Review article: mechanisms and management of hepatotoxicity in ecstasy (MDMA) and amphetamine intoxications

Abstract

The social use of ecstasy (methylenedioxymethampheta-mine, MDMA) and amphetamines is widespread in the UK and Europe, and they are popularly considered as 'safe'. However, deaths have occurred and hepatotoxicity has featured in many cases of intoxication with amphetamine or its methylenedioxy analogues such as ecstasy. Recreational use of these drugs presents an important but often concealed cause of hepatitis or acute liver failure, particularly in young people. The patterns of liver damage and multiple putative mechanisms of injury are discussed. Recognition of the aetiological agent requires a high index of suspicion. Optimum management of the resultant liver damage, including the controversial role of liver transplantation for fulminant hepatic failure, is also discussed.

D-Amphetamine Toxicity in Freshly Isolated Rat Hepatocytes: A Possible Role of CYP3A

“…Beside the risk of developing tolerance and addiction, chronic abusers may experience neurotoxic effects (14) and hepatocellular damage (15). The latter has increasingly been reported in humans (16,17).…”

S(n)orting Out the Problem: Fever of Unknown Origin and Unexplained Abnormal Transaminases in a Young Male

“…Zonality and components of injury vary according to activity/modulation of cytochrome P450 enzymes [8][9], as was seen in our patient. The concomitant use of MDMA could have led to the absence of steatosis and more of portal-based and central venulitis with cholestatic injury, the latter seen more with MDMA [10]. Fever of unknown origin and unexplained elevated transaminases warrants an exhaustive history taking with focused dissection of drug history.…”

A mechanistic insight into 3,4-methylenedioxymethamphetamine (“ecstasy”)-mediated hepatotoxicity

“…Two suggested pathways that play a role in the onset of DILI are direct hepatotoxicity due to toxic metabolites and adverse immune responses. Beside the MDMA bioactivation, we described in the previous section that the evidence of MDMA-related idiosyncratic reactions has been observed in cases of severe liver damage, which could not be explained by the amount or the frequency of MDMA consumption (Jones and Simpson 1999;Schwab et al 1999). Since some drugs of abuse are known to possess immunomodulating properties (Friedman et al 2003), the immune system has also been suggested to be involved in MDMA-induced hepatotoxicity.…”

“…Hence, fatality cases have been described after consumption of one tablet, while up to 40-50 tablets on a single occasion did not cause mortality (Henry et al 1992;Parrott 2001). In addition, evidence of MDMA-related idiosyncratic drug reactions have been observed in the cases of severe liver damage, which stresses the importance of the liver as a major organ for detoxification of xenobiotics (Jones and Simpson 1999;Schwab et al 1999). Most likely, more cases of hepatotoxicity due to MDMA are subclinical and remain undetected.…”