The effects of tryptamine psychedelics in the brain: a meta-analysis of functional and review of molecular imaging studies
This meta-analysis (2021) of brain imaging studies finds that under the influence of psychedelics (tryptamines), the most changes in connectivity are indeed the ones where there are the most 5-HT1a/2a receptors. Other regions are also highlighted, and these regions most influenced are responsible for mental imagery, theory of mind, and affective regulation.
Authors
- Castelhano, J. M.
- Lima, G. M.
- Teixeira, M.
Published
Abstract
There is an increasing interest in the neural effects of psychoactive drugs, in particular tryptamine psychedelics, which has been incremented by the proposal that they have potential therapeutic benefits, based on their molecular mimicry of serotonin. It is widely believed that they act mainly through 5HT2A receptors but their effects on neural activation of distinct brain systems are not fully understood. We performed a quantitative meta-analysis of brain imaging studies to investigate the effects of substances within this class (e.g. LSD, Psilocybin, DMT, Ayahuasca) in the brain from a molecular and functional point of view. We investigated the question whether the changes in activation patterns and connectivity map into regions with larger 5HT1A/5HT2A receptor binding, as expected from indolaemine hallucinogens (in spite of the often reported emphasis only on 5HT2AR). We did indeed find that regions with changed connectivity and/or activation patterns match regions with high density of 5HT2A receptors, namely visual BA19, visual fusiform regions in BA37, dorsal anterior and posterior cingulate cortex, medial prefrontal cortex, and regions involved in theory of mind such as the surpramarginal gyrus, and temporal cortex (rich in 5HT1A receptors). However, we also found relevant patterns in other brain regions such as dorsolateral prefrontal cortex. Moreover, many of the above-mentioned regions also have a significant density of both 5HT1A/5HT2A receptors, and available PET studies on the effects of psychedelics on receptor occupancy are still quite scarce, precluding a metanalytic approach. Finally, we found a robust neuromodulatory effect in the right amygdala. In sum, the available evidence points towards strong neuromodulatory effects of tryptamine psychedelics in key brain regions involved in mental imagery, theory of mind and affective regulation, pointing to potential therapeutic applications of this class of substances.
Research Summary of 'The effects of tryptamine psychedelics in the brain: a meta-analysis of functional and review of molecular imaging studies'
Introduction
Castelhano and colleagues frame tryptamine hallucinogens (for example LSD, psilocybin, DMT, ayahuasca) as both experimental models for psychosis and as candidate therapeutics for psychiatric disorders. Earlier work has emphasised their agonist action at serotonin receptors, particularly 5-HT2A, and has reported altered perceptual, cognitive and affective states as well as changes in large-scale brain networks such as the default mode network (DMN). However, the authors note uncertainty about which brain systems show reliable changes across studies, and whether those functional effects map onto the regional distribution of serotonin receptor subtypes (notably 5-HT2A and 5-HT1A).
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- APA Citation
Castelhano, J., Lima, G., Teixeira, M., Soares, C., Pais, M., & Castelo-Branco, M. (2021). The effects of tryptamine psychedelics in the brain: a meta-analysis of functional and review of molecular imaging studies. Frontiers in Pharmacology, 12. https://doi.org/10.3389/fphar.2021.739053
References (63)
Papers cited by this study that are also in Blossom
Barone, W., Beck, J., Mitsunaga-Whitten, M. et al. · Journal of Psychoactive Drugs (2019)
Barrett, F. S., Doss, M. K., Sepeda, N. D. et al. · Scientific Reports (2020)
Barrett, F. S., Krimmel, S. R., Griffiths, R. R. et al. · NeuroImage (2020)
Belser, A. B., Agin-Liebes, G. I., Swift, T. C. et al. · Journal of Humanistic Psychology (2017)
Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A. et al. · Journal of Psychopharmacology (2015)
Carhart-Harris, R. L., Erritzoe, D., Williams, T. et al. · PNAS (2012)
Carhart-Harris, R. L., Bolstridge, M., Rucker, J. et al. · Lancet Psychiatry (2016)
Carhart-Harris, R. L., Muthukumaraswamy, S., Roseman, L. et al. · PNAS (2016)
