Estimated Risks of MDMA use in People with Hepatitis C
Ilsa Jerome PhD , Research Specialist
Multidisciplinary Association for Psychedelic Studies (MAPS)
Caveat: Limitations of this Review
I am not a medical doctor nor am I well-versed in hepatology (study of the liver). My job includes reviewing the published, peer-reviewed scientific literature on MDMA. For comprehensive reviews, see mdma/protocol/litreview.html. My doctorate is in social psychology and my expertise is in MDMA, not hepatitis C. Hence I am forced to take information I receive concerning hepatitis C and its drugs far less critically than information on MDMA. The information below was reviewed with respect to general accuracy by a medical doctor familiar with MDMA research.
“Ecstasy” in this report refers to material represented as MDMA. MDMA refers to 3,4-methylenedioxymethamphetamine.
No Reports concerning MDMA/ecstasy and hepatitis C
A search of the NIH-maintained database PubMed (www.pubmed.gov) failed to produce any results directly pertaining to effects relating to either “ecstasy” or “MDMA” and hepatitis C. The search did located a number of reports or reviews, but their chief concerns were demographics of drug users or people with hepatitis C or causes of liver disease (Breen et al. 2006; Brncic et al. 2006; White et al. 2006). This does not mean that MDMA does not have any specific beneficial or deleterious effects on people with hepatitis C, but that no one has written any published reports on the matter.
An account provided by an individual who has had hepatitis C for 25 years suggests that his use of MDMA, at a frequency of about 3-4 times a year for about 15 years, did not produce any unusual or unexpected effects in this person. He also reported tracking the liver enzyme alanine aminotransferase, or ALT, before and after use, and did not detect any significant changes. The individual did not report worsening of symptoms of hepatitis C. However, like a small but notable minority of people in controlled studies, this person reported sometimes experiencing a period of low mood or depression a few days after ecstasy use.
Potential concerns for people with hepatitis C
There are five points of concern in relation to MDMA and hepatitis C. Perhaps the most significant issue concerns the identity and purity of illicit “ecstasy” tablets or powders. Beyond this crucial matter, there are issues pertaining to MDMA, to treatments for hepatitis C and to indirect effects of MDMA and their potential effects on people with hepatitis C. Two of these additional points concern the possibility of direct interactions between MDMA and the liver, one relates to the potential for interactions between MDMA and drugs or herbs used to treat hepatitis C, and the last point concerns indirect effects of MDMA that may be relevant to people with hepatitis C.
Is it MDMA?
Both inside and beyond the US, MDMA is placed amongst the most tightly regulated substances, meaning that it is prohibited to possess or sell except within the case of permitted research. Outside of the few controlled research studies employing MDMA, individuals will not know for certain if they are ingesting MDMA or some other drug. Investigations of the purity and identity of ecstasy over the years reported a great deal of variability in the degree of adulteration within ecstasy tablets, but most studies noted that a sizable minority of street ecstasy tablets either contained MDMA and substances other than MDMA or consisted entirely of substances that were not MDMA (Baggott et al. 2000; Cole et al. 2002; Kalasinsky et al. 2004; Parrott 2004; Tanner-Smith 2006). These substances are varied, from stimulants such as caffeine and methamphetamine to dissociatives, as dextromethorphan, as well as relatively obscure psychedelic drugs. All the issues listed below assume that an individual has consumed MDMA. As well, dose ranged from a threshold dose of 25 mg to a large dose of 150 mg MDMA, Taken together, this means that people with hepatitis C who take “ecstasy” may face problems or issues from other drugs, and that MDMA dosage can vary widely even within ecstasy that does contain MDMA only.
MDMA effects on the liver
Reviews of MDMA, including reviews presented on the MAPS website, note that hepatotoxicity can arise from ecstasy use. Within the very small percentage of individuals experiencing serious adverse events after ecstasy use, liver disease or liver damage (hepatotoxicity) is one of the most relatively common events of this sort, following hyperthermia and psychiatric and psychological problems (Andreu et al. 1998; Baggott et al. 2001; Cole and Sumnall 2003a; b; Liechti et al. 2005). One source of hepatotoxicity occurs from hyperthermia and can be very severe and even fatal (Caballero et al. 2002). The other is transient liver disease with an unknown etiology but that is likely a form of immunological or idiosyncratic reaction to MDMA or another substance in illicit ecstasy. As symptoms stop when people abstain from ecstasy and re-appear upon use, the hypothesized explanations above seem to be a likely cause (Hall and Henry 2006). There is no evidence that people with hepatitis C would be either more or less affected by either condition.
