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Review

The Use of Classic Hallucinogens/Psychedelics in a Therapeutic Context: Healthcare Policy Opportunities and Challenges

ORCID Icon, , , ORCID Icon &
Pages 901-910 | Published online: 05 Mar 2021

References

  • Nichols DE. Psychedelics. Pharmacol Rev. 2016;68(2):64–355. doi:10.1124/pr.115.011478
  • Nichols DE. Hallucinogens. Pharmacol Ther. 2004;101(2):131–181.
  • Escobar JÁ, Roazzi A. Panorama contemporâneo do uso terapêutico de substâncias psicodélicas: ayahuasca e psilocibina. Neurobiologia. 2010;73(3):159–172.
  • Grispoon L, Bakalar JB. Psychedelic Drugs Reconsidered. New York: Basic Books; 1979.
  • Schultes RE, Hofmann A. Plants of the Gods: Their Sacred, Healing, and Hallucinogenic Powers. Rochester: Healing Arts Press; 1992.
  • Ott J. Pharmacotheon: drogas enteogénicas, sus fuentes vegetales y su historia (Pharmacotheon: entheogenic drugs, their plant sources and history). La Liebre de Marzo, Barcelona; 2004. Spanish.
  • Dos Santos RG, Hallak JE. Therapeutic use of serotoninergic hallucinogens: a review of the evidence and of the biological and psychological mechanisms. Neurosci Biobehav Rev. 2020;108:423–434. doi:10.1016/j.neubiorev.2019.12.001
  • Bogenschutz MP, Ross S. Therapeutic applications of classic hallucinogens. Curr Topics Behav Neurosci. 2018;36:361–391.
  • Liechti ME, Dolder PC, Schmid Y. Alterations of consciousness and mystical-type experiences after acute LSD in humans. Psychopharmacology (Berl). 2017;234(9–10):1499–1510. doi:10.1007/s00213-016-4453-0
  • Dos Santos RG, Bouso JC, Alcázar-Córcoles MÁ, Hallak JE. 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;11:889–902. doi:10.1080/17512433.2018.1511424
  • Timmermann C, Roseman L, Williams L, et al. DMT models the near-death experience. Front Psychol. 2018;9. doi:10.3389/fpsyg.2018.01424
  • Johnson M, Richards W, Griffiths R. Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008;22(6):603–620. doi:10.1177/0269881108093587
  • Dos Santos RG, Osório FL, Crippa JA, Hallak JE. Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies. Rev Bras Psiquiatr. 2016a;38:65–72. doi:10.1590/1516-4446-2015-1701
  • Barker SA. N, N-dimethyltryptamine (DMT), an endogenous hallucinogen: past, present, and future research to determine its role and function. Front Neurosci. 2018;12:536. doi:10.3389/fnins.2018.00536
  • Cohen S. The Beyond Within, the LSD Story. New York: Atheneum; 1967.
  • Carhart-Harris RL, Nutt DJ. Serotonin and brain function: a tale of two receptors. J Psychopharmacol. 2017;31(9):1091–1120. doi:10.1177/0269881117725915
  • Davis AK, Barrett FS, May DG, et al. Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2020. doi:10.1001/jamapsychiatry.2020.3285
  • Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol. 2016;30(12):1181–1197. doi:10.1177/0269881116675513
  • Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016;30(12):1165–1180. doi:10.1177/0269881116675512
  • Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa PC, Strassman RJ. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J Psychopharmacol. 2015;29(3):289–299. doi:10.1177/0269881114565144
  • Johnson MW, Garcia-Romeu A, Cosimano MP, et al. Pilot study of the 5-HT2A agonist psilocybin in the treatment of tobacco addiction. J Psychopharmacol. 2014;28(11):983–992. doi:10.1177/0269881114548296
  • Krebs TS, Johansen PØ. Psychedelics and mental health: a population study. PLoS One. 2013;8(8):e63972. doi:10.1371/journal.pone.0063972
  • Gasser P, Holstein D, Michel Y, et al. 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. doi:10.1097/NMD.0000000000000113
  • Dos Santos RG, Landeira-Fernandez J, Strassman RJ, et al. Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members. J Ethnopharmacol. 2007;112(3):507–513. doi:10.1016/j.jep.2007.04.012
  • Sanches RF, De Lima Osório F, Dos Santos RG, et al. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a SPECT study. J Clin Psychopharmacol. 2016;36(1):77–81. doi:10.1097/JCP.0000000000000436
  • Palhano-Fontes F, Barreto D, Onias H, et al. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychol Med. 2019;49(4):655–663. doi:10.1017/S0033291718001356
  • Zeifman RJ, Palhano-Fontes F, Hallak J, Arcoverde E, Maia-Oliveira JP, Araujo DB. The impact of ayahuasca on suicidality: results from a randomized controlled trial. Front Pharmacol. 2019;10:1325. doi:10.3389/fphar.2019.01325
