Promethazine

Description

Promethazine is a first-generation antihistamine used for a variety of medical conditions, such as allergies or nausea due to motion sickness or surgery. Promethazine is one of the ingredients of ‘lean’ or ‘purple drank’ alongside codeine, taken for its sedating properties.

Pharmacology

Promethazine is a strong histamine H1 receptor antagonist. By blocking the H1 receptor, promethazine stops the neurotransmitter histamine from sending nausea, allergy and itch signals in the nervous system. It also acts as a moderate-strength muscarinic acetylcholine (mACh) receptor antagonist, which may contribute to the anti-nausea and sedative effects as well as its side effects profile.

Promethazine is a member of the phenothiazine class of drugs often with anti-psychotic effects. However, therapeutic doses of promethazine show no anti-psychotic effect, and much less potent dopamine antagonism than others of this class.

Harm Reduction

• Start low, go slow: Take a small amount and wait until you can feel the effects before taking more/anything else
• Try not to use alone: If something goes wrong, someone is there to get help
• Be careful mixing: Mixing promethazine with other depressants can increase overdose risk – avoid if you can, otherwise take less of each, as they can increase the effects and risks
• Carry naloxone: Lean contains opioids, meaning that overdose can be reversed by naloxone. Additionally several counterfeit pills across the UK have been found to contain strong opioids.
• Test your stuff: You can’t see by eye whether your stuff is what it was sold as. Find out how to send a sample to WEDINOS for testing here: https://www.wedinos.wales or pick up some test strips at our Harm Reduction Hub
• If you’ve been prescribed promethazine and you notice a tolerance starting to develop (you need to keep taking more to get the same effect) speak to your doctor – don’t just start increasing your dose yourself.
• If you have become physically dependent on lean, the symptoms of abruptly stopping are likely to be even worse. It’s important to get proper medical advice on how to reduce your intake slowly.
• It’s also possible to become psychologically dependent on the drug (feeling like you need it all the time). If you think this is happening, see your doctor as soon as possible, but don’t suddenly stop taking it.

History

Promethazine was invented by scientists at the French pharmaceutical company Rhône-Poulenc in the 1940s, and approved for medical use in 1951.

In the 21st century, the liquid combination of promethazine with the opioid codeine became colloquially known as ‘lean’, ‘purple drank’ or ‘sizzurp’. Lean has gained cultural prominence across the US, with frequent mentions in the charts including Lil Nas X’s 2019 song “Old Town Road”. Although frequently attributed to the African-American community in the US media, research suggests lean is used by predominantly young men of diverse racial/ethnic groups.

In 2026, WEDINOS detected a number of counterfeit benzodiazepine pills across the UK containing a mixture of ethylbromazolam and promethazine.

Law

• Pharmacy (over the counter) medication