Serotonin

While dopamine and the dopamine reward system are often referenced when discussing addiction, other neurotransmitters are affected by drug use. These include GABA, glutamate, noradrenaline and serotonin.

What is serotonin?

Serotonin is many things. It’s a chemical messenger, and its main role in the body is as a neurotransmitter, but it also performs hormone functions in some areas of the body.

Only about 10% of serotonin is made in the brain – it’s mainly found in the gut. It’s unsurprising, then, that serotonin performs a wide range of functions, influencing digestion, mood, temperature, sleep, wound healing, bone health, sexual behaviour, hunger and sleep. Problems with serotonin signalling are linked to a range of problems, including obsessive-compulsive disorder, anxiety, and depression.

Most people know serotonin for its role in mood and the use of SSRIs (selective serotonin reuptake inhibitors) to increase serotonin in the brain to treat depression. While serotonin does play a role in regulating mood, the serotonin hypothesis of depression has been recently examined in a systematic review in the journal Nature – and found to be lacking in evidence.

While the review didn’t find a link between low serotonin and depression, people do find relief from taking SSRIs. This means that scientists don’t actually know how SSRIs work – only that they do. This emerging research highlights how psychology and neuroscience are developing fields and how new research can force us to reevaluate theories that have been established knowledge for decades.

Serotonin and addiction – the link

Unlike the dopamine reward system and addiction, where the link is very clear, the link between serotonin and addiction is more subtle. Several drugs work primarily on serotonin, such as MDMA, LSD, psilocybin and DMT. Interestingly, these drugs are less associated with addiction, potentially because their primary mechanism of action is not located in the brain’s dopamine reward system but instead in serotonin.

However, alcohol and illicit drugs still work on serotonin, just not primarily. Studies have looked at the role of serotonin when these drugs are taken and found it actually acts as a counterbalance, diminishing and inhibiting the pleasurable and reinforcing effects of these drugs in the brain. This has led scientists to theorise that serotonin could act as a brake for the addictive properties of these drugs.

However, much like the low serotonin hypothesis of depression, research has not validated this claim – or at least, attempts to boost serotonin in the brain to treat addiction have not yet been successful. Clinical trials have shown mixed results when attempting to use serotonin-boosting drugs to treat addiction, and there’s currently no evidence that it works. While SSRIs can be beneficial for treating depression, which commonly accompanies withdrawal, it doesn’t seem to be effective when used to treat the addiction itself.

Can you get addicted to Serotonin?

In short, no, you cannot get addicted to serotonin. You cannot get addicted to dopamine either, even though it’s highly associated with reward and heavily embedded in the neurobiological processes that lead to addiction. Serotonin is a naturally occurring neurotransmitter that we cannot directly ingest – we can only boost its levels in our body.

Some people mistakenly believe that serotonin addiction is possible because they experience discontinuation effects when they stop taking drugs that boost serotonin, like SSRIs. 

Much like the reasons why SSRIs work, the reasons for SSRI withdrawal are currently poorly understood, and we only have theories. Currently, it is believed that SSRI withdrawal is caused by the brain readjusting to lower levels of serotonin. After SSRI use is discontinued, levels of serotonin in the brain reduce rapidly, and the brain must get used to this change. This is partially supported by the fact that people discontinuing SSRIs report worse withdrawals the longer they have been taking the drug – meaning the brain has had longer to adapt to the changes and will take longer to readjust to lowered levels. However, attempts to find an explanation for SSRI withdrawal have been challenging. Withdrawals only occur in about half of patients and are highly subjective, which makes studying them challenging.

While SSRIs do have associated discontinuation effects, they do not cause a high or compulsive drug-seeking behaviour – which means that they aren’t classed as addictive.

Drugs that affect serotonin

• Psychedelics 

LSD, psilocybin, and DMT are also known as serotonergic hallucinogenics. Their mechanism of action is not yet fully understood, but research suggests that one way they work is as serotonin agonists. This means they act like serotonin in the brain and bind to and trigger serotonin receptors. Psychedelics bind to specific serotonin receptors called 5-HT2A receptors.

Current research suggests that psychedelic drugs are not physically addictive, as they don’t promote dependence or reinforcement and tolerance is very rapid. This doesn’t mean that you cannot become psychologically dependent on psychedelics, only that it’s rarer.

• MDMA

MDMA is a methamphetamine derivative and affects noradrenaline and dopamine, as well as serotonin.

MDMA addiction hasn’t been widely studied. It has been found that animals will self-administer MDMA given the opportunity, which does point towards addictive potential, but they do so less than drugs understood to be addictive, like cocaine. Some people do report symptoms of addictions to MDMA, including continuing to use it despite negative outcomes, tolerance, cravings and withdrawal.

Serotonin syndrome

High levels of serotonin in the body are dangerous and can even be fatal. It’s caused by overactivity in certain serotonin receptors, namely the 5HT-1A and 5HT-2A receptors. 5HT-2A receptors are the same ones acted upon by psychedelic drugs – therefore, it isn’t a surprise that psychedelics are capable of causing serotonin syndrome. Serotonin syndrome can be caused by taking a high dose of a serotonin-boosting drug or combining one or more serotonin-boosting drugs.

Serotonin syndrome causes a wide range of unpleasant symptoms, including agitation, insomnia, confusion, rapid heart rate and high blood pressure, loss of coordination, sweating, diarrhoea and headaches. Serious symptoms include fevers, seizures, irregular heartbeat and unconsciousness. These symptoms are primarily caused by high serotonin levels, which causes the body to be unable to regulate vital functions such as body temperature, heart rate, and blood pressure.

Many people are aware that mixing SSRI antidepressants and MDMA can lead to serotonin syndrome, but many drugs work on serotonin, and many combinations can be dangerous. For instance, some opioid drugs, such as fentanyl or tramadol, increase serotonin, as do many other classes of antidepressants, not just SSRIs. This means mixing these drugs could also lead to dangerously high levels of serotonin. Even herbs like St John’s Wort or Panax ginseng can increase serotonin levels, or dextromethorphan, a common ingredient found in cough syrups.