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Drug Abuse

Drug abuse

Drug abuse has a wide range of definitions, all of them relating to the use, misuse or overuse of a drug for a non-therapeutic or non-medical effect. Some of the most commonly abused drugs include alcohol, amphetamines, barbiturates, caffeine, cannabis, cocaine, methaqualone, nicotine, opium alkaloids, and minor tranquilizers. Use of these drugs may lead to criminal penalty in addition to physical, social, and pyschologic harm. Other definitions of drug abuse fall into four main categories:

Definitions

Public health definitions

In recent decades, public health practicitioners have attempted to look at drug abuse from a broader perspective than the individual, emphasising the role of society, culture and availability. Rather than alcohol or drug "abuse" many public health professionals have adopted the terms "alcohol and drug problems" or "harmful/problematic use" of drugs.

Mass communication and vernacular usage

The term may be used in newspapers, television, etc. in a ambiguous, catch-all sense rather than as a medical or legal term, sometimes disapprovingly to refer to any drug use at all, particularly of illicit drugs.

Medical definitions

In the modern medical profession, the two most used diagnostic tools in the world, the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM) and the World Health Organization's International Statistical Classification of Diseases and Related Health Problems (ICD), no longer recognise 'drug abuse' as a current medical diagnosis. Instead, they have adopted substance abuse as a blanket term to include drug abuse and other things. However, other definitions differ; they may entail psychological or physical dependence, and may focus on treatment and prevention in terms of the social consequences of substance use.

Historical positions of the American Psychiatric Association

In the early 1950s, the first edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders refered to both alcohol and drug abuse as part of Sociopathic Personality Disturbances, which were thought to be symptoms of deeper psychological disorders or moral weakness . By the third edition, in the 1980s, drug abuse was grouped into 'substance abuse'. In 1972, the American Psychiatric Association created a definition that used legality, social acceptability, and even cultural familiarity as qualifying factors:

…as a general rule, we reserve the term drug abuse to apply to the illegal, nonmedical use of a limited number of substances, most of them drugs, which have properties of altering the mental state in ways that are considered by social norms and defined by statute to be inappropriate, undesirable, harmful, threatening, or, at minimum, culture-alien.

Historical positions of the American Medical Association

In 1966, the American Medical Association's Committee on Alcoholism and Addiction defined abuse of stimulants (amphetamines, primarily) in terms of "medical supervision":

…"use" refers to the proper place of stimulants in medical practice; "misuse" applies to the physician's role in initating a potentially dangerous course of therapy; and "abuse" refers to self-administration of these drugs without medical supervision and particularly in large doses that may lead to psychological dependency, tolerance and abnormal behavior.

Handbook on Drug and Alcohol Abuse

The Handbook on Drug and Alcohol Abuse defines drug abuse as "nonmedical use of drugs, both drugs that have and those that do not have generally accepted medical value".

Political and criminal justice definitions

Most countries have legislation designed to criminalise some drug use. Usually however the legislative process is self-referential, defining abuse in terms of what is made illegal. The legislation concerns lists of drugs specified by the legislation. These drugs are often called illegal drugs but, generally, what is illegal is their unlicensed production, supply and possession. The drugs are also called controlled drugs or controlled substances.

World Health Organization

The World Health Organization (WHO), a public health agency comprised of delegates appointed by the governments of member nations, is considered by many to be a medical authority. Definitions found in WHO reports are often used as the basis for legislation at national, regional and local levels. The WHO also produces the ICD, a major diagnostic resource used by medical professionals worldwide. Although it consists largely of public health professionals, the WHO is an arm of the United Nations political body, and is therefore responsive to the needs of, demands from, and prevailing views among the UN member states that appoint WHO delegates. The manner in which the WHO has recognized and dealt with 'drug abuse' over the years reflects a continuing struggle to reconcile conflicting historical, political, social, cultural, and medical viewpoints. In its early reports, the WHO Expert Committee on Addiction-Producing Drugs used the terms 'abuse' and 'addiction' interchangeably. Beginning in 1950s, attempts were made to distinguish between scientific and emotionally-charged terminology. However, the term 'abuse' was still inserted into definitions of addiction and dependency. In 1957, while not explicitly saying that 'drug abuse' was synonymous with 'addiction', the committee first attempted to clarify existing definitions of addiction and habituation as had been in common parlance since at least 1931:

Drug addiction is a state of periodic or chronic intoxication produced by the repeated consumption of a drug (natural or synthetic). Its characteristics include: (i) an overpowering desire or need (compulsion) to continue taking the drug and to obtain it by any means; (ii) a tendency to increase the dose; (iii) a psychic (psychological) and generally a physical dependence on the effects of the drug; and (iv) detrimental effects on the individual and on society.

