Login Register Cart 0
Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Psychedelics and Hallucinogens in Psychiatry: Finding New Pharmacological Targets

Author(s): Teresa Reynolds Sousa*, João Rema, Sergio Machado and Filipa Novais

Volume 22, Issue 15, 2022

Published on: 15 December, 2021

Page: [1250 - 1260] Pages: 11

DOI: 10.2174/1568026621666211201145800

Price: $65

Abstract

Background: The therapeutic options for neurobehavioral disorders are still limited, and in many cases, they lack a satisfactory balance between efficacy and side effects.

Objectives: This work aims to review current evidence regarding the potential contribution of psychedelics and hallucinogens to the discovery of new drugs for treating different psychiatric disorders.

Discussion: Ayahuasca/N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and psilocybin have evidence supporting their use in depression, and psilocybin and ayahuasca have also shown good results in treatment-resistant depression. In randomized controlled trials (RCTs) conducted with anxious patients, there were symptomatic improvements with psilocybin and LSD. Psilocybin diminished Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores in a small obsessive- compulsive disorder (OCD) sample. The evidence is less robust regarding substance use disorders, but it suggests a possible role for LSD and psilocybin in alcohol use disorders and for psilocybin in tobacco addiction. In a clinical setting, these substances seem to be safe and well-tolerated. Their mechanisms of action are not fully elucidated, but there seems to be a preponderant role of 5-hydroxytryptamine (5HT) 2A agonism, as well as connectivity changes within the default mode network (DMN) and amygdala and some other molecular modifications.

Conclusion: The studies underlying the conclusions have small samples and are heterogeneous in their methods. However, the results suggest that the use of psychedelics and hallucinogens could be considered in some disorders. More studies are needed to reinforce their evidence as potential new drugs.

Keywords: Psychedelics, LSD, Psilocybin, Ayahuasca, DMT, Psychiatry, Depression, Anxiety, Substance use, Obsessive-compulsive.