Researchers have studied the effects of MDMA on rodent liver tissue “in vitro” (meaning outside the body), and found that very large doses of MDMA could damage or kill liver cells (Beitia et al. 2000; Carvalho et al. 2002; Varela-Rey et al. 1999). This may occur through oxidative stress. These studies uses doses of MDMA up to 11 times those seen in humans, so it is unlikely that these effects occur after typical human doses of MDMA. However, since at least one review indicated that the hepatitis C virus also may generate oxidative stress (Farinati et al. 2007), people should be aware that they may be adding another oxidative stressor into their bodies when taking ecstasy/MDMA.
MDMA and drugs or treatments for hepatitis C
Several drugs and herbs are listed as being used to treat hepatitis C or its associated symptoms. These include combination therapy with interferon alpha and ribavirin, various protease inhibitors, and the complementary treatments of licorice root and milk thistle (CDC 2008; NCCAM 2008a).
MDMA is metabolized via the liver through several CYP450 enzymes, including CYP2D6, CYP1A2 and CYP3A4 (de la Torre et al. 2004; Kreth et al. 2000; Maurer et al. 2000). Monoamine oxidase and catechol-O-methyltransferase (COMT) also metabolize MDMA. Hence any medication or herb metabolized by these enzymes could interfere with or alter metabolism of MDMA, and vise versa. MDMA also increases heart rate and blood pressure, and it may increase release of the neurohormones oxytocin and vasopressin, which regulate blood salt and water as well as playing a role in affiliation or social bonding in mammals (Harris et al. 2002; Liechti et al. 2001; Mas et al. 1999; Tancer and Johanson 2003; Wolff et al. 2006). Like a number of other psychoactive drugs, MDMA has transient immunological effects (more details below).
Ribavirin does not seem to be metabolized via any of these enzymes, but milk thistle may be metabolized via unnamed CYP450 enzymes (Glue 1999). I have found an indication that interferon alpha, at least used in cancer patients, may interfere with clearance of some drugs, though specifics are not given (Israel et al. 1993).
Licorice root, used as a complementary treatment, can increase blood pressure at high doses (NCCAM 2008b). People using licorice may want to be cautious in combining two substances that can elevate blood pressure.
Side effects of interferon alpha can include, amongst other things, flu-like symptoms at the start of treatment and can involve fatigue, depression, impaired cognition or concentration and moodiness. These side effects are notable because they are similar to side effects some people report one to three days after MDMA (Baggott et al. 2001; Hoshi et al. 2004; Huxster et al. 2006; Vollenweider et al. 1998). Hence people who are taking combination treatment with ribavirin and interferon alpha may amplify these effects a few days after the MDMA. On the other hand, if the side effects are the result of effects of interferon alpha on cytokines, special immune-system regulating proteins, it is possible that MDMA use will reduce these effects for a few days (Pacifici et al. 2004; Pacifici et al. 2001b).
More generally, it is possible that any drug, herb or other medical treatment that affects the metabolic pathways above could be affected by MDMA or could affect MDMA metabolism. Other drugs or treatments might amplify, attenuate or alter specific effects of MDMA. Liver disease and MDMA metabolism
Because MDMA is metabolized by the liver, any condition that compromises the liver may impair or alter MDMA metabolism. This could mean that a person with liver damage could have higher levels of ecstasy/MDMA than would a person without liver damage.
There is a large literature on the potential relevance of specific MDMA metabolites, and MDMA metabolism in general, on the neurotoxic potential of MDMA (de la Torre and Farre 2004; Green et al. 2003; Maurer et al. 2004). It is far from certain whether any of the findings in rodents relate directly to humans, and so it is not clear whether less or more metabolism fosters or hinders oxidative stress from a typical dose of ecstasy/MDMA, and so as of now, it cannot be stated whether inefficient metabolism produces more or less risk of oxidative stress. However, higher blood MDMA levels will increase psychological and physiological effects listed above.
