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

Stress family environment may spark early puberty in girls

While a stressful family environment in childhood has long been blamed for various psychological effects later in life, new research suggests that hostile situations at home may also have big physical implications for young girls.

In a study released Thursday, researchers at the University of Arizona and the University of Wisconsin-Madison looked at families of 227 preschool children, following them as they progressed through middle school. Specifically, the researchers looked for the first hormonal signs of puberty in these children.

What they found was that parental support -- or lack of it -- may partially determine at what age young girls hit puberty. Specifically, young girls with families who were more supportive in preschool years tended to hit puberty later than their counterparts in less supportive family environments.

The research stops short of drawing a bold link between early stress and early puberty, as factors such as family income and other environmental factors may also be at play. But lead study author Bruce Ellis said that while it is still too early for parents to make solid conclusions based on the evidence, the findings hint at an interesting evolutionary link between sexual maturation and stress.

"Children adjust their development to match the environments in which they live," said Ellis, an associate professor in the Division of Family Studies and Human Development at the University of Arizona in Tucson.

"Children who grow up in environments that are dangerous and unpredictable tend to grow up faster," he said. "In the world in which humans evolved, danger and uncertainty meant a shorter lifespan, and going into puberty earlier in this context increased chances of surviving, reproducing and passing on your genes."

Source

Drug research center launch speeded up

The Food and Drug Administration is moving with unprecedented speed to launch a drug research center to be paid for by companies it regulates.

The goal of the Reagan-Udall Foundation, approved by Congress and signed into law late last month, is to streamline and improve the development of drugs and medical devices, a goal long sought by regulators and the biggest players in the industry, such as Merck & Co. Inc., Pfizer Inc., Wyeth, GlaxoSmithKline PLC and Johnson & Johnson.

At a time when the FDA's reputation has been battered by perceptions that it is lax on some safety issues and too cozy with drug makers, consumer advocates say the loosely defined partnership increases the agency's vulnerability to industry clout despite its promise of groundbreaking success. It's an ambitious undertaking that puts regulators and companies in a relationship unlike that of any other industry.

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China recalls tainted leukemia drugs

Chinese authorities ordered the recall of tainted leukemia drugs blamed for leg pains and other problems, state media reported Sunday, the latest crisis to strike the country's embattled food and drug industries.

Most of the drugs involved — methotrexate and cytarabin hydrochloride — have been recovered and authorities have traced the remainder, the Xinhua News Agency said. The report did not say if any of the drugs had been exported.

Authorities have banned the sale and distribution of the drugs, produced by the Shanghai Hualian Pharmaceutical Co., it said.

China, a major global supplier, has been facing growing international pressure to improve the quality of its exports after dangerous toxins — from lead to an antifreeze ingredient — were found in goods including toys and toothpaste.

China has been eager to cast itself as a victim, too, of unsafe imports. Xinhua on Saturday announced that inspectors recently found residue of the banned stimulant ractopamine in frozen pig kidneys imported from the United States and frozen pork spareribs from Canada. The names of the exporting companies were not identified. Ractopamine is forbidden for use as veterinary medicine in China.

RA Drugs Linked to Slight Skin Cancer Risk

People taking rheumatoid arthritis drugs such as etanercept (Enbrel) or infliximab (Remicade) may be at a slightly increased risk for skin cancer, researchers report.

However, the risk is probably not significant enough to outweigh the benefits of these drugs, the researchers said.

These so-called biologic treatments work by blocking tumor necrosis factor alpha (TNF-alpha), which previous studies had found to be linked with increased risk of skin, lung and blood cancers.

"The risk of skin cancer is marginally increased among people with rheumatoid arthritis," said lead researcher Dr. Frederick Wolfe, a clinical professor of internal medicine at the University of Kansas School of Medicine. "But it's nothing that anybody should be worried about," he added.

For the study, Wolfe and his colleagues collected data on 13,001 patients with rheumatoid arthritis included in the National Data Bank for Rheumatic Diseases and the U.S. National Cancer Institute SEER (Surveillance, Epidemiology, and End-Results). The researchers found a total of 623 cases of skin cancer and 537 cases of other cancers.