« Previous Next »
Graphical Abstract

[1]
Psychedelics. Pharmacol. Rev., 2016, 68(2), 356-356. http://pharmrev.aspetjournals.org/content/68/2/356 abstract
[2]
Fuentes, J.J.; Fonseca, F.; Elices, M.; Farré, M.; Torrens, M. Therapeutic use of LSD in psychiatry: a systematic review of randomized-controlled clinical trials. Front. Psychiatry, 2020, 10, 943.
[http://dx.doi.org/10.3389/fpsyt.2019.00943] [PMID: 32038315]
[3]
Andersen, K.A.A.; Carhart-Harris, R.; Nutt, D.J.; Erritzoe, D. Therapeutic effects of classic serotonergic psychedelics: a systematic review of modern-era clinical studies. Acta Psychiatr. Scand., 2021, 143(2), 101-118.
[http://dx.doi.org/10.1111/acps.13249] [PMID: 33125716]
[4]
Roth, B.L.; Berry, S.A.; Kroeze, W.K.; Willins, D.L.; Kristiansen, K. Serotonin 5-HT2A receptors: molecular biology and mechanisms of regulation. Crit. Rev. Neurobiol., 1998, 12(4), 319-338.
[http://dx.doi.org/10.1615/CritRevNeurobiol.v12.i4.30] [PMID: 10348614]
[5]
Carhart-Harris, R.L.; Erritzoe, D.; Williams, T.; Stone, J.M.; Reed, L.J.; Colasanti, A.; Tyacke, R.J.; Leech, R.; Malizia, A.L.; Murphy, K.; Hobden, P.; Evans, J.; Feilding, A.; Wise, R.G.; Nutt, D.J. Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc. Natl Acad. Sci., 2012, 109(6), 2138-2143.
[http://dx.doi.org/10.1073/pnas.1119598109]
[6]
Johnson, M.W.; Griffiths, R.R. Potential therapeutic effects of psilocybin. Neurotherapeutics, 2017, 14(3), 734-740.
[http://dx.doi.org/10.1007/s13311-017-0542-y] [PMID: 28585222]
[7]
Halberstadt, A.L.; Nichols, D.E.; Vollenweider, F.X. Behavioral neurobiology of psychedelic drugs. Curr. Top. Behav. Neurosci; 1st ed Springer Nature: Berlin, 2017, p. 2. http://www.springer.com/series/7854
[8]
National center for biotechnology information. PubChem Compound Summary for CID 5202, Serotonin 2021. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Serotonin
[9]
National center for biotechnology information. PubChem Compound Summary for CID 6089, N,N-Dimethyltryptamine 2021. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/N_N-Dimethyltryptamine
[10]
National center for biotechnology information PubChem Compound Summary for CID 5761, Lysergide 2021. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Lysergide
[11]
National center for biotechnology information. PubChem Compound Summary for CID 10624, Psilocybine 2021. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Psilocybine
[12]
Reiff, C.M.; Richman, E.E.; Nemeroff, C.B.; Carpenter, L.L.; Widge, A.S.; Rodriguez, C.I.; Kalin, N.H.; McDonald, W.M. Psychedelics and psychedelic-assisted psychotherapy. Am. J. Psychiatry, 2020, 177(5), 391-410.
[http://dx.doi.org/10.1176/appi.ajp.2019.19010035] [PMID: 32098487]
[13]
Kim, K.; Che, T.; Panova, O.; DiBerto, J.F.; Lyu, J.; Krumm, B.E.; Wacker, D.; Robertson, M.J.; Seven, A.B.; Nichols, D.E.; Shoichet, B.K.; Skiniotis, G.; Roth, B.L. Structure of a hallucinogen-activated Gq-coupled 5-HT2A serotonin receptor. Cell, 2020, 182(6), 1574-1588.e19.
[http://dx.doi.org/10.1016/j.cell.2020.08.024] [PMID: 32946782]
[14]
Halberstadt, A.L. Recent advances in the neuropsychopharmacology of serotonergic hallucinogens. Behav. Brain Res., 2015, 277, 99-120.
[http://dx.doi.org/10.1016/j.bbr.2014.07.016] [PMID: 25036425]
[15]
Vollenweider, F.X.; Vollenweider-Scherpenhuyzen, M.F.I.; Bäbler, A.; Vogel, H.; Hell, D. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport, 1998, 9(17), 3897-3902.
[http://dx.doi.org/10.1097/00001756-199812010-00024] [PMID: 9875725]
[16]
