Substituted indoles. Tryptamines.

Tryptamines belong to a class of substituted indoles. These chemicals are also derivatives of the amino acid L-tryptophan. These compounds are often serotonergic and dopaminergic agonists. In vitro evidence suggests that simpler substituted tryptamines have protective effects against neuronal cell death from hypoxia [1]. Animal evidence suggests that they may be useful in repairing pre-existing neurological damage via the induction neurogenesis of new brain cells [2]. Additionally, tryptamines have been shown to have reverse fear conditioning and psychobehavioural inhibition in mice, as measured by responsiveness (or lack thereof) to conditioned stimulus [2]. Thanks to modern brain imaging (ormagnetoencephalography, aka MEG), it has been determined experimentally that pyramidal neurons (those found in the cerebral cortex, amygdala, and hippocampus) are most strongly affected by serotonergic tryptamines (using psilocybin as the control) [3].

Placebo controlled, human trials involving psilocybin found a correlation between the action of the drug and decreased cerebral blood flow in cortices of the brain, including hub regions such as the anterior and posterior cingulate cortices. The intensity of the action of the drug was correlated strongly with the decrease in cerebral blood flow in these areas of the brain, leading to a highly unconstrained cognitive state in which there was no centralized blood flow in any hub regions of the brain [4].

Despite of this, while blood flow is reduced in hub regions and overall connectivity in the brain becomes decentralized, fMRI scans in human trials have also noted a dramatic increase in new networks in the brain, both transient and persistent in connectivity, that are distinct from the homology of the typical network found in our brain’s hub regions [5]. The study warns that psilocybin does not simply “relax the constraints on brain function, ascribing cognition a more flexible quality”, and emphasizes that “the brain does not simply become a random system after psilocybin injection”. Instead, it argues that its psilocybin allows for new functional connections, ones which are “only present in the psychedelic state”, to become persistently integrated into homological scaffolds (e.g. connective networks in hub regions) of the brain. Disruption of the homological scaffolds of the brain were only temporary and not persistent, but the introduction of new connectivities were. Therefore, it is possible that learned behaviour under the influence of a serotonergic tryptamine (such as psilocybin) can become ingrained even after the experience. [5]

These compounds are not available for in vivo research or consumption.

[1] – Szabo, Attila, Attila Kovacs, Jordi Riba, Srdjan Djurovic, Eva Rajnavolgyi, and Ede Frecska. “The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells.” Frontiers in Neuroscience 10 (2016): n. pag. Web.

[2] – Catlow, Briony J., Shijie Song, Daniel A. Paredes, Cheryl L. Kirstein, and Juan Sanchez-Ramos. “Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning.” Experimental Brain Research 228.4 (2013): 481-91. Web.

[3] – Muthukumaraswamy, S. D., R. L. Carhart-Harris, R. J. Moran, M. J. Brookes, T. M. Williams, D. Errtizoe, B. Sessa, A. Papadopoulos, M. Bolstridge, K. D. Singh, A. Feilding, K. J. Friston, and D. J. Nutt. “Broadband Cortical Desynchronization Underlies the Human Psychedelic State.” Journal of Neuroscience 33.38 (2013): 15171-5183. Web.

[4] – Carhart-Harris, R. L., D. Erritzoe, T. Williams, J. M. Stone, L. J. Reed, A. Colasanti, R. J. Tyacke, R. Leech, A. L. Malizia, K. Murphy, P. Hobden, J. Evans, A. Feilding, R. G. Wise, and D. J. Nutt. “Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin.” Proceedings of the National Academy of Sciences 109.6 (2012): 2138-143. Web.

[5] – Petri, G., P. Expert, F. Turkheimer, R. Carhart-Harris, D. Nutt, P. J. Hellyer, and F. Vaccarino. “Homological scaffolds of brain functional networks.” Journal of The Royal Society Interface 11.101 (2014): 20140873. Web.

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