Serotonin Toxicity (overdose)

Note: This text has been put together using several excellent data sources. The wording is relayed ala BP style, but we recommend if you wish to know more about this issue – to please start with the links that we have found as amongst the best on this subject. All links at the bottom of the page: Thanks to those hardworking and smart harm reductionists who think outside the box and discuss issues that we really need discussing, researching and debating.

A Serotonin OVERDOSE? What the hell is that then??

If someone takes too much of a drug – that can be almost any drug – they can overdose and you will need to get the casualty medical help as quickly as possible. However, as we have mentioned, overdoses come in all shapes and sizes -and too often we are just fed information for the usual opiate OD’s or sometimes stimulant OD’s. But we need to think about poly drug use -what happens when we take a combination of drugs – we need to know about what symptoms are connected to what overdoses so we don’t try and give our friends the wrong help, or worse.

But here, we want to talk about serotonin toxicity – something quite common – especially with people who are on SSRI antidepressants like Prozac and Citalopram – those anti D’s that contain Selective Seratonin Reuptake Inhibitors. So common today and yet so little is ever told to active users about interactions with other drugs -in particular – other drugs that affect serotonin levels. Also, people can have bad symptoms (see below) but still be on this side of OK -but it is clearly their body telling them ‘enough already’! ‘I can’t take any more toxins in my brain, please knock it off, no more’!

Drugs Commonly Involved:

Some drugs, such as MDMA, have serotonergic properties, meaning they affect
the levels of the neurotransmitter serotonin. Too much serotonin can cause serotonin syndrome which can be potentially life-threatening. Often however, you may find it is a combination, such as being on a SSRI antidepressant -then going out for the night or weekend and taking methamphetamine, or MDMA on top of your SSRI meds. It is very important to be VERY careful if you are taking SSRI’s or a lot of MDMA or mixing these drugs – take it very slowly if you MUST use.

Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder and anxiety disorders. The exact mechanism of action of SSRIs is unknown. People forget about interactions with these drugs and other illicit stimulants etc. But there can be serious knock-on or worrying effects.


Hyperthermia (overheating)
Severe nausea and vomiting
Rapid heart rate/chest pains
Unexpected hallucinations
Difficulty breathing
Blue/pale tingeing of knees, hands
and lips


Rigid, jerky, twitchy unusual movements, often involving the legs shaking; fully dilated
pupils; overheating; shivering; racing heart; the person appearing agitated and confused.
If in doubt, ring for an ambulance.

NOTE: It is important if they have rigid, jerky movements, not to hold people down because of the risk of muscle tissue breaking down (rhabdomyolysis). As with people who have been using volatile substances (solvents) it can also be risky to startle or frighten people as this can lead to heart failure [UK DrugWatch, Overdose and Emergencies Sheet, 2014]

Quote from someone who had experienced mild serotonin syndrome:

“I had been taking an SSRI for about 6 months. Then I got some good quality methamphetamine which I smoked. After about 15 hours I was trying to wind down but it wasn’t going to happen, despite taking heroin and valium. I had to attend a protest and even though I thought I was ok at that stage, I was absolutely not making sense when I rang or texted my friends. After about 36 hours when I lay down, I was twitching like crazy, half unconscious I think, but almost hitting the ceiling with electric type shocks going through me all night. My heart just kept racing and I really wasn’t making much sense to my partner I was sharing the bed with – but luckily he kept a close eye on me and I had a couple of valium in the end which sort of helped but I kind of had to ride it out. It was a very strange experience but what was weirder was that I thought I wasn’t too bad but my friends said I was really confused and they didn’t understand what on earth was wrong with me. Now I know what it was and I won’t take meth with SSRIs ever again. If I was prescribed them again – I think I would research a lot more about side effects. It was scary and very strange.

A Fabulous booklet from Crew 2000 on Psychoactive Drugs – which includes overdoses on various drugs and some really useful info. Click here to download free.

