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December 04, 2001
Presented by Glen R. Hanson, D.D.S., Ph.D., Acting Director, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services
Presented to Senate Caucus on International Narcotics Control

Statement for the Record

Mr. Chairman and distinguished members of the Caucus, thank you for inviting the National Institute on Drug Abuse (NIDA) to participate in this important and timely hearing that focuses on a category of drugs commonly referred to as "club or rave drugs." I am Dr. Glen Hanson, the newly designated Acting Director of NIDA, and am pleased to be able to represent NIDA this afternoon.

As the world's largest supporter of research on the health aspects of drug abuse and addiction, I will share with you today what NIDA-supported research is telling us about club drugs particularly 3,4-methylenedioxymethamphetamine (MDMA). I will also discuss briefly what we know about other drugs, including methamphetamine, ketamine, rohypnol, and gamma hydroxybutyrate (GHB) that are also reportedly being used in rave, dance party, night club settings, and other social settings frequented by adolescents and young adults.

There is now substantial scientific evidence demonstrating that these drugs are not benign. In fact, studies conducted to date in both animals and more recently in humans overwhelmingly confirm that club drugs are not harmless "fun party drugs" as they are often portrayed. While users of "club drugs" often take some of these drugs for energy to keep on dancing or partying, research reveals these drugs can cause long-lasting negative effects on the brain altering memory and other behaviors. "Club drugs" include a group of diverse compounds that are capable of producing a range of unwanted effects, including hallucinations, hyperthermia, paranoia, amnesia, unconsciousness, and, in some cases, even death. When used with alcohol, these drugs can be even more harmful. We have also learned like most other drugs of abuse, the "club drugs" are rarely used alone. "Polydrug use" appears to be the norm, especially among young "club drug" or "rave drug" users. It is not uncommon for users to mix substances such as MDMA for example, with both alcohol and GHB or to "bump" and take sequential doses of a drug or drugs when the initial dose begins to fade. This is confirmed by both treatment admission reports and medical examiner reports. Also, drugs that are sold to individuals as "Ecstasy" tablets frequently contain not only MDMA, but other drugs or drug combinations that can be harmful. Because of these drug combinations, it is extremely challenging to anticipate with certainty all the potential medical consequences that can result from the use of these popular party drugs. However, despite, the challenges that confront us in studying such a diverse pharmacological group of drugs, we have learned a great deal about each one of the compounds.

Because of MDMA's increasing fascination both to young people and the popular media, and the fact that our research on the long-term effects of this drug is progressing at a rapid pace, I will discuss it first.

3,4-methylenedioxymethamphetamine, which is frequently referred to by the acronym, MDMA, and also known on the street as "Ecstasy," has both stimulant and hallucinogenic properties. While MDMA does not cause overt hallucinations, many people report distorted time and exaggerated sensory perception while under the influence of the drug. It also causes an amphetamine-like hyperactivity in people and laboratory animals and like other stimulants, it appears to have the ability to cause addiction. Use of MDMA increases heart rate, blood pressure and can disable the body's ability to regulate its own temperature. Because of its stimulant properties, when it is used in club or dance settings, it enables users to dance vigorously for extended periods, but can also lead to severe rises in body temperature, referred to as hyperthermia, as well as dehydration, hypertension, and even heart or kidney failure in particularly susceptible people.

MDMA is typically available in capsule or tablet form and is usually taken orally, although there are documented cases suggesting that more and more it is being administered by other routes, including injection and snorting. MDMA's acute effects typically last from three to six hours depending on the dosage, with the reported average dose of MDMA being consumed by a user being between one and two tablets, with each containing approximately 60-120 mg of MDMA. However, much higher doses of five tablets and greater are not unusual. MDMA appears to be well absorbed from the gastrointestinal tract, and peak levels are reached in about an hour.

