Much Ado About Meth - The Body, Spring 2005

"Huge Sale! Buy Crystal, Get HIV Free." This was the text of a provocative ad that appeared on Verizon phone booths in the Chelsea neighborhood of New York City in January 2004. The ads were conceived and paid for by Peter Staley, a longtime AIDS activist and recovering crystal meth addict. Staley contends that the ads were meant to provoke discussion and, ultimately, action by others. This mission was accomplished, judging by the recent upswing in media attention focusing on the use of crystal meth (and its connections to HIV), the appearance of public service announcements by Gay Men's Health Crisis and other groups, and a slew of well-attended community forums focusing on the widely unacknowledged crystal meth problem in New York City.

What is all the fuss about? This article reviews much of what we do -- and don't -- know about crystal meth, including its relationship to HIV infection. There are few black-and-white conclusions, given that research into crystal meth and the negative effects it can have on individuals and public health is limited. It is hoped, however, that the increased attention now being placed on the potential dangers of crystal meth will yield the necessary information needed to curb the use and abuse of this drug.

Party Now, Pay Later
The ease with which crystal meth can be manufactured is a major contributing factor to the increase in its use. Law enforcement officials identify and close hundreds of clandestine methamphetamine labs each year. Large operations produce methamphetamine in Mexico and California. Outside of these areas, small rural laboratories are more common. Rural areas are popular sites for production because strong odors are produced in the process of "cooking" the drug, which can draw immediate attention to the manufacturing operation.

The manufacturing of crystal meth begins with large quantities of ephedrine or pseudophedrine, a chemical found in numerous over-the-counter cold medications. It is then cooked with a variety of other readily available substances, including red phosphorous, hydrochloric acid, drain cleaner, battery acid, lye, paint thinner, Freon, and/or antifreeze (every pound of crystal meth produced leaves behind five to six pounds of toxic waste). And because it is so easily and rapidly produced, it remains one of the cheapest drugs available.

With the manufacturing process completed, crystal meth is bagged and sold as shiny yellowish-white rocks of various sizes or as a crystalline powder resembling small fragments of glass. It can be ingested by snorting or smoking, or dissolved in water to be swallowed, inserted into the rectum ("booty bump"), or injected into muscle or a vein. On the street, it goes by a variety of names, including crystal, glass, crank, Tina, Crissy, and ice (in its rock form).

Upon being ingested, the drug rapidly and aggressively stimulates cells in the brain to produce high levels of dopamine, the "pleasure" neurotransmitter, and norepinephrine, the "alertness" neurotransmitter. The flood of these chemicals amplifies sensory perceptions and induces a long-lasting rush of euphoria, energy, elation, and confidence. However, what goes up must come down.

Six to eight hours after the drug is taken, the flood of dopamine and norepeniphrine in the brain dries up, leading to the inevitable "crash and burn." Energy levels drop and the feelings of joy, happiness, and pleasure are replaced with feelings of paranoia, anxiety, fatigue, aggression, and self-doubt. And the greater or longer the high, the greater the depletion of dopamine and norepinephrine levels afterwards.

With persistent use, natural dopamine production decreases, either because of permanent damage to dopamine-releasing terminals in the brain or because of physical dependence on the drug. In other words, life's basic pleasures -- watching an enjoyable movie, indulging in a gourmet meal, spending time with friends or a loved one, etc. -- will no longer trigger the natural dopamine production that our bodies depend on to interpret these experiences as rewarding.

Side effects of crystal meth don't end with the central nervous system. Other short-term effects, brought on through the release of norepinephrine, include: irregular, rapid heartbeat; elevated blood pressure; trouble sleeping; increased body temperature; and dehydration. What's more, there have been numerous anecdotal reports of methamphetamine use sending individuals to the hospital with heart attack symptoms and rhabdomyolosis (the rapid breakdown of muscle fibers resulting in the release of muscle fiber contents into the bloodstream, which can be highly toxic to the liver and kidneys).
Long-term use of crystal meth is associated with an increased risk of heart attacks, stroke, cardiomyopathy (swelling of the heart), and pulmonary hypertension (a buildup of pressure in the pulmonary artery). Periodontal disease and dental problems are also frequent among crystal meth users.