Serotonin Syndrome

Serotonin syndrome is an uncommon, but potentially serious, set of side effects linked to SSRIs. Serotonin syndrome occurs when the levels of a chemical in your brain called serotonin become too high. It’s usually triggered when you take an SSRI in combination with another medication (or substance) that also raises serotonin levels, such as another antidepressant or St John’s wort.

Symptoms of serotonin syndrome can include:

  • confusion
  • agitation
  • muscle twitching
  • sweating
  • shivering
  • diarrhoea

If you experience these symptoms, you should stop taking the medication and seek immediate advice from your GP or specialist. If this isn’t possible, call NHS 111.

Symptoms of severe serotonin syndrome include:

MDMA/ecstasy is one example of a drug that may be involved in this interaction; certain opioid medications such as tramadol and meperidine also have serotonergic properties and may increase the risk of serotonin syndrome when combined with SSRIs (selective serotonin reuptake inhibitors) and other antidepressants. If you or someone you know experience symptoms of severe serotonin syndrome, seek emergency medical help immediately by dialing for an ambulance.

Cocaine, methamphetamine and SSRI’s

GPs have been reminded that they should ask patients whether they use cocaine before prescribing selective serotonin reuptake inhibitors (SSRIs). Click here for article.

The warning, contained in the Government’s 2016 July Drug Safety Update, followed a coroner’s report which ruled a man who died of sub-arachnoid haemorrhage may have suffered an interaction between citalopram and cocaine.

Discussing the case, the UK Commission on Human Medicine’s Pharmacovigilance Expert Advisory Group said that ‘there are plausible mechanisms for an interaction between cocaine and citalopram that could lead to subarachnoid haemorrhage, including hypertension related to cocaine and an additive increased bleeding risk in combination with citalopram’.

Stimulants and Anti D’s – thoughts from The Fix (ask the expert – Click for full article)

Larissa Mooney says in The Fix’s 2015 article on this issue: “Antidepressants may interact with street drugs, but the risks are often difficult to quantify or predict. For example, antidepressants may increase the potential for seizure, and stimulant drugs such as cocaine and methamphetamine carry a similar risk. Therefore when stimulants and antidepressants are taken together, seizure risk may be further increased, particularly in the presence of more “stimulating” antidepressants such as bupropion or tricyclics. Other factors may also contribute to seizure risk, including medical conditions, electrolyte imbalances, and brain injuries. Therefore it is very important to discuss all drug use, medication use, and health conditions with your doctor so that risks and benefits may be weighed when making treatment decisions.

“Other factors may also contribute to seizure risk, including medical conditions, electrolyte imbalances, and brain injuries. Therefore it is very important to discuss all drug use, medication use, and health conditions with your doctor so that risks and benefits may be weighed when making treatment decisions….”

“Elevations in blood pressure may occur when amphetamines are combined with antidepressants that enhance noradrenergic activity, such as tricyclics, venlafaxine, or MAOIs (monoamine oxidase inhibitors). Certain antidepressants, such as fluoxetine and paroxetine, may also increase the concentration of amphetamines in the blood by inhibiting liver enzymes; this effect may also increase the potential for toxicity.  It is difficult to determine the frequency of adverse interactions, and though amphetamines are not prescribed in combination with MAOIs due to the potential for severe events, many stimulant users take other antidepressants without consequences. ”

Drugs of Sedation…

“In general, medications with sedating properties enhance the risk of oversedation and of suppression of breathing when combined with other sedating drugs, such as heroin and other opioids. And while sleeping medications, alcohol, and tranquilizers are well known to enhance the potential for overdose when combined with opioids, this risk may be exacerbated in the presence other medications with sedating properties, such as mirtazipine and tricyclic antidepressants.”

BP will add more links to this piece shortly. Please do add your experiences to or comments section – people learn a lot from reading them and feel comfort from knowing they are not alone. Be careful out there!

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