  • Zeifman RJ, Singhal N, Dos Santos RG, et al. Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial. Psychopharmacology (Berl). 2020;238(2):453–459. doi:10.1007/s00213-020-05692-9
  • Nichols DE. Differences between the mechanism of action of MDMA, MBDB, and the classic hallucinogens. Identification of a new therapeutic class: entactogens. J Psychoactive Drugs. 1986;18(4):305–313. doi:10.1080/02791072.1986.10472362
  • Danforth AL, Grob CS, Struble C, et al. Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study. Psychopharmacology (Berl). 2018;235(11):3137–3148. doi:10.1007/s00213-018-5010-9
  • Mithoefer MC, Mithoefer AT, Feduccia AA, et al. 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, Phase 2 clinical trial. Lancet Psychiatry. 2018;5(6):486–497. doi:10.1016/S2215-0366(18)30135-4
  • Reiff CM, Richman EE, Nemeroff CB, et al. Psychedelics and psychedelic-assisted psychotherapy. Am J Psychiatry. 2020;177(5):391–410. doi:10.1176/appi.ajp.2019.19010035
  • de la Torre R, Farré M, Roset PN, et al. Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition. Ther Drug Monit. 2004;26(2):137–144. doi:10.1097/00007691-200404000-00009
  • Nardou R, Lewis EM, Rothhaas R, et al. Oxytocin-dependent reopening of a social reward learning critical period with MDMA. Nature. 2019;569(7754):116–120. doi:10.1038/s41586-019-1075-9
  • Feduccia AA, Mithoefer MC. MDMA-assisted psychotherapy for PTSD: are memory reconsolidation and fear extinction underlying mechanisms?. Prog Neuropsychopharmacol Biol Psychiatry. 2018;84:221–228. doi:10.1016/j.pnpbp.2018.03.003
  • Vollenweider FX, Leenders KL, Scharfetter C, et al. Positron emission tomography and fluorodeoxyglucose studies of metabolic hyper frontality and psychopathology in the psilocybin model of psychosis. Neuro Psychopharmacol. 1998;16(5):357–372. doi:10.1016/S0893-133X(96)00246-1
  • Preller KH, Herdener M, Pokorny T, et al. The fabric of meaning and subjective effects in LSD-induced states depend on serotonin 2A receptor activation. Curr Biol. 2017;27(3):451–457. doi:10.1016/j.cub.2016.12.030
  • Rickli A, Moning OD, Hoener MC, et al. Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. Eur Neuropsychopharmacol. 2016;26(8):1327–1337. doi:10.1016/j.euroneuro.2016.05.001
  • Marek GJ. Interactions of hallucinogens with the glutamatergic system: permissive network effects mediated through cortical layer V pyramidal neurons. Curr Top Behav Neurosci. 2018;36:107–135.
  • Bouso JC, Fábregas JM, Antonijoan RM, et al. Acute effects of ayahuasca on neuropsychological performance: differences in executive function between experienced and occasional users. Psychopharmacology. 2013;230(3):415–424. doi:10.1007/s00213-013-3167-9
  • Ly C, Greb AC, Cameron LP, et al. Psychedelics promote structural and functional neural plasticity. Cell Rep. 2018;23(11):3170–3182. doi:10.1016/j.celrep.2018.05.022
  • Carhart-Harris RL, Leech R, Hellyer PJ, et al. The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Front Hum Neurosci. 2014;8:20. doi:10.3389/fnhum.2014.00020
  • Palhano-Fontes F, Andrade KC, Tofoli LF, et al. The psychedelic state induced by ayahuasca modulates the activity and connectivity of the default mode network. PLoS One. 2015;10(2):e0118143. doi:10.1371/journal.pone.0118143
  • Pasquini L, Palhano-Fontes F, Araujo DB. Subacute effects of the psychedelic ayahuasca on the salience and default mode networks. J Psychopharmacol. 2020;34(6):623–635. doi:10.1177/0269881120909409
  • Galvao ACM, de Almeida RN, Silva E, et al. Cortisol modulation by ayahuasca in patients with treatment resistant depression and healthy controls. Front Psychiatry. 2018;9:185. doi:10.3389/fpsyt.2018.00185
  • de Almeida RN, Galvao ACM, da Silva FS, et al. Modulation of serum brain-derived neurotrophic factor by a single dose of ayahuasca: observation from a randomized controlled trial. Front Psychol. 2019;10:1234. doi:10.3389/fpsyg.2019.01234
  • Galvao-Coelho NL, de Menezes Galvao AC, de Almeida RN, et al. Changes in inflammatory biomarkers are related to the antidepressant effects of Ayahuasca. J Psychopharmacol. 2020;34(10):1125–1133. doi:10.1177/0269881120936486
  • De araujo DB, Ribeiro S, Cecchi GA, et al. Seeing with the eyes shut: neural basis of enhanced imagery following Ayahuasca ingestion. Hum Brain Mapp. 2012;33(11):2550–2560. doi:10.1002/hbm.21381
  • Rocha JM, Osório FL, Crippa JA, et al. Serotonergic hallucinogens and recognition of facial expressions. Therapy Adv Psychopharmacol. 2019;9:2045125319845774. doi:10.1177/2045125319845774.
