Cardinal Health Gets Controlled-Substance Suspension

Drug wholesaler Cardinal Health Inc. (CAH) has notified customers that the U.S. Drug Enforcement Agency suspended the company's license to distribute controlled substances from a third distribution center.

The Dublin, Ohio, company wrote to customers of its Swedesboro, N.J., pharmaceutical-distribution center last week that the DEA would suspend the license to distribute controlled substances from that facility effective Dec. 13.

Cardinal didn't issue a news release about the latest suspension, which followed its recent announcements that the DEA was suspending its licenses to distribute controlled substances from centers in Auburn, Wash., and Lakeland, Fla.

The company operates a network of 25 pharmaceutical-distribution centers.

The DEA, in an order to Cardinal suspending the Auburn license, said the company had failed to maintain effective controls against the diversion of a particular controlled substance, and cited the sale of hydrocodone to a pharmacy that allegedly dispensed excessive amounts of the drug based on illegitimate Internet prescriptions.

An updated version of Cardinal's letter to its Auburn customers says the company cannot distribute any products containing ephedrine, pseudoephedrine or iodine from that center.

In its recent letter to Swedesboro center customers, Cardinal said: "We are cooperating fully with the DEA in an effort to address the DEA's concerns and resolve the suspension. Cardinal Health also is implementing near- and long-term enhancements in our controls that guard against theft and distribution to pharmacies engaged in diversion."

Cardinal said it was making arrangements to fill customer orders for controlled substances from some of its other distribution centers.

News Source

Methcathinone is a structural analogue of methamphetamine and cathinone. It is potent and it, along with the parent compound, are easily manufactured.

They are sold in the U.S. under the name CAT. It is distributed as a white to off-white chunky powdered material and is sold in the hydrochloride salt form. Outside of the U.S., methcathinone is known as ephedrone and is a significant drug of abuse in Russia and some of the Baltic States.



Methcathinone was permanently placed in Schedule I of the Controlled Substances Act in October 1993. Prior to its scheduling, two federal cases were effectly prosecuted in Ann Arbor and Marquette, Michigan, utilizing the analogue provision of the Controlled Substances Analogue and Enforcment Act of 1986.

PHENETHYLAMINES

The class of compounds with the largest number of individual compounds on the illicit drug market is the Phenethylamines. This class of compounds consists of a series of compounds having a phenethylamine skeleton. Phenethylamines are easily modified chemically by adding or changing substituents at various positions on the molecule.

Phenethylamines fall into one of two categories in terms of physiological effects — these compounds are either stimulants or hallucinogens. Phenethylamines are suitable for clandestine laboratory production. The parent compound in the phenethylamine series is amphetamine, a central nervous system stimulant(CNS). With this molecule, the modifications begin by adding a methyl group to the nitrogen on the side chain. The resulting structure is the most popular clandestinely produced controlled substance in the U.S. in 1995 — methamphetamine

Like amphetamine, methamphetamine is also a CNS stimulant. It is easily produced in clandestine laboratories using two basic synthetic routes. The traditional route used by “methcooks” began with phenyl-2-propanone; however, when bulk sales were limited by law, most clandestine chemists began using ephedrine as a precursor, although some now synthesize their own supply of phenyl-2-propanone, and still other routes are possible New legislation has now limited bulk purchases of ephedrine in the U.S., though not in neigboring countries. And the chemical structure is such that further molecular synthetic modifications are easily accomplished resulting in a number of homologues and analogues. Few of the synthetic modifications of phenethylamines by clandestine laboratory “chemists” are novel. Most have been documented either in the scientific literature or in underground scientific literature. And the Internet now provides answers to anyone tenacious enough to search for a simple method to synthesize any analogue or homologue of a phenethylamine.

The parent compound of a second set of phenethylamine homologues and analogues is 3,4-methylenedioxyamphetamine (MDA). This compound was first reported in the literature in 1910.14 In the mid-1980s, the N-methyl analogue of MDA came into vogue and was known then and is still referred to as “Ecstasy”.

The synthesis of 3,4-methylenedioxymethamphetamine (MDMA) follows the same synthetic protocols as the less complicated phenethylamines. The clandestine laboratory operator or research chemist selectively adds one N-methy group, an N,N-dimethyl group, an N-ethyl group, an N-propyl, an N-isopropyl group, and so on. In 1985 the N-hydroxy MDA derivative was reported.

