Cold water extraction of codeine/paracetamol combination products: a case series and literature review

Clin Toxicol (Phila). 2020 Feb;58(2):107-111. doi: 10.1080/15563650.2019.1612069. Epub 2019 May 13.


Introduction: Tampering with opioid containing medications for use other than their prescribed indication is well documented; however, the published literature has concentrated on stronger, prescription opioids. Less potent opioids, such as codeine, are available without prescription in many European countries in the form of combination analgesic products and these can also be altered, with reports in particular of "cold-water extraction" being a tampering method achievable using household kitchen equipment.Methods: We searched a database of patients attending two South London emergency departments for cases of self-reported ingestion of the products of cold-water extraction, with subsequent review of their case notes. We searched the scientific and grey literature to identify current knowledge of this technique.Results: We identified seven presentations in six patients, none of whom developed paracetamol toxicity or had concentrations suggesting ingestion of a significant dose of paracetamol. A review of the scientific literature on the method also demonstrated that the technique reduces recovered paracetamol in experimental laboratory settings. Additionally, the established literature characterizes the use of codeine in a recreational setting and reports one fatality associated with the method. Review of grey literature user-forums further describes recreational codeine use in relation to the method and frequent adverse events including hospital admission for paracetamol toxicity.Discussion: Whilst the method appears capable of providing a recreational dose of codeine with reduction in the recovered paracetamol, it cannot be considered safe. Pharmaceutical production methods have been successfully developed to prevent tampering through other means but none thus far have been directed at the cold water extraction technique.Conclusions: Clinicians should be aware of the potential toxicity from tampered nonprescription analgesics. There is also the need for public health education regarding the potential risks associated with these methods.

Keywords: Paracetamol; analgesics; opioids.

Publication types

  • Review

MeSH terms

  • Acetaminophen / administration & dosage*
  • Acetaminophen / adverse effects
  • Acetaminophen / chemistry
  • Administration, Oral
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / chemistry
  • Chemistry, Pharmaceutical
  • Codeine / administration & dosage*
  • Codeine / adverse effects
  • Codeine / chemistry
  • Drug Combinations
  • Humans
  • Injections, Intravenous
  • Opioid-Related Disorders* / epidemiology
  • Opioid-Related Disorders* / etiology
  • Solid Phase Extraction / methods*
  • Solubility
  • Water / chemistry


  • Analgesics, Opioid
  • Drug Combinations
  • acetaminophen, codeine drug combination
  • Water
  • Acetaminophen
  • Codeine