They also found that anti-TNF-alpha medications were associated with a slight increased risk of skin cancer. But, they did not find any increased risk for other cancers, according to the report in the September issue of Arthritis & Rheumatism.

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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.

LYSERGIC ACID DIETHYLAMIDE (LSD)

LSD is an hallucinogenic substance produced from lysergic acid, a substance derived from the ergot fungus (Clavica purpurea) which grows on rye. It can also be derived from lysergic acid amide which is found in morning glory seeds.1 LSD is also refered to as LSD-25 because it was the twenty-fifth in a series of compounds produced by Dr. Albert Hofmann in Basel, Switzerland.

Hoffman was interested in the chemistry of ergot compounds, especially their effect on circulation. He was trying to produce compounds that might improve circulation without exhibiting the other toxic effects associated with ergot poisoning. One of the products he produced was Methergine™, which is still in use today.

When LSD-25 was first tested on animals, in 1938, the results were disappointing. Five years later, in 1943, Hoffman decided to reevaluate LSD-25. The hallucinogenic experience that ensued when he accidentally ingested some of the compound led to the start of experimentation with “psychedelic” drugs.

LSD is the most potent hallucinogenic substance known to man. Dosages of LSD are
measured in micrograms (one microgram equals one-one millionth of a gram). By comparison, dosage units of cocaine and heroin are measured in milligrams (one milligram equals one-one thousanth of a gram). LSD is available in the form of very small tablets (“microdots”), thin squares of gelatin (“window panes”), or impregnated on blotter paper (“blotter acid”).

The most popular of these forms in the 1990s is blotter paper perforated into 1/4 inch squares. This paper is usually brightly colored with psychedelic designs or line drawing. There have been recent reports of LSD impregnated on sugar cubes.2 These LSD-laced sugar cubes were commonplace in the 1970s. The precursor to LSD, Lysergic Acid, is a Schedule III controlled substance. LSD is classified as a Schedule I controlled substance.

PSILOCYBIN MUSHROOMS

The naturally occuring indoles responsible for the hallucinogen properties in some species of mushrooms are psilocybin and psilocin. 12 The use of hallucinogenic mushrooms dates back to the 16th century occuring during the coronation of Montezuma in 1502.8 In 1953, R. G. Wassen and V.P. Wasson were credited with the rediscovery of the ritual of the Indian cultures of Mexico and Central America. 13 They were able to obtain samples of these mushrooms. The identification of the mushrooms as the species Psilocybe is credited to the French mycologist, Roger Heim. 14

Albert Hofmann (the discoverer of lysergic acid diethlamine) and his colleagues at Sandoz laboratories in Switzerland are credited with the isolation and identification of psilocybin (phosphorylated 4-hydroxydimethyltryptamine) and psilocin (4-hydroxydimethyltryptamine).15

Psilocybin was the major component in the mushrooms, and psilocin was found to be a minor component. However, psilocybin is very unstable and is readily metabolized to psilocin in the body. This phonomenon of phosphate cleavage from the psilocybin to form the psilocin occurs quite easily in the forensic science laboratory. This can be a concern in ensuring the specifity of identification.

The availability of the mushroom has existed worldwide wherever proper climactic conditions exist — that means plentiful rainfall. In the U.S., psilcoybib mushrooms are reported to be plentiful in Florida, Hawaii,16 the Pacific Northwest, and Northern California.17 Mushrooms that are analyzed in the forensic science laboratory confirm the fact that the mushrooms spoil easily. The time factor between harvesting the mushrooms and the analysis proves to be the greatest detriment to successfully identifying the psilocybin or pscilocyn. Storage prior to shipment is best accomplished by drying the mushrooms. Entrepreneurs reportedly resort to
storage of mushrooms in honey to preserve the psychedelic properties.18

Progressing through the analytical scheme of separating and isolating the psilocybin and psilocin from the mushroom matrix, cleavage of the phosphate occurs quite easily. Prior to beginning the analysis, drying the mushrooms in a desicator with phosphorous pentoxide ensures a dry starting material. In many instances, the clean-up procedure involves an extraction process carried out through a series of chloroform washes from a basic extract and resolution of the components by TLC.

