The synthesis of MDMA is analogous to that of MDA, requires no elaborate apparatus or sophisticated techniques, and can be made from readily available materials. Recently, MDMA has received considerable attention from the media, which report that MDMA, known on the street as "Ecstasy" or "Adam," is widely used as a euphoriant among college students and to some extent by physicians as an adjunct to psychotherapy. These therapeutic applications have been carried out in humans in the absence of FDA approval or appropriate preclinical toxicity studies in animals.

The adverse health effects of amphetamines such as MDA have been known for years. One recent survey of relevant research describes studies which show that a single dose of MDA can selectively destroy serotonergic nerve terminals in the brains of a variety of animal species. More recently it has been shown that MDMA causes the same type of neuronal damage at even lower doses. The serotonergic system which is also present in man plays a role in regulating sleep, mood, sexual activity, and sensitivity to aversive stimuli. It should be noted that the doses producing MDA neurotoxicity are very close to those producing amphetamine-like and LSD-like subjective effects. This suggests that, in order to produce significant psychological effects, humans may very well be exposing themselves to neurotoxic doses of these compounds.

Because of the neurotoxic effects of structurally related compounds, an effort to place MDMA in Schedule I of the CSA was initiated on July 27, 1984. The DEA has hastened the scheduling process by placing MDMA into Schedule I on an emergency basis after receiving new reports of its widespread abuse and possible neurotoxicity.

Subsequent to the scheduling of MDMA in July of 1985, another analog appeared which was identified as 3,4-methylenedioxy-N-ethylamphetamine (MDE). Street reports indicate similar psychopharmacological effects to those reported for MDMA.

THE FEDERAL RESPONSE

In order to respond adequately to the designer drug problem, Federal law enforcement and health agencies have taken positive steps over the past several years. The overall response to the problem involves actions taken by the Department of Justice, chiefly the Drug Enforcement Administration, and several agencies of the Public Health Service in the Department of Health and Human Services. I would like to tell you what has been accomplished by the agencies of the Public Health Service.

As you know, the Public Health Service conducts health research programs and provides information and technical assistance to States on numerous health related problems. PHS efforts have been important in understanding the synthetic analog problem, and I would like to highlight specifically actions that have been taken.

One of the most important contributions of the PHS was the early identification of MPTP and the development of the animal model for Parkinson's disease. These scientific findings not only illuminated the

dangers of clandestinely produced drugs, they also provided researchers investigating Parkinson's disease with a long-needed animal model of the disease's process. Since 1982, numerous PHS sponsored research studies have begun to examine the process by which brain cells are selectively attacked and destroyed by MPTP and other substances. Last year, the Public Health Service sponsored a two-day symposium on MPTP in Bethesda, Maryland where scientists from several countries presented findings on the toxicity, clinical pathology, and epidemiology of MPTP. Other research into MPTP, and synthetic analogs in general, has been initiated.

Investigations of the nature and extent of MPTP first used in California were conducted through an interagency agreement between NIDA and CDC. In January 1985, NIDA and CDC began to interview and locate persons who may have used MPPP and MPTP. Preliminary results from the study, conducted at the request of the State of California, suggest several hundred persons may been exposed to meperidine in California based on reported symptoms similar to those reported by known users of the drug.

NIDA continues to support research projects seeking to understand basic mechanisms of action of these new synthetic analogs. In order to provide controlled substances analogs to researchers for this purpose, NIDA is synthesizing these compounds and distributing them to research laboratories for chemical and pharmacologic evaluation. In 1985, NIDA produced large quantities of MDMA and MDE in order to study its abuse liability in animal models. The production of 3-methylfentanyl was carried out in June 1985 to provide DEA with an authentic sample of this recently controlled substance. Since October 1985, NIDA has prepared 15 fentanyl and meperidine analogs including MPPP and PEPAP, and the synthesis of an additional five are either in process or have been planned for the next few months. Five of the 15 have already been tested by NIDA for abuse liability and the remaining compounds will be tested by November. These tests indicate that the potency of some of these compounds is up to 600 times that of morphine. Additionally, NIDA has been actively soliciting, through the regular and small business grant programs, analytical methods for the detection of these drugs in human biological fluids.

PHS activities have not been limited to research. NIDA notified the drug abuse treatment and prevention community nationwide of the dangers of MPTP. Together with the National Institute on Mental Health (NIMH), NIDA prepared a report on MPTP for publication in the Morbidity and Mortality Weekly Report (MMWR). This CDC published report, which reaches a national audience of physicians, served as the basis for an article later published in the Journal of the American Medical Association, where the information reached an even wider audience. NIDA has engaged in extensive networking with State treatment programs, community-based drug abuse prevention and treatment programs, parents groups, including the National Federation of Parents for Drug Free Youth, interdisciplinary conferences involving education, law enforcement, parents, and health profession groups, and other national prevention networks.

In carrying out this responsibility, the Institute shared information with regard to the dangers associated with designer drugs through publication of

materials in the NIDA Notes, the ADAMHA News, and the publication and dissemination of a NIDA News Capsule. The Notes are mailed to all drug abuse treatment programs, prevention programs, State agency directors, and State prevention coordinators; while the News Capsules are shared with the press and policymaking officials in the drug abuse area.