  • Kometer M, Schmidt A, Bachmann R, et al. Psilocybin biases facial recognition, goal-directed behavior, and mood state toward positive relative to negative emotions through different serotonergic sub receptors. Biol Psychiatry. 2012;72(11):898–906. doi:10.1016/j.biopsych.2012.04.005
  • Gonzalez D, Cantillo J, Perez I, et al. Therapeutic potential of ayahuasca in grief: a prospective, observational study. Psychopharmacology (Berl). 2020;237(4):1171–1182. doi:10.1007/s00213-019-05446-2
  • Sampedro F, Revenga MF, Valle M, Roberto N, Domínguez-Clavé E, Elices M. Assessing the psychedelic “after-glow” in ayahuasca users: post-acute neurometabolic and functional connectivity changes are associated with enhanced mindfulness capacities. Int J Neuropsychopharmacol. 2017;20(9):698–711. doi:10.1093/ijnp/pyx036
  • Soler J, Elices M, Franquesa A, et al. Exploring the therapeutic potential of Ayahuasca: acute intake increases mindfulness-related capacities. Psychopharmacology (Berl). 2016;233(5):823–829. doi:10.1007/s00213-015-4162-0
  • Soler J, Elices M, Dominguez-Clave E, et al. Four weekly Ayahuasca sessions lead to increases in “Acceptance” capacities: a comparison study with a standard 8-week mindfulness training program. Front Pharmacol. 2018;9:224. doi:10.3389/fphar.2018.00224
  • Franquesa A, Sainz-Cort A, Gandy S, Soler J, Alcazar-Corcoles MA, Bouso JC. Psychological variables implied in the therapeutic effect of ayahuasca: a contextual approach. Psychiatry Res. 2018;264:334–339. doi:10.1016/j.psychres.2018.04.012
  • Aixalà M, dos Santos RG, Hallak JEC, Bouso JC. Psychedelics and personality. ACS Chem Neurosci. 2018;9(10):2304–2306. doi:10.1021/acschemneuro.8b00237
  • Bouso JC, Dos Santos RG, Alcázar-Córcoles MA, et al. Serotonergic psychedelics and personality: a systematic review of contemporary research. Neurosci Biobehav Rev. 2018;87:118–132. doi:10.1016/j.neubiorev.2018.02.004
  • Gøtzsche PC. Deadly Psychiatry and Organised Denial. People’s Press; 2015.
  • Jerome L, Feduccia AA, Wang JB, et al. Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology (Berl). 2020;237(8):2485–2497. doi:10.1007/s00213-020-05548-2
  • Morales-Garcia JA, Calleja-Conde J, Lopez-Moreno JA, et al. N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo. Transl Psychiatry. 2020;10(1):1–14. doi:10.1038/s41398-020-01011-0
  • Oña G, Bouso JC. Psychedelic drugs as a long-needed innovation in psychiatry. Qeios. 2020. doi:10.32388/T3EM5E.2
  • Johansen P-Ø, Krebs TS. Psychedelics not linked to mental health problems or suicidal behavior: a population study. J Psychopharmacol. 2015;29(3):270–279. doi:10.1177/0269881114568039
  • Ona G, Kohek M, Massaguer T, et al. Ayahuasca and public health: health status, psychosocial well-being, lifestyle, and coping strategies in a large sample of ritual ayahuasca users. J Psychoactive Drugs. 2019;51:135–145. doi:10.1080/02791072.2019.1567961
  • Jiménez-Garrido DF, Gómez-Sousa M, Ona G, et al. Effects of ayahuasca on mental health and quality of life in naïve users: a longitudinal and cross-sectional study combination. Sci Rep. 2020;10:4075. doi:10.1038/s41598-020-61169-x
  • Hendricks PS, Thorne CB, Clark CB, Coombs DW, Johnson MW. Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. J Psychopharmacol. 2015;29(3):280–288. doi:10.1177/0269881114565653
  • Berman RM, Cappiello A, Anand A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47(4):351–354. doi:10.1016/S0006-3223(99)00230-9
  • Jauhar S, Morrison P. Esketamine for treatment resistant depression. BMJ. 2019;366:l55–72.
