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Review

Safety issues of psilocybin and LSD as potential rapid acting antidepressants and potential challenges

ORCID Icon, , ORCID Icon & ORCID Icon
Pages 761-776 | Received 01 Jan 2022, Accepted 12 Apr 2022, Published online: 27 Apr 2022

References

  • Penn E, Tracy DK. The drugs don’t work? Antidepressants and the current and future pharmacological management of depression. Ther Adv Psychopharmacol. 2012 Oct;2(5):179–188.
  • Malhi GS, Mann JJ. Depression. Lancet. 2018 Nov 24;392(10161):2299–2312.
  • Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018 Apr 7;391(10128):1357–1366.
  • Feltes KP, Doorduin J, Klein HC, et al. Anti-inflammatory treatment for major depressive disorder: implications for patients with an elevated immune profile and non-responders to standard antidepressant therapy. J Psychopharmacol. 2017 Sep;31(9):1149–1165.
  • Mitchell AJ, Chan M, Bhatti H, et al. Prevalence of depression, anxiety, and adjustment disorder in oncological, haematological, and palliative-care settings: a meta-analysis of 94 interview-based studies. Lancet Oncol. 2011 Feb;12(2):160–174.
  • Reiche S, Hermle L, Gutwinski S, et al. 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 Feb 2;81:1–10.
  • Arrieta O, Angulo LP, Núñez-Valencia C, et al. Association of depression and anxiety on quality of life, treatment adherence, and prognosis in patients with advanced non-small cell lung cancer. Ann Surg Oncol. 2013 Jun;20(6):1941–1948.
  • Dos Santos RG, Bouso JC, Alcázar-Córcoles M, et al. 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 Sep;11(9):889–902.
  • Galvão-Coelho NL, Marx W, Gonzalez M, et al. Classic serotonergic psychedelics for mood and depressive symptoms: a meta-analysis of mood disorder patients and healthy participants. Psychopharmacology (Berl). 2021;238(2):341–354.
  • Psiuk D, Nowak E, Cholewa K, et al. The potential role of serotonergic hallucinogens in depression treatment. Life (Basel). 2021 Jul 29;11(8). DOI:10.3390/life11080765.
  • Wieckiewicz G, Stoklosa I, Piegza M, et al. Lysergic acid diethylamide, psilocybin and dimethyltryptamine in depression treatment: a systematic review. Pharmaceuticals (Basel). 2021 Aug 12;14(8):793.
  • Dos Santos RG, Bouso JC, Hallak JE. Hallucinogens/psychedelics resurrected as new tools in psychiatric therapy. Braz J Psychiatry. 2021a Mar-Apr;43(2):119–120.
  • Kometer M, Schmidt A, Jäncke L, et al. Activation of serotonin 2A receptors underlies the psilocybin-induced effects on α oscillations, N170 visual-evoked potentials, and visual hallucinations. J Neurosci. 2013 Jun 19;33(25):10544–10551.
  • Madsen MK, Fisher PM, Burmester D, et al. Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Neuropsychopharmacology. 2019 Jun;44(7):1328–1334.
  • Halpern JH, Pope HG Jr. Do hallucinogens cause residual neuropsychological toxicity? Drug Alcohol Depend. 1999 Feb 1;53(3):247–256.
  • Grob CS, Danforth AL, Chopra GS, et al. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry. 2011 Jan;68(1):71–78.
  • 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 Jul;202(7):513–520.
  • 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 Dec;30(12):1181–1197.
  • 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 Dec;30(12):1165–1180.
  • Carhart-Harris R, Giribaldi B, Watts R, et al. Trial of psilocybin versus escitalopram for depression. N Engl J Med. 2021 Apr 15;384(15):1402–1411.
  • 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 Jan;29(1):57–68.
  • Agin-Liebes GI, Malone T, Yalch MM, et al. Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. J Psychopharmacol. 2020 Feb;34(2):155–166.
  • Breitbart W, Rosenfeld B, Pessin H, et al. Meaning-centered group psychotherapy: an effective intervention for improving psychological well-being in patients with advanced cancer. J Clin oncol. 2015 Mar 01;33(7):749–754.
