-Harris, R. L., & Nutt, D. (2013) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2013.825034 · Cited by 54 · cited 3×
“In a similar study (Carhart-Harris and Nutt, 2013), experienced drug users rated harms to “self” and to “others.”
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Heal, D. J., Gosden, J., & Smith, S. L. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.01.049 · Cited by 52
Les champignons hallucinogènes du Mexique /
Kraft, M.-M. (1959) · BCU · doi:10.22005/bcu.18361 · Cited by 51
A fatal case of ‘magic mushroom’ ingestion in a heart transplant recipient
Lim, T. H., Wasywich, C. A., & Ruygrok, P. (2012) · Internal Medicine Journal · doi:10.1111/j.1445-5994.2012.02955.x · Cited by 50
Debating the Controlled Substances Act
Spillane, J. F. (2004) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2004.04.011 · Cited by 49 · cited 3×
“As discussed elsewhere in this journal issue and in other publications (Nutt, 2015; Nutt et al., 2013; Scientific American Editors, 2014; Sinha, 2001; Spillane, 2004; Woodworth, 2011), legal restrictions have greatly constrained research; however, research did not altogether”
InfluentialStudies on the Diethylamide of Lysergic Acid (LSD-25)
Isbell, H. (1957) · A M A Archives of Neurology & Psychiatry · doi:10.1001/archneurpsyc.1957.02330340026002 · Cited by 49
Lysergic acid diethylamide (LSD) as a discriminative cue: Drugs with similar stimulus properties
Schechter, M., & Rosecrans, J. A. (1972) · Psychopharmacology · doi:10.1007/bf00422707 · Cited by 49
Brandenburg, N. A., Bwire, R., Freeman, J., Houn, F., Sheehan, P., & Zeldis, J. B. (2017) · Drug Safety · doi:10.1007/s40264-016-0501-2 · Cited by 47
Sexton, J. D., Nichols, C. D., & Hendricks, P. S. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00896 · Cited by 46
Self-citationMutagenicity testing of 3 hallucinogens: LSD, psilocybin and‡ 9-THC using the micronucleus test
Went, G. (1978) · Cellular and Molecular Life Sciences · doi:10.1007/bf01923013 · Cited by 43 · cited 1×
“A micronucleus study in mice found no evidence that psilocybin administration resulted in Please cite this article in press as: Johnson, M.W., et al., The abuse potent Substances Act, Neuropharmacology (2018), https://doi.org/10.1016/j.neu chromosome breaking (Van Went, 1978).”
InfluentialBigwood, J., & Beug, M. W. (1982) · Journal of Ethnopharmacology · doi:10.1016/0378-8741(82)90014-9 · Cited by 42 · cited 4×
“Cultivated psilocybin-containing mushrooms have been shown to vary in psilocybin content by a factor of 4, while “street samples” of psilocybin-containing mushrooms have been shown to vary in psilocybin content by an astonishing factor of 10 (Bigwood and Beug, 1982).”
InfluentialStudies with psychedelic drugs in human volunteers
Sellers, E. M., Romach, M. K., & Leiderman, D. B. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.11.029 · Cited by 42 · cited 8×
“Nonetheless, the pharmacology and mechanisms of action of psilocybin and LSD are similar in many respects, although psilocybin is shorter acting and at least 100 times less potent than LSD (Isbell, 1959a; Sellers et al., 2017).”
InfluentialClinical, biochemical and psychologic effects of psilocybin.
Hollister, L. E. (1961) · PubMed · Cited by 40
Wasson, R. G. (1959) · Transactions of the New York Academy of Sciences · doi:10.1111/j.2164-0947.1959.tb00681.x · Cited by 39 · cited 2×
“indigenous people (Mazatec society in Mexico) since European colonization (Wasson, 1959; Wasson and Wasson, 1957)”
Trends in drug use among drivers killed in U.S. traffic crashes, 1999–2010
Rudisill, T. M., Zhao, S., Abate, M. A., Coben, J. H., & Zhu, M. (2014) · Accident Analysis & Prevention · doi:10.1016/j.aap.2014.04.003 · Cited by 36 · cited 1×
“The exception to this trend appears to be the category of “hallucinogens” (Rudisill et al., 2014).”