FENTANYL

Fentanyl [the technical nomeclature is N-(1-phenethyl-4-piperidyl)propionanilide] is a synthetic narcotic analgesic approximately 50 to 100 times as potent as morphine.6 The drug had its origin in Belgium as a synthetic product of Janssen Pharmaceutica.7

In the 1960s in Europe and in the 1970s in the U.S., it was introduced for use as an anesthesia and for the relief of post-operative pain. Almost 70% of all surgical procedures in the U.S. use fentanyl for one of these purposes.

Fentanyl has been called “synthetic heroin”. This is a misnomer. Victims of fentanyl
overdoses were often heroin abusers with “tracks” and the typical paraphenalia. The fentanyls as a class of drugs are highly potent synthetic narcotic analgesics with all the properties of opiates and opinoids.9 However, the fentanyl molecule does not resemble heroin. Fentanyl is strictly a synthetic product while the morphine used in heroin production is derived from the opium poppy.

Beginning in the late 1970s with -methylfentanyl,10 nine homologues and one analogue
(excluding enantiomers) of fentanyl appeared in the illicit marketplace.11 The degrees of potency vary among the fentanyl homologues and analogues. The potencies of the fentanyl derviatives are much higher than those of the parent compound. But the high potencies cited above explain why even dilute exhibits result in the deaths of users who believe they are dealing with heroin. Another name used by addicts when referring to Fentanyl and its derivatives is “China White”. This term was first used to described substances seized and later identified as alpha-methylfentanyl in 1981.

There are many fentanyl homologues and analogues . Because of the size and complexity of fentanyl derivatives, the interpretation of IR, MS, and NMR spectral data prove very valuable in elucidating specific structural information required for the identification of the material.

PHENCYCLIDINE (PCP)

The chemical nomenclature of phencyclidine is phenylcyclohexylpiperidine. The term “PCP” is used most often used when referring to this drug. The acronym PCP has two origins that are consistent. In the 1960s phencyclidine was trafficked as a peace pill (“PeaCePill”). PhenylCyclohexylPiperidine can also account for the PCP acronym.



PCP was first synthesized in 1926.3 It was developed as a human anesthetic in 1957, and found use in veterinary medicine as a powerful tranquilizer. In 1965 human use was discontinued because, as the anesthetic wore off confusional states and freightening hallucinations were common. Strangely, these side effects were viewed as desirable by those inclined to experiment with drugs. Today even the use of phencyclidine as a primate anesthetic has been all but discontinued. In 1978, the commercial manufacture of phencyclidine ceased and the drug was transferred from Schedule III to Schedule II of the Controlled Substances Act. Small amounts of PCP are manufactured for research purposes and as a drug standard.

The manufacture of PCP in clandestine laboratories is simple and inexpensive. The first clandestinely produced PCP appeared in 1967 shortly after Parke Davis withdrew phencyclidine as a pharmaceutical.4 The clandestine laboratory production of PCP requires neither formal knowledge of chemistry nor a large inventory of laboratory equipment. The precursor chemicals produce phencyclidine when combined correctly using what is termed “bucket chemistry”.

The opportunities for a contaminated product from a clandestine PCP are greatly enhanced because of the recognized simplicity of the chemical reactions in the production processes. The final product is often contaminated with starting materials, reaction intermediates, and by-products.

Clandestine laboratory operators have been known to modify the manufacturing processes to obtain chemically related analogues capable of producing similar physiological responses. The most commonly encountered analogues are N-ethyl-1-phenylcyclohexylamine (PCE), 1-(1-phenylcyclohexyl)- pyrrolidine (PCPy), and 1-[1-(2-thienyl-cyclohexyl)]-piperidine (TCP).

In the 1960s, PCP was distributed as a white to off-white powder or crystalline material and ingested orally. In recent years, PCP has been encountered as the base and dissolved in diethyl ether. The liquid is then placed into small bottles which are recognized to hold commercial vanilla extract. This ether solution is then sprayed on leaves such as parsley and smoked. PCP is commonly encountered on long thin dark cigarettes (“Sherms”) which have been dipped in the PCP/ether solution.