González-Maeso, J.; Weisstaub, N.V.; Zhou, M.; Chan, P.; Ivic, L.; Ang, R.; Lira, A.; Bradley-Moore, M.; Ge, Y.; Zhou, Q.; Sealfon, S.C.; Gingrich, J.A. Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior. Neuron, 2007, 53(3), 439-452.
[http://dx.doi.org/10.1016/j.neuron.2007.01.008] [PMID: 17270739]
[17]
González-Maeso, J.; Yuen, T.; Ebersole, B.J.; Wurmbach, E.; Lira, A.; Zhou, M.; Weisstaub, N.; Hen, R.; Gingrich, J.A.; Sealfon, S.C. Transcriptome fingerprints distinguish hallucinogenic and nonhallucinogenic 5-hydroxytryptamine 2A receptor agonist effects in mouse somatosensory cortex. J. Neurosci., 2003, 23(26), 8836-8843.
[http://dx.doi.org/10.1523/JNEUROSCI.23-26-08836.2003] [PMID: 14523084]
[18]
Karaki, S.; Becamel, C.; Murat, S.; Mannoury la Cour, C.; Millan, M.J.; Prézeau, L.; Bockaert, J.; Marin, P.; Vandermoere, F. Quantitative phosphoproteomics unravels biased phosphorylation of serotonin 2A receptor at Ser280 by hallucinogenic versus nonhallucinogenic agonists. Mol. Cell. Proteomics, 2014, 13(5), 1273-1285.
[http://dx.doi.org/10.1074/mcp.M113.036558] [PMID: 24637012]
[19]
Barnes, N.M.; Sharp, T. A review of central 5-HT receptors and their function. Neuropharmacology, 1999, 38(8), 1083-1152.
[http://dx.doi.org/10.1016/S0028-3908(99)00010-6] [PMID: 10462127]
[20]
Hannon, J.; Hoyer, D. Molecular biology of 5-HT receptors. Behav. Brain Res., 2008, 195(1), 198-213.
[http://dx.doi.org/10.1016/j.bbr.2008.03.020] [PMID: 18571247]
[21]
Kurrasch-Orbaugh, D.M.; Watts, V.J.; Barker, E.L.; Nichols, D.E. Serotonin 5-Hydroxytryptamine<sub>2A</sub> Receptor-Coupled phospholipase C and Phospholipase A<sub>2</sub> Signaling pathways have different receptor reserves. J. Pharmacol. Exp. Therap., 2003, 304(1), 229-237.
[22]
Kurrasch-Orbaugh, D.M.; Parrish, J.C.; Watts, V.J.; Nichols, D.E. A complex signaling cascade links the serotonin2A receptor to phospholipase A2 activation: The involvement of MAP kinases. J. Neurochem., 2003, 86(4), 980-991.
[http://dx.doi.org/10.1046/j.1471-4159.2003.01921.x] [PMID: 12887695]
[23]
Raymond, J.R.; Mukhin, Y.V.; Gelasco, A.; Turner, J.; Collinsworth, G.; Gettys, T.W.; Grewal, J.S.; Garnovskaya, M.N. Multiplicity of mechanisms of serotonin receptor signal transduction. Pharmacol. Ther., 2001, 92(2-3), 179-212.
[http://dx.doi.org/10.1016/S0163-7258(01)00169-3] [PMID: 11916537]
[24]
Schmid, C.L.; Bohn, L.M. Serotonin, but not N-methyltryptamines, activates the serotonin 2A receptor via a ß-arrestin2/Src/Akt signaling complex in vivo. J. Neurosci., 2010, 30(40), 13513-13524.
[http://dx.doi.org/10.1523/JNEUROSCI.1665-10.2010] [PMID: 20926677]
[25]
Robertson, D.N.; Johnson, M.S.; Moggach, L.O.; Holland, P.J.; Lutz, E.M.; Mitchell, R. Selective interaction of ARF1 with the carboxy-terminal tail domain of the 5-HT2A receptor. Mol. Pharmacol., 2003, 64(5), 1239-1250.
[http://dx.doi.org/10.1124/mol.64.5.1239] [PMID: 14573774]
[26]
González-Maeso, J.; Ang, R.L.; Yuen, T.; Chan, P.; Weisstaub, N.V.; López-Giménez, J.F.; Zhou, M.; Okawa, Y.; Callado, L.F.; Milligan, G.; Gingrich, J.A.; Filizola, M.; Meana, J.J.; Sealfon, S.C. Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature, 2008, 452(7183), 93-97.
[http://dx.doi.org/10.1038/nature06612] [PMID: 18297054]
[27]
Delille, H.K.; Mezler, M.; Marek, G.J. The two faces of the pharmacological interaction of mGlu2 and 5-HT2A - Relevance of receptor heterocomplexes and interaction through functional brain pathways. Neuropharmacology, 2013, 70, 296-305.
[http://dx.doi.org/10.1016/j.neuropharm.2013.02.005] [PMID: 23466331]
[28]
Dos Santos, R.G.; Bouso, J.C.; Alcázar-Córcoles, M.Á.; Hallak, J.E.C. Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews. Expert Rev. Clin. Pharmacol., 2018, 11(9), 889-902.