Crystal Meth and the Risk of HIV and STD Infections
While crystal meth users cite a number of different reasons for using the drug -- use among suburban teens, as well as students, professionals, and homemakers who work long hours isn't uncommon -- its use in the context of sexual activity has been of particular concern, especially among men who have sex with men (MSM). For many users, the biochemical effects of crystal meth dramatically reduce inhibitions while increasing sexual desire and feelings of invincibility, making it a powerful drug in terms of initiating, enhancing, and prolonging sexual activity. However, crystal meth intoxification is also associated with serious lapses of judgment.

Various research teams have documented that, when crystal meth is used in association with sexual activity, condoms are more likely to be abandoned, numerous sex partners are more likely to be had, and trauma to the lining of the anus is more likely to be experienced (which greatly increases the risk of HIV transmission). This has many community activists, public health officials, and healthcare providers very worried about the possibility of increased HIV and sexually transmitted infection among individuals using crystal meth as a component of sex.

Recent data collected by the Center for HIV/AIDS Education Studies and Training (CHEST) at New York University indicate that, in New York City, MSM who use crystal meth are three times more likely to contract HIV through receptive anal intercourse than MSM who do not use the drug. Moreover, the CHEST study found that, among gay or bisexual male "party drug" users, approximately 62% indicated significant and frequent use of crystal meth. This is an increase from the early 1990s when usage rates among gay and bisexual men ranged between 5% and 25%. CHEST also found that MSM who reported crystal meth use were diverse in terms of ethnicity, age, income, and HIV status; 45% of the samples were men of color, and half the men reported being HIV-positive. Researchers with the San Francisco Department of Public Health (SFDPH) have also found that MSM who used crystal and Viagra together were six times more likely to be diagnosed with syphilis than those who didn't use either drug. In another study from SFDPH, researchers found that 17.4% of 1,263 MSM who attended the city's public STD clinic had used crystal in the month before their visit. Those who used the drug were more than twice as likely as non-users to be HIV-positive, four times as likely to be diagnosed with syphilis, and almost twice as likely to test positive for gonorrhea.

Some experts argue that these numbers may only be the tip of the iceberg. Presently, most city and state departments of health do not routinely track crystal meth use among people newly infected with HIV, leading to an incomplete picture of the extent of the role of crystal meth use on HIV infection statistics. Organizations like the New York AIDS Coalition argue that, in order for community-based organizations and departments of public health to be able to provide effective prevention interventions to crystal meth-using populations, prevention experts must first gain a better understanding of who is using crystal meth and its prevalence among MSM and people infected with HIV.

Crystal Meth and HIV Disease Progression
A frequent concern is that crystal meth speeds up disease progression in people who are already infected with HIV. Does crystal meth have a negative effect on immune function? Does crystal meth increase viral load? The short answer to these questions is that we don't really know.
There haven't been any studies documenting the effects of crystal meth on immune function in HIV-positive people, most notably its effects on CD4 cell counts. Most studies completed to date have been test tube or rodent experiments. One test tube study published in 1994 suggested that methamphetamine can reduce interleukin-2 levels, a cytokine that promotes immune function in the body and plays a significant role in the immune system's response to HIV infection. It was also shown to decrease the function of CD8 cells, which play a role in the control of HIV replication, particularly during the early stages of infection. Another study involving retrovirus-infected rats, published in 2002, demonstrated a significant increase in tumor necrosis factor (TNF), an inflammatory cytokine that can negatively affect the immune system's response to HIV and increase viral replication. While these studies pave the way for further investigation, they do not conclusively answer whether crystal meth speeds up immune suppression in HIV-infected people.