Drug habituation (habit) is a condition resulting from the repeated consumption of a drug. Its characteristics include (i) a desire (but not a compulsion) to continue taking the drug for the sense of improved well-being which it engenders; (ii) little or no tendency to increase the dose; (iii) some degree of psychic dependence on the effect of the drug, but absence of physical dependence and hence of an abstinence syndrome [withdrawal], and (iv) detrimental effects, if any, primarily on the individual.

In 1964, a new WHO committee found these definitions to be inadequate, and suggested using the blanket term 'drug dependence':

The definition of addiction gained some acceptance, but confusion in the use of the terms addiction and habituation and misuse of the former continued. Further, the list of drugs abused increased in number and diversity. These difficulties have become increasingly apparent and various attempts have been made to find a term that could be applied to drug abuse generally. The component in common appears to be dependence, whether psychic or physical or both. Hence, use of the term 'drug dependence', with a modifying phase linking it to a particular drug type in order to differentiate one class of drugs from another, had been given most careful consideration. The Expert Committee recommends substitution of the term 'drug dependence' for the terms 'drug addiction' and 'drug habituation'. (emphasis added)

The committee did not clearly define dependence, but did go on to clarify that there was a distinction between physical and psychological ('psychic') dependence. It said that drug abuse was "a state of psychic dependence or physical dependence, or both, on a drug, arising in a person following administration of that drug on a periodic or continued basis." Psychic dependence was defined as a state in which "there is a feeling of satisfaction and psychic drive that requires periodic or continuous administration of the drug to produce pleasure or to avoid discomfort" and all drugs were said to be capable of producing this state:

There is scarcely any agent which can be taken into the body to which some individuals will not get a reaction satisfactory or pleasurable to them, persuading them to continue its use even to the point of abuse — that is, to excessive or persistent use beyond medical need. (emphasis added)

This is believed to be the first reference to "medical need" as a factor in the distinction between use and abuse. In 1965, the same WHO committee commented further, now providing a specific definition of abuse:

Drug abuse is the consumption of a drug apart from medical need or in unnecessary quantities. Its nature and significance may be considered from two points of view: one relates to the interaction between the drug and the individual, the other to the interaction between drug abuse and society. The first viewpoint is concerned with drug dependence and the interplay between the pharmacodynamic actions of the drug and the physiological and psychological status of the individual. The second — the interaction between drug abuse and society — is concerned with the interplay of a wide range of conditions, environmental, sociological, and economic.

Individuals may become dependent upon a wide variety of chemical substances that produce central nervous system effects ranging from stimulation to depression. All of these drugs have one effect in common: they are capable of creating, in certain individuals, a particular state of mind that is termed "psychic dependence ".

Some drugs… induce physical dependence, which is an adaptive state that manifests itself by intense physical disturbances when the administration of the drug is suspended or when its action is affected by the administration of a specific antagonist.

The committee offered several disclaimers of its definitions:

It must be emphasized that drug dependence and drug abuse, as used by the Committee, are general terms and carry no connotation of the degree of risk to public health or of the need for drug control or for a particular type of drug control. The Committee would point out again that the recommendation for the use of the terms drug abuse and drug dependence of this or that type must not be regarded as a re-definition; rather, these terms are intended as descriptive expressions for clarification in scientific reference, interdisciplinary discussions, and national and international procedures.

The 1969 edition of the WHO's International Statistical Classification of Diseases and Related Health Problems (ICD) manual defined drug abuse as "persistent or sporadic excessive drug use inconsistent with or unrelated to acceptable medical practice", modern editions have not used the term because of it's ambiguity, prefering instead to refer to the cluster of symptoms previously called 'drug abuse' as 'substance abuse'. In 1973, these statements and recent legislation based upon the term "dependence" rather than "addiction" or "abuse" were praised by President Richard M. Nixon's National Commission on Marihuana and Drug Abuse in its final report:

The Commission applauds the much-belated attempt by the scientific community to sever its conceptual apparatus from the vocabulary of politics and emotion. "Addiction," like "narcotics" and "drug abuse," has a general connotation of evil, suggesting illicit ecstasy, guilt and sin. Because the public image is conditioned more by cultural perceptions than by medical ones, medically-precise meanings simply cannot be harmonized with common parlance.