[http://dx.doi.org/10.1080/17512433.2018.1511424] [PMID: 30102078]
[29]
Dos Santos, R.G.; Osório, F.L.; Crippa, J.A.S.; Hallak, J.E.C. Classical hallucinogens and neuroimaging: a systematic review of human studies: Hallucinogens and neuroimaging. Neurosci. Biobehav. Rev., 2016, 71, 715-728.
[http://dx.doi.org/10.1016/j.neubiorev.2016.10.026] [PMID: 27810345]
[30]
Muttoni, S.; Ardissino, M.; John, C. Classical psychedelics for the treatment of depression and anxiety: a systematic review. J. Affect. Disord., 2019, 258, 11-24.
[http://dx.doi.org/10.1016/j.jad.2019.07.076] [PMID: 31382100]
[31]
Dos Santos, R.G.; Osório, F.L.; Crippa, J.A.S.; Riba, J.; Zuardi, A.W.; Hallak, J.E.C. Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years. Ther. Adv. Psychopharmacol., 2016, 6(3), 193-213.
[http://dx.doi.org/10.1177/2045125316638008] [PMID: 27354908]
[32]
Carhart-Harris, R.L.; Leech, R.; Erritzoe, D.; Williams, T.M.; Stone, J.M.; Evans, J.; Sharp, D.J.; Feilding, A.; Wise, R.G.; Nutt, D.J. Functional connectivity measures after psilocybin inform a novel hypothesis of early psychosis. Schizophr. Bull., 2013, 39(6), 1343-1351.
[http://dx.doi.org/10.1093/schbul/sbs117] [PMID: 23044373]
[33]
Gouzoulis-Mayfrank, E.; Schreckenberger, M.; Sabri, O.; Arning, C.; Thelen, B.; Spitzer, M.; Kovar, K-A.; Hermle, L.; Büll, U.; Sass, H. Neurometabolic effects of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE) and d-methamphetamine in healthy volunteers. A double-blind, placebo-controlled PET study with [18F]FDG. Neuropsychopharmacology, 1999, 20(6), 565-581.
[http://dx.doi.org/10.1016/S0893-133X(98)00089-X] [PMID: 10327426]
[34]
Vollenweider, F.X.; Leenders, K.L.; Scharfetter, C.; Maguire, P.; Stadelmann, O.; Angst, J. Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis. Neuropsychopharmacology, 1997, 16(5), 357-372.
[http://dx.doi.org/10.1016/S0893-133X(96)00246-1] [PMID: 9109107]
[35]
Riba, J.; Romero, S.; Grasa, E.; Mena, E.; Carrió, I.; Barbanoj, M.J. Increased frontal and paralimbic activation following ayahuasca, the pan-Amazonian inebriant. Psychopharmacology (Berl.), 2006, 186(1), 93-98.
[http://dx.doi.org/10.1007/s00213-006-0358-7] [PMID: 16575552]
[36]
Kraehenmann, R.; Preller, K.H.; Scheidegger, M.; Pokorny, T.; Bosch, O.G.; Seifritz, E.; Vollenweider, F.X. Psilocybin-Induced decrease in amygdala reactivity correlates with enhanced positive mood in healthy volunteers. Biol. Psychiatry, 2015, 78(8), 572-581.
[http://dx.doi.org/10.1016/j.biopsych.2014.04.010] [PMID: 24882567]
[37]
Kraehenmann, R.; Schmidt, A.; Friston, K.; Preller, K.H.; Seifritz, E.; Vollenweider, F.X. The mixed serotonin receptor agonist psilocybin reduces threat-induced modulation of amygdala connectivity. Neuroimage Clin., 2015, 11, 53-60.
[http://dx.doi.org/10.1016/j.nicl.2015.08.009] [PMID: 26909323]
[38]
Carhart-Harris, R.L.; Roseman, L.; Bolstridge, M.; Demetriou, L.; Pannekoek, J.N.; Wall, M.B.; Tanner, M.; Kaelen, M.; McGonigle, J.; Murphy, K.; Leech, R.; Curran, H.V.; Nutt, D.J. Psilocybin for treatment-resistant depression: FMRI-measured brain mechanisms. Sci. Rep., 2017, 7(1), 13187.
[http://dx.doi.org/10.1038/s41598-017-13282-7] [PMID: 29030624]
[39]
Carhart-Harris, R.L.; Muthukumaraswamy, S.; Roseman, L.; Kaelen, M.; Droog, W.; Murphy, K.; Tagliazucchi, E.; Schenberg, E.E.; Nest, T.; Orban, C.; Leech, R.; Williams, L.T.; Williams, T.M.; Bolstridge, M.; Sessa, B.; McGonigle, J.; Sereno, M.I.; Nichols, D.; Hellyer, P.J.; Hobden, P.; Evans, J.; Singh, K.D.; Wise, R.G.; Curran, H.V.; Feilding, A.; Nutt, D.J. Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proc. Nat. Acad. Sci, 2016, 113(17), 4853-4858.
