The gastrointestinal (GI) tract contains approximately 90 to 95% of the body's total serotonin, making it by far the largest serotonin compartment in the human body. This is not incidental: serotonin serves as a critical paracrine and neurocrine signaling molecule throughout the gut wall, coordinating intestinal motility, fluid secretion, visceral sensation, and immune activity. Understanding gut serotonin biology is essential for comprehending not only GI pharmacology but also the systemic consequences of conditions that dysregulate enteric serotonin, including carcinoid syndrome and certain functional bowel disorders.
The primary serotonin-producing cells of the gut are the enterochromaffin (EC) cells, specialized enteroendocrine cells scattered throughout the mucosa of the small intestine, colon, and to a lesser extent the stomach. EC cells synthesize serotonin from tryptophan via the same two-step pathway described in Module 1: tryptophan hydroxylase (TPH1, the peripheral isoform) converts tryptophan to 5-hydroxytryptophan, and aromatic L-amino acid decarboxylase (AADC) converts 5-hydroxytryptophan to serotonin. Approximately 70% of EC cell-derived serotonin is released basolaterally into the lamina propria, where it can activate submucosal nerve terminals and enter the portal circulation. The remaining serotonin is released apically into the gut lumen, where it may regulate luminal reflexes. Unlike neurons, EC cells do not reuptake the serotonin they release; instead, SERT (serotonin transporter, SLC6A4) on adjacent intestinal epithelial cells and on platelets in the portal blood captures and inactivates serotonin, preventing it from reaching the systemic circulation in significant quantities under normal conditions.1
EC cells release serotonin in response to a variety of mechanical and chemical stimuli. Mechanical distension of the gut wall, the primary physiological trigger, activates EC cells through mechanosensitive ion channels, releasing serotonin that then acts on 5-HT3 and 5-HT4 receptors on intrinsic primary afferent neurons (IPANs) of the submucosal and myenteric plexuses. This activation initiates the peristaltic reflex: ascending excitation of longitudinal muscle above the bolus and descending inhibition of circular muscle below it, propelling luminal contents aborally. Chemical stimuli including luminal nutrients, short-chain fatty acids, bile acids, and certain bacterial metabolites also trigger EC cell serotonin release, linking gut microbiome composition to enteric serotonin signaling in ways that are now recognized as relevant to functional bowel disorders.2 EC cells also bear receptors for gut hormones including glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) that modulate their serotonin secretion.1
The enteric nervous system (ENS) is the largest collection of neurons outside the central nervous system, containing approximately 500 million neurons in two main plexuses embedded in the gut wall: the myenteric plexus (between the longitudinal and circular muscle layers, primarily controlling motility) and the submucosal plexus (between the circular muscle and mucosa, primarily controlling secretion and blood flow). Serotonin acts as a key neurotransmitter and neuromodulator within the ENS through multiple receptor types. The 5-HT3 receptor, an ionotropic receptor, mediates fast excitatory neurotransmission between sensory and interneurons in the submucosal and myenteric plexuses. The 5-HT4 receptor, a Gs-coupled metabotropic receptor, facilitates neurotransmitter release from enteric neurons, enhances the peristaltic reflex, and accelerates gut transit. The 5-HT1A and 5-HT1B receptors serve inhibitory autoreceptor and heteroceptor functions, modulating serotonin release from enteric neuron terminals. The coordinated activity of these receptor subtypes makes enteric serotonin a master regulator of gut motor and secretory function.3
Gut serotonin also participates in bidirectional communication with the central nervous system via the vagus nerve. Vagal afferent neurons express 5-HT3 receptors on their terminals in the gut wall; serotonin released from EC cells activates these terminals, transmitting information about luminal conditions and distension to the brainstem nucleus tractus solitarius. This vagal serotonin signaling is the same pathway blocked by 5-HT3 antagonists such as ondansetron to prevent chemotherapy-induced nausea, as emetogenic chemotherapy triggers massive EC cell serotonin release that activates vagal afferents. In the reverse direction, descending serotonergic projections from the raphe nuclei can modulate ENS function and gut motility, contributing to the well-documented relationship between psychological stress, central serotonergic dysregulation, and GI symptoms including diarrhea, constipation, and visceral hypersensitivity.4
SERT (serotonin transporter) on intestinal epithelial cells and platelets performs in the periphery the same function it performs at CNS synapses: terminating serotonin signaling by reuptake. Under normal conditions, nearly all gut-derived serotonin is captured by SERT before it reaches systemic circulation, explaining why plasma serotonin levels do not reflect gut serotonin production. When SERT is blocked by SSRIs, peripheral serotonin bioavailability increases, which may contribute to the GI side effects of SSRIs (nausea, diarrhea, increased motility) through excess 5-HT3 and 5-HT4 receptor activation in the gut. In carcinoid syndrome, the massive overproduction of serotonin exceeds SERT capacity, allowing serotonin to reach the systemic circulation and produce the characteristic clinical syndrome.