And in 1975, the WHO further distanced itself from the term 'drug abuse':

"Drug abuse" is a term in need of some clarification. …The term is really a convenient, but not very precise, way of indicating that (1) an unspecified drug is being used in an uspecified manner and amount … and (2) such use has been judged by some person or group to be wrong (illegal or immoral) and/or harmful to the user or society, or both. What might be called "drug abuse" by some would not necessarily be considered so by others. … For these reasons, the term "drug abuse" is avoided here

The World Health Organization presently prefers to use the terms harmful use and hazardous use (of drugs), in order to distinguish between the health effects of drug abuse rather than the social consequences. Another preferred term is drug misuse, defined as the "use of a substance for a purpose not consistent with legal or medical guidelines, as in the non-medical use of prescription medications." According to WHO, the term misuse is preferred by some in the belief that it is less judgmental. However, the 1957 and 1964–1965 WHO definitions of addiction, dependence and drug abuse persist to the present day in medical literature and have become entrenched in global legislation, despite the disclaimers and reliance on contentious assumptions. The WHO itself continues to use 'drug abuse' in its publications, and uses the term 'abuse' consistently and exclusively when discussing the control and consumption of illegal substances. This is in keeping with guidelines issued by the WHO's parent organization, the United Nations, which discourages any recognition of "recreational" or "responsible" use of drugs. Researchers may take note that somewhat less contentious definitions of addiction, dependence, and tolerance (with no speculation as to their roles in the definition of drug abuse) were jointly issued in 2001 by the American Academy of Pain Medicine, the American Pain Society, and the American Society of Addiction Medicine in the publication "Definitions Related to the Use of Opioids for the Treatment of Pain".

NIDA

The US National Institute on Drug Abuse defines drug abuse as "The use of illegal drugs or the inappropriate use of legal drugs. The repeated use of drugs to produce pleasure, to alleviate stress, or to alter or avoid reality (or all three)."

Nixon Administration

In 1975, psychiatrist Jerome H. Jaffe (in his role as Drug Policy Director in the Nixon Administration) defined drug abuse as "the use, usually by self-administration, of any drug in a manner that deviates from the approved medical or social patterns within a given culture". According to Jaffe, the term "conveys the notion of social disapproval, and it is not necessarily descriptive of any particular pattern of drug use or its potential adverse consequences".

Alcohol

In general usage, alcohol (from Arabic al-ghawl الغول) refers almost always to ethanol, also known as grain alcohol, and often to any beverage that contains ethanol (see alcoholic beverage). This sense underlies the term alcoholism (addiction to alcohol). Other forms of alcohol are usually described with a clarifying adjective, as in isopropyl alcohol or by the suffix -ol, as in isopropanol. In chemistry, alcohol is a more general term, applied to any organic compound in which a hydroxyl group (-O H) is bound to a carbon atom, which in turn is bound to other hydrogen and/or carbon atoms. The general formula for a simple acyclic alcohol is C_nH_2n+1OH. As a drug, common alcohol (ethanol) is known to have a depressing effect that decreases the responses of the central nervous system.

Structure

central nervous system The functional group of an alcohol is a hydroxyl group bonded to an sp³ hybridized carbon. It can therefore be regarded as a derivative of water, with an alkyl group replacing one of the hydrogens. If an aryl group is present rather than an alkyl, the compound is generally called a phenol rather than an alcohol. The oxygen in an alcohol has a bond angle of around 109° (c.f. 104.5° in water), and two nonbonded electron pairs. The O-H bond in methanol (CH₃OH) is around 96 picometres long.