Involvement of 5-HT receptor subtypes in the discriminative stimulus properties of mescaline
Appel, J. B., & Callahan, P. M. (1989) · European Journal of Pharmacology · doi:10.1016/0014-2999(89)90041-1 · Cited by 34
Corti, E. C., & ENGLAND, P. J. (1932) · Medical Entomology and Zoology · Cited by 32
New Records of Mushroom Stones from Guatemala
Lowy, B. (1971) · Mycologia · doi:10.1080/00275514.1971.12019194 · Cited by 32 · cited 8×
“Then, following earlier suggestive evidence by R. Schultes (Schultes, 1939, 1940), R.G. Wasson became the first non-indigenous individual to participate in and document sacramental psilocybin-containing mushroom use by indigenous people (Mazatec society in Mexico) since European colonization (Wasson, 1959; Wasson and…”
InfluentialHistorical overview of psychoactive mushrooms
Matsushima, Y., Eguchi, F., Kikukawa, T., & Matsuda, T. (2009) · Inflammation and Regeneration · doi:10.2492/inflammregen.29.47 · Cited by 31 · cited 2×
“While Indocybin was used safely as an adjunct to psychotherapy, eventually the societal backlash in the US and other countries in the 1960s (Matsushima et al., 2009) led to a ban on marketing and possession of “hallucinogenic” drugs in the US in 1965, and led Sandoz to discontinue manufacturing and marketing”
Signal detection in post-marketing surveillance for controlled substances
Dasgupta, N., & Schnoll, S. H. (2009) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2009.05.019 · Cited by 30 · cited 1×
“The REMSwould be based on the studies and approaches used to ensure safe and effective use and could include: a) limitations on the dose and the number of doses that could be administered to a given patient, b) administration of the drug in clinic settings with psychological support of specially trained staff, c) a va…”
Wu, J., & Juhaeri, J. (2016) · Clinical Therapeutics · doi:10.1016/j.clinthera.2016.11.007 · Cited by 30 · cited 1×
“The REMSwould be based on the studies and approaches used to ensure safe and effective use and could include: a) limitations on the dose and the number of doses that could be administered to a given patient, b) administration of the drug in clinic settings with psychological support of specially trained staff, c) a va…”
Drug Regulation and Innovation: Empirical Evidence and Policy Options
Grabowski, H. G. (1976) · DigitalGeorgetown (Georgetown University Library) · Cited by 28
STUDIES ON MODIFICATION OF THE MORPHINE ABSTINENCE SYNDROME BY DRUGS
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“the development of tolerance and the emergence of withdrawal signs and symptoms upon discontinuation of drug administration (Himmelsbach and Andrews, 1943).”
Case histories in pharmaceutical risk management
McCormick, C. G., Henningfield, J. E., Haddox, J. D., Varughese, S., Lindholm, A., Rosen, S. I., Wissel, J., Waxman, D., Carter, L. P., Seeger, V., et al. (2009) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2009.08.003 · Cited by 26 · cited 4×
“, psilocybin) as a medicine because risk management, particularly in the legally binding approach of REMS, is intended to provide conditions for distribution, use, oversite and other factors to ensure safe use (McCormick et al., 2009; U.S. Food and Drug Administration, 2015).”
InfluentialSelf-citationComparative abuse liability of GHB and ethanol in humans.
Johnson, M. W., & Griffiths, R. R. (2013) · Experimental and Clinical Psychopharmacology · doi:10.1037/a0031692 · Cited by 26 · cited 3×
“Approval of drugs with REMS anticipates the likelihood that emerging clinical Please cite this article in press as: Johnson, M.W., et al., The abuse potent Substances Act, Neuropharmacology (2018), https://doi.org/10.1016/j.neu experience, further research, and the relatively high level of oversight and data collectio…”
InfluentialSelf-citationA regulatory perspective on the evaluation of hallucinogen drugs for human use
Calderon, S. N., Hunt, J., & Klein, M. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.11.028 · Cited by 23
Blanchette, C., Nunes, A. P., Lin, N. U., Mortimer, K., Noone, J., Tangirala, K., Johnston, S. S., & Gutiérrez, B. (2015) · Drugs in Context · doi:10.7573/dic.212272 · Cited by 22
Active cocaine immunization attenuates the discriminative properties of cocaine.
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Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H., & Griffiths, R. R. (2021) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2020.3285 · Cited by 1,301
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“procedure based on research evidence (143).”
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Self-citationGukasyan, N., Davis, A. K., Barrett, F. S., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., & Griffiths, R. R. (2022) · Journal of Psychopharmacology · doi:10.1177/02698811211073759 · Cited by 425
“Although evidence to date suggests that psilocybin has relatively low abuse potential (Johnson et al., 2018), there remains concern for its potential to cause harm or encourage substance misuse in vulnerable populations (Reiff et al., 2020; Schatzberg, 2020).”
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Metadata
- Authors
- Johnson, M. W., Griffiths, R. R., Hendricks, P. S., & Henningfield, J. E.
- Affiliations
- Johns Hopkins University (US)
- University of Alabama (US)
- Corresponding author
- Johnson, Matthew W.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 142
- Pages
- 143-166
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC6791528
- OpenAlex
- W2806419184
- Cited by
- 354
- References
- 180
- Citations by year
- 2026: 36 · 2025: 61 · 2024: 57 · 2023: 55 · 2022: 60 · 2021: 31 · 2020: 33 · 2019: 15 · 2018: 4
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuropharmacology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Heffter Research Institute
- NIH (RO1DA03889)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Alkaloids: synthesis and pharmacology
- Keywords
- psilocybin, abuse liability, Controlled Substances Act, drug scheduling, classic psychedelics, substance use disorders, adverse effects, psychosis, risk management, dose control
- MeSH terms
- Animals, Drug and Narcotic Control, Hallucinogens, Humans, Psilocybin, Substance-Related Disorders
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