Data on the extent of abuse and the adverse health consequences of drugs are needed to schedule substances under the CSA. The controlled substances analogs, however, are extremely difficult to track through existing drug abuse data systems operated by NIDA. Not only are the substances so closely related chemically to a parent compound thus creating identification problems but, as in the case of the fentanyl analogs, toxic doses are often so small that they are easily overlooked by routine laboratory analysis. As a result, data collected from hospital emergency rooms and medical examiners across the nation and reported to NIDA's Drug Abuse Warning Network do not provide a valid measure of the designer drug problem in this country. Data also can be gathered through special epidemiologic studies such as the collaborative project with CDC and through NIDA's Community Epidemiology Work Group (CEWG). In its most recent semi-annual meeting held in December 1985, CEWG members reported that the fentanyl compounds continue to be a severe problem in southern California, and that some 704 grams of Fentanyl were confiscated by law enforcement agencies in 1985. In San Diego, 24 fentanyl-related deaths have been reported since mid-1982, with 10 deaths occurring during 1984 and 4 more deaths in 1985. Fentanyl-like compounds are being sold as heroin in the street, but only from select dealers. Indications that fentanyl analogs are available in other areas of the country, including New York and Atlanta, were also noted by CEWG members. Several preliminary reports from the CEWG also suggest that meperidine analogs may have become available in other parts of the country outside California, including Detroit and Florida. Efforts of PHS agencies to further understand the health implications of the synthetic analog problem will continue to include epidemiologic studies, research investigations, synthesis and distribution of compounds, and knowledge dissemination activities.

Before closing my remarks, I would like to stress that synthetic analogs do present a serious hazard to those who use them, but that the use of these substances has so far been confined to relatively few areas of the country. Certainly, as of now, the synthetic analogs I have discussed today have not begun to present problems as widespread as those posed by marijuana, cocaine, or heroin. Yet, as we have seen, many of these drugs lack any known health benefit and are indeed causing very severe adverse health consequences.

We must exercise our options for controlling these substances, including the emergency scheduling authority which can be used to place them under the CSA. Because current laws are not adequate for addressing the unique problems of designer drug manufacture and distribution, PHS staff has worked with the DEA to formulate the legislation which is now under consideration in the House. In developing this proposal, we were careful to avoid inhibiting research or interfering with the legitimate manufacture of drugs by focusing upon the intent of manufacturing the drug. If the intent of manufacture is for legitimate scientific purposes and not for sale to humans, it is not prohibited. Protection is provided where the intent of manufacture is for

legitimate sale to humans by exempting individuals or companies which apply for and receive appropriate FDA approval to develop a new drug. Thus

legitimate scientific research is sufficiently protected. We believe this legislation will tackle the synthetic drug problem at its source, and it is my hope that Congress will enact this needed control so that we can be more successful in stopping the abuse of these dangerous drugs.

Mr. HUGHES. Gentlemen, we are just delighted to have you with us this morning. We have your statements, which will be made a part of the record in full, and you may proceed as you see fit.

Dr. Hawks, why don't we begin with your statement?

STATEMENT OF RICHARD HAWKS, PH.D., CHIEF, RESEARCH TECHNOLOGY BRANCH, DIVISION OF PRECLINICAL RESEARCH, NATIONAL INSTITUTE ON DRUG ABUSE, PUBLIC HEALTH SERVICE, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, ACCOMPANIED BY VERNON HOUK, M.D., DIRECTOR, CENTER FOR ENVIRONMENTAL HEALTH, CENTERS FOR DISEASE CONTROL, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES; EDWARD C. TOCUS, PH.D., DIRECTOR, DRUG ABUSE STAFF, CENTER FOR DRUGS AND BIOLOGICS, FOOD AND DRUG ADMINISTRATION, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

Dr. HAWKS. Thank you, Mr. Chairman, members of the subcommittee.

We have already covered much of the background description of the problem and the kinds of drugs we are dealing with, with a lot of nice statements from yourselves. As indicated in previous testimony, we are dealing with underground chemists who have been active in producing compounds designed simply to circumvent legal liability under the Controlled Substances Act without much regard to the toxic danger of these compounds themselves or the possible impurities of side products in those preparations.

While the actual numbers of persons affected so far have not been great, at least in comparison to the people affected by cocaine, marijuana, PCP, in this country, these particular kinds of synthetic analogs, or designer drugs, do present special problems and have great potential for adverse and large-scale effect on the public health.

The super potent narcotic compounds such as 3-methyl fentanyl, which was used as an example here already, and was manufactured by the chemist at DuPont, is several hundred times more potent than morphine, as recent studies that NIDA has done indicate. An ounce of this material can produce 5 million doses. And an ounce of material doesn't take up much space if one wants to move it around clandestinely. This has implications not only for health of individuals who might use this drug in terms of the potential for overdose, but also for law enforcement. It is very hard to keep up with such small amounts of material that will go so far. Another synthetic narcotic which has been the subject of a number of the comments made in the video tapes that we have seen so far is MPTP, which is a side product that results in the synthesis of MPPP. I won't give you the whole chemical name, but MPPP is a narcotic. It is a synthetic heroin made to be sold on the street. But just about any street synthesis of this material produces smaller or larger amounts of MPTP as a side product. And this one side product, a very simple chemical molecule, is very unusual in that it causes such a tremendous amount of neurotoxicity. It produces the devastating effect as we have seen on these videos.