[http://dx.doi.org/10.1073/pnas.1518377113]
[40]
Barrett, F.S.; Doss, M.K.; Sepeda, N.D.; Pekar, J.J.; Griffiths, R.R. Emotions and brain function are altered up to one month after a single high dose of psilocybin. Sci. Rep., 2020, 10(1), 2214.
[http://dx.doi.org/10.1038/s41598-020-59282-y] [PMID: 32042038]
[41]
Roseman, L.; Leech, R.; Feilding, A.; Nutt, D.J.; Carhart-Harris, R.L. The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers. Front. Hum. Neurosci., 2014, 8, 204.
[http://dx.doi.org/10.3389/fnhum.2014.00204] [PMID: 24904346]
[42]
Petri, G.; Expert, P.; Turkheimer, F.; Carhart-Harris, R.; Nutt, D.; Hellyer, P.J.; Vaccarino, F. Homological scaffolds of brain functional networks. J. R. Soc. Interface, 2014, 11(101), 20140873.
[http://dx.doi.org/10.1098/rsif.2014.0873] [PMID: 25401177]
[43]
Lebedev, A.V.; Lövdén, M.; Rosenthal, G.; Feilding, A.; Nutt, D.J.; Carhart-Harris, R.L. Finding the self by losing the self: neural correlates of ego-dissolution under psilocybin. Hum. Brain Mapp., 2015, 36(8), 3137-3153.
[http://dx.doi.org/10.1002/hbm.22833] [PMID: 26010878]
[44]
Palhano-Fontes, F.; Andrade, K.C.; Tofoli, L.F.; Santos, A.C.; Crippa, J.A.S.; Hallak, J.E.C.; Ribeiro, S.; de Araujo, D.B. The psychedelic state induced by ayahuasca modulates the activity and connectivity of the default mode network. PLoS One, 2015, 10(2), e0118143.
[http://dx.doi.org/10.1371/journal.pone.0118143] [PMID: 25693169]
[45]
Smigielski, L.; Scheidegger, M.; Kometer, M.; Vollenweider, F.X. Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects. Neuroimage, 2019, 196, 207-215.
[http://dx.doi.org/10.1016/j.neuroimage.2019.04.009] [PMID: 30965131]
[46]
Alonso, J.F.; Romero, S.; Mañanas, M.À.; Riba, J. Serotonergic psychedelics temporarily modify information transfer in humans. Int. J. Neuropsychopharmacol., 2015, 18(8), pyv039.
[http://dx.doi.org/10.1093/ijnp/pyv039] [PMID: 25820842]
[47]
Carhart-Harris, R.L.; Friston, K.J. REBUS and the anarchic brain: Toward a unified model of the brain action of psychedelics. Pharmacol. Rev., 2019, 71(3), 316-344.
[48]
Aday, J.S.; Mitzkovitz, C.M.; Bloesch, E.K.; Davoli, C.C.; Davis, A.K. Long-term effects of psychedelic drugs: a systematic review. Neurosci. Biobehav. Rev., 2020, 113, 179-189.
[http://dx.doi.org/10.1016/j.neubiorev.2020.03.017] [PMID: 32194129]
[49]
Vollenweider, F.X.; Preller, K.H. Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders. Nat. Rev. Neurosci., 2020, 21(11), 611-624.
[http://dx.doi.org/10.1038/s41583-020-0367-2] [PMID: 32929261]
[50]
Vaidya, V.A.; Marek, G.J.; Aghajanian, G.K.; Duman, R.S. 5-HT2A receptor-mediated regulation of brain-derived neurotrophic factor mRNA in the hippocampus and the neocortex. J. Neurosci., 1997, 17(8), 2785-2795.
[http://dx.doi.org/10.1523/JNEUROSCI.17-08-02785.1997] [PMID: 9092600]
[51]
Ross, S.; Bossis, A.; Guss, J.; Agin-Liebes, G.; Malone, T.; Cohen, B.; Mennenga, S.E.; Belser, A.; Kalliontzi, K.; Babb, J.; Su, Z.; Corby, P.; Schmidt, B.L. 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, 30(12), 1165-1180.
[http://dx.doi.org/10.1177/0269881116675512] [PMID: 27909164]
[52]
Roseman, L.; Nutt, D.J.; Carhart-Harris, R.L. Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression. Front. Pharmacol., 2018, 8, 974.
[http://dx.doi.org/10.3389/fphar.2017.00974] [PMID: 29387009]
[53]
Garcia-Romeu, A.; Griffiths, R.R.; Johnson, M.W. Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Curr. Drug Abuse Rev., 2014, 7(3), 157-164.
