America's Habit

Drug Abuse, Drug Trafficking, & Organized Crime

President's Commission on Organized Crime, 1986

Consultant Paper: Recommendations for the Regulation of Selected Chemicals and Controlled Substance Analogs

By Frank Monastero. Submitted: September 1985. Frank Monastero retired in 1985, having served as the Chief of Operations of the Drug Enforcement Administration.

As we can see from media reports, cocaine has fast become the nation's number one drug abuse problem. The supply of cocaine coming from South America has reached overwhelming proportions. In 1985 alone the Drug Enforcement Administration (DEA) estimates seizures will reach 50,000 pounds, and this, of course, does not account for that part of the supply that ultimately reaches the more than 20 million regular users.

Another facet of the drug abuse problem, which could grow as rapidly if not addressed promptly, is that of controlled substance analogs, known as "designer drugs." These are clandestinely produced substances not covered by the Controlled Substances Act because of their chemical structure.

Most drugs, including those manufactured illicitly, are produced at least in part from commercially available chemicals. The purpose of this paper is to examine the feasibility and desirability of regulating certain of these chemicals. It will also analyze how to curtail illicit production and examine what legal mechanism would be effective to control the manufacture of synthetic analogs (designer drugs), produced for illicit purposes.

Cocaine abused in the United States has its origin from the coca bush, a very hardy plant, grown in certain areas of South and Central America. As in the case with almost all drugs, whether produced from plants or totally synthetic, one or more precursors, reagents or solvents is used in the process. These chemicals are defined as follows: a precursor is a raw material used in the production of a controlled substance that becomes part of the finished product; a reagent reacts chemically with one or more precursors but does not become part of the finished product; a solvent, which does not react chemically with a precursor or reagent and does not become part of the finished product, is used to dissolve solid precursors or reagents, to dilute reaction mixtures, and to separate and purify other chemicals. For example, a precursor for cocaine is coca leaves, a reagent is sulfuric acid, and a solvent used in the manufacturing process is acetone. With respect to methamphetamine, a precursor is phenyl-2-propanone, a reagent is sulfuric acid, and a solvent is methanol. It is important to understand that, in the case of these and other controlled substances, there are many other precursors, reagents and solvents, which can easily be substituted to produce the same final product.

With some exceptions only the final product drug itself, is a controlled substance. Many of the chemicals used to produce or refine illicit drugs are needed in industry to produce a myriad of items and are produced in tremendous quantities. Controlling their distribution would, in most cases, be impossible and probably undesirable because of the cost alone. Acetone, for instance, which is used as a solvent in processing opium and coca leaves, is used to make paints, lubricants, pharmaceuticals, cosmetics and agricultural products.

Although controlling all precursors, reagents and solvents used to manufacture illicit drugs is neither desirable nor feasible, the idea of controlling certain chemicals has merit. In fact, some chemicals are now subject to regulation. Piperidine is a precursor to the controlled substance phencyclidine, commonly known as PCP, which can have serious physical and psychological consequences when abused. Piperidine is subject to reporting requirements under the Controlled Substances Act, although its possession and distribution are not subject to penalties, as is the case with the possession and distribution of PCP. Forms recording the sale of piperidine and the purchaser's name must be maintained for two years. Anyone who sells piperidine must report the sale. This reporting procedure allows DEA to monitor sales of piperidine and to investigate those sales recognized as suspicious by either DEA or the seller. As a result of concerted efforts begun in late 1984, DEA has seized four clandestine PCP laboratories and has located at least ten operations that received chemicals from legitimate channels by posing as legitimate businesses. In one case a manufacturer shipped a substantial amount of piperidine to a "chemical company" over an extended period, all in good faith based on the company's name. A check of the address by DEA showed it to be an auto repair shop.

Precursors, reagents and solvents are used to manufacture many drugs, including synthetic analogs, drugs so close in structure to controlled substances that they create virtually the same effect for the user. These are not covered under the Controlled Substances Act because of minor differences in molecular structure. Synthetic analogs, commonly known as "designer drugs," pose particular health threats.