The spots or, more probably, streaks are then scaped from the plate, separated by a back-extraction, and then analyzed by IR. Direct analysis by GC is very difficult because both psilocybin and psilocin are highly polar and not suitable for direct GC analysis. Derivatization followed by GC/MS is an option except in those instances where the mushrooms have been preserved in sugar.19 With the development and availability of HPLC, the identification and quatitation of psilocybin and psilocyn in mushrooms are becoming more feasible for many forensic science laboratories. 20

Peyote

Peyote is a cactus plant which grows in rocky soil in the wild. Historical records document use of the plant by Indians in northern Mexico from as far back as pre-Christian times, when it was used by the Chichimaec tribe in religious rites. The plant grows as small cylindrical-like “buttons”. The buttons were used to relieve fatigue and hunger, and to treat victims of disease. The peyote buttons were used in group settings to achieve a trance state in tribal dances.

It was used by native Americans in ritualistic ceremonies. In the U.S., peyote was cited in 1891 by James Mooney of the Bureau of American Ethology. 9 Mooney talked about the use of peyote by the Kiowa Indians, the Comanche Indians, and the Mescalero Apache Indians, all in the southern part of the country. In 1918, he came to the aid of the Indians by incorporating the “Native American Church” in Oklahoma to ensure their rights in the use of peyote in religious ceremonies. Although several bills have been introduced over the years, the U.S. Congress has never passed a law prohibiting the Indians’ religious use of peyote. Both mescaline and peyote are listed as Schedule I controlled substances in the Comprehensive Drug Abuse Prevention and Control Act of 1970.

The principal alkaloid of peyote responsible for its hallucinogenic response is mescaline, a derivative of ß-phenethylamine.

Lab Analysis of Marijuana

The specificity of a marijuana analysis is still a widely discussed topic among those in the forensic and legal communities. In the course of the past 25 years, the concensus of opinion concerning the analysis of marijuana has remained fairly consistent. In those situations where plant material is encountered, the marijuana is first examined using a stereomicroscope. The presence of the bear claw cystolithic hairs and other histological features are noted using a compound microscope.

The plant material is then examined chemically using Duquenois – Levine reagent in a modified Duenois Levine testing sequence. These two tests are considered to be conclusive within the realm of existing scientific certainty in establishing the presence of marijauana.3–5. The Modified Duquenois–Levine test is conducted using Duquenois reagent, concentrated hydrochloric acid, and chloroform. The Duquenois reagent is prepared by dissolving 2g of vanillin and 0.3 ml of acetaldehyde in 100 ml of ethanol. Small amounts (25 to 60 mg is usually sufficient) of suspected marijuana leaf is placed in a test tube and approximately 2 ml of Duquenois reagent is added. After 1 min, approximately 1 ml of concentrated hydrochloric acid is added. Small bubbles rise from the leaves in the liquid. These are carbon dioxide bubbles produced by the reaction of the hydrochloric acid with the calcium carbonate at the base of the cystolithic hair of the marijuana. A blue to blue-purple color forms very quickly in the solution.

Approximately 1 ml of chloroform is then added to the Duquenois reagent/ hydrochloric acid mixture. Because chloroform is not miscible with water, and because it is heavier than water, two liquid layers are visible in the tube—the Duquenois reagent/hydrochloric acid layer is on top, and the chloroform layer is on the bottom. After mixing with a vortex stirrer and on settling, the two layers are again clearly distinguishable. However, the chloroform layer has changed from clear to the blue to blue-purple color of the Duquenois reagent/hydrochloric acid mixture.

One variation in this testing process involve pouring off the Duquenois reagent sitting in the tube with the leaves before adding the hydrochloric acid. The remainder of the test is conducted using only the liquid. Another variation involves conducting the test in a porcelain spot plate. This works, although some analysts find the color change a bit more difficult to detect. A third variation involves extracting the cannabis resin with ether or some other solvent, separating the solvent from the leaves, allowing the solvent to evaporate, and conducting the Modified Duquenois–Levine test on the extract.

