Recommended readings 2
Altered States of Consciousness (ASCs) can be generally induced by psychoactive substances or non-pharmacological methods. Such substances include psychedelics and their intake is characterized by profound psychological and cognitive changes. These changes can be observed in sensory perception, emotion, thought, and sense of self.1
Serotonin (5-hydroxytryptamine or 5HT) was identified in the 19th century as a substance involved in smooth muscle contraction, but its relationship with hallucinogens was first established shortly after the discovery of LSD by Albert Hofmann.2 In the 1980s it was proposed that serotonin receptors play a role in the cellular and behavioral mechanisms of action of psychedelics. This was verified in 2003 in experiments with genetically engineered mice lacking serotonin receptors.3
Today, it is established that serotonin is found in the whole body and the molecule has no odor, no flavor, and no single distinctive function. However, it is responsible for a broad spectrum of physiological processes, depending on its receptors’ location and subtype. Outside of the brain, serotonin acts mostly as a hormone involved in a multitude of functions, such as embryonic development and regulation of the gut contractions. Within the brain serotonin receptors are instrumental and represent a primary drug target in various clinical areas.4
Serotonin cannot cross the blood-brain barrier, and therefore it is synthesized from tryptophan (an essential amino acid found in food) within the brain, where it acts as a neurotransmitter. Serotonin receptors are found across all brain regions. The 5HT-system in the brain modulates cognitive and behavioral functions, such as sleep, mood, learning, memory, anxiety and stress, patience and coping, and plasticity-mediated adaptability5 to name just a few. The system’s malfunction can lead to the development of common mental disorders.
Our current understanding of 5HT receptor’s function predicts that the Altered States of Consciousness are highly likely to be induced by 5HT receptor agonists. Classical psychedelics, such as LSD and psilocybin, act as 5HT2A receptor agonists. The following articles discuss the putative effects of 5HT signaling on a molecular, neurological, and psychological level.
This list of recommended readings will explore the diversity among serotonin receptors, the history of their discovery, their relationships with psychedelics, and their mechanisms of mediating subjective experiences and therapeutic effects.
1. Geyer, M.A., and Vollenweider, F.X. (2008) Serotonin research: contributions to understanding psychoses. Trends Pharmacol. Sci. 29, 445–453.
2. Green, A.R. (2008) Gaddum and LSD: the birth and growth of experimental and clinical neuropharmacology research on 5-HT in the UK. Br J Pharmacol. 154:1583–1599.
3. Gonzalez-Maeso, J., Yuen, T., Ebersole, B.J., Wurmbach, E., Lira, A., Zhou, M., Weisstaub, N., Hen, R., Gingrich, J.A., and Sealfon, S.C. (2003) Transcriptome fingerprints distinguish hallucinogenic and non-hallucinogenic 5-hydroxytryptamine 2A receptor agonist effects in mouse somatosensory cortex. J Neurosci. 23:8836–8843.
4. McCorvy, J.D. and Roth, B.L. (2015) Structure and function of serotonin G protein-coupled receptors. Pharmacology & Therapeutics 150:129-142.
5. Carhart-Harris, R. L. and Nutt, D. J. (2017) Serotonin and Brain Function: a Tale of Two Receptors. Journal of Psychopharmacology, 31(9):1091–1120.