Serotonin, Hallucinations & Psychosis

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Serotonin, Hallucinations & Psychosis

By Neuroskeptic | March 26, 2009

Serotonin, as every newspaper reader knows, is the brain’s “feel good chemical”. Of course, it’s a little bit more complicated than that. A lot more complicated, in fact. But even amongst scientists who are aware of the complexity of serotonin pharmacology, the functions of serotonin are still generally thought of in the context of mood and emotion.

What everyone tends to forget is that serotonin has a wild side. There’s a long line of research, stretching back to the 40s, on the role of serotonin in perception and hallucinations.

It all started on Bicycle Day – the 1943 day that Albert Hofmann first experienced the psychedelic effects of LSD (“acid”) while riding his bike home from the lab where he first synthesized the drug. Serotonin was discovered in 1948. It was soon noticed that the chemical structure of LSD bears a striking similarity to serotonin – as does psilocybin, the major psychoactive ingredient in “magic mushrooms”: You don’t need to be a chemist to appreciate the resemblance. So it would be a very reasonable assumption that hallucinogenic drugs work by interfering with the brain’s serotonin pathways, and therefore that the serotonin system is somehow involved in regulating thought and perception. Somehow, LSD interferes with the serotonin system in the brain to cause profoundly altered states of consciousness. That’s pretty important…

Scientists way back in the '50s realized a connection between serotonin and sleep.  It is known that stimulation of the raphe nuclei, a region of the brain that contains most of the brain's serotonergic neurons, increases cortical EEG readings.  Additionally, like norepinephrine, serotonergic neurons become virtually zero during REM sleep.

    Despite our understanding of serotonin in REM sleep, we are unclear in whether serotonin induces/maintains sleep or whether sleep maintains/restores the serotonin system.  We can test these theories by examining the effects of sleep deprivation on serotonin levels.  If the former is true, then sleep deprivation should increase serotonin levels.  On the contrary, if the latter is correct, deprivation should decrease the serotonin system.  Findings of the effects of total- and REM-sleep deprivation on serotonin levels have been inconsistent.

    Support for an increase in serotonin function during total sleep deprivation comes from the finding that sleep deprivation produces an antidepressant response in humans.  Most antidepressant drugs increase serotonergic activity.   Additionally, findings of increases in serotonin and 5-HIAA (a metabolite of serotonin) levels in the whole brain, cortex, and midbrain, in both rats and cats, have been reported following REM and total sleep deprivation.   Moreover, serotonergic neurons have been shown to fire more frequently during total sleep deprivation. Finally, it has been suggested that sleep deprivation increases serotonin turnover, as determined by the 5-HIAA/serotonin ratio, in the frontal cortex, hippocampus, hypothalamus and brainstem.

    However, not all studies have confirmed an increase in serotonin during sleep deprivation.  Studies have reported no changes in serotonin or 5-HIAA in the cortex, diencephalon, telecephalon, brainstem, or whole brain after REM sleep deprivation and total sleep deprivation have been reported.

Supporting Study:

Kasamatsu and Hirai (1999)

Aim: To investigate how sensory deprivation affects the brain.


  1. A field study was conducted on a group of Buddhist monks as they embarked on an annual spiritual pilgrimage

  2. The monks went on a 72-hour pilgrimage in Japan and did not speak, sleep, or consume food or water and were exposed to the cold autumn weather.

  3. Before they left, blood samples were taken, and serotonin levels were recorded.

  4. After 2 days, they reported having hallucinations of ancestors – which was the purpose of their pilgrimage

  5. After the pilgrimage, researches took blood samples and tested the serotonin levels.


  • Researchers found that serotonin levels had increased in the monks' brains

  • This activated the hypothalamus and frontal cortex to trigger the hallucinations.

  • Sensory deprivation was the cause of the release of the serotonin, which altered the way the monks experienced the world.

Name:___________________________________ Block:_____

Serotonin and Behavior

Directions: Read the article and answer the questions which follow

  1. Based on the article, how can effects of sleep deprivation mimic the effects of LDS usage?

  1. The article states that those suffering from sleep deprivation may have the same response as those who take antidepressants. Based on this statements, what is the link between Serotonin and Depression?

  1. In a one page written response answer the following question as an 8-mark response.

“To what extent does Serotonin affect human behavior?”
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