An average of seven people died every week from a drug overdose in 2017, according to a new report.
The Health Research Board says there were a total of 376 drug-related deaths due to poisoning in 2017.
Their data shows that cocktails of drugs contribute to three in five poisoning deaths.
Alcohol was a factor in a third of the cases, and it alone was responsible for 61 poisoning deaths.
Heroin contributed to 77 deaths, while cocaine-related poisoning deaths increased to 53 (compared to 42 in 2017).
Meanwhile, prescribale drugs were implicated in two out of every three overdoses - with benzodiazepines implicated in 139 deaths and methadone in 95 cases.
The figures also show there were 410 deaths as a result of medical causes or trauma among people who use drugs, with deaths due to hanging increasing from 98 in 2016 to 114 in 2017.
Speaking about the newly released figures, HRB researcher Ena Lynn said many people lose their lives after taking a combination of substances.
She explained: "We see that people taking cocktails of drugs contribute to three in five of our poison deaths in 2017.
"When we talk about a cocktail of drugs, we're talking about [for example] a person taking alcohol with opioids such as methadone or heroin."
Ms Lynn also suggested the increase in cocaine-related overdoses is linked to Ireland's improving financial situation.
She said: "We see it mirrors our economy in Ireland - we saw it peaking in 2007, followed by a decline.
"Unfortunately, similar to our economy, we've seen an increase in cocaine-related deaths since 2010."
