Disulfiram plus alcohol, even small amounts, produces flushing, throbbing in the head and neck, a throbbing headache, respiratory difficulty, nausea, copious vomiting, sweating, thirst, chest pain, palpitation, shortness of breath, hyperventilation, fast heart rate, low blood pressure, fainting, marked uneasiness, weakness, vertigo, blurred vision, and confusion.
When the dehydrogenase enzyme is inhibited, acetaldehyde builds up, causing unpleasant side effects (see Disulfiram-alcohol reaction).
The clinical use of disulfiram mimics the genetic predisposition to alcohol intolerance that is found in East Asian populations due to the mutation of the ALDH2 gene.
As acetaldehyde is one of the major causes of the symptoms of a hangover, this produces immediate and severe negative reaction to alcohol intake.
Symptoms usually include flushing of the skin, accelerated heart rate, low blood pressure, nausea, and vomiting.
Uncommon adverse events include shortness of breath, throbbing headache, visual disturbance, mental confusion, postural syncope, and circulatory collapse.
[medical citation needed] Although disulfiram remained the most common pharmaceutical treatment of alcohol abuse until the end of the 20th century, today it is often replaced or accompanied with newer drugs, primarily the combination of naltrexone and acamprosate, which directly attempt to address physiological processes in the brain associated with alcohol abuse.
[11] Less common side effects include decrease in libido, liver problems, skin rash, and nerve inflammation.
[20] By inhibiting ALDH, disulfiram prevents the inactivation and detoxification of acetaldehyde and thereby induces a variety of unpleasant symptoms when alcohol is consumed.
[22] DBH inhibition by disulfiram may explain its possible therapeutic benefits in cocaine dependence as well as cases of psychosis and mania associated with the drug.
In 1937, a plant physician in the American rubber industry described adverse reactions to alcohol in workers exposed to tetramethylthiuram monosulfide and disulfide, and proposed that this effect of disulfiram and related compounds might lead to ”the cure for alcoholism”; the effect was also noticed in workers at a Swedish rubber boot factory.
[24] Around that time, during the German occupation of Denmark, Erik Jacobsen and Jens Hald at the Danish drug company Medicinalco picked up on that research and began exploring the use of disulfiram to treat intestinal parasites.
[24][25]: 98–105 They made that discovery in 1945, and did nothing with it until two years later, when Jacobsen gave an impromptu talk and mentioned that work, which was discussed afterwards in newspapers at the time, leading them to further explore the use of the drug for that purpose.
[33] When disulfiram creates complexes with metals (dithiocarbamate complexes), it is a proteasome inhibitor and as of 2016 it had been studied in in vitro experiments, model animals, and small clinical trials as a possible treatment for liver metastasis, metastatic melanoma, glioblastoma, non-small cell lung cancer, and prostate cancer.