Indirect effects of MDMA on hepatitis C
MDMA has a number of systemic and physiological effects in humans. These include elevation in blood pressure and heart rate, described above, and a slight increase in body temperature. MDMA produces a number of side effects, including tight jaw or jaw clenching, loss of appetite, impaired concentration, and impaired gait or balance as well as other odd sensations (parasthesias) during the duration of drug effects, and a smaller number of people report fatigue the next day (Baggott et al. 2001; Liechti et al. 2001). MDMA also produces transient effects on the immune system (Pacifici et al. 2004; Pacifici et al. 2000; Pacifici et al. 1999; Pacifici et al. 2002). Such transient immunological effects are not unique to MDMA and apparently occur after substances as diverse as ethanol and cocaine. The immunological effects of MDMA are generally immunosuppressive and anti-inflammatory. It reduces some proinflammatory cytokines, as interleukin1, and increases some anti-inflammatory ones, as interleukin-10 (Connor et al. 2005; Pacifici et al. 2001a). MDMA also elevates natural killer (NK) cells. These effects last from up to 24 to 48 hours. To date no studies have clarified whether MDMA increases vulnerability to infection or reduces inflammation in people or nonhuman animals, but either or both effects are possible. Given the information that I have about hepatitis C, the role of the immune system in this disease is complex. The immune system may be playing role of “hero” and “villain,” staving off the virus but also causing or exacerbating some of the liver damage in its attempt to protect the body (Guidotti and Chisari 2006). However, if an individual is concerned about increased vulnerability to infection or if he or she is on a medication that is a known immunosuppressant, he or she may want to consider the additional immunological effects of MDMA.
People interested in questions concerning the effects of MDMA on people with hepatitis C may wish to conduct web searches, as with Google or other search engines to look up further information on specific treatments for hepatitis C and their metabolism. There are also governmental sites, as the Centers for Disease Control (http://www.cdc.gov) and the National Center for Complementary and Alternative Medicine (http://nccam.nih.gov) that can contain information about hepatitis C and any treatments for this condition. If an individual has a comfortable relationship with his or her physician, broaching the topic of possible effects from MDMA might be worthwhile. However, it is likely that liver specialists will be as uninformed about MDMA as I am about liver ailments.
Seeking Personal Reports
If anyone wishes to provide any further information on MDMA/ecstasy use and hepatitis C, including personal experiences, these can be posted to Ilsa@maps.org. If wishing to remain anonymous and concerned about email or internet security, consider posting to a site like Erowid.org (www.erowid.org) that archives and maintains libraries of experiences with psychoactive plants and chemicals, or use remailers or anonymizing email services.
I thank one reviewer for insight and guidance toward verifying information first seen in Wikipedia and another correspondent for providing me with initial information on some treatments and issues for people with hepatitis C.
- Andreu V, Mas A, Bruguera M, Salmeron JM, Moreno V, Nogue S, Rodes J (1998) Ecstasy: a common cause of severe acute hepatotoxicity. J Hepatol 29: 394-7
- Baggott M, Heifets B, Jones RT, Mendelson J, Sferios E, Zehnder J (2000) Chemical analysis of ecstasy pills. Jama 284: 2190
- Baggott M, Jerome L, Stuart R (2001) 3,4-Methylenedioxymethamphetamine (MDMA); A review of the English-language scientific and medical literature Original Investigator’s Brochure for MDMA. Multidiscplinary Association for Psychedelic Studies
- Beitia G, Cobreros A, Sainz L, Cenarruzabeitia E (2000) Ecstasy-induced toxicity in rat liver. Liver 20: 8-15
- Breen C, Degenhardt L, Kinner S, Bruno R, Jenkinson R, Matthews A, Newman J (2006) Alcohol use and risk taking among regular ecstasy users. Subst Use Misuse 41: 1095-109
- Brncic N, Kraus I, Viskovic I, Mijandrusic-Sincic B, Vlahovic-Palcevski V (2006) 3,4-methylenedioxymethamphetamine (MDMA): an important cause of acute hepatitis. Med Sci Monit 12: CS107-9
- Caballero F, Lopez-Navidad A, Cotorruelo J, Txoperena G (2002) Ecstasy-induced brain death and acute hepatocellular failure: multiorgan donor and liver transplantation. Transplantation 74: 532-7
- Carvalho M, Carvalho F, Remiao F, de Lourdes Pereira M, Pires-Das-Neves R, de Lourdes Bastos M (2002) Effect of 3,4-methylenedioxymethamphetamine (“ecstasy”) on body temperature and liver antioxidant status in mice: influence of ambient temperature. Arch Toxicol 76: 166-72.