Carhart-Harris, R. L., Kaelen, M., Bolstridge, M. et al. · Psychological Medicine (2016)
Carhart-Harris, R. L., Roseman, L., Bolstridge, M. et al. · Scientific Reports (2017)
Show all 63 referencesShow fewer
Castellanos, J. P., Woolley, C., Bruno, K. A. et al. · Regional Anesthesia and Pain Medicine (2020)
Danforth, A. L., Grob, C. S., Struble, C. et al. · Psychopharmacology (2018)
De Araujo, D. B., Ribeiro, S., Cecchi, G. A. et al. · Human Brain Mapping (2011)
Dolder, P. C., Schmid, Y., Müller, F. et al. · Neuropsychopharmacology (2016)
Domínguez-Clavé, E., Soler, J., Elices, M. et al. · Brain Research Bulletin (2016)
Dos Santos, R. G., Osório, F. L., Crippa, J. A. et al. · Neuroscience and Biobehavioral Reviews (2016)
Gasser, P., Holstein, D., Michel, Y. et al. · Journal of Nervous and Mental Disease (2014)
Kirchner, K. · Journal of Psychopharmacology (2014)
Gouzoulis-Mayfrank, E., Schreckenberger, M., Sabri, O. et al. · Neuropsychopharmacology (1999)
Griffiths, R. R., Johnson, M. W. · Journal of Psychopharmacology (2016)
Halberstadt, A. L., Geyer, M. A. · Neuropharmacology (2011)
Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P. et al. · Journal of Psychopharmacology (2014)
Kaelen, M., Roseman, L., Kahan, J. et al. · European Neuropsychopharmacology (2016)
Kometer, M., Vollenweider, F. X. · Behavioral Neurobiology of Psychedelic Drugs (2016)
Kometer, M., Pokorny, T., Seifritz, E. et al. · Psychopharmacology (2015)
Kraehenmann, R., Preller, K. H., Scheidegger, M. et al. · Biological Psychiatry (2015)
Kraehenmann, R., Schmidt, A., Friston, K. et al. · NeuroImage (2015)
Kraehenmann, R. · Current Neuropharmacology (2017)
Luppi, A. I., Carhart-Harris, R. L., Roseman, L. et al. · NeuroImage (2021)
Madsen, M. K., Stenbaek, D. S., Arvidsson, A. et al. · European Neuropsychopharmacology (2021)
Mason, N. L., Mischler, E., Uthaug, M. V. et al. · Journal of Psychoactive Drugs (2019)
Mason, N. L., Kuypers, K. P. C., Reckweg, J. T. et al. · Translational Psychiatry (2021)
McKenna, D., Riba, J. · Current Topics in Behavioral Neurosciences (2016)
Mitchell, J., Bogenschutz, M. P., Lilienstein, A. et al. · Nature Medicine (2021)
Moreno, F. A., Wiegand, C. B., Taitano, E. K. et al. · Journal of Clinical Psychiatry (2006)
Mueller, F., Lenz, C., Dolder, P. C. et al. · Translational Psychiatry (2017)
Netzband, N., Ruffell, S., Linton, &. S. et al. · Psychopharmacology (2020)
Nichols, D. E. · Pharmacology and Therapeutics (2004)
Noorani, T., Garcia-Romeu, A., Swift, T. C. et al. · Journal of Psychopharmacology (2018)
Nour, M. R., Evans, J., Nutt, D. J. et al. · Frontiers in Human Neuroscience (2016)
Palhano-Fontes, F., Andrade, K. C., Tófoli, L.F. et al. · PLOS ONE (2015)
Palhano-Fontes, F., Barreto, D., Onias, H. et al. · Psychological Medicine (2018)
Pokorny, T., Preller, K. H., Kometer, M. et al. · International Journal of Neuropsychopharmacology (2017)
Preller, K. H., Vollenweider, F. X. · Frontiers in Psychiatry (2019)
Preller, K. H., Pokorny, D., Hock, A. et al. · PNAS (2016)
Preller, K. H., Herdener, M., Pokorny, T. et al. · Current Biology (2017)
Preller, K. H., Schilbach, L., Pokorny, T. et al. · Journal of Neuroscience (2018)
Quednow, B. B., Kometer, M., Geyer, M. A. et al. · Neuropsychopharmacology (2011)
Riba, J., Anderer, P., Jané, F. et al. · Neuropsychobiology (2004)
Rocha, J. M., Osório, F. L., Crippa, J. A. et al. · Therapeutic Advances in Psychopharmacology (2019)
Roseman, L., Demetriou, L., Wall, M. B. et al. · Neuropharmacology (2018)
Ross, S., Bossis, A. P., Guss, J. et al. · Journal of Psychopharmacology (2016)
Schmid, Y., Enzler, F., Gasser, P. et al. · Biological Psychiatry (2015)
Schmidt, A., Müller, F., Lenz, C. et al. · Psychological Medicine (2017)
Studerus, E., Kometer, M., Hasler, F. et al. · Journal of Psychopharmacology (2010)
Swanson, L. R. · Frontiers in Pharmacology (2018)
Swift, T. C., Belser, A. B., Agin-Liebes, G. et al. · Journal of Humanistic Psychology (2017)
Tagliazucchi, E., Roseman, L., Kaelen, M. et al. · Current Biology (2016)
Teixeira, P. J., Johnson, M. W., Timmermann, C. et al. · Journal of Psychopharmacology (2021)
Uthaug, M. V., Mason, N. L., Toennes, S. W. et al. · Psychopharmacology (2021)
Vollenweider, F. X., Kometer, M. · Nature Reviews Neuroscience (2010)
Vollenweider, F. X., Leenders, K. L., Maguire, P. et al. · Neuropsychopharmacology (1997)
Watts, R., Day, C. M., Krzanowski, J. et al. · Journal of Humanistic Psychology (2017)
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