Get smart with substances

Home»Health & treatment»Healthy living»Alcohol and other drugs»Get smart with substances
Post by Paul Kidd15 Feb 2004

Using recreational drugs has always been a risky business. For people living with HIV, combining them with antiretrovirals can bring negative consequences ranging from the merely inconvenient (the good time you were planning to have fails to materialise) to the utterly catastrophic (illness, a trip to the emergency room or even an untimely demise).

To avoid negative consequences, the best advice is, as always, not to use recreational drugs at all. But, that said, many positive people do use recreational substances at least occasionally, and being forewarned about the ways in which they might interact with antiretrovirals can be the key to staying out of trouble.

In a widely reported 1998 case, an HIV-positive gay man in the UK died after taking just a single dose of the popular party drug ecstasy. The 32-year-old man had been HIV-positive for three years and had taken ecstasy on numerous previous occasions without adverse effects, but had recently switched to an antiviral combination including the protease inhibitor ritonavir, which can slow down elimination of many drugs via the liver.

An autopsy of the man’s body found drug concentrations about ten times what would be expected for the amount of ecstasy he had taken.

The dead man’s partner lobbied the manufacturer of ritonavir, Abbott Pharmaceuticals, eventually leading to the inclusion of a inclusion of a warning about combining ritonavir and ecstasy in the patient information brochure for the drug.

Part of the difficulty of knowing about interactions between recreational and pharmaceutical drugs is that there is little concrete evidence on which to base our understanding. Research involving recreational drugs is ethically and legally problematic, and specific trials involving HIV antiretrovirals and recreational substances are very thin on the ground.

In a groundbreaking article (PDF) published in The Annals of Pharmacotherapy in October 2002, pharmacologists Tony Antoniou and Alice Lin-in Tseng performed a careful review of the available evidence about a wide range of legal and illegal substances, and used this to predict the likely effect of interactions between these drugs and HIV antiretrovirals. Much of the information in this article is based on that study.

Before we move on to the specific interactions for each type of substance, however, it’s worth mentioning first the plain, and perhaps challenging truth: all recreational drugs, whether legal or not, are likely to have a negative effect on your health if you’re HIV-positive. Taken in moderation and with forewarning about possible interactions, that negative effect can most likely be contained to a manageable level, but it cannot be eliminated completely.

We know that drug use among people with HIV in Australia, particularly gay men, is relatively high. In the HIV Futures 3 survey, more than a quarter of respondents had used ecstasy in the previous twelve months, around one in six had used speed, and more than half had used marijuana. Disturbingly, 6.9% of respondents said they had had a bad experience from mixing antiretroviral and illegal drugs, and 21.6% said they had missed one or more doses of their antiretrovirals as a consequence of using recreational drugs.

Remembering to take your antiretrovirals on time is perhaps the simplest and most effective form of harm reduction when using recreational drugs. Plan ahead and develop strategies to ensure you don’t miss doses. If your drug use is causing you to miss doses frequently, there’s a real risk that you could develop resistance to your treatments and your health could suffer enormously.

How drugs are metabolised

Almost all drugs (recreational or pharmaceutical) are slowly metabolised (broken down and removed from the bloodstream) by the liver. Inside the liver, a specific pathway called the CYP450 system is the usual way in which many drugs are metabolised.

Some antiretrovirals — most notably ritonavir but also the other protease inhibitors and the non-nucleoside drug delavirdine — inhibit (slow down) the operation of the CYP450 system. When this system is inhibited, and you take a drug which your body uses CYP450 to metabolise, the amount of the drug in your bloodstream increases, and the amount of time before your body eliminates that drug also increases.

This is a phenomenon that is used medically to our advantage when low-dose ritonavir is included with some antiviral combinations. Kaletra tablets, for example, contain a small amount of ritonavir which increases the effect of the main drug (lopinavir) and reduces the amount of lopinavir needed to fight HIV effectively.