[http://dx.doi.org/10.2174/1874473708666150107121331] [PMID: 25563443]
[54]
Griffiths, R.R.; Johnson, M.W.; Carducci, M.A.; Umbricht, A.; Richards, W.A.; Richards, B.D.; Cosimano, M.P.; Klinedinst, M.A. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J. Psychopharmacol., 2016, 30(12), 1181-1197.
[http://dx.doi.org/10.1177/0269881116675513] [PMID: 27909165]
[55]
Palhano-Fontes, F.; Barreto, D.; Onias, H.; Andrade, K.C.; Novaes, M.M.; Pessoa, J.A.; Mota-Rolim, S.A.; Osório, F.L.; Sanches, R.; dos Santos, R.G.; Tófoli, L.F.; de Oliveira Silveira, G.; Yonamine, M.; Riba, J.; Santos, F.R.; Silva-Junior, A.A.; Alchieri, J.C.; Galvão-Coelho, N.L.; Lobão-Soares, B.; Hallak, J.E.C.; Arcoverde, E.; Maia-de-Oliveira, J.P.; Araújo, D.B.; Maia-de-Oliveira, J.P.; Araújo , D.B. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychol. Med., 2019, 49(4), 655-63.
[http://dx.doi.org/10.1017/S0033291718001356]
[56]
Sanches, R.F.; de Lima Osório, F.; Dos Santos, R.G.; Macedo, L.R.H.; Maia-de-Oliveira, J.P.; Wichert-Ana, L.; de Araujo, D.B.; Riba, J.; Crippa, J.A.S.; Hallak, J.E.C. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a SPECT study. J. Clin. Psychopharmacol., 2016, 36(1), 77-81.
[http://dx.doi.org/10.1097/JCP.0000000000000436] [PMID: 26650973]
[57]
Carhart-Harris, R.L.; Bolstridge, M.; Day, C.M.J.; Rucker, J.; Watts, R.; Erritzoe, D.E.; Kaelen, M.; Giribaldi, B.; Bloomfield, M.; Pilling, S.; Rickard, J.A.; Forbes, B.; Feilding, A.; Taylor, D.; Curran, H.V.; Nutt, D.J. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology (Berl.), 2018, 235(2), 399-408.
[http://dx.doi.org/10.1007/s00213-017-4771-x] [PMID: 29119217]
[58]
Carhart-Harris, R.L.; Bolstridge, M.; Rucker, J.; Day, C.M.J.; Erritzoe, D.; Kaelen, M.; Bloomfield, M.; Rickard, J.A.; Forbes, B.; Feilding, A.; Taylor, D.; Pilling, S.; Curran, V.H.; Nutt, D.J. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry, 2016, 3(7), 619-627.
[http://dx.doi.org/10.1016/S2215-0366(16)30065-7] [PMID: 27210031]
[59]
Castro Santos, H.; Gama Marques, J. What is the clinical evidence on psilocybin for the treatment of psychiatric disorders? a systematic review. Porto Biomed. J., 2021, 6(1), e128.
[http://dx.doi.org/10.1097/j.pbj.0000000000000128] [PMID: 33884324]
[60]
Johnson, M.W.; Garcia-Romeu, A.; Griffiths, R.R. Long-term follow-up of psilocybin-facilitated smoking cessation. Am. J. Drug Alcohol Abuse, 2017, 43(1), 55-60.
[http://dx.doi.org/10.3109/00952990.2016.1170135] [PMID: 27441452]
[61]
Carhart-Harris, R.; Giribaldi, B.; Watts, R.; Baker-Jones, M.; Murphy-Beiner, A.; Murphy, R.; Martell, J.; Blemings, A.; Erritzoe, D.; Nutt, D.J. Trial of psilocybin versus escitalopram for depression. N. Engl. J. Med., 2021, 384(15), 1402-1411.
[http://dx.doi.org/10.1056/NEJMoa2032994] [PMID: 33852780]
[62]
Hendricks, P.S.; Thorne, C.B.; Clark, C.B.; Coombs, D.W.; Johnson, M.W. Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. J. Psychopharmacol., 2015, 29(3), 280-288.
[http://dx.doi.org/10.1177/0269881114565653] [PMID: 25586402]
[63]
Grob, C.S.; Danforth, A.L.; Chopra, G.S.; Hagerty, M.; McKay, C.R.; Halberstadt, A.L.; Greer, G.R. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch. Gen. Psychiatry, 2011, 68(1), 71-78.
[http://dx.doi.org/10.1001/archgenpsychiatry.2010.116] [PMID: 20819978]
[64]
Vargas, A.S.; Luís, Â.; Barroso, M.; Gallardo, E.; Pereira, L. Psilocybin as a new approach to treat depression and anxiety in the context of life-threatening diseases-A systematic review and meta-analysis of clinical trials. Biomedicines, 2020, 8(9), E331.