Primary, secondary, and tertiary alcohols

There are three major subsets of alcohols- 'primary' (1°), 'secondary' (2°) and 'tertiary' (3°), based upon the number of carbons the C-OH carbon (shown in red) is bonded to. Methanol is the simplest 'primary' alcohol. The simplest secondary alcohol is isopropanol (propan-2-ol), and a simple tertiary alcohol is tert-butanol (2-methylpropan-2-ol). butanol

Methanol & ethanol

The simplest and most commonly used alcohols are methanol and ethanol (common names methyl alcohol and ethyl alcohol, respectively), which have the structures shown above. Methanol was formerly obtained by the distillation of wood, and was called "wood alcohol". It is now a cheap commodity chemical produced by the high pressure reaction of carbon monoxide with hydrogen. In common usage, "alcohol" often refers simply to ethanol or "grain alcohol". Methylated spirits ("Meths"), also called "surgical spirits", is a form of ethanol rendered undrinkable by the addition of methanol. Aside from its major use in alcoholic beverages, ethanol is also used (though highly controlled) as an industrial solvent and raw material.

Uses

Alcohols are in wide use in industry and science as reagents, solvents, and fuels. Ethanol and methanol can be made to burn more cleanly than gasoline or diesel. Because of its low toxicity and ability to dissolve non-polar substances, ethanol is often used as a solvent in medical drugs, perfumes, and vegetable essences such as vanilla. In organic synthesis, alcohols frequently serve as versatile intermediates. Ethanol is also commonly used in beverages after fermentation to promote flavor or induce a euphoric intoxication commonly known as "drunkenness" or "being drunk". The use of ethanol for this purpose is illegal in some jurisdictions.

Sources

Many alcohols can be created by fermentation of fruits or grains with yeast, but only ethanol is commercially produced this way, chiefly for fuel and drink. Other alcohols are generally produced by synthetic routes from natural gas, petroleum, or coal feed stocks, for example via acid catalyzed hydration of alkenes. For more details see Chemistry of alcohols

Nomenclature

Systematic names

In the IUPAC system, the name of the alkane chain loses the terminal "e" and adds "ol", e.g. "methanol" and "ethanol". When necessary, the position of the hydroxyl group is indicated by a number between the alkane name and the "ol": propan-1-ol for CH₃CH₂CH₂OH, propan-2-ol for CH₃CH(OH)CH₃. Sometimes, the position number is written before the IUPAC name: 1-propanol and 2-propanol. If a higher priority group is present (such as an aldehyde, ketone or carboxylic acid), then it is necessary to use the prefix "hydroxy", for example: 1-hydroxy-2-propanol (CH₃COCH₂OH). Some examples of simple alcohols and how to name them: carboxylic acid Common names for alcohols usually take the name of the corresponding alkyl group and add the word "alcohol", e.g. methyl alcohol, ethyl alcohol or tert-butyl alcohol. Propyl alcohol may be n-propyl alcohol or isopropyl alcohol depending on whether the hydroxyl group is bonded to the 1st or 2nd carbon on the propane chain. Isopropyl alcohol is also occasionally called sec-propyl alcohol. As mentioned above alcohols are classified as primary (1°), secondary (2°) or tertiary (3°), and common names often indicate this in the alkyl group prefix. For example (CH₃)₃COH is a tertiary alcohol is commonly known as tert-butyl alcohol. This would be named 2-methylpropan-2-ol under IUPAC rules, indicating a propane chain with methyl and hydroxyl groups both attached to the middle (#2) carbon. An alcohol with two hydroxyl groups is commonly called a "glycol", e.g. HO-CH₂-CH₂-OH is ethylene glycol. The IUPAC name is ethane-1,2-diol, "diol" indicating two hydroxyl groups, and 1,2 indicating their bonding positions. Geminal glycols (with the two hydroxyls on the same carbon atom), such as ethane-1,1-diol, are generally unstable. For three or four groups, "triol" and "tetraol" are used.

Etymology

The word "alcohol" almost certainly comes from the Arabic language (the "al-" prefix being the Arabic definite article); however, the precise origin is unclear. It was introduced into Europe, together with the art of distillation and the substance itself, around the 12th century by various European authors who translated and popularized the discoveries of Islamic alchemists. A popular theory, found in many dictionaries, is that it comes from الكحل = ALKHL = al-kuhul, originally the name of very finely powdered antimony sulfide Sb₂S₃ used as an antiseptic and eyeliner. The powder is prepared by sublimation of the natural mineral stibnite in a closed vessel. According to this theory, the meaning of alkuhul would have been first extended to distilled substances in general, and then narrowed to ethanol. This conjectured etymology has been circulating in England since 1672 at least (OED). However, this derivation is suspicious since the current Arabic name for alcohol, الكحول = ALKHWL = al???, does not derive from al-kuhul. The Qur'an in verse 37:47 uses the word الغول = ALGhWL = al-ghawl — properly meaning "spirit" ("spiritual being") or "demon" — with the sense "the thing that gives the wine its headiness". The word al-ghawl also originated the English word "ghoul", and the name of the star Algol. This derivation would, of course, be consistent with the use of "spirit" or "spirit of wine" as synonymous of "alcohol" in most Western languages. (Incidentally, the etymology "alcohol" = "the devil" was used in the 1930s by the U.S. Temperance Movement for propaganda purposes.) According to the second theory, the popular etymology and the spelling "alcohol" would not be due to generalization of the meaning of ALKHL, but rather to Western alchemists and authors confusing the two words ALKHL and ALGhWL, which have indeed been transliterated in many different and overlapping ways.