As for the effect of crystal meth on viral load, one study published in 2003 in the Journal of Infectious Diseases (JID) compared HIV levels in HIV-positive individuals who were currently using meth to HIV-positive people no longer actively using the drug and HIV-positive people with no history of crystal meth use. Among those who weren't on any antiretroviral therapy, viral loads were similar among the three groups. In other words, HIV levels in the active crystal meth users were not significantly higher than the non-using individuals in the study. However, among those who were taking antiretroviral therapy during the study, the active crystal meth users had significantly higher viral loads than the non-using individuals. In simpler terms, active crystal meth users were significantly less likely to have undetectable viral loads in response to antiretroviral therapy than HIV-positive folks not using crystal meth.

This is a potential source of concern, given that a detectable viral load in someone on antiretroviral treatment is often a sign of drug resistance and treatment failure. Given the limitations of this study, it wasn't possible to determine why the active crystal meth users taking antiretroviral therapy had higher viral loads than the non-using study participants. However, two possible explanations were offered by the study authors: poor adherence and/or a negative interaction between the crystal meth and the antiretrovirals being taken.

Crystal Meth and Treatment Adherence
Studies have been extremely limited with respect to documenting adherence in HIV-infected individuals using crystal meth. However, there is no shortage of data from other studies evaluating the pill-taking habits of HIV-positive folks actively using other drugs and alcohol to know that adherence may be a problem among HIV-positive individuals actively using crystal meth. Common sense also dictates that a drug like crystal meth, a spontaneous and impulsive activity, doesn't mix well with antiretroviral medication adherence, which requires forethought and planning. The fact that crystal meth keeps individuals awake for long hours, away from food, provides a feeling of "liberation" from all responsibilities (to themselves and to others), and engaged in behavior that won't be conducive to stopping for regular medication dosing, may not exactly support the strict adherence needed to maintain the effectiveness of antiretroviral treatment.

One interesting adherence study, published in AIDS Care in 2003, surveyed 23 HIV-positive individuals in recovery for crystal meth addiction about their antiretroviral adherence practices while they were actively using. All 23 reported missing doses of their antiretroviral therapy. Approximately half of the survey volunteers reported taking "planned" breaks in therapy, defined as a conscious decision to stop medications while using crystal, either because it would interfere with their ability to enjoy whatever it was that they were doing while high or because they feared a negative drug interaction (with their antiretrovirals or other illicit drugs they were using). The other survey volunteers reported "unplanned" breaks in their therapy because their crystal meth use interfered with their ability to maintain a schedule, keep track of time, eat and drink regularly, and sleep.

Even though these 23 study participants did not take their medications according to prescribed directions, they did not interpret skipping, stretching, or modifying their medication doses as non-adherence. For some, these medication adjustments were viewed as a positive coping strategy to create a sense of control over their lives and activities while using crystal meth. Other study participants believed that if they caught up with missed doses by increasing their dosage for two or three days following a treatment interruption, they would still qualify as adherent.

Crystal Meth and Drug Interactions
It is possible that crystal meth does not mix well with some antiretroviral medications. All of the amphetamines -- including crystal meth and ecstasy (MDMA) -- are metabolized (broken down) by one of the liver enzymes responsible for metabolizing Norvir (ritonavir) and all three approved non-nucleoside reverse transcriptase inhibitors (Sustiva, Viramune, and Rescriptor). There have been a few case reports -- but no comprehensive studies -- involving individuals who died as a result of high blood concentrations of methamphetamine after taking ecstasy or crystal meth with one of these antiretrovirals. What we don't yet know is to what extent antiretrovirals affect methamphetamine drug levels, nor do we know to what extent methamphetamine affects antiretroviral drug levels in the body. If a decrease in antiretroviral drug levels occurs, this could translate into premature treatment failure, drug resistance, and disease progression.