[http://dx.doi.org/10.3390/biomedicines8090331] [PMID: 32899469]
[65]
Gasser, P.; Holstein, D.; Michel, Y.; Doblin, R.; Yazar-Klosinski, B.; Passie, T.; Brenneisen, R. Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. J. Nerv. Ment. Dis., 2014, 202(7), 513-520.
[http://dx.doi.org/10.1097/NMD.0000000000000113] [PMID: 24594678]
[66]
Gasser, P.; Kirchner, K.; Passie, T. LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: a qualitative study of acute and sustained subjective effects. J. Psychopharmacol., 2015, 29(1), 57-68.
[http://dx.doi.org/10.1177/0269881114555249] [PMID: 25389218]
[67]
Santos, R.G.; Landeira-Fernandez, J.; Strassman, R.J.; Motta, V.; Cruz, A.P.M. Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members. J. Ethnopharmacol., 2007, 112(3), 507-513.
[http://dx.doi.org/10.1016/j.jep.2007.04.012] [PMID: 17532158]
[68]
Krebs, T.S.; Johansen, P-Ø. Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. J. Psychopharmacol., 2012, 26(7), 994-1002.
[http://dx.doi.org/10.1177/0269881112439253] [PMID: 22406913]
[69]
Johnson, M.W.; Garcia-Romeu, A.; Cosimano, M.P.; Griffiths, R.R. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J. Psychopharmacol., 2014, 28(11), 983-992.
[http://dx.doi.org/10.1177/0269881114548296] [PMID: 25213996]
[70]
Bogenschutz, M.P.; Forcehimes, A.A.; Pommy, J.A.; Wilcox, C.E.; Barbosa, P.C.R.; Strassman, R.J. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J. Psychopharmacol., 2015, 29(3), 289-299.
[http://dx.doi.org/10.1177/0269881114565144] [PMID: 25586396]
[71]
Dos Santos, R.G.; Balthazar, F.M.; Bouso, J.C.; Hallak, J.E.C. The current state of research on ayahuasca: a systematic review of human studies assessing psychiatric symptoms, neuropsychological functioning, and neuroimaging. J. Psychopharmacol., 2016, 30(12), 1230-1247.
[http://dx.doi.org/10.1177/0269881116652578] [PMID: 27287824]
[72]
Barbosa, P.C.R.; Mizumoto, S.; Bogenschutz, M.P.; Strassman, R.J. Health status of ayahuasca users. Drug Test. Anal., 2012, 4(7-8), 601-609.
[http://dx.doi.org/10.1002/dta.1383] [PMID: 22761152]
[73]
Garcia-Romeu, A.; Davis, A.K.; Erowid, F.; Erowid, E.; Griffiths, R.R.; Johnson, M.W. Cessation and reduction in alcohol consumption and misuse after psychedelic use. J. Psychopharmacol., 2019, 33(9), 1088-1101.
[http://dx.doi.org/10.1177/0269881119845793] [PMID: 31084460]
[74]
Barbosa, P.C.R.; Tófoli, L.F.; Bogenschutz, M.P.; Hoy, R.; Berro, L.F.; Marinho, E.A.V.; Areco, K.N.; Winkelman, M.J. Assessment of alcohol and tobacco use disorders among religious users of ayahuasca. Front. Psychiatry, 2018, 9, 136.
[http://dx.doi.org/10.3389/fpsyt.2018.00136] [PMID: 29740355]
[75]
Moreno, F.A.; Wiegand, C.B.; Taitano, E.K.; Delgado, P.L. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. J. Clin. Psychiatry, 2006, 67(11), 1735-1740.
[http://dx.doi.org/10.4088/JCP.v67n1110] [PMID: 17196053]
[76]
Dos Santos, R.G.; Bouso, J.C.; Hallak, J.E.C. Ayahuasca, dimethyltryptamine, and psychosis: a systematic review of human studies. Ther. Adv. Psychopharmacol., 2017, 7(4), 141-157.
[http://dx.doi.org/10.1177/2045125316689030] [PMID: 28540034]
[77]
van Amsterdam, J.; Opperhuizen, A.; van den Brink, W. Harm potential of magic mushroom use: a review. Regul. Toxicol. Pharmacol., 2011, 59(3), 423-429.
[http://dx.doi.org/10.1016/j.yrtph.2011.01.006] [PMID: 21256914]
[78]
Martinotti, G.; Santacroce, R.; Pettorruso, M.; Montemitro, C.; Spano, M.C.; Lorusso, M.; di Giannantonio, M.; Lerner, A.G. Hallucinogen persisting perception disorder: etiology, clinical features, and therapeutic perspectives. Brain Sci., 2018, 8(3), 47.