  • Carhart-Harris RL, Bolstridge M, Rucker J, et al. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 2016;3(7):619–627.
  • Carhart-Harris RL, Bolstridge M, Cmj D, et al. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology (Berl). 2018a Feb;235(2):399–408.
  • Anderson BT, Danforth A, Daroff PR, et al. Psilocybin-assisted group therapy for demoralized older long-term AIDS survivor men: an open-label safety and feasibility pilot study. EClinicalMedicine. 2020 Oct;27:100538.
  • Davis AK, Barrett FS, May DG, et al. Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2021 May 1;78(5):481–489.
  • Ona G. Inside bad trips: exploring extra-pharmacological factors. Journal of Psychedelic Studies. 2018 Jun 01;2(1):53–60.
  • Alexander A. Headache may be caused by activation of 5-HT2A receptors in serotonin toxicity. Bmj. 2014 Mar 19;348:g2159.
  • Srikiatkhachorn A, Anthony M. Serotonin receptor adaptation in patients with analgesic-induced headache. Cephalalgia. 1996 Oct;16(6):419–422.
  • Sewell RA, Halpern JH, Pope HG Jr. Response of cluster headache to psilocybin and LSD. Neurology. 2006 Jun 27;66(12):1920–1922.
  • Andersson M, Persson M, Kjellgren A. Psychoactive substances as a last resort-a qualitative study of self-treatment of migraine and cluster headaches. Harm Reduct J. 2017 Sep 5;14(1):60.
  • Schindler EAD, Sewell RA, Gottschalk CH, et al. Exploratory controlled study of the migraine-suppressing effects of psilocybin. Neurotherapeutics. 2021 Jan;18(1):534–543.
  • Minami M, Endo T, Hirafuji M. Role of serotonin in emesis. Nihon Yakurigaku Zasshi. 1996 Nov;108(5):233–242.
  • Basak S, Kumar A, Ramsey S, et al. High-resolution structures of multiple 5-HT(3A)R-setron complexes reveal a novel mechanism of competitive inhibition. Elife. 2020 Oct 16;9. DOI:10.7554/eLife.57870.
  • Gregory RE, Ettinger DS. 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting. A comparison of their pharmacology and clinical efficacy. Drugs. 1998 Feb;55(2):173–189.
  • Halberstadt AL, Geyer MA. Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology. 2011 Sep;61(3):364–381.
  • Vanhoutte PM. Cardiovascular effects of serotonin. J Cardiovasc Pharmacol. 1987;10(Suppl 3):S8–11.
  • Saxena PR, Villalón CM. Cardiovascular effects of serotonin agonists and antagonists. J Cardiovasc Pharmacol. 1990;15(Suppl 7):S17–34.
  • Carhart-Harris RL. The entropic brain - revisited. Neuropharmacology. 2018b Nov;142:167–178.
  • Healy CJ. The acute effects of classic psychedelics on memory in humans. Psychopharmacology (Berl). 2021 Mar;238(3):639–653.
  • Holze F, Avedisian I, Varghese N, et al. Role of the 5-HT(2A) receptor in acute effects of lsd on empathy and circulating oxytocin. Front Pharmacol. 2021;12:711255.
  • Barrett FS, Bradstreet MP, Leoutsakos JS, et al. The challenging experience questionnaire: characterization of challenging experiences with psilocybin mushrooms. J Psychopharmacol. 2016 Dec;30(12):1279–1295.
  • Rocha JM, Rossi GN, Osório FL, et al. Adverse effects after ayahuasca administration in the clinical setting. J of Clinical Psychopharmacol. 2022 Mar; Ahead of print.;Publish Ahead of Print. DOI: 10.1097/JCP.0000000000001536.
  • Dos Santos RG, Bouso JC, Rocha JM, et al. The use of classic hallucinogens/psychedelics in a therapeutic context: healthcare policy opportunities and challenges. Risk Manag Healthc Policy. 2021b;14:901–910.
  • 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 Feb;36(1):77–81.
  • 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 Mar;49(4):655–663.
  • Goldberg SB, Shechet B, Nicholas CR, et al. Post-acute psychological effects of classical serotonergic psychedelics: a systematic review and meta-analysis. Psychol Med. 2020 Dec;50(16):2655–2666.

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