Some other antiretrovirals work the other way — in inducing (speeding up) parts of the CYP450 system, and making the liver work harder. Just to make things especially confusing, many antiretrovirals inhibit some of the enzymes that make up CYP450 while inducing others.


Ecstasy (MDMA) is one of the most commonly used recreational drugs in our communities — 25.8% of Futures 3 respondents had used this drug in the previous year.

MDMA is an amphetamine-like drug which is removed from the body via the CYP450 pathway. While overdoses of MDMA are relatively rare, if they occur they can be fatal. There is also strong evidence that long-term ecstasy use can have toxic effects on the brain.

  • Combining ecstasy with ritonavir should definitely be avoided. Be aware that antiretroviral combinations containing low dose ritonavir are becoming more common. Kaletra contains ritonavir.
  • Combining ecstasy with other protease inhibitors, delavirdine or efavirenz has the potential to increase ecstasy levels in the bloodstream. Avoid if at all possible, or reduce the amount of ecstasy you take to one-quarter or one-half the usual dose.
  • Some studies have suggested that CD4 counts drop dramatically for a short period after ecstasy use. A UK report also suggested that people on antiretrovirals who take ecstasy may be at risk of developing anaemia.
  • If you do use ecstasy, take breaks from dancing, drink water (not alcohol) to avoid dehydration, and seek medical help quickly if you experience any negative effects.
  • Be aware that ecstasy tablets often contain drugs other than MDMA which could interact with HIV antivirals in unpredictable ways.


Amphetamine (‘speed’) and methamphetamine (‘crystal’, ‘ice’, ‘shabu’) are used for their euphoric and stimulant effects.

Like ecstasy, amphetamines are removed via the CYP450 system, meaning that people taking ritonavir, other PIs, delavirdine or efavirenz may be at risk of increased blood levels and/or overdose.

Additionally, there is widespread concern in Australia about increasing levels of unprotected sex among gay men using methamphetamine. Several US studies have found that methamphetamine users are more likely to have unprotected sex, and that HIV-positive gay men are more likely to use the drug than their HIV-negative counterparts.

  • Avoid using speed if you are taking ritonavir. If you’re taking other PIs, delavirdine or efavirenz, use less than the usual dose.
  • Be aware of the effect of speed on your inhibitions and maintain safe sex.
  • There is evidence of reduced survival among people with HIV who inject drugs, and the negative consequences of injecting are likely to be more significant among people with HIV. Don’t inject if possible, be careful to maintain safe injecting practice if you do.


GHB, sometimes called ‘liquid ecstasy’ or just ‘G’, has become increasingly popular in Australia over the last few years. In Futures 3, 4.2% of respondents had used this drug in the last year. GHB has been frequently in the news due to the narrow margin of safety between an effective dose and overdose, making it very easy to overdose and slip into a coma.

The precise mechanism by which GHB is removed from the body is not known, however it is believed that the primary route is via exhaled breath as carbon dioxide. It’s possible, however, that the CYP450 system has some role in metabolising this drug — taking GHB with some antiretrovirals could possibly result in increased GHBlevels.

There is at least one reported case of interaction between GHB and antiretrovirals. In 1999, a 29-year-old man, who was on ritonavir and saquinavir, developed symptoms of GHB overdose and lapsed into a coma after taking a small amount of GHB to counter the agitation he was still feeling after taking two ecstasy tablets 29 hours previously.

  • If you use GHB, reduce the amount you use if you are taking ritonavir, other PIs, delavirdine or efavirenz.
  • Never mix alcohol and GHB, drink plenty of water and take regular breaks from dancing. Never take GHB if you are alone.

Special K

Ketamine, ‘Special K’ or ‘K’ is a dissociative anaesthetic used recreationally for its psychedelic and amnesic effects.