Marquis reagent is prepared by mixing 1 ml of formaldehyde solution with 9 ml of sulfuric acid. The test is done by placing a small amount of sample (1 to 5 mg) into the depression of a spot plate, adding one or two drops of reagent, and observing the color produced. This color will usually be indicative of the class of compounds, and the first color is usually the most important. A weak reponse may fade, and samples containing sugar will char on standing because of the sulfuric acid. Marquis reagent produces the following results:

1. Purple with opiates (heroin, codeine).
2. Orange turning to brown with amphetamine and methamphetamine.
3. Black with a dark purple halo with 3,4-methylenedioxyamphetamine (MDA) and
3,4- methylenedioxymethamphetamine (MDMA).
4. Pink with aspirin.
5. Yellow with diphenhydramine.

A thin-layer chromatographic (TLC) analysis, which detects a systematic pattern of colored bands, can then be employed as an additional test.6,7 Though it is not required, some analysts will run a gas chromatograph/mass spectrometrometer (GC/MS) analysis to identify the cannabinoids in the sample.

The solvent insoluble residue of hashish should be examined with the compound microscope. Cystolythic hairs, resin glands, and surface debris should be present. However, if most of the residue is composed of green leaf fragments, the material is pulverized marijuana or imitation hashish.

MARIJUANA

History and Terminology of Marijuana

Marijuana is a Schedule I controlled substance. In botanical terms, “marijuana” is defined as Cannabis sativa L. Legally, marijuana is defined as all parts of the plant, Canabis sativa L. (and any of its varieties) whether growing or not, the seeds thereof, the resin extracted from any part of the plant, and every compound, manufacture, salt, derivative, mixture, or preparation of such plant; its seeds and resins. Such terms do not include the mature stalk of the plants, fibers
produced from such plants, oils or cakes made from the pressed seeds of such plants, any other compound, manufacture, salt derivative, mixture or preparation of such mature stalks (except the resin extracted therefrom), fiber, oil or cake, pressed seed, or the sterilized seed which is incapable of germination.1 Pharmaceutical preparations that contained the resinous extracts of cannabis were available on the commercial market from the 1900s to 1937. These products were prescribed for their analgesic and sedative effects. In 1937 the Food and Drug Administration declared these products to be of little medical utility and they were removed from the market in 1937. Cannabis, in the forms of the plant material, hashish, and hashish oil, is the most abused illicit drug in the world.

Cannabis is cultivated in many areas of the world. Commerical Cannabis sativa L. is
referred to as “hemp”. The plant is cultivated for cloth and rope from its fiber. A valuable drying oil used in art and a substitute for linseed oil is available from the seeds. Bird seed mixtures are also found to contain sterilized marijuana seeds. In the early days of the U.S., hemp was grown in the New England colonies. Its cultivation spread south into Pennsylvania and Virginia. From there it spread south and west most notably into Kentucky and Missouri.

Its abundance in the early days of the country is still evident by the fact that it still grows wild in many fields and along many roadways. The plant is now indigenous to many areas, and adapts easily to most soil and moderate climatic conditions.

Marijuana is classifed as a hallucinogenic substance. The primary active constituents in the plant are cannabinol, cannabidiol, and the tetrahydrocannabinols, The tetrahydrocannabinols (THCs) are the active components responsible for the hallucinogenic properties of marijuana. The THC of most interest is the Δ9- tetrahydrocannabinol. The other THCs of interest in marijuana are the Δ 1 cis- and trans- tetrahydrocannabinols, the Δ6 cis- and trans- tetrahydrocannabinols, and the Δ 3- and Δ4- tetrahydrocannibinols. The concentrations varies dramatically from geographic area to geographic area, from field to field, and from sample to sample. This concentration range varies from less than 1% to as high as 30%. In recent hash oil exhibits, the highest official reported concentration of Δ9-THC is 43%. 2 Five other terms associated with marijuana are:

Hashish: Resinous material removed from cannabis. Hashish is usually found in the form of a brown to black cake of resinous material. The material is ingested by smoking in pipes or by consuming in food.

Hashish oil: Extract of the marijuana plant which has been heated to remove the extracting solvents. The material exists as a colorless to brown or black oil or tarlike substance.