- CDC (2008) Hepatitis C Frequently Asked Questions. Accesssed March 30, 2008. Centers for Disease Control: http://www.cdc.gov/ncidod/diseases/hepatitis/c/faq.htm
- Cole JC, Bailey M, Sumnall HR, Wagstaff GF, King LA (2002) The content of ecstasy tablets: implications for the study of their long-term effects. Addiction 97: 1531-6
- Cole JC, Sumnall HR (2003a) Altered states: the clinical effects of Ecstasy. Pharmacol Ther 98: 35-58
- Cole JC, Sumnall HR (2003b) The pre-clinical behavioural pharmacology of 3,4-methylenedioxymethamphetamine (MDMA). Neurosci Biobehav Rev 27: 199-217
- Connor TJ, Harkin A, Kelly JP (2005) Methylenedioxymethamphetamine suppresses production of the proinflammatory cytokine tumor necrosis factor-alpha independent of a beta-adrenoceptor-mediated increase in interleukin-10. J Pharmacol Exp Ther 312: 134-43
- de la Torre R, Farre M (2004) Neurotoxicity of MDMA (ecstasy): the limitations of scaling from animals to humans. Trends Pharmacol Sci 25: 505-8
- de la Torre R, Farre M, Roset PN, Pizarro N, Abanades S, Segura M, Segura J, Cami J (2004) Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition. Ther Drug Monit 26: 137-44
- Farinati F, Cardin R, Bortolami M, Burra P, Russo FP, Rugge M, Guido M, Sergio A, Naccarato R (2007) Hepatitis C virus: from oxygen free radicals to hepatocellular carcinoma. J Viral Hepat 14: 821-9
- Glue P (1999) The clinical pharmacology of ribavirin. Semin Liver Dis 19 Suppl 1: 17-24
- Green AR, Mechan AO, Elliott JM, O’Shea E, Colado MI (2003) The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). Pharmacol Rev 55: 463-508
- Guidotti LG, Chisari FV (2006) Immunobiology and pathogenesis of viral hepatitis. Annu Rev Pathol 1: 23-61
- Hall AP, Henry JA (2006) Acute toxic effects of ‘Ecstasy’ (MDMA) and related compounds: overview of pathophysiology and clinical management. Br J Anaesth 96: 678-85
- Harris DS, Baggott M, Mendelson JH, Mendelson JE, Jones RT (2002) Subjective and hormonal effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology (Berl) 162: 396-405
- Hoshi R, Bisla J, Curran HV (2004) The acute and sub-acute effects of ‘ecstasy’ (MDMA) on processing of facial expressions: preliminary findings. Drug Alcohol Depend 76: 297-304
- Huxster JK, Pirona A, Morgan MJ (2006) The sub-acute effects of recreational ecstasy (MDMA) use: a controlled study in humans. J Psychopharmacol 20: 281-90
- Israel BC, Blouin RA, McIntyre W, Shedlofsky SI (1993) Effects of interferon-alpha monotherapy on hepatic drug metabolism in cancer patients. Br J Clin Pharmacol 36: 229-35
- Kalasinsky KS, Hugel J, Kish SJ (2004) Use of MDA (the “love drug”) and methamphetamine in Toronto by unsuspecting users of ecstasy (MDMA). J Forensic Sci 49: 1106-12
- Kreth K, Kovar K, Schwab M, Zanger UM (2000) Identification of the human cytochromes P450 involved in the oxidative metabolism of “Ecstasy”-related designer drugs. Biochem Pharmacol 59: 1563-71
- Liechti ME, Gamma A, Vollenweider FX (2001) Gender differences in the subjective effects of MDMA. Psychopharmacology (Berl) 154: 161-8
- Liechti ME, Kunz I, Kupferschmidt H (2005) Acute medical problems due to Ecstasy use. Case-series of emergency department visits. Swiss Med Wkly 135: 652-7
- Mas M, Farre M, de la Torre R, Roset PN, Ortuno J, Segura J, Cami J (1999) Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans. J Pharmacol Exp Ther 290: 136-45
- Maurer HH, Bickeboeller-Friedrich J, Kraemer T, Peters FT (2000) Toxicokinetics and analytical toxicology of amphetamine-derived designer drugs (‘Ecstasy’). Toxicol Lett 112-113: 133-42