Some Controlled Substances - Heroin

Whenever one thinks about drugs of abuse and addiction, heroin is one of the most recognized drugs. Heroin is a synthetic drug, produced from the morphine contained in the sap of the opium poppy. The abuse of this particular controlled substance has been known for many years. The correct chemical nomenclature for heroin is O3, O6 -diacetylmorphine.

Heroin is synthesized from morphine in a relatively simple process. The first synthesis of diacetylmorphine reported in the literature was in 1875 by two English chemists, G.H. Beckett and C.P. Alder Wright. 1 In 1898 in Eberfield, Germany, the Farbenfarbriken vorm Friedrich Bayer and Company produced the drug commercially. An employee of the company, H. Dresser, named the morphine product “Heroin”.2 There is no definitive documentation as to where the name “heroin” originated. However, it probably had its origin in the “heroic remedies” class of drugs of the day.

Heroin was used in place of codeine and morphine for patients suffering from lung diseases such as tuberculosis. Additionally, the Bayer Company advertised heroin as a cure for morphine addiction. The analgesic properties of the drug were very effective. However, the addictive properties were quite devastating.

In 1924, Congress amended the Narcotic Drug Import and Export Act to prohibit the importation of opium for the manufacture of heroin. However, stockpiles were still available and could be legally prescribed by physicians. The 1925 International Opium Convention imposed drug controls that began to limit the supply of heroin from Europe. Shortly thereafter, the clandestine manufacture of heroin was reported in China.

The supplies of opium in the Far East provided a ready source of morphine—the starting material for the synthesis. The medical use of heroin in the U.S. was not banned until July 19, 1956 with the passage of Public Law 728, which required all inventories to be surrendered to the federal government by November 19, 1956.

Controlled Substance Analogue Enforcement Act

In recent years, the phenomenon of controlled substance analogues and homologues has presented a most serious challenge to the control of drug trafficking and successful prosecution of clandestine laboratory operators. These homologues and analogues are synthesized drugs that are chemically and pharmacologically similar to substances that are listed in the Controlled Substances Act, but which themselves are not specifically controlled by name. (The term “designer drug” is sometimes used to describe these substances.)

The concept of synthesizing controlled substances analogues in an attempt to circumvent existing drug law was first noticed in the late 1960s. At about this time there were seizures of clandestine laboratories engaged in the production of analogues of controlled phenethylamines.

In the 1970s variants of methaqualone and phencyclidine were being seized in clandestine laboratories. By the 1980s, Congress decided that the time had come to deal with this problem with a federal law enforcement initiative. The Controlled Substance Analogue Enforcement Act of 1986 amends the Comprehensive Drug Abuse Prevention and Control Act of 1970 by including the following section:

Section 203. A controlled substance analogue shall to the extent intended for human consumption, be treated, for the purposes of this title and title III as a controlled substance in schedule I.

The 99th Congress went on to define the meaning of the term “controlled substance
analogue” as a substance:

(i) the chemical structure of which is substantially similar to the chemical structure of a
controlled substance in schedule I or II;
(ii) which has a stimulant, depressant, or hallucinogenic effect on the central nervous system that is substantially similar to or greater than the stimulant, depressant, or hallucinogenic effect
on the central nervous system of a controlled substance in schedule I or II; or
(iii) with respect to a particular person, which person represents or intends to have a stimulant, depressant, or hallucinogenic effect on the central nervous system of a controlled substance in schedule I or II.”

The Act goes on to exclude:
(i) a controlled substance
(ii) any substance for which there is an approved new drug application
(iii) with respect to a particular person any substance, if an exemption is in effect for investigational use, for that person, under section 505...to the extent conduct with respect to such substance is pursuant to such exemption; or
(iv) any substance to the extent not intended for human consumption before such an exemption takes effect with respect to that substance.

Treatment of exhibits falling under the purview of the federal court system is described in Public Law 91-513 or Part 1308 of the Code of Federal Regulations. Questions relating to controlled substance analogues and homologues can usually be answered by reference to the Controlled Substances Analogue and Enforcement Act of 1986.

Scheduling of Controlled Substances

A “controlled substance” is a drug or substance of which the use, sale, or distribution is regulated by the federal government or a state government entity.

These controlled substances are listed specifically or by classification on the federal level in the Controlled Substances Act (CSA) or in Part 1308 of the Code of Federal Regulations. The purpose of the CSA is to minimize the quantity of useable substances available to those who are likely to abuse them.