The production of controlled substance analogs, pharmacologically active, chemically related substances, to avoid the laws regulating controlled substances, was first observed in the mid-1960's with the synthesis of amphetamine analogs of mescaline, such as MDA and others. Some of this group of hallucinogenic amphetamines sold on the illicit market were brought under the Drug Abuse Control Amendments, a predecessor to the Controlled Substances Act. Others in the group were subsequently controlled under the Controlled Substances Act after its passage in 1970. Later three PCP analogs were controlled.

The process of designing analogs is, therefore, not new, and the formulas are not primarily a phenomenon of clandestine laboratories. Most of these drugs were developed by legitimate pharmaceutical chemists in search of better medicinal agents through the testing of numerous analogs of a parent compound. It is not surprising, therefore, that some of their precursors have names such as N-(1-phenethyl-4-piperidinyl)-aniline (for fentanyl) or N-[1-(2-phenylisopropyl)]-4-piperidinone-4-one (for alpha-methylfentanyl). These analogs, in many cases, mimic the qualitative actions of the original compound but may vary in potency or duration of action. Thus, there is a need to deal both with the problem of chemicals used in the production of illicit drugs and with the problem of controlled substance analogs.

Factors Affecting the Regulation of Chemicals

There are in excess of 200 precursors, reagents and solvents used in the production of the 37 most commonly abused substances. Among these are amphetamines, barbiturates, cocaine, Diazepam, hash oil, heroin, LSD, MDA, PCP and methaqualone. In considering what should be regulated two factors are most significant: (1) How common is the chemical interest? (2) How great is the workload to track the needed information? Each situation must be examined individually, if the objective is to reach an ultimate solution for each drug.

It is quickly apparent that there is no ultimate, universal solution to absolute chemical control for all drugs. Acetone and ether, although widely used, are subject to tracing. Piperidine, less available commercially, is easily synthesized. The first conclusion might well be that if the source of the chemical is known and that source will identify and report suspicious sales, the investigator will be able to pursue the investigation. Obviously, this will not help when all chemicals can be obtained from illicit sources. But when the source will provide assistance or at least when sales information is available for review, tracing can be attempted.

The problem then becomes one of resources. How much information can be reviewed and how many people are available to pursue leads. These are very significant factors to consider. If, indeed, all chemicals used in the production of controlled substances were reported it is unlikely the responsible agency could cull the most suspicious orders, let alone investigate them. The computer input itself would be substantial. Furthermore, the drug abuse situation is constantly changing, and a chemical, not of interest today, might be a prime target as a new drug emerges.

Case Study: Ether

Because cocaine abuse is a serious problem in the United States at this time and because an increasing number of cocaine laboratories are being seized, it is important to examine the chemical control of cocaine. To refine coca, dried leaves are moistened with an alkaline solution, such as lime water, sodium or potassium carbonate. The moistened leaves are soaked in kerosene, which extracts cocaine and similar compounds. The kerosene is extracted with aqueous sulfuric acid, and the acid neutralized with limestone or lime. After the cocaine precipitates and is removed by filtering, it becomes coca paste. To become cocaine base, the paste is dissolved in a solution of sulfuric acid, and a solution of potassium permanganate is added to aridize impurities. The solution is filtered to remove impurities and manganese oxides. Anmoniun hydroxide is added to the filtrate, and the precipitate is collected and dried, forming the base. The base is dissolved in acetone or ether and filtered to remove insoluble material. Concentrated hydrochloric acid is added in acetone along with ether. Cocaine hydrochloride will crystallize from this solution and is collected by filtration and dried. The ratio of base to cocaine hydrochloride is one to one.

Because ether and acetone are readily available in the United States, traffickers recognized the advantage of processing here, and the number of base to hydrochloride laboratories seized increased steadily from 3 in 1980 to 21 in 1984; as of mid-1985, there were already 25.