[http://dx.doi.org/10.3390/brainsci8030047] [PMID: 29547576]
[79]
Johansen, P-Ø.; Krebs, T.S. Psychedelics not linked to mental health problems or suicidal behavior: a population study. J. Psychopharmacol., 2015, 29(3), 270-279.
[http://dx.doi.org/10.1177/0269881114568039] [PMID: 25744618]
[80]
Krebs, T.S.; Johansen, P-Ø. Psychedelics and mental health: a population study. PLoS One, 2013, 8(8), e63972.
[http://dx.doi.org/10.1371/journal.pone.0063972] [PMID: 23976938]
[81]
Riba, J.; McIlhenny, E.H.; Bouso, J.C.; Barker, S.A. Metabolism and urinary disposition of N,N-dimethyltryptamine after oral and smoked administration: a comparative study. Drug Test. Anal., 2015, 7(5), 401-406.
[http://dx.doi.org/10.1002/dta.1685] [PMID: 25069786]
[82]
Perkins, D.; Sarris, J.; Rossell, S.; Bonomo, Y.; Forbes, D.; Davey, C.; Hoyer, D.; Loo, C.; Murray, G.; Hood, S.; Schubert, V.; Galvão-Coelho, N.L.; O’Donnell, M.; Carter, O.; Liknaitzky, P.; Williams, M.; Siskind, D.; Penington, D.; Berk, M.; Castle, D. Medicinal psychedelics for mental health and addiction: Advancing research of an emerging paradigm. Aust. N. Z. J. Psychiatry, 2021. Online ahead of print.
[PMID: 33745287]
[83]
Convention on psychotropic substances. In Vienna, 1971.
[84]
US Drug Enforcement Administration. Schedules of Controlled Substances. Code of Federal Regulations 2020. Available from: https://www.govinfo.gov/content/pkg/CFR-2020-title21-vol9/pdf/CFR-2020-title21-vol9-part1308.pdf
[85]
Nutt, D.J.; King, L.A.; Phillips, L.D. Drug harms in the UK: A multicriteria decision analysis. Lancet, 2010, 376(9752), 1558-1565.
[http://dx.doi.org/10.1016/S0140-6736(10)61462-6] [PMID: 21036393]
[86]
van Amsterdam, J.; Nutt, D.; Phillips, L.; van den Brink, W. European rating of drug harms. J. Psychopharmacol., 2015, 29(6), 655-660.
[http://dx.doi.org/10.1177/0269881115581980] [PMID: 25922421]
[87]
Morgan, C.J.A.; Muetzelfeldt, L.; Muetzelfeldt, M.; Nutt, D.J.; Curran, H.V. Harms associated with psychoactive substances: Findings of the UK national drug survey. J. Psychopharmacol., 2010, 24(2), 147-153.
[http://dx.doi.org/10.1177/0269881109106915] [PMID: 19939875]
[88]
Johnson, M.W.; Griffiths, R.R.; Hendricks, P.S.; Henningfield, J.E. The abuse potential of medical psilocybin according to the 8 factors of the controlled substances act. Neuropharmacology, 2018, 142, 143-166.
[http://dx.doi.org/10.1016/j.neuropharm.2018.05.012] [PMID: 29753748]
[89]
Gable, R.S. Toward a comparative overview of dependence potential and acute toxicity of psychoactive substances used nonmedically. Am. J. Drug Alcohol Abuse, 1993, 19(3), 263-281.
[http://dx.doi.org/10.3109/00952999309001618] [PMID: 8213692]
[90]
Gable, R.S. Comparison of acute lethal toxicity of commonly abused psychoactive substances. Addiction, 2004, 99(6), 686-696.
[http://dx.doi.org/10.1111/j.1360-0443.2004.00744.x] [PMID: 15139867]
[91]
Reiche, S.; Hermle, L.; Gutwinski, S.; Jungaberle, H.; Gasser, P.; Majić, T. Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: a systematic review. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2018, 81, 1-10.
[http://dx.doi.org/10.1016/j.pnpbp.2017.09.012] [PMID: 28947181]
[92]
Mahase, E. Depression: EU approves expanded use of esketamine for rapid reduction of symptoms. BMJ, 2021, 372(398), n398.
[http://dx.doi.org/10.1136/bmj.n398] [PMID: 33568423]
[93]
Canady, V.A. FDA approves esketamine treatment for MDD, suicidal ideation. Ment. Health Wkly., 2020, 30(31), 6-7.
[http://dx.doi.org/10.1002/mhw.32471]

Rights & Permissions Print Cite
Article Metrics
64
1
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy