Psychedelics and cognitive function: A systematic review
DOI:
https://doi.org/10.33448/rsd-v12i14.44436Keywords:
Psychedelics; Healthy volunteers; Cognitive function.Abstract
Introduction: With the progressive advancement of clinical and experimental trials aimed at investigating the pharmacotherapeutic potential of psychedelic substances, there is also the development of other conceptions of use, not only for the treatment of psychiatric disorders, but also for the improvement of emotional/cognitive functions. Objective: The present study is a systematic review of investigations aimed at evaluating the effects of psychedelics on cognitive functions in healthy volunteers. Methods: A search was performed in PubMed database, using the search terms “psychedelics and cognitive enhancement” and “psychedelics and cognitive performance”. Results and conclusions: Of the experimental studies analyzed, only forty-six (46) met the inclusion criteria. The results obtained showed that 3,4-methylenedioxy-methamphetamine (MDMA) was the most studied drug, with eighteen (18) articles. Fourteen (14) articles were published with psilocybin. Lysergic acid diethylamide (LSD) ranked third, with six (6) articles; other two (2) studies focused on investigating the beverage ayahuasca, and another (1) its psychoactive-containing molecule: dimethyltryptamine (DMT). Eight (8) studies investigated the effects of other psychedelic drugs, like S-ketamine, mescaline, 3,4-methylenedioxy-amphetamine (MDE), and ibogaine. Although there were no serious adverse effects resulting from the use of the investigated psychedelic drugs, rigorous assessment of the potential risks of long-term use and of the advantages of the continuous use of these drugs through neuropsychological assessments are still warranted.
References
Andersson, M. & Kjellgren, A. (2019). Twenty percent better with 20 micrograms? A qualitative study of psychedelic microdosing self-rapports and discussions on Youtube. Harm Reduction Journal; 16 (63), 2-12. 10.1186/s12954-019-0333-3.
Barrett, F. S., Theresa M., Carbonaro, E., Hurwitz, Matthew W. J., & Roland R. G. (2018). “Double-Blind Comparison of the Two Hallucinogens Psilocybin and Dextromethorphan: Effects on Cognition”. Psychopharmacology; 235 (10), 2915–27. 10.1007/s00213-018-4981-x
Bedi, G. H. & D. Wit, H. (2010). Is Ecstasy an “Empathogen”? Effects of ±3,4-Methylenedioxymethamphetamine on Prosocial Feelings and Identification of Emotional States in Others. Biol Psychiatry; 68 (12), 1134-1140. 10.1016/j.biopsych.2010.08.003.
Cameron, L. P. & Nazarian, A., & Olson, D. E. (2010). Psychedelic Microdosing: prevalence and subjective effects. Journal of Psychoactive Drugs. 52 (2), 113-122. 10.1080/02791072.2020.1718250.
Carhart-Harris, R. L. et al. (2018). Psychedelics and the essential importance of context. Journal of Psychopharmacology, 32 (7), 725-731. 10.1177/0269881118754710.
Carhart-Harris, R. L. et al. (2012a). Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. PNAS, 109 (6), 2138-2143. doi.org/10.1073/pnas.1119598109.
Carhart-Harris, R. Leech, R., Williams, T., Erritzoe, D., Abbasi, N., Bargiotas, T., & Nutt, D. (2012b). Implications for psychedelic-assisted psychotherapy: Functional magnetic resonance imaging study with psilocybin. The British Journal of Psychiatry, 200 (3), 238-244. 10.1192/bjp.bp.111.103309.
Cavanna, F. Stephanie Muller, L. A., de la Fuente, F., Zamberlan, M., Palmucci, L., Janeckova, M., Kuchar, C., & Pallavicini, E. T. (2022). Microdosing with Psilocybin Mushrooms: A Double-Blind Placebo-Controlled Study. Translational Psychiatry, 12 (1), 307. 10.1038/s41398-022-02039-0.
Danforth, A. L. Struble, C. M., Yazar-Klosinski, B., & Grob, C. S. (2016). MDMA-assisted therapy: A new treatment model for social anxiety in autistic adults. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 64, 237–249. 10.1016/j.pnpbp.2015.03.011.
Daumann, J. et al. (2010). Neuronal Correlates of Visual and Auditory Alertness in the DMT and Ketamine Model of Psychosis. Journal of Psychopharmacology. 24 (10), 1515–24. 10.1177/0269881109103227.
Dolder, P. C. Felix Müller, Y., Schmid, S. J., & Borgwardt, M. E. L. (2018). Direct Comparison of the Acute Subjective, Emotional, Autonomic, and Endocrine Effects of MDMA, Methylphenidate, and Modafinil in Healthy Subjects. Psychopharmacology, 235 (2), 467–79. 10.1007/s00213-017-4650-5.
Dumont, G. J. H. & Wezenberg, E., Valkenberg, M. M. G. J. et al. (2008). Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers. Psychopharmacology, 197, 465–474. 10.1007/s00213-007-1056-9.
Duke, R. B. & Keeler, M. H. (1968). The effects of Psilocybin, dextro-amphetamine and placebo on performance of the trail making test. J. Clin. Psychol. 24, 316-317.
Fadiman, J. & Korb, S. (2019). Might microdosing psychedelics be safe and beneficial? An Initial Exploration. Journal of Psychoactive Drugs. 51 (2), 118-122. 10.1080/02791072.2019.1593561.
Forsyth, B., Liana Machado, T., Jowett, H., Jakobi, K., Garbe, H., Winter, P. G. (2016). Effects of Low Dose Ibogaine on Subjective Mood State and Psychological Performance. Journal of Ethnopharmacology. 189, 10–13. 10.1016/j.jep.2016.05.022.
Gabay, A., Kempton, M., J., James Gilleen, & Mitul A. M. (2019). MDMA Increases Cooperation and Recruitment of Social Brain Areas When Playing Trustworthy Players in an Iterated Prisoner’s Dilemma. The Journal of Neuroscience. 39 (2), 307–20. 10.1523/JNEUROSCI.1276-18.2018.
Gasser P., Holstein D, Michel Y, Doblin R, Yazar-Klosinski B, Passie T, & Brenneisen R. (2014). Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. J Nerv Ment Dis. 202 (7), 513-520. 10.1097/NMD.0000000000000113.
Grob, C. S., & Danforth, A. L., Chopra, G. S., Hagerty, M., McKay, C. R., Halberstadt, A. L., Greer, G. R. (2011). Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry. 68 (1), 71-78. 10.1001/archgenpsychiatry.2010.116.
Goldberger L. (1966). Cognitive test performance under LSD-25, placebo and isolation. J Nerv Ment Dis. 142 (1), 4-9. 10.1097/00005053-196601000-00002.
Gouzoulis-Mayfrank, E. Schreckenberger, M., Sabri, O. et al. (1999). Neurometabolic Effects of Psilocybin, 3,4-Methylenedioxyethylamphetamine (MDE) and d-Methamphetamine in Healthy Volunteers A Double-Blind, Placebo-Controlled PET Study with [18F]FDG. Neuropsychopharmacol. 20, 565–581. 10.1016/S0893-133X(98)00089-X.
Haijen, E. Farre, M., de la Torre, R. et al. (2018). Peripheral endocannabinoid concentrations are not associated with verbal memory impairment during MDMA intoxication (2018). Psychopharmacology. 235, 709–717. 10.1007/s00213-017-4787-2.
Halpern, J. H. & Sherwood, A. R., Hudson, J. I., Yurgelum-Todd, D., & Pope Jr., H.G. (2005). Psychological and Cognitive Effects of Long-Term Peyote Use Among Native Americans. Biological Psychiatry. 58 (8), 624-631. 10.1016/j.biopsych.2005.06.038.
Hasler, F., Ulrike Grimberg, M. A., Benz, T., & Huber, F. X. V. (2004). Acute Psychological and Physiological Effects of Psilocybin in Healthy Humans: A Double-Blind, Placebo-Controlled Dose? Effect Study. Psychopharmacology. 172 (2), 145-156. 10.1007/s00213-003-1640-6.
Hasler, F., E. Studerus, K. Lindner, S. & Ludewig, F. X. V. (2009). Investigation of Serotonin-1A Receptor Function in the Human Psychopharmacology of MDMA. Journal of Psychopharmacology. 23 (8), 923–35. doi.org/10.1177/0269881108094650.
Holze, F. et al. (2021). Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants. Clinical Pharmacology & Therapeutics. 109 (3), 658–666. 10.1002/cpt.2057.
Hutten N. R. P. W. et al. (2020). Mood and cognition after administration of low LSD doses in healthy volunteers: A placebo-controlled dose-effect finding study). European Neuropsychopharmacology. 41, 81-91. 10.1016/j.euroneuro.2020.10.002.
Hysek, C. M. et al. (2014). MDMA Enhances Emotional Empathy and Prosocial Behavior. Social Cognitive and Affective Neuroscience. 9 (11), 1645–1652. 10.1093/scan/nst161.
Jardim, A. V. et al. (2020). 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for victims of sexual abuse with severe post-traumatic stress disorder: an open label pilot study in Brazil. Revista Brasileira de Psiquiatria; 00:000-000. dx.doi.org/10.1590/1516-4446-2020-0980.
Johnson, M. W., Garcia-Romeu, A, Cosimano, M. P., & Griffiths, R. R. (2014) Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction). J Psychopharmacol. 28 (11), 983-992. 10.1177/0269881114548296.
Kirkpatrick, M., & Andrew W., Delton, T. E., Robertson, H. de W. (2015) Prosocial Effects of MDMA: A Measure of Generosity. Journal of Psychopharmacology. 29 (6), 661–668. doi.org/10.1177/0269881115573806.
Kometer, M. & Schmidt, A.; Jäncke, L.; & Vollenweider. F. X. (2013). Activation of Serotonin 2A Receptors Underlies the Psilocybin-Induced Effects on Oscillations, N170 Visual-Evoked Potentials, and Visual Hallucinations. Journal of Neuroscience. 33 (25), 10544-10551. 10.1523/JNEUROSCI.3007-12.2013.
Kuypers, K. P. C. Rafael de la Torre, M., Farre, S., Yubero-Lahoz, I., Dziobek, W., & Van den Bos, J. G. R. (2014). No Evidence That MDMA-Induced Enhancement of Emotional Empathy Is Related to Peripheral Oxytocin Levels or 5-HT1a Receptor Activation. PLoS ONE. 9 (6). 10.1371/journal.pone.0100719.
Kuypers, K. P. C. et al. (2016). Verbal Memory Impairment in Polydrug Ecstasy Users: A Clinical Perspective. PLOS ONE. 11 (2). doi.org/10.1371/journal.pone.0149438.
Kuypers, K. P. C. et al. (2018). MDMA-Induced Indifference to Negative Sounds Is Mediated by the 5-HT2A Receptor. Psychopharmacology. 235 (2), 481–90. 10.1007/s00213-017-4699-1.
Lansbergen, M. M. & Dumont, G. J. H., van Gerven, J. M. A. et al. (2011). Acute effects of MDMA (3,4-methylenedioxymethamphetamine) on EEG oscillations: alone and in combination with ethanol or THC (delta-9-tetrahydrocannabinol). Psychopharmacology. 213, 745–756. 10.1007/s00213-010-2031-4
Lamers, C. T. J., J. G. Ramaekers & N. D. Muntjewerff, K. L. Sikkema, W. J. Riedel, N. Samyn, N. L. & Read, K. A. B. (2003). Dissociable Effects of a Single Dose of Ecstasy (MDMA) on Psychomotor Skills and Attentional Performance. Journal of Psychopharmacology. 17 (4), 379–387. 10.1177/0269881103174015.
Ley, L. & Holze, F., Arikci, D. et al. (2023). Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants. Neuropsychopharmacol. 48, 1659–1667. 10.1038/s41386-023-01607-2.
Lofwall, M. et al. (2006). Cognitive and Subjective Acute Dose Effects of Intramuscular Ketamine in Healthy Adults. Experimental and Clinical Psychopharmacology. 14 (4), 439–49. 10.1037/1064-1297.14.4.439.
Magaraggia I., Kuiperes, Z., & Schreiber, R. (2021) Improving cognitive functioning in major depressive disorder with psychedelics: A dimensional approach (2021). Neurobiol Learn Mem. 183, 107467. doi.org/10.1016/j.nlm.2021.107467.
Mason, N. L. K. P. C. Kuypers, J. T. Reckweg, F. Müller, D. H. Y. Tse, B. Da Rios, S. W. Toennes, P. Stiers, A. & Feilding, J. G. R. (2021). Spontaneous and Deliberate Creative Cognition during and after Psilocybin Exposure. Translational Psychiatry. 11 (1), 209. doi.org/10.1038/s41398-021-01335-5.
Mithoefer M C., Feduccia A. A., Jerome L., Mithoefer A., Wagner M., Walsh Z., Hamilton S., Yazar-Klosinski, B., Emerson, A., & Doblin, R. (2019). MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology (Berl). 236 (9), 2735-2745. 10.1007/s00213-019-05249-5.
Mitchell, J. M. & Bogenschutz, M., Lilienstein, A. et al. (2021). MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med 27, 1025–1033. /10.1038/s41591-021-01336-3.
Pokorny, T., Katrin H Preller, M., Kometer, I., Dziobek, F. X V. (2017). Effect of Psilocybin on Empathy and Moral Decision-Making. International Journal of Neuropsychopharmacology 20 (9), 747–57. 10.1093/ijnp/pyx047.
Prochazkova, L. et al. (2018). Exploring the Effect of Microdosing Psychedelics on Creativity in an Open-Label Natural Setting. Psychopharmacology. 235 (12), 3401–3413. 10.1007/s00213-018-5049-7.
Reiff, C. M. et al. (2020). Psychedelics and Psychedelic-Assisted Psychotherapy. The American Journal of Psychiatry. 177 (5), 391-410. 10.1176/appi.ajp.2019.19010035.