Carcinoid tumors, now classified as well-differentiated neuroendocrine tumors (NETs), are neoplasms arising from enterochromaffin cells and other neuroendocrine cells throughout the body. Their clinical significance in serotonin pharmacology lies in their ability to produce massive, unregulated quantities of serotonin and other vasoactive substances that produce the carcinoid syndrome. Understanding their biology, biochemical diagnosis, and pharmacological management is a direct clinical application of the GI serotonin physiology described in this module.
Carcinoid tumors arise most commonly in the small intestine (particularly the ileum), appendix, and rectum, with smaller proportions in the stomach, bronchi, and other sites. The anatomical location determines clinical behavior: appendiceal carcinoids are almost invariably small and clinically benign, rarely producing metastasis or carcinoid syndrome; ileal carcinoids are smaller at presentation but have a substantially higher rate of lymph node and liver metastasis; bronchial carcinoids may produce the carcinoid syndrome without liver metastasis by releasing serotonin directly into the systemic circulation, bypassing hepatic first-pass catabolism by MAO. Gastric carcinoids are further classified by associated conditions (type I gastric NETs are associated with autoimmune atrophic gastritis and hypergastrinemia; type III are sporadic and have a more aggressive phenotype).5 The World Health Organization (WHO) classification grades neuroendocrine tumors by Ki-67 proliferation index and mitotic rate, with grade 1 (Ki-67 less than 3%) representing the classic well-differentiated carcinoid.6
Carcinoid syndrome develops when serotonin and other vasoactive substances produced by the tumor reach the systemic circulation in sufficient quantities to produce clinical effects. For midgut carcinoids (the most common type causing carcinoid syndrome), this almost always requires liver metastasis, because serotonin released into the portal circulation is normally cleared by the liver via MAO before reaching the systemic circulation. The classic carcinoid syndrome consists of episodic flushing (mediated primarily by histamine and bradykinin in gastric carcinoids, and by serotonin and tachykinins in midgut carcinoids), watery secretory diarrhea (mediated by serotonin acting on enteric 5-HT3 and 5-HT4 receptors and stimulating intestinal secretion), bronchospasm, and carcinoid heart disease. Carcinoid heart disease is the most dangerous long-term complication: chronic serotonin exposure causes fibrotic plaque deposition on the endocardium of the right heart (tricuspid and pulmonary valves), producing tricuspid regurgitation and pulmonary stenosis. Left heart involvement is rare because pulmonary MAO clears serotonin before it reaches the left heart; bronchial carcinoids are an exception because they bypass pulmonary clearance.6