Six reagents are used to refine cocaine: ammonia, hydrochloric acid, lime, limestone, potassium carbonate, potassium permanganate and sulfuric acid. The four solvents used are acetone, ethanol, ether and kerosene. These could be targets for monitoring or control. However, after considering the availability and usage of each chemical, the possible targets can be narrowed to acetone and ether. As mentioned earlier, acetone has a number of legitimate uses. An estimated 2.5 billion pounds is produced each year in the United States, a commercial value of about $400 million.

There are 12 major U.S. producers and over 40 foreign sources. Although usually produced from petroleum or synthesized from benzene, there are other processes to produce it. Nonetheless, acetone, in fact, was selected as a target, and the targeting did produce results. Ether, likewise, has broad use, with a U.S. production estimate of over 60 million pounds, but with only five U.S. producers and seven major foreign sources. Ether, therefore, represents, and did turn out to be, an even better target.

Early in 1982 a project was undertaken to determine how much ether was being shipped to Colombia and to what, if any, legitimate uses it was put. Colombia was selected because, although most of the coca is grown in Bolivia and Peru, most of the cocaine processing laboratories were known to be in Colombia. The Colombian government determined that thousands of gallons of ether were being imported annually, but that there was virtually no legitimate need for it. Most of the ether was imported from the Federal Republic of Germany and the United States. Through liaison with those ether manufacturers and distributors who would cooperate, hundreds of barrels of the chemical were tracked to clandestine laboratories deep in the Amazon jungles of Colombia. Many of these labs were destroyed and thousands of pounds of cocaine were seized. In the celebrated Tranquilandia raid in March 1984, 10,000 kilograms of cocaine paste and base were seized and destroyed, along with thousands of barrels of chemicals. Through court testimony and media attention, cocaine producers have, no doubt, become aware of the detection techniques used to locate laboratories, and they are or will take action to avoid detection. Opportunities for a continuing supply of ether exist through unscrupulous manufacturers and distributors and through clandestine production from ethanol. However, the program has been useful and demonstrates the effectiveness of the monitoring approach.

Case Study: P2P

In addition to tracking chemicals, such as ether, another approach is to bring certain chemicals under the Controlled Substances Act. For experience with this approach, it is important to examine methamphetamine and one of its precursors, phenyl-2-propanone (P2P). Domestic methamphetamine production is significant. In fact, during a 45 month period beginning in September 1981, more than 50 percent of the 751 clandestine laboratories seized by DEA were methamphetamine labs. In order to control clandestine methamphetamine production, P2P was placed in Schedule II of the Controlled Substance Act on February 11, 1980. P2P is an immediate precursor (used in the step just prior to completion) in the most desirable synthesis and was, therefore, a good choice for targeting. Furthermore, with the exception of its use as a cleaning solution, most of its uses are in connection with pharmaceutical manufacturing. Annual production in the U.S. is estimated to be about 10,000 pounds, with only two principal domestic producers and nine foreign sources. Full control of P2P under the Control Substances Act resulted in a significant increase in the number of clandestine methamphetamine laboratory operators synthesizing P2P. More than 75 percent of the laboratories seized after passage were refluxing phenylacetic acid and acetic anhydride with sodium acetate or pyridine. In addition, one laboratory was synthesizing phenylacetic acid as well.

Recommendations for Action

(1) That legislation be enacted requiring the reporting of all sales of selected chemicals used in the production of controlled substances, subject to public notice by the Administrator of DEA that a particular chemical was selected for such control. This would create a requirement similar to that affecting piperidine; however, reporting would only be required for those chemicals specified for a particular period of time. The requirement should apply to the importing and exporting of the specified chemicals.

(2) That legislation be enacted to empower the Administrator of DEA or some other appropriate authority to identify and add new chemicals to the list of those requiring reporting, as it becomes known they are being used for the production of controlled substances.

(3) That DEA identify the resources needed for the computerization, analysis and follow up on reporting and that those resources be acquired through the budget process.