Rocha, J. M. et al. (2021). Effects of Ayahuasca on the Recognition of Facial Expressions of Emotions in Naive Healthy Volunteers: A Pilot, Proof-of-Concept, Randomized Controlled Trial. Journal of Clinical Psychopharmacology. 41 (3), 267–274. 10.1097/JCP.0000000000001396.
Rodrigues, S. (2019). Introdução ao uso de psicodélicos em psicoterapia (apostila do minicurso da Associação Psicodélica do Brasil). Rio de Janeiro: Associação Psicodélica do Brasil.
Roseman, L. et al. (2016). LSD alters eyes-closed functional connectivity within the early visual cortex in a retinotopic fashion. Hum. Brain Mapp. 37, 3031-3040. 10.1002/hbm.23224.
Ross, S., et al. (2016). Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 30 (12), 1165-1180. 10.1177/0269881116675512.
Rossi, G. N. et al. (2023). Interactive Effects of Ayahuasca and Cannabidiol in Social Cognition in Healthy Volunteers: A Pilot, Proof-of-Concept, Feasibility, Randomized-Controlled Trial. Journal of Clinical Psychopharmacology 43 (4), 339-349. 10.1097/JCP.0000000000001691.
Schmid, Y. et al. (2014). Differential Effects of MDMA and Methylphenidate on Social Cognition. Journal of Psychopharmacology 28 (9), 847–856. 10.1177/0269881114542454.
Schmid, Y. et al. (2015). Effects of Methylphenidate and MDMA on Appraisal of Erotic Stimuli and Intimate Relationships. European Neuropsychopharmacology 25 (1), 17–25. 10.1016/j.euroneuro.2014.11.020.
Schmidt, A. et al. Comparative Effects of Methylphenidate, Modafinil, and MDMA on Response Inhibition Neural Networks in Healthy Subjects (2017). International Journal of Neuropsychopharmacology. 20 (9), 712–720. 10.1093/ijnp/pyx037.
Schmidt, A., Müller, F.; Dolder, P. C.; Schmid, Y.; Zanchi, D.; Egloff, L.; Liechti, M.E.; Borgwardt, S. (2018a). Acute Effects of Methylphenidate, Modafinil, and MDMA on Negative Emotion Processing. International Journal of Neuropsychopharmacology, 21 (4), 345–354. https://doi.org/10.1093/ijnp/pyx112.
Schmidt, A. et al. (2018b). Acute LSD Effects on Response Inhibition Neural Networks. Psychological Medicine. 48 (9), 1464–1473. 10.1017/S0033291717002914.
Schreckenberger, M. Gouzoulis-Mayfrank, E, Sabri, O, Arning, C, Tuttass, T, Schulz, G, Kaiser, H. J., Wagenknecht, G, Sass H., Büll, U. Untersuchungen zum Einfluss von (1998). Investigations on the effect of "ecstasy" on cerebral glucose metabolism: an 18-FDG PET study. Nuklearmedizin. 37 (8), 262-267. 10.1007/s002590050497.
Schenberg, E. E. (2020). Psychedelic drugs as new tools in psychiatric therapeutics. Revista Brasileira de Psiquiatria. 43 (2). 10.1590/1516-4446-2020-0012.
Selçuk, A. A. (2019). A guide for systematic reviews: PRISMA. Turkish archives of otorhinolaryngology, 57 (1), 57-58. 10.5152/tao.2019.4058.
Smigielski, L., Kometer, M., Scheidegger, M., et al. (2020). P300-mediated modulations in self–other processing under psychedelic psilocybin are related to connectedness and changed meaning: A window into the self–other overlap. Hum Brain Mapp. 41 (17), 4982–4996. 10.1002/hbm.25174.
Spitzer, M. et al. (2001). Enantio-selective cognitive and brain activation effects of N-ethyl-3,4-methylenedioxyamphetamine in humans. Neuropharmacology. 41 (2), 263-271. 10.1016/S0028-3908(01)00060-0.
Vollenweider, F. X. Matthias E. & Liechti, M. P. P. (2005). MDMA Affects Both Error-Rate Dependent and Independent Aspects of Decision-Making in a Two-Choice Prediction Task. Journal of Psychopharmacology 19 (4), 366–374. 10.1177/0269881105053287.
Wit, H. & Hanna M., Molla, A., Bershad, M., Bremmer, R. L. (2022). Repeated Low Doses of LSD in Healthy Adults: A Placebo-Controlled, Dose–Response Study, Addiction Biology. 27 (2). https://doi.org/10.1111/adb.13143.
Wittmann, M. et al. (2007). Effects of Psilocybin on Time Perception and Temporal Control of Behaviour in Humans. Journal of Psychopharmacology. 21 (1), 50–64. 10.1177/0269881106065859.
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