Biochemical diagnosis of carcinoid syndrome relies primarily on measurement of urinary 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of serotonin produced by MAO-catalyzed deamination followed by aldehyde dehydrogenase-catalyzed oxidation. A 24-hour urine 5-HIAA collection has sensitivity of approximately 70% and specificity of approximately 90% for functioning carcinoid tumors with active serotonin secretion. False positives can occur with dietary tryptophan-rich foods (walnuts, bananas, avocados, pineapple, kiwi) and certain medications (acetaminophen, cough syrups containing guaifenesin), and patients should avoid these for 48 hours before collection. Chromogranin A (CgA), a protein co-secreted with serotonin from neuroendocrine secretory granules, provides a more sensitive (approximately 80%) but less specific blood-based tumor marker, as it is elevated in any neuroendocrine tumor regardless of hormonal activity and also in patients on proton pump inhibitors (PPIs). Somatostatin receptor scintigraphy (OctreoScan) or gallium-68 DOTATATE positron emission tomography (PET) imaging exploits somatostatin receptor overexpression on neuroendocrine tumors for anatomical localization.7
Pharmacological management of carcinoid syndrome centers on somatostatin analogs, which are the first-line agents for symptom control and tumor stabilization. Octreotide and lanreotide are synthetic somatostatin analogs that bind to somatostatin receptors (SST2 and SST5) expressed on neuroendocrine tumor cells, suppressing serotonin and peptide secretion and inhibiting tumor cell proliferation. Long-acting release (LAR) formulations of octreotide (Sandostatin LAR, administered monthly) and lanreotide autogel (Somatuline, administered every 4 weeks) are standard maintenance therapy. Telotristat ethyl is an orally administered TPH1 inhibitor that blocks the rate-limiting step in peripheral serotonin synthesis (tryptophan hydroxylase 1, the gut isoform), reducing serotonin production directly at the source. Because it does not cross the blood-brain barrier, telotristat does not affect central serotonin synthesis (mediated by TPH2), avoiding CNS effects. Telotristat reduces diarrhea frequency in patients with carcinoid syndrome inadequately controlled on somatostatin analogs and reduces urinary 5-HIAA significantly, indicating reduced systemic serotonin burden.8
Carcinoid crisis is a life-threatening exacerbation of carcinoid syndrome precipitated by physical or pharmacological stressors, most commonly during anesthetic induction, surgical manipulation of the tumor, or administration of catecholamines and other stimulants. Features include severe flushing, profound hypotension or hypertension, bronchospasm, tachyarrhythmias, and altered consciousness. All patients with known carcinoid syndrome undergoing surgery or invasive procedures should receive prophylactic octreotide (a bolus dose of 250–500 mcg intravenously, followed by continuous infusion) before and during the procedure. Vasopressors for hypotension must be chosen carefully: catecholamines (epinephrine, norepinephrine) can paradoxically worsen flushing and hypotension by triggering further peptide release from the tumor; vasopressin or phenylephrine are preferred.
Irritable bowel syndrome (IBS) is the most common functional bowel disorder and one of the most prevalent conditions encountered in primary care and gastroenterology. Evidence from EC cell studies, mucosal biopsies, and serotonin kinetics measurements implicates dysregulated enteric serotonin signaling in its pathophysiology. This mechanistic insight has driven the development of drugs that selectively manipulate 5-HT3 and 5-HT4 receptors in the gut to normalize bowel function, with a regulatory history that illustrates the tension between therapeutic benefit and cardiovascular risk.
