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.