  • Dos Santos RG, Grasa E, Valle M, et al. Pharmacology of ayahuasca administered in two repeated doses. Psychopharmacology. 2012;219:1039–1053. doi:10.1007/s00213-011-2434-x
  • Fábregas JM, González D, Fondevila S, et al. Assessment of addiction severity among ritual users of ayahuasca. Drug Alcohol Depend. 2010;111(3):257–261. doi:10.1016/j.drugalcdep.2010.03.024
  • Rodd R. Reassessing the cultural and psychopharmacological significance of Banisteriopsis caapi: preparation, classification and use among the Piaroa of Southern Venezuela. J Psychoactive Drugs. 2008;40(3):301–307. doi:10.1080/02791072.2008.10400645
  • Kjellgren A, Eriksson A, Norlander T. Experiences of encounters with ayahuasca–”the vine of the soul”. J Psychoactive Drugs. 2009;41(4):309–315. doi:10.1080/02791072.2009.10399767
  • Labate BC, MacRae E, editors. Ayahuasca, Ritual and Religion in Brazil. London: Equinox; 2010.
  • Luna LE. Indigenous and mestizo use of Ayahuasca: an overview. In: Dos Santos RG, editor. The Ethnopharmacology of Ayahuasca. Trivandrum: Transworld Research Network; 2011.
  • Labate BC, Feeney K. Ayahuasca and the process of regulation in Brazil and internationally: implications and challenges. Int J Drug Policy. 2012;23(2):154–161. doi:10.1016/j.drugpo.2011.06.006
  • Rucker JJ. Psychedelic drugs should be legally reclassified so that researchers can investigate their therapeutic potential. BMJ. 2015;350:h2902. doi:10.1136/bmj.h2902
  • Sessa B. Turn on and tune in to evidence-based psychedelic research. Lancet Psychiatry. 2015;2(1):10–12. doi:10.1016/S2215-0366(14)00120-5
  • Schmid Y, Gasser P, Oehen P, Liechti ME. Acute subjective effects in LSD- and MDMA-assisted psychotherapy. J Psychopharmacol. 2020;026988112095960. doi:10.1177/0269881120959604
  • Bouso JC, Sánchez-Avilés C. Traditional healing practices involving psychoactive plants and the global mental health agenda: opportunities, pitfalls, and challenges in the “right to science” framework. Perspect Mental Health Human Rights. 2020;22(1):145–150.
  • Bonson KR. Regulation of human research with LSD in the United States (1949–1987). Psychopharmacology (Berl). 2018;235(2):591–604. doi:10.1007/s00213-017-4777-4
  • Richert L, Dyck E. Psychedelic crossings: American mental health and LSD in the 1970s. Med Humanit. 2020;46(3):184–191. doi:10.1136/medhum-2018-011593
  • Sánchez C, Bouso JC. Drug Policy Briefing: ayahuasca: from the Amazon to the Global Village. Drug Policy Briefing. 2015.
  • Global psychedelic therapeutics market, 2020–2030 [homepage on the Internet]. Available from: https://www.rootsanalysis.com/reports/global-psychedelic-therapeutics-market.html. Accessed November 20, 2020.
  • Bauer B. Usona follows COMPASS in receiving breakthrough therapy designation for psilocybin to treat depression. Psychedelic Sci Rev. 2019.
  • Berlowitz I, Walt H, Ghasarian C, O’shaughnessy DM, Mabit EJ, Rush FB. Who turns to Amazonian medicine for treatment of substance use disorder? Patient characteristics at the Takiwasi addiction treatment center. J Stud Alcohol Drugs. 2020;81(4):416–425. doi:10.15288/jsad.2020.81.416