The serotonin hypothesis of IBS is supported by evidence that postprandial serotonin release from EC cells is abnormally elevated in diarrhea-predominant IBS (IBS-D) and reduced in constipation-predominant IBS (IBS-C), and that SERT expression in colonic mucosa is reduced in IBS patients compared to healthy controls. Excess serotonin in IBS-D would amplify 5-HT3-mediated fast excitatory signaling in the submucosal plexus, accelerating intestinal transit and increasing secretion, producing diarrhea and urgency. Deficient serotonin in IBS-C would reduce 5-HT4-mediated facilitation of the peristaltic reflex, slowing transit and producing constipation. Visceral hypersensitivity, the subjective experience of pain at lower distension thresholds that characterizes IBS, is partly mediated by sensitized 5-HT3 receptors on visceral afferent neurons, explaining why 5-HT3 antagonism can reduce abdominal pain in IBS-D beyond its effect on stool consistency.9
Alosetron is a potent selective 5-HT3 antagonist approved in the United States for women with severe IBS-D who have failed conventional therapy. By blocking 5-HT3 receptors on intrinsic sensory neurons in the submucosal plexus and on extrinsic vagal afferents, alosetron slows colonic transit, reduces intestinal secretion, and decreases visceral afferent sensitivity, collectively reducing stool frequency, urgency, and abdominal pain. Its clinical development was complicated by a serious adverse effect: ischemic colitis, occurring in approximately 1 per 700 patients, and severe constipation leading to bowel obstruction. These risks led to its market withdrawal in 2000, followed by a restricted re-approval in 2002 under a risk evaluation and mitigation strategy (REMS) program that limits its prescription to gastroenterologists and requires patient enrollment and consent. At the standard dose of 0.5–1 mg twice daily, alosetron provides meaningful symptom benefit to women with severe IBS-D but requires careful patient selection and monitoring for any signs of constipation or ischemic colitis.10
Tegaserod was a partial agonist at 5-HT4 receptors, and also had antagonist activity at 5-HT2B receptors. Its 5-HT4 partial agonism facilitated peristaltic reflex activation, accelerating colonic transit in patients with IBS-C and chronic idiopathic constipation. Tegaserod was voluntarily withdrawn from the US market in 2007 following a post-marketing analysis showing a small but statistically significant increase in the combined rate of major adverse cardiovascular events (myocardial infarction, stroke, unstable angina) in treated patients compared to placebo. The mechanism was postulated to involve 5-HT4 receptor effects on cardiac electrophysiology and coronary vasomotor function. It was later reapproved in 2019 under a restricted access program for women under 65 with IBS-C without cardiovascular disease, with a reassessment concluding that the absolute risk increase is very small (approximately 1 in 10,000 patients) in appropriately selected patients.11
Prucalopride is a selective high-affinity 5-HT4 agonist approved for chronic idiopathic constipation, distinguished from tegaserod by its high selectivity for the 5-HT4 receptor and virtual absence of activity at 5-HT2B and other receptors implicated in cardiovascular risk. Prucalopride activates 5-HT4 receptors on myenteric plexus neurons, promoting acetylcholine release and enhancing the peristaltic reflex, increasing colonic transit and stool frequency. Its receptor selectivity translates into a cleaner cardiovascular safety profile: multiple large randomized controlled trials and post-marketing surveillance have not identified a cardiovascular signal comparable to tegaserod. Prucalopride is metabolized primarily by CYP3A4 with additional contribution from renal excretion of unchanged drug; dose reduction is recommended in severe renal impairment. It received FDA approval in 2018 for use in adults of both sexes with chronic idiopathic constipation, a broader indication than either alosetron or tegaserod.12
Alosetron (5-HT3 antagonist): approved for severe IBS-D in women; REMS program required; risk of ischemic colitis. Prucalopride (selective 5-HT4 agonist): approved for chronic idiopathic constipation in adults; favorable cardiovascular profile. Tegaserod (5-HT4 partial agonist / 5-HT2B antagonist): restricted approval for IBS-C in women under 65 without cardiovascular disease; small cardiovascular risk. Ondansetron and other 5-HT3 antagonists: approved for chemotherapy-induced and post-operative nausea; not approved for IBS but used off-label in IBS-D. Telotristat (TPH1 inhibitor): approved for diarrhea in carcinoid syndrome inadequately controlled on somatostatin analogs.
Classical psychedelics including psilocybin and lysergic acid diethylamide (LSD) are among the most pharmacologically selective agents known, producing their profound perceptual and psychological effects primarily through agonism at 5-HT2A receptors on cortical pyramidal neurons. Their re-emergence as subjects of serious clinical investigation for treatment-resistant depression, major depressive disorder, and other psychiatric conditions represents one of the most significant developments in psychopharmacology in decades, and understanding their receptor pharmacology is essential to evaluating the growing clinical evidence base.