- Maurer HH, Kraemer T, Springer D, Staack RF (2004) Chemistry, pharmacology, toxicology, and hepatic metabolism of designer drugs of the amphetamine (ecstasy), piperazine, and pyrrolidinophenone types: a synopsis. Ther Drug Monit 26: 127-31
- NCCAM (2008a) Hepatits C and Complementary and Alternative Medicine. Accessed April 1, 2008. National Center for Complementary and Alternative Medicine: http://nccam.nih.gov/health/hepatitisc/”
- NCCAM (2008b) Licorice Root. Accessed March 30, 2008. National Center for Complementary and Alternative Medicine: http://nccam.nih.gov/health/licoriceroot/
- Pacifici R, Pichini S, Zuccaro P, Farre M, Segura M, Ortuno J, Di Carlo S, Bacosi A, Roset PN, Segura J, de la Torre R (2004) Paroxetine inhibits acute effects of 3,4-methylenedioxymethamphetamine on the immune system in humans. J Pharmacol Exp Ther 309: 285-92
- Pacifici R, Zuccaro P, Farre M, Pichini S, Di Carlo S, Roset PN, Lopez CH, Ortuno J, Segura J, Cami J, de la Torre R (2000) Immunomodulating activity of MDMA. Ann N Y Acad Sci 914: 215-24
- Pacifici R, Zuccaro P, Farre M, Pichini S, Di Carlo S, Roset PN, Ortuno J, Pujadas M, Bacosi A, Menoyo E, Segura J, de la Torre R (2001a) Effects of repeated doses of MDMA (“ecstasy”) on cell-mediated immune response in humans. Life Sci 69: 2931-41
- Pacifici R, Zuccaro P, Farre M, Pichini S, Di Carlo S, Roset PN, Ortuno J, Segura J, de la Torre R (1999) Immunomodulating properties of MDMA alone and in combination with alcohol: a pilot study. Life Sci 65: PL309-16
- Pacifici R, Zuccaro P, Farre M, Pichini S, Di Carlo S, Roset PN, Palmi I, Ortuno J, Menoyo E, Segura J, de la Torre R (2002) Cell-mediated immune response in MDMA users after repeated dose administration: studies in controlled versus noncontrolled settings. Ann N Y Acad Sci 965: 421-33
- Pacifici R, Zuccaro P, Hernandez Lopez C, Pichini S, Di Carlo S, Farre M, Roset PN, Ortuno J, Segura J, Torre RL (2001b) Acute effects of 3,4-methylenedioxymethamphetamine alone and in combination with ethanol on the immune system in humans. J Pharmacol Exp Ther 296: 207-15
- Parrott AC (2004) Is ecstasy MDMA? A review of the proportion of ecstasy tablets containing MDMA, their dosage levels, and the changing perceptions of purity. Psychopharmacology (Berl) 173: 234-41
- Tancer M, Johanson CE (2003) Reinforcing, subjective, and physiological effects of MDMA in humans: a comparison with d-amphetamine and mCPP. Drug Alcohol Depend 72: 33-44
- Tanner-Smith EE (2006) Pharmacological content of tablets sold as “ecstasy”: results from an online testing service. Drug Alcohol Depend 83: 247-54
- Varela-Rey M, Montiel-Duarte C, Beitia G, Cenarruzabeitia E, Iraburu MJ (1999) 3,4-methylenedioxymethamphetamine (“Ecstasy”) stimulates the expression of alpha1(I) procollagen mRNA in hepatic stellate cells. Biochem Biophys Res Commun 259: 678-82
- Vollenweider FX, Gamma A, Liechti M, Huber T (1998) Psychological and cardiovascular effects and short-term sequelae of MDMA (“ecstasy”) in MDMA-naive healthy volunteers. Neuropsychopharmacology 19: 241-51
- White B, Day C, Degenhardt L, Kinner S, Fry C, Bruno R, Johnston J (2006) Prevalence of injecting drug use and associated risk behavior among regular ecstasy users in Australia. Drug Alcohol Depend 83: 210-7
- Wolff K, Tsapakis EM, Winstock AR, Hartley D, Holt D, Forsling ML, Aitchison KJ (2006) Vasopressin and oxytocin secretion in response to the consumption of ecstasy in a clubbing population. J Psychopharmacol 20: 400-10
The list of articles and information on potential risks of MDMA now includes a report of estimated risk of MDMA in people with hepatitis C. While there is nothing in the medical literature on the topic, this report draws on information about MDMA, heptatitis C, and drugs used to treat it.