Serotonin (5-hydroxytryptamine: 5-HT) is a neurotransmitter produced in the human brainstem and synthesized from L-Tryptophan, an essential amino acid. Considered a hormone, it is found in the brain, gastrointestinal tract, whole blood, plasma and pineal gland. Serotonin provides the regulation and mediation of various physiological functions in several systems and contributes significantly to a feeling of overall well-being, calm and pleasure.
Serotonin affects the cardiovascular system by regulating normal cardiovascular activity. Elevated serotonin levels induce tachycardia (rapid heart rate), increase cardiac stress and the possibility of cardiac disease. Reduced serotonin levels can result in a slowed heart rate, suppressed cardiovascular activity and heart failure.
Serotonin levels appear to affect the regulation of bleeding through mechanisms such as clotting. Gastrointestinal discomfort and disease such as ulcers, irritable bowel syndrome, bloody stool, diarrhea and constipation have been linked to abnormal serotonin levels found in the gastrointestinal system. Serotonin excess is processed and excreted from the body through the kidneys. Renal damage can occur with the processing and excretion of elevated levels of serotonin over prolonged periods. Such renal complications can occur in substance use disorders and in serotonin toxicity syndrome.
Substances of abuse and dependence such as hallucinogens, cannabis, alcohol, opioids and stimulants affect serotonin levels by raising serotonin levels and creating a sense of well-being, pleasure and euphoria. Further substance use is reinforced by the immediate positive effects; however, the prolonged use of psychoactive chemicals can negatively affect the brain’s ability to produce and use serotonin. Substance-induced elevated levels of serotonin can decrease the number of serotonin receptors in the brain. Elevated levels over a prolonged period can also negatively affect functioning of available serotonin receptors. Cessation of substance use can result in serotonin ‘deficiency’ and associated discomfort in abstinence. Symptoms of interrupted serotonin processes can appear for some time after abstinence from prolonged and/or excessive use of psychoactive substances that have elevated serotonin levels. These symptoms are found in the Post Acute Withdrawal Syndrome (PAWS) and contribute to relapse to substance use.
Several psychiatric conditions including depression, anxiety and phobias are associated with low levels of serotonin and medications used to treat them are pro-serotonergic. Antidepressants directly affect the production of serotonin and its processes. Such medications are tricyclics (TCAs), monoamine oxidase inhibitors (MAOIs), and selective serotonin reuptake inhibitors (SSRIs).