Psilocybin is a prodrug tryptamine that is rapidly dephosphorylated in vivo to psilocin, its active form, by alkaline phosphatases in the gut and liver. Psilocin is a potent partial to full agonist at multiple serotonin receptors, with highest affinity at 5-HT2A receptors and significant activity at 5-HT2C, 5-HT1A, and 5-HT2B receptors. Its psychedelic effects are mediated predominantly by 5-HT2A agonism on layer V pyramidal neurons in the prefrontal cortex and posterior cortical areas. LSD (d-lysergic acid diethylamide) is a semi-synthetic ergot alkaloid that similarly acts as a potent 5-HT2A agonist; it has a substantially longer duration of action than psilocybin (8–12 hours versus 4–6 hours for psilocybin), which has practical implications for therapeutic session design. Both compounds also have partial agonist activity at dopamine D2 receptors, though the contribution of this activity to the psychedelic experience is minor relative to 5-HT2A agonism, as selective 5-HT2A antagonists such as ketanserin block the psychedelic effects of both substances.13
The mechanism by which 5-HT2A receptor activation produces the psychedelic state is an active area of research. 5-HT2A receptors on cortical pyramidal neurons are Gq-coupled and, when activated, produce asynchronous glutamate release from thalamocortical afferents (via presynaptic mGluR2 receptor modulation) and depolarize pyramidal neurons, increasing cortical excitability and disrupting the organized oscillatory activity that normally constrains sensory processing. Neuroimaging studies during psilocybin administration reveal a global increase in functional connectivity between brain regions that are normally not strongly connected, with simultaneous dissolution of the default mode network (DMN), the resting-state network associated with self-referential processing and rumination. This increased cross-network connectivity and DMN dissolution are thought to underlie the subjective experience of ego dissolution, expanded awareness, and the proposed therapeutic mechanism: disruption of maladaptive, rigidly entrenched patterns of thought that characterize depression and other psychiatric conditions.14
Clinical evidence for psilocybin in treatment-resistant depression (TRD) has grown substantially since 2016. The COMPASS Pathways phase 2b trial randomized 233 patients with TRD to a single dose of psilocybin 1 mg, 10 mg, or 25 mg under psychological support; the 25 mg dose produced response rates of 37% and remission rates of 29% at week 3, with a rapid onset that distinguishes it from conventional antidepressants. The Johns Hopkins and Imperial College London trials have demonstrated significant antidepressant effects of two doses of psilocybin (combined with structured psychological support) in major depressive disorder (MDD), with effects sustained at 1 to 3 months. Psilocybin has also demonstrated significant effects in tobacco cessation, alcohol use disorder, and cancer-related depression and anxiety. The FDA granted breakthrough therapy designation to psilocybin for TRD in 2018 and for MDD in 2019, acknowledging the preliminary evidence while mandating rigorous additional trials. The critical regulatory and ethical question is how to structure the necessary clinical context (trained therapists, controlled settings, preparatory and integration sessions) within a conventional pharmaceutical approval framework.15
Both psilocybin and LSD have agonist activity at 5-HT2B receptors, which when activated chronically in the heart can promote valvular fibrosis (the same mechanism implicated in fenfluramine and ergotamine-induced valvulopathy). This is not a practical concern at the low doses and infrequent administration used in therapeutic protocols; it would become relevant only with chronic, frequent recreational exposure. More immediate cardiovascular considerations include dose-dependent increases in blood pressure and heart rate, which are self-limited but require monitoring during therapeutic sessions in patients with hypertension or cardiac disease. The combination of psilocybin with lithium has been associated with seizures and should be avoided; combination with MAOIs can prolong and intensify the psychedelic experience unpredictably.