Controlled Substance Analogs

As previously stated, the controlled substance analog problem is not new. However, their wider illicit use and the greater recognition of their use has heightened concern. There have been three major types of analogs available in the United States: analogs of PCP, analogs of amphetamine and methamphetamine having hallucinogenic properties, and the newer trend, analogs of fentanyl and meperidine. There are, of course, hazards common to all three groups. They are likely to contain toxic impurities. Dosage is not consistent, i.e., one dose of a substance is likely to contain a different amount of the active ingredient than another. As a result, a single dose could contain a lethal amount of the drug in question. Because they are analogs, they may well produce toxic effects not caused by their parent drug. Another critical consideration associated with designer drugs is the difficulty of identifying them in the body. Recent testimony at a Senate hearing indicated there are now only two laboratories in the country, capable of identifying certain "designer drugs" in body fluids, because standards for identifying the drugs are not widely available. This creates two serious problems: (1) Without the ability to detect and determine what drugs are being used on the street it is impossible to even identify that a problem exists let alone judge its magnitude; and (2) without being able to determine positively what drugs has been ingested, it is impossible to identify the correct antidote, which in many cases could be a matter of life and death.

The Situation in More Detail

PCP was originally developed in the early 1950's as an anesthetic for humans, but it was soon limited to veterinary use because of its adverse side effects. Licit production ceased in 1978, and PCP is controlled in Schedule I of the Controlled Substances Act, as are three of its analogs. They now are recognized as having no medical use. The National Institute on Drug Abuse has identified 35 other analogs, but none has presented an abuse problem as far as is known.

Many analogs of amphetamine and methamphetamine are known to have hallucinogenic affects. One receiving considerable media attention recently, known on the street as "Ecstasy," is MDMA or 3,4-methylene dioxymethamphetamine from the parent compound MDA. Its psychopharmacological effects are similar to those of MDA, altered consciousness, increased acoustic, visual and tactile sensory perceptions and mild intoxication. There is considerable concern among some experts that MDMA is likely to cause damage to the serotonergic system, which has to do with regulating sleep, mood, sexual activity and sensitivity to aversive stimuli. The conclusion is based on research indicating that MDA can selectively destroy serotonergic nerve terminals in the rat brain. First recognized in the illicit traffic by DEA in 1970, MDMA was proposed for control under the Controlled Substances Act in July 1984 because of increasing incidents of discovery. However, because of rapidly mounting evidence of abuse since then and possible serious neurological damage, the emergency provisions contained in the Comprehensive Crime Control Act of 1984 were used, and the drug was controlled as of July 1, 1985.

Fentanyl is widely used by the medical community as an analgesic and anesthetic. It was first marketed in the United States for this purpose in 1968 and is the most popular analgesic used in surgical procedures in this country. There are likely several hundred fentanyl analogs, many with pharmacological properties similar to heroin or morphine but far more powerful. The alpha-methyl analog was the first synthetic analog drug recognized in the illicit traffic and was associated with overdose deaths in California in 1979. Sold on the streets as synthetic heroin, or "China White," it was placed in Schedule I of the Controlled Substances Act in September 1981, substantially eliminating its appearance in the illicit traffic. DEA has identified seven additional fentanyl analogs in the illicit traffic since then, however. Interestingly, two analogs have not been recognized in the scientific literature.

There are two dramatic concerns related to the fentanyl analogs: (1) their potency; and (2) their production/profit margin. This second element will be of obvious importance to traditional organized crime elements. Three methyl-fentanyl, the latest analog to appear in the illicit market, is 3,000 times as potent as morphine and has already been responsible for over a dozen overdose deaths in the San Francisco Bay area alone. This is the highest rate of fentanyl related deaths to date. Dosages for fentanyl analogs are measured in micrograms and are likely to be less than 1 percent of the dosage unit sold to the user. The Drug Enforcement Administration has estimated that one kilogram of fentanyl analog could be manufactured for under $2,000 and that this amount might equal as many as 50 million dosage units, with a street value exceeding one billion dollars.