At the same time, the CSA provides for the legitimate medical, scientific, and industrial needs
of these substances in the U.S.

Eight factors are considered when determining whether or not to schedule a drug as a controlled substance:

1. Actual or relative potential for abuse.
2. Scientific evidence of pharmacological effect.
3. State of current scientific knowledge.
4. History of current pattern of abuse.
5. Scope, duration, and significance of abuse.
6. Risk to the public health.
7. Psychic or physiological dependence liability.
8. Immediate precursor.

The definition of potential for abuse is based upon an individual taking a drug of his own volition in sufficient amounts to cause a health hazard to himself or to others in the community. Data is then collected to evaluate three factors: (1) actual abuse of the drug; (2) the clandestine manufacture of the drug; (3) trafficking and diversion of the drug or its precursors from legitimate channels into clandestine operations. Pre-clinical abuse liability studies are then conducted on animals to evaluate physiological responses to the drug. At this point, clinical abuse liability studies can be conducted with human subjects, which evaluate preference studies and epidemiology.

Accumulating scientific evidence of a drug’s pharmacological effects involves examining
the scientific data concerning whether the drug elicits a stimulant, depressant, narcotic, or
hallucinogenic response. A determination can then be made as to how closely the pharmacology
of the drug resembles that of other drugs that are already controlled.

Evidence is also accumulated about the scientific data on the physical and chemical
properties of the drug. This can include determining which salts and isomers are possible and
which are available. There is also a concern for the ease of detection and identification using
analytical chemistry. Since many controlled substances have the potential for clandestine
synthesis, there is a requirement for evaluating precursors, possible synthetic routes, and
theoretical yields in these syntheses. At this phase of the evaluation, medical uses are also
evaluated.

The next three factors—(1) history and patterns of abuse; (2) scope, duration, and
significance of abuse; and (3) risks to public health—all involve sociological and medical
considerations. The results of these studies focus on data collection and population studies.
Psychic and physiological dependence liability studies must be satisfied for a substance to be
placed into Schedules II through V. This specific finding is not necessary to place a drug into
Schedule I. A practical problem here is that it is not always easy to prove a development of
dependence.

The last factor is one that can involve the forensic analyst. Under the law, an “immediate
precursor” is defined as a substance that is an immediate chemical intermediary used or likely
to be used in the manufacture of a specific controlled substance. Defining synthetic pathways
in the clandestine production of illicit controlled substances requires knowledge possessed by
the experienced analyst.

A controlled substance will be classified and named in one of five schedules. Schedule I
includes drugs or other substances that have a high potential for abuse, no currently accepted
use in the treatment of medical conditions, and little, if any, accepted safety criteria under the
supervision of a medical professional. Use of these substances will almost always lead to abuse
and dependence. Some of the more commonly encountered Schedule I controlled substances are heroin, marijuana, lysergic acid diethylamide (LSD), 3,4-methylenedioxy-amphetamine
(MDA), and psilocybin mushrooms.

Progressesing from Schedule II to schedule V, abuse potential decreases. Schedule II
controlled substances also include drugs or other substances that have a high potential for
abuse, but also have some currently accepted, but severely restricted, medical uses. Abuse of
Schedule II substances may lead to dependence which can be both physical and/or psychological. Because Schedule II controlled substances do have some recognized medical uses, they are usually available to health professionals in the form of legitimate pharmaceutical preparations.

Cocaine hydrochloride is still used as a topical anesthetic in some surgical procedures. Methamphetamine, up until a few years ago, was used in the form of Desoxyn to treat hyperactivity in children. Raw opium is included in Schedule II. Amobarbital and secobarbital, which are used as central nervous system depressants are included, as is phencyclidine (PCP) which was used as a tranquilizer in veterinary pharmaceutical practices. In humans, PCP acts as a hallucinogen.

Though many of the substances seized under Schedule II were not prepared by
legitimate pharmaceutical entities, cocaine hydrochloride and methamphetamine are two
examples of Schedule II drugs which, when confiscated as white to off-white powder or
granules in plastic or glassine packets, have almost always been prepared on the illicit market
for distribution. As one progresses from Schedules III through V, most legitimate pharmaceutical preparations will be encountered.