Sinsemilla: The flowering tops of the unfertilized female cannabis plant. (There are no seeds on such a plant.) Sensemilla is usually considered a “gourmet” marijuana because of its appearance and relatively high concentrations of the THCs.

Thai sticks: Marijuana leaves tied around stems or narrow diameter bamboo splints. Thai sticks are considered a high quality product by the drug culture. The THC concentrations of the marijuana leaves on Thai sticks are higher than domestic marijuana. Unlike hashish and sinsemilla, seeds, and small pieces of stalks and stems are found in Thai sticks.

Brick or Kilo: Marijuana compressed into a brick-shaped package with leaves, stems, stalk, and seeds. The pressed marijauna is usually tightly wrapped in paper and tape. This is the form of marijuana encountered in most large scale seizures. These large scale seizure packages weigh approximately 1000 g (1 kg). This is the packaging form of choiced for clandestine operators because of the ease of handling, packaging, shipping, and distribution.

Sources of Cocaine

Cocaine is just one of the alkaloidal substances present in the coca leaf. Cocaine is extracted from the leaves of the coca plant. The primary of source of cocaine imported into the U.S. is South America, but the coca plant also grows in the Far East in Ceylon, Java, and India. The plant is cultivated in South America on the eastern slopes of the Andes in Peru, and Bolivia. There are four varieties of coca plants — Erythroxylon coca var. coca (ECVC), Erythroxylon coca var. ipadu, Erythroxylum novogranatense var. novogranatense, and Erythroxylum novogranatense var. truxillense.1–3 ECVC is the variety that has been used for the manufacture of illicit cocaine.

While cultivated in many countries of South America, Peru and Bolivia are the world’s leading producers of the coca plant. Cocaine is present in the coca leaves from these countries at dry weight concentrations of from 0.1 to 1%. The average concentration of cocaine in the leaf is 0.7%. The coca shrub has a life expectancy of 50 years and can be harvested three or four times a year.

The method of isolating cocaine from the coca leaf does not require a high degree of technical expertise or experience. It requires no formal education or expensive scientific equipment or chemicals. In most instances the methodology is passed from one generation to the next.

Cocaine

The social implications of cocaine abuse in the U.S. have been the subject of extensive media coverage during much of the 1980s and most of the 1990s. As a result, the general public has acquired some of the terminology associated with the cocaine usage. “Smoking crack” and “snorting coke” are terms that have become well understood in the American culture from elementary school through adulthood. However, there are facts associated with this drug which are not well understood by the general public.

There are documented historical aspects associated with coca and cocaine abuse which go back 500 years. Recognizing some of these historical aspects enables the public to place today’s problem in perspective. Cocaine addiction has been with society for well over 100 years.

There are four areas of interest this section will address: (1) Where does cocaine come from? (2) How is cocaine isolated from the coca plant? (3) What does one take into the body from cocaine purchased on the street? (4) How does the chemist analyzing the drug identify and distinguish between the different forms of cocaine?

Cocaine is a Schedule II controlled substance. The wording in Title 21, Part 1308.12(b)(4) of the Code of Federal Regulations states:

Coca leaves (9040) and any salt, compound, derivative or preparation of coca leaves (including cocaine (9041) and ecgonine (9180) and their salts, isomers, derivatives and salts of isomers and derivatives), and any salt, compound, derivative, or preparation thereof which is chemically equivalent or identical with any of these substances, except that the substances shall not include decocanized coca leaves, or extractions of coca leaves, do not contain cocaine or ecgonine.

It is significant that the term “coca leaves” is the focal point of that part of the regulation controlling cocaine. The significance of this fact will become more apparent as this discussion progresses.