Crystal Meth and HIV-Associated Dementia
One of the most significant concerns surrounding crystal meth use in HIV-positive people is the possibility of an increased risk of HIV-associated dementia (HAD). HAD normally occurs in approximately 20% to 35% of people with advanced HIV disease and is one of the few AIDS-related complications that can be caused by HIV itself (HIV can damage nerve cells in the brain, although researchers don't totally understand how this happens). Symptoms of HAD include slower reaction times, poorer decision-making abilities, and poorer performance on measures of memory, attention, and concentration -- many of the same problems seen in chronic crystal meth users.
Studies have demonstrated that HIV -- most notably its gp120 and Tat proteins -- can damage dopamine receptors in the brain. As discussed above, crystal meth can also have a profound effect on dopamine in the brain, which, some experts argue, could exacerbate or increase the risk of HAD as HIV disease progresses.

In a 2003 issue of the Journal of Acquired Immune Deficiency Syndromes, researchers found that methamphetamine users with advanced HIV infection had evidence of a specific type of brain damage not usually seen in HIV-infected patients with HAD: the loss of a specific group of neurons (nerve cells) and an increase in the number of glial cells (cells that repair damaged neurons).

It's also possible that crystal meth fuels HIV replication in the brain, leading to an increased likelihood of HAD and other neurological problems. There have been studies demonstrating that crystal meth can damage the walls of blood vessels in the head, allowing HIV to enter the brain much more easily. In a 2002 issue of the Journal of Neurovirology, researchers found that crystal meth increased replication of the feline version of HIV (FIV) five to fifteen times in test tubes containing astrocytes (a type of glial cell). However, in the 2003 JID article discussed above, HIV levels were not significantly higher in the cerebrospinal fluids (CSF) of HIV-infected individuals actively using crystal meth, compared to HIV levels in the CSF of their non-using HIV-infected counterparts.

Additional data from studies exploring the impact of crystal meth on the central nervous systems of HIV-positive people are just now beginning to surface.

Treatment of Crystal Meth Addiction
At the present time, there is no pharmacological treatment for crystal addiction, like methadone or buprenorphine for opiate (heroin) addiction. Anecdotal reports suggest that available psychotropic and anti-anxiety medications -- including Bupropion, Celexa, Ambien, Depakote, Zyprexa, and Riseperdal -- may be useful in terms of managing some of the psychiatric complications that frequently arise upon stopping crystal meth. However, the effectiveness of these medications for this purpose has not been evaluated in clinical trials. One pharmacological treatment currently being studied is Abilify (aripiprazole), approved for the treatment of schizophrenia. Abilify may reduce crystal meth cravings among individuals who are dependent on it.

The majority of crystal meth users end up seeking help through cognitive behavioral therapy (CBT) programs, motivational enhancement therapy (MET) programs, or 12-step programs like crystal meth anonymous (CMA). CBT programs usually involve a therapist or counselor, in one-on-one or group sessions, to help explore the causes, symptoms, and results of crystal meth use. CBT focuses on personal examinations of the events leading up to dependency on crystal meth. MET programs also involve a therapist or counselor and focus on a client's perceptions of his or her current drug-using behavior and the personal goals that he or she has for himself. Emphasis is placed on eliciting self-motivational statements of desire for and commitment to change.

CMA has become an increasingly popular approach to recovery by many crystal meth users (www.crystalmeth.org). Some choose to go the CMA route without other forms of intervention, while others use CMA to supplement other forms of addiction therapy. In short, CMA embraces a peer-support approach to recovery -- similar to the Alcoholics Anonymous (AA) model -- encouraging members to confront their addiction, surrender to a higher power, and empower themselves as a way of overcoming their addiction. Numerous CMA groups have sprouted up all over the United States, including groups focusing exclusively on gay and bisexual men and HIV-positive individuals.

Of course, recovery varies from person to person. The effects of withdrawal can linger for several weeks or months for casual users and years for chronic, heavy users. Sadly, the relapse rate is very high -- one of the highest relapse rates of any illicit drug addiction. But help is available and, as the saying goes, it's about taking things one day at a time.

Tim Horn is Executive Editor of The PRN Notebook, a quarterly publication for HIV-treating clinicians. He is also Senior Editor of AIDSmeds.com, an educational website for people living with HIV and AIDS.
This newsletter was provided by the AIDS Community Research Initiative of America (ACRIA).