Does Caffeine Lower Serotonin Levels?

In this article, we will closely examine the neurobiology of caffeine and its interaction with serotonin production in the brain. We will understand how caffeine works in the brain and how serotonin levels can be modulated. The article looks into mechanisms of increasing and decreasing serotonin and combines them with existing literature on the neurobiology of caffeine neurobiology.
Klara Hatinova

Klara Hatinova

Klara is postgraduate researcher in experimental psychology at the
University of Oxford.

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Does Caffeine Lower Serotonin Levels?

While caffeine can temporarily boost your mood by stimulating the central nervous system, it does not necessarily lower serotonin levels. However, excessive caffeine consumption can disrupt your sleep patterns, indirectly affecting serotonin production. Consuming caffeine in moderation is important to maintain balanced serotonin levels. In this blog, we will discuss the neurobiology of caffeine and the production of serotonin to understand whether caffeine can lower serotonin levels in your brain.

What is the Neurobiology of Caffeine?

Caffeine is the most popular psychoactive substance globally, with multiple health benefits. Soft drinks and tea are the most popular caffeinated drinks in African and East Asian countries, whereas coffee remains a staple in Europe and North America [1]. Other forms of caffeine include energy drinks or even chocolate. Caffeine intake can stimulate brain function, reduce fatigue and, in case studies, was also found to improve mental health symptoms, particularly in individuals with mood disorders, ADHD or OCD.

Caffeine contains the active molecule Methylxanthine, which stimulates the brain by reducing fatigue and increasing alertness. The effects of caffeine arise from a complex neurobiology involving several action mechanisms. 

There are three main mechanisms of how caffeine works in the brain: 

  1. Antagonist of the adenosine receptor. Adenosine is a well-known depressant of brain function, meaning it reduces brain activity [3]. Caffeine counteracts this depressant effect, making your brain more active, alert, and awake. 
  2. Mobilisation of intracellular calcium. Calcium is stored within specific sub-components of the neuron called the sarcoplasmic reticulum. Caffeine can stimulate the release of this calcium into the central nervous system synapses, making them more excitable. This effect is distinct from caffeine's effect on specific neurotransmitters, such as dopamine and noradrenaline [4].
  3. Inhibition of phosphodiesterase. Phosphodiesterase is an important enzyme in the body that breaks down cAMP, a molecular messenger. Increased accumulation of cAMP can increase the release of neurotransmitters such as dopamine, noradrenaline, and epinephrine, all of which have stimulatory effects and improve cognition [5, 6].

How can you increase or lower serotonin levels?

Serotonin levels can be reduced by either lowering the synthesis of serotonin or increasing serotonin reuptake into pre-synaptic neurons or glial cells.

Serotonin Reuptake

Serotonin reuptake is commonly reduced by selective serotonin reuptake inhibitors - a class of antidepressants that increase serotonin levels in the brain. More serotonin, however, isn't always a good thing, as serotonin levels being too high increases the risk of serotonin syndrome.

On the other hand, tryptophan depletion can significantly reduce serotonin levels, which is utilised in studies of serotonin's effects on mood and behaviour [7].

How is Serotonin Produced?

Serotonin, also known as 5-hydroxytryptamine or 5-HT, is a neurotransmitter that plays a crucial role in the nervous system. It is synthesised in the brainstem's raphe nuclei and is involved in the central control (meaning control arising from the central nervous system) of food intake, sleep, and mood [8].

Biosynthesis of Serotonin

The production of serotonin begins with the amino acid tryptophan. The first step in serotonin biosynthesis is the hydroxylation of L-tryptophan, a process catalysed by the enzyme tryptophan hydroxylase. This enzyme is the rate-limiting factor in serotonin synthesis, meaning that the speed of serotonin production depends on the enzyme's activity [9].

The hydroxylation of L-tryptophan results in the formation of 5-hydroxy-L-tryptophan (5-HTP). The 5-HTP is then decarboxylated to serotonin, a second step catalysed by the enzyme aromatic L-amino acid decarboxylase [9].

In addition to the brain, serotonin can also be produced in the gut and other specific cells. For instance, spiral ganglion neurons in the spinal cord can synthesise serotonin themselves, suggesting that they may serve as an additional source of serotonin in the body outside the raphe nuclei [10].

Does Caffeine Lower Serotonin?

The relationship between caffeine and serotonin is complex. Caffeine does not directly lower serotonin levels. Different doses of caffeine through coffee and tea were found to increase total levels of tryptophan and serotonin [7]. Nonetheless, this effect may be highly variable between individuals. An older study found that the beneficial effects of caffeine on mood and alertness depended on the individual's pre-existing mood. 

Looking at the rate of serotonin usage in the brain, both animal and human studies found that caffeine increases the usage of serotonin in the limbic system. The limbic system is a central part of the brain, including the basal ganglia, which regulates emotions and sleep. This modulation of serotonin in the limbic system may account for many important effects of serotonin [11]

To date, there have been sparse cases reporting serotonin syndrome, a side effect of excess serotonin, in people who have drunk too much caffeine [12]. Therefore, serotonin syndrome is not a side effect of caffeine consumption, although you should seek medical advice if you are taking antidepressants or other psychoactive medication.

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Klara Hatinova

Klara Hatinova

Klara is a postgraduate researcher in experimental psychology at the University of Oxford. She has worked across a spectrum of hot topics in neuroscience, including her current project measuring reinforcement learning strategies in Parkinson’s disease. Previously, she studied the efficacy of psilocybin as a therapy for critical mental health conditions and examined molecular circadian rhythms of migraine disorders. She completed her undergraduate degree in Neuroscience at the University of Glasgow and participated in a year abroad at the University of California, where she worked on a clinical trial for spinal cord injury.