Beyond the well-characterized receptor subtypes targeted by existing drugs, the serotonin receptor family contains several members that are the focus of active drug development but have not yet produced approved therapeutics for CNS indications. The 5-HT4, 5-HT6, and 5-HT7 receptors are each expressed in brain regions relevant to cognition, mood, and circadian rhythm regulation, and each has generated compelling preclinical and early clinical data supporting their development as therapeutic targets. Understanding their pharmacology positions the clinician to evaluate emerging literature as this field matures.
The 5-HT4 receptor is a Gs-coupled receptor expressed in the hippocampus, striatum, and frontal cortex, as well as throughout the gut. In the CNS, 5-HT4 receptor activation increases cyclic AMP (cAMP), which activates protein kinase A (PKA) and the transcription factor CREB, stimulating BDNF (brain-derived neurotrophic factor) expression in the hippocampus. This neuroplastic mechanism is the same cascade activated by SSRIs after autoreceptor desensitization, but 5-HT4 agonism engages it through a distinct receptor pathway that could theoretically produce antidepressant effects with faster onset. Preclinical data show that 5-HT4 agonists produce antidepressant-like effects in rodent models within days rather than weeks, and promote neurogenesis in the dentate gyrus. Prucalopride and newer CNS-penetrant 5-HT4 agonists are being investigated for cognitive benefit in Alzheimer disease, where postmortem studies show reduced 5-HT4 receptor expression in the hippocampus that correlates with the degree of cognitive impairment. Increased cholinergic neurotransmission following 5-HT4 activation in the hippocampus (through enhanced acetylcholine release from presynaptic terminals) provides a mechanistic link to acetylcholine-dependent memory processes.16
The 5-HT6 receptor is expressed almost exclusively in the CNS, with high density in the striatum, nucleus accumbens, and frontal cortex. It is a Gs-coupled receptor that, when activated, modulates glutamatergic and GABAergic neurotransmission in the frontal cortex and limbic system. Most currently used atypical antipsychotics, including clozapine, olanzapine, quetiapine, and asenapine, have significant 5-HT6 receptor antagonist activity as part of their broad receptor binding profiles, which has led to the hypothesis that 5-HT6 antagonism contributes to the procognitive effects observed with these agents compared to typical antipsychotics. Selective 5-HT6 antagonists have been developed specifically as cognitive enhancers and as augmentation agents for antipsychotic treatment of schizophrenia; idalopirdine was the most advanced of these compounds but failed to demonstrate cognitive benefit in phase 3 trials in Alzheimer disease, tempering enthusiasm for 5-HT6 as a cognitive target but not eliminating it. The mechanistic basis for cognitive benefit from 5-HT6 antagonism is thought to involve disinhibition of frontal glutamatergic neurotransmission and normalization of the glutamate-GABA balance in cortical circuits.16
The 5-HT7 receptor is a Gs-coupled receptor with high expression in the hypothalamus (suprachiasmatic nucleus, SCN), thalamus, hippocampus, and cortex. Its hypothalamic expression makes it a key mediator of circadian rhythm regulation: activation of 5-HT7 receptors in the SCN modulates the phase of circadian oscillators, contributing to the circadian phase-shifting effects of serotonergic drugs. The observation that several antidepressants and antipsychotics with mood-stabilizing properties have significant 5-HT7 receptor antagonist activity (including amisulpride, aripiprazole, and lurasidone) has generated interest in 5-HT7 antagonism as a mechanism contributing to antidepressant and mood-stabilizing effects, beyond what is explained by monoamine reuptake inhibition or dopamine receptor modulation. Vortioxetine's 5-HT7 antagonism (described in Module 3) is the most clinically implemented example of this mechanism, contributing to its cognitive benefits and possible circadian normalization. Animal models suggest 5-HT7 antagonism may also have antidepressant effects through hippocampal BDNF induction, providing a convergent mechanism with 5-HT4 agonism.17
The fourteen human serotonin receptor subtypes span seven families (5-HT1 through 5-HT7) and encompass GPCRs (Gi, Gs, and Gq-coupled) and a single ionotropic receptor (5-HT3). Each subtype has a distinct distribution, signaling mechanism, and functional role. The drugs discussed across this four-module series illustrate the breadth of therapeutics achievable by exploiting this receptor family: SSRIs and SNRIs (SERT inhibition with downstream receptor effects), MAOIs (enzyme inhibition), triptans (5-HT1B/1D agonism), buspirone (5-HT1A partial agonism), 5-HT3 antagonists (antiemetics), vortioxetine (multimodal), alosetron (5-HT3 antagonism), prucalopride (5-HT4 agonism), telotristat (TPH1 inhibition), and psilocybin (5-HT2A agonism). Emerging targets (5-HT4, 5-HT6, 5-HT7) extend this platform further into cognition, circadian biology, and neuroprotection. No other neurotransmitter system offers a comparable combination of receptor diversity, pharmacological tractability, and breadth of therapeutic application.
Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology. 2007;132(1):397–414.
doi:10.1053/j.gastro.2006.11.002Yano JM, Yu K, Donaldson GP, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161(2):264–276.
doi:10.1016/j.cell.2015.02.047Furness JB. The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol. 2012;9(5):286–294.
doi:10.1038/nrgastro.2012.32Mayer EA. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci. 2011;12(8):453–466.
doi:10.1038/nrn3071Delle Fave G, Kwekkeboom DJ, Van Cutsem E, et al. ENETS consensus guidelines for the management of patients with gastroduodenal neoplasms. Neuroendocrinology. 2012;95(2):74–87.
doi:10.1159/000335595Modlin IM, Oberg K, Chung DC, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9(1):61–72.
doi:10.1016/S1470-2045(07)70410-2Oberg K, Knigge U, Kwekkeboom D, Perren A; ESMO Guidelines Working Group. Neuroendocrine gastro-entero-pancreatic tumors: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):vii124–vii130.
doi:10.1093/annonc/mds295Kulke MH, Horsch D, Dobbe E, et al. Telotristat ethyl, a tryptophan hydroxylase inhibitor for the treatment of carcinoid syndrome. J Clin Oncol. 2017;35(1):14–23.
doi:10.1200/JCO.2016.69.2780Camilleri M, Lasch K, Zhou W. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. The confluence of increased permeability, inflammation, and pain in irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2012;303(7):G775–G785.
doi:10.1152/ajpgi.00155.2012Chang L, Chey WD, Harris L, Olden K, Surawicz C, Schoenfeld P. Incidence of ischemic colitis and serious complications of constipation among patients using alosetron: systematic review of clinical trials and post-marketing surveillance data. Am J Gastroenterol. 2006;101(5):1069–1079.
doi:10.1111/j.1572-0241.2006.00511.xTack J, Camilleri M, Chang L, et al. Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther. 2012;35(7):745–767.
doi:10.1111/j.1365-2036.2012.05011.xCamilleri M, Kerstens R, Rykx A, Vandeplassche L. A placebo-controlled trial of prucalopride for severe chronic constipation. N Engl J Med. 2008;358(22):2344–2354.
doi:10.1056/NEJMoa0800670Nichols DE. Psychedelics. Pharmacol Rev. 2016;68(2):264–355.
doi:10.1124/pr.115.011478Carhart-Harris RL, Roseman L, Bolstridge M, et al. Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Sci Rep. 2017;7(1):13187.
doi:10.1038/s41598-017-13282-7Davis AK, Barrett FS, May DG, et al. Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2021;78(5):481–489.
doi:10.1001/jamapsychiatry.2020.3285Meltzer HY, Massey BW. The role of serotonin receptors in the action of atypical antipsychotic drugs. Curr Opin Pharmacol. 2011;11(1):59–67.
doi:10.1016/j.coph.2011.02.007Hedlund PB. The 5-HT7 receptor and disorders of the nervous system: an overview. Psychopharmacology (Berl). 2009;206(3):345–354.
doi:10.1007/s00213-009-1626-0