  • There are no studies relating to interactions between ketamine and antiretrovirals, however as the drug is eliminated partially via the CYP450 system, it’s possible that ritonavir, nelfinavir and efavirenz could increase blood levels of ketamine.
  • There have been case reports in the US linking ritonavir and ketamine to acute inflammation of the liver (drug-induced hepatitis).
  • Ketamine also inhibits part of the CYP450 system itself, possibly leading to increased levels of some pharmaceutical drugs, especially if large quantities of ketamine are used. Ketamine should be avoided if you are taking the ulcer drugcisapride (Propulsid), or the antihistamines terfenadine (Teldane) or astemizole (Hismanal).


LSD, sometimes just called ‘a trip’, is a popular hallucinogenic drug. The Futures 3survey found that 8.5% of positive people said they had taken LSD in the previous 12 months.

The effective dose for LSD is extremely small, and the exact method by which it is eliminated from the body is unknown. It is possible that the CYP450 system plays a part, so interactions with antiretrovirals are possible, however there are no recorded cases of this occurring.


The prescription drug Viagra is widely used by people with HIV — 20.1% of theFutures 3 sample said they had used it, or another treatment for erectile dysfunction, in the previous year.

  • People taking ritonavir should not take more than 25mg of Viagra in a 24-hour period, as ritonavir increases blood levels of Viagra by up to 300%.
  • The anti-fungal drugs ketoconazole and itraconazole, and the antibiotic erythromycin can also increase Viagra blood levels
  • Viagra should not be combined with amyl nitrate. Using the two together can create a potentially serious drop in blood pressure, leading to headaches, dizziness, stroke or heart attack. The likelihood of this occurring is increased when taking drugs which increase Viagra blood levels.


Methadone is a long-acting synthetic opiate drug which is used in Australia as a treatment for heroin addiction.

Interactions between methadone and HIV antiretrovirals are common and extensively described in medical literature.

  • Most significantly, people on methadone maintenance who commence treatment with efavirenz or nevirapine are at risk of developing withdrawal symptoms, and may require an increase in the methadone dose.
  • Combining methadone with AZT can increase antiretroviral drug levels, possibly resulting in increased toxicities.
  • Combining methadone with delavirdine may result in increased methadone blood levels.
  • The protease inhibitors indinavir, nelfinavir, ritonavir or saquinavir may reduce methadone blood concentrations leading to withdrawal, and should be monitored carefully.


Marijuana is the single most commonly used illegal drug among people with HIV — 53.6% of respondents in Futures 3 said they had used the drug in the previous year. As well as its recreational use, many people with HIV/AIDS use marijuana as a complementary medicine to reduce nausea and improve appetite.

  • There are no known significant adverse interactions between marijuana and antiretrovirals, however marijuana users who are starting antiretroviral treatment may find that the effect of smoked marijuana is increased, especially with PI-containing combinations.
  • People taking efavirenz sometimes report that marijuana worsens the central nervous system (CNS) side effects (vivid dreams, agitation, sleep disturbances) of efavirenz. People on efavirenz can also falsely test positive for marijuana use on some drug tests.


Alcohol is the most commonly used recreational drug — 81.1% of Futures 3respondents said they drank alcohol.

Unlike most of the other drugs described in this article, alcohol is not metabolised via the CYP450 system, but by a completely different liver mechanism.

  • When taken together, alcohol and abacavir compete for the liver’s attention. In a clinical study, people who took alcohol in combination with abacavir had increased blood levels of abacavir, however the researchers did not think the increase was likely to lead to abacavir toxicities.
  • There is a theoretical possibility that alcohol could increase the rate at which protease inhibitors and non-nucleoside drugs are removed from the body, possibly leading to blood levels too low to control HIV, however no studies have been done to confirm this.
  • People who take ddI and who drink heavily are at increased risk of developing pancreatitis. Reduce or eliminate alcohol, or discuss switching combinations with your doctor.
  • People who drink alcohol more than three to four times per week are statistically less likely to achieve undetectable viral loads compared to non-drinkers, according to a US study.