MDMA works in the brain by increasing the activity levels of at least three neurotransmitters: serotonin, dopamine, and norepinephrine. Much like the way amphetamines work, MDMA causes these neurotransmitters to be released from their storage sites in neurons resulting in increased brain activity. Compared to the very potent stimulant, methamphetamine, MDMA causes greater serotonin release and somewhat lesser dopamine release. Serotonin is the neurotransmitter that plays an important role in regulation of mood, sleep, pain, emotion, appetite, and other behaviors. By releasing large amounts of serotonin and also interfering with its synthesis, MDMA causes the brain to become significantly depleted of this important neurotransmitter. As a result, it takes the human brain time to rebuild its serotonin levels. For people who take MDMA at moderate to high doses, depletion of serotonin may be long-term. These persistent deficits in serotonin are likely responsible for many of the long-lasting behavioral effects that the user experiences and what concerns us most about this drug.

There is also ample evidence to show that MDMA damages brain cells. We know that even one dose of MDMA (10 mg/kg in rats) has the ability to decrease serotonin levels for up to 2 weeks. Through the use of brain imaging technology, we can also see that human MDMA abusers may have fewer serotonin-producing neuronal processes in the brain than non-users. Despite what we have come to know about the detrimental consequences of this drug, there are increasing numbers of students and young adults who continue to use MDMA and other "club, rave or designer drugs" at increasingly higher doses. Several of our Nation's top monitoring mechanisms, including NIDA's long-standing national survey of drug use among 8th, 10th and 12th graders, Monitoring the Future (MTF), and our Community Epidemiology Work Group (CEWG), as well as findings from the Substance Abuse Mental Health Service Administration's (SAMHSA) National Household Survey on Drug Abuse, and the Drug Abuse Warning Network (DAWN) Survey, are reporting that the use of club drugs, particularly MDMA, is increasing in popularity among high school and college students. The most recent findings from SAMHSA's 2000 National Household Survey on Drug Abuse, which was released in October 2001, also shows an increase in MDMA use, with about 6.5 million people aged 12 or older reporting that they tried ecstasy at least once in their lifetime; up from 5.1 million lifetime users in 1999. NIDA's new MTF findings will be released later this month and will provide us with a better percentage of drug use trends among our Nation's youth, which in turn will help assist in developing better prevention approaches.

What the research is revealing about another drug used by some of our Nation's youth, gamma hydroxybutyrate (GHB), is equally disturbing. GHB is a central nervous system depressant (CNS) that is manufactured in clandestine labs and is typically sold in clear liquid in small bottles at night clubs or raves and is often added by the capful to beverages, particularly alcohol, and consumed orally. It is also available in capsule form. The onset of action is within 15 to 60 minutes and the effects typically last from 1-3 hours.

Although the predominant effects of GHB are sedative, GHB can produce a wide range of pharmacological effects depending on the dose. At lower doses GHB relieves anxiety and produces relaxation. However, as the dose increases, the sedative effects result in sleep and eventual coma or if the individual is left unattended, even death.

Overdoses tend to be more frequent with GHB than with other "club drugs," especially when used in combination with alcohol. Reported GHB-related emergency episodes in the U.S. have increased dramatically in recent years, from 56 in 1994 to 4,969 in 2000, according to SAMHSA's DAWN Survey. Some emergency room physicians are reporting a withdrawal syndrome that appears in patients who have self-administered the drug in a consistent dosing schedule (i.e. every 2 to 3 hours) for several months. The symptoms, which may include anxiety, restlessness, insomnia, rapid heartbeat, nausea, vomiting, may be alleviated under the proper medical supervision.

As our knowledge about the GHB and its use patterns evolve, so do the number of questions that need to be further explored. For example, we need to know more about the basic pharmacology of GHB; what the long-term consequences (e.g., tolerance, dependence, withdrawal) of using it are; who is using it; and most importantly, how to develop effective prevention and treatment strategies for it.