Meperidine, a synthetic narcotic used to control pain, is frequently used by heroin users when the street supply of heroin is low. Meperidine, known more commonly by its trade name "Demerol," is in the Controlled Substances Act, Schedule II. Two analogs of meperidine have been found in current use. The first apparent MPPP (1-Methyl-4-Propionoxy piperidine) abuse came to light in 1976 when a young man synthesized what he thought was the analog for his own use. He soon sought treatment for symptoms of Parkinson's disease. In revealing his drug use he provided the formula and procedures he had used. Subsequent analysis revealed he had, in fact, created MPTP. Additional research by a National Institute of Health grantee showed that MPTP had produced the Parkinson's type symptoms. MPPP was first identified by a DEA laboratory in 1982; and samples of MPPP have been discovered to contain the neurotoxic byproduct MPTP, formed during the synthesis of MPPP. The neurological damage produced by MPTP is irreversible and apparently worsens with time. The State of California has identified more than 500 people who have used MPTP; many users thought it was a new synthetic heroin. Twenty of those involved have been permanently crippled. A group of seven young addicts, who appeared at a California medical center several years ago with symptoms resembling advanced Parkinson's disease, were unable to move or talk. Treatment with anti-Parkinson's therapy was, according to California authorities, probably life saving, yet the patients continued to be severely handicapped, requiring medication every one to three hours just to be able to eat and drink.

The other meperidine analog with effects similar to heroin is PePAP (l-(2-Phenylethyl)-4-Acetyloxpiperidine). The analgesic potency of PePAP, measured in rodents, is described as from 12 to 72 times the potency of meperidine itself. This analog has so far been discovered in California, although a clandestine laboratory operation in Texas may have been attempting the process but did not succeed.

Proposed Legislation

As mentioned at the outset of this discussion, unless the specific chemical makeup of the substance being abused can be determined by all laboratories regularly engaged in the analysis of substances being abuse, serious problems could go unrecognized for long periods, even years. Those who examine for and record overdose deaths and injuries must likewise be able to determine the abused substance involved. Further, that information must be collected and analyzed at a central point. There is currently only a limited mechanism for this collection (the NIDA DAWN system). When a situation needing attention is discovered, enforcement authorities must be empowered to act quickly. This means that a mechanism must exist by which these "designer drugs" can be controlled under the Controlled Substances Act and appropriate State laws. The Comprehensive Crime Control Act of 1984 does contain such a provision. Under that statute the Administrator of DEA can bring a drug under Schedule I for up to one year, with a six month extension where justified, and on emergency basis, while the normal control mechanism is in progress. The Administrator must decide that such scheduling is necessary to avoid an imminent hazard to public safety. Control of the substances occurs 30 days after public notice. The efficacy of this legislation is yet undetermined, since it was only first used in the Spring of 1985.

On July 16, 1985, a bill was introduced in the U.S. Senate, S. 1437, known as the "Designer Drug Enforcement Act of 1985." This proposed legislation would make it a felony to manufacture or distribute a designer drug for human consumption. The proposed act, which would amend the Controlled Substance Act, reads in part "(31) The term 'designer drug' as used in section 403A means a substance other than a controlled substance that has a chemical structure substantially similar to that of a controlled substance in Schedule I or II." During a Senate hearing on the legislation by the Subcommittee on Children, Family and Drugs and Alcoholism, July 25, 1985, both the DEA Administrator and the Administrator of the Alcohol, Drug Abuse and Mental Health Administration, supported the bill.

Recommended Actions

(1) That DEA provide assistance to the States in acquiring laboratory standards for use in identifying "designer drugs."

(2) That legislation be enacted requiring the reporting by anyone authorized to sign a death certificate, to an appropriate Federal authority (perhaps the Public Health Service) of deaths caused wholly or in part from the ingestion of any substance.

(3) That legislation be enacted requiring the reporting to an appropriate Federal authority (DEA) by all laboratories performing drug analysis for law enforcement purposes: (a) the total amount of each controlled substance as defined in the Controlled Substances Act, received for analysis each calendar year, and (b) immediate notice of the receipt of samples of any substance suspected of being or found to be a "designer drug" as defined in the proposed bill.

1. That DEA formulate model "designer drug" legislation for the States as has been done for other aspects of the drug abuse problem.