Isolation of Morphine and Heroin Production

same four steps: (1) The opium poppy (Papaver Somniferum L.) is cultivated; (2) the poppy head is scored and the opium latex is collected; (3) the morphine is the isolated from the latex; and (4) the morphine is treated with an acetylating agent. Isolation of the morphine in Step 3 is accomplished using a rendition of one of the following five methods:

1. The Thiboumery and Mohr Process (TMP)—This is the most well known of the reported methods for isolating morphine followed by the acetylation to heroin. Dried opium latex is dissolved in three times its weight of hot water. The solution is filtered hot which removes undissolved botanical substances. These undissolved botanicals are washed with hot water and filtered. This is done to ensure a maximized yield of morphine in the final product. The filtrate is reduced to half its volume by boiling off the water. The laboratory operator then adds to the filtrate a boiling solution of calcium hydroxide which forms the water soluble calcium morphinate. The precipitates, which include the insoluble alkaloids from the opium, and the insoluble materials from this step are filtered. These insolubles are then washed three more times with water and filtered. The resulting filtrate, which contains calcium morphinate still in solution, is then evaporated to a weight of approximately twice the weight of the original weight of the opium and then filtered. This results in a concentrated calcium morphinate solution which is heated to a boil. Ammonium chloride is then added to reduce the pH below 9.85. When this solution cools, morphine base precipitates and is collected by filtration. The morphine base is dissolved in a minimum volume of warm hydrochloric acid. When this solution cools the morphine hydrochloride precipitates. The precipitated morphine hydrochloride is then isolated by filtration.

2. The Robertson and Gregory Process (RGP)—This method is similar to the Thiboumery and Mohr Process. The laboratory operator washes the opium with five to ten times its weight of cold water. The solution is then evaporated to a syrup which is then re-extracted with cold water and filtered. The filtrate is evaporated until the specific gravity of the solution is 1.075. The solution is boiled and calcium chloride is added. Cold water is added to the calcium morphinate solution which is then filtered. The solution is concentrated and the calcium morphinate then precipitates out of solution as the liquid evaporates. The calcium morphinate is then redissolved in water and filtered. To the filtrate is added ammonia which allows the morphine base to precipitate. This morphine base can then be further treated to produce the pharmaceutical quality morphine.

The Thiboumery and Mohr Process and the Robertson and Gregory Process are used by commercial suppliers for the initial isolation of morphine from opium. In clandestine laboratories, the same methodologies and rudimentary steps are followed. However, since the operators are using “bucket chemistry”, there are modifications to hasten and shortcut the processes.

Three other methods can then be utilized to convert the relatively crude morphine base through purification processes to high quality morphine base or morphine hydrochloride crystals. Modifications of these purifications are used by clandestine laboratory operators.

3. The Barbier Purification—The morphine base is dissolved in 80ｰC water. Tartaric acid is added until the solution becomes acidic to methyl orange. As the solution cools, morphine bitartrate precipitates, is filtered, washed with cold water, and dried. The morphine bitartrate is then dissolved in hot water and ammonia is added to pH 6. This results in a solution of morphine monotartrate. The laboratory operator then adds activated carbon black, sodium bisulfite, sodium acetate, and ammonium oxalate. This process results in a decolorization of the morphine. When this decolorization process is complete, ammonia is added to the solution which results in white crystals of morphine base. These purified morphine base crystals are then filtered and dried. This high quality morphine base is converted to morphine hydrochloride by adding 30% ethanolic HCl to a warm solution of morphine in ethanol. The morphine hydrochloride crystallizes from solution as the solution cools.

4. The Schwyzer Purification—The acetone insoluble morphine base (from either the TMB or RGP) is washed in with acetone. The morphine base is then recrystallized from hot ethyl alcohol.

5. The Heumann Purification—The laboratory operator washes the morphine base from either the TMB or RGP) with trichloroethylene, followed by a cold 40% ethanol wash. This is subsequently followed by an aqueous acetone wash. The quality of the clandestine product is usually evaluated by the color and texture of the morphine from one of these processes. If the clandestine laboratory operator is producing morphine as his end product, with the intention of selling the morphine for conversion by a second laboratory, the morphine will usually be very pure. However, if he continues with the acetylation of the morphine to heroin, the “intermediate” morphine will frequently be relatively impure.

Heroin can be produced synthetically, but requires a 10-step process and extensive expertise in synthetic organic chemistry. The total synthesis of morphine has been reported by Gates and Tschudi in 1952 and by Elad and Ginsburg in 1954.3,4 A more recent synthesis was reported by Rice in 1980.5 All of these methods require considerable forensic expertise and result in low yield. There are also methods reported in the literature for converting codeine to morphine using an O-demethylation. The morphine can then be acetylated to heroin.

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.