Another drug that I'll briefly focus on today is methamphetamine. Although methamphetamine is not often considered under the umbrella term of "club drugs," there continues to be populations that regularly abuse this powerfully addictive stimulant in the "club" scene.

Methamphetamine is a stimulant that has pronounced effects on the central nervous system. It can enter the bloodstream very quickly and can increase activity, decrease appetite, and cause a general sense of well-being. The effects of methamphetamine can last 6 to 8 hours. After the initial "rush," there is typically a state of high agitation that in some individuals can lead to violent and dangerous behavior. The long-term effects of this drug on the brain may be particularly damaging when taken at the high doses typically used by drug abusers. Methamphetamine has been shown in both laboratory animals and more recently humans, to be toxic to dopamine cells, meaning it can literally damage the nerve endings of human brain cells, resulting in cognitive impairments.

Methamphetamine is an inexpensive and highly addictive drug. Its heaviest use is in the Western states and in some rural areas elsewhere. While it remains the most common primary drug problem in Honolulu and San Diego, the drug does not appear to be generally increasing in popularity among young Americans throughout the country, although some indicators suggest pockets of increasing use in some cities.

We are attempting to develop more effective treatments for some of these addictions. For example, we will be starting a clinical trial of ondansetron (used to treat nausea and vomiting) in methamphetamine-dependent patients. This drug has some amphetamine-blocking properties in clinical pharmacology studies. Additionally, medications that have demonstrated some success in treating other ailments, such as bupropion, which is often used to treat depression, and selegiline, typically prescribed to treat Parkinson's disease, are currently being tested in Phase 1 clinical trials. Behavioral therapies also have shown promising results in treating patients who suffer from addiction to stimulants.

Ketamine is another drug that is used in rave or club settings. Ketamine is a rapid-acting general anaesthetic. It has sedative-hypnotic, analgesic, and hallucinogenic properties and is marketed in the United States and a number of foreign countries for use as a general anesthetic in both human and veterinary medical practice. Ketamine is similar to phencyclidine (PCP), although ketamine is more rapid in onset and less potent. Its effects typically last approximately an hour or less, with the overt hallucinatory effects also being short-acting. However, the user's senses, judgment and coordination can be affected for up to two days after initial use of the drug and reports show that even three days after ingestion ketamine users continue to show persistent memory impairment and elevated psychotic symptoms. There have been significant increases in ketamine-related emergency department visits reported in this country between 1994 and 2000, increasing from 19 to 263, according to SAMHSA's DAWN Survey.

Rohypnol is currently licensed overseas, but not in this country, as an anti-seizure drug. It is an extremely potent benzodiazepine and is typically sold as individually wrapped tablets that are colorless, odorless and tasteless when mixed in beverages and taken orally. Because of its ability to sedate and to cause amnesia, it has been used to diminish women's resistance to sexual assault, giving it the reputation of being associated with "date rape."

These are a few of the illicit drugs that are reportedly being used by some of our youth in social settings such as all night dance parties, raves or night clubs. NIDA will continue to monitor the constantly evolving patterns and trends of drug abuse. By supporting a comprehensive research portfolio, that includes basic research to prevention and treatment, NIDA is poised to utilize the power of science and its application to inform the public and policy makers about the harmful consequences of these drugs, making informed public health decisions possible. NIDA is already actively sharing the scientific findings about these drugs. For example, we teamed with "In the Mix," this past Spring to develop a television show on Ecstasy for their award-winning PBS series for teens. We also brought together the world's leading researchers this past summer to candidly discuss with over 500 participants the latest scientific findings on MDMA at the conference, "MDMA/Ecstasy Research: The Advances, Challenges, and Future Directions." We have and will continue to develop publications on all drugs of abuse, particularly those used in the rave culture to inform the public about these substances. We will also continue to make all of these materials available on our website. As new findings become available, we will be able to alert the public immediately through this and other venues.

Thank you for the opportunity to testify before this Caucus. I will be happy to respond to any questions you may have.