Physical and chemical properties

The hydroxyl group generally makes the alcohol molecule polar. Those groups can form hydrogen bonds to one another and to other compounds. Two opposing solubility trends in alcohols are: the tendency of the polar OH to promote solubility in water, and of the carbon chain to resist it. Thus, methanol, ethanol, and propanol are miscible in water because the hydroxyl group wins out over the short carbon chain. Butanol, with a four-carbon chain, is moderately soluble because of a balance between the two trends. Alcohols of five or more carbons (Pentanol and higher) are effectively insoluble because of the hydrocarbon chain's dominance. Because of hydrogen bonding, alcohols tend to have higher boiling points than comparable hydrocarbons and ethers. All simple alcohols are miscible in organic solvents. This hydrogen bonding means that alcohols can be used as protic solvents. The lone pairs of electrons on the oxygen of the hydroxyl group also makes alcohols nucleophiles. Alcohols, like water, can show either acidic or basic properties at the O-H group. With a pK_a of around 16-19 they are generally slightly weaker acids than water, but they are still able to react with strong bases such as sodium hydride or reactive metals such as sodium. The salts that result are called alkoxides, with the general formula RO^- M⁺. Meanwhile the oxygen atom has lone pairs of nonbonded electrons that render it weakly basic in the presence of strong acids such as sulfuric acid. For example, with methanol: sulfuric acid Alcohols can also undergo oxidation to give aldehydes, ketones or carboxylic acids, or they can be dehydrated to alkenes. They can react to form ester compounds, and they can (if activated first) undergo nucleophilic substitution reactions. For more details see the #Chemistry of alcohols section below.

Toxicity

Alcohols often have an odor described as 'biting' that 'hangs' in the nasal passages. Ethanol in the form of alcoholic beverages has been consumed by humans since pre-historic times, for a variety of hygienic, dietary, medicinal, religious, and recreational reasons. While infrequent consumption of ethanol in small quantities may be harmless or even beneficial, larger doses result in a state known as drunkenness or intoxication and, depending on the dose and regularity of use, can cause acute respiratory failure or death and with chronic use has medical repercussions. Other alcohols are substantially more poisonous than ethanol, partly because they take much longer to be metabolized, and often their metabolism produces even more toxic substances. Methanol, or wood alcohol, for instance, is oxidized by alcohol dehydrogenase enzymes in the liver to the poisonous formaldehyde, which can cause blindness or death. Interestingly, an effective treatment to prevent formaldehyde toxicity after methanol ingestion is to administer ethanol. This will bind to alcohol dehydrogenase, preventing methanol from binding and thus acting as a substrate. Any formaldehyde will be converted to formic acid and excreted before it causes damage.

Chemistry of alcohols

Preparation

Laboratory

There are three common methods:
- From alkyl halides: react with aqueous NaOH or KOH (mainly 1° alcohols). :R-Br + KOH → R-OH + KBr
- From aldehydes or ketones: reduction with sodium borohydride or lithium aluminium hydride. :R-CHO - [O] → R-OH
- From alkenes: an acid catalysed hydration reaction using concentrated sulfuric acid as a catalyst (gives usually 2° or 3° alcohols). :C₂H₄ + H₂SO₄ (l) → C₂H₅-HSO₄ :C₂H₅-HSO₄ + H₂O → C₂H₅OH + H₂SO₄ The formation of a secondary alcohol via the last two methods is shown: sulfuric acid

Industrial

- Fermentation: using glucose produced from sugar from the hydrolysis of starch, in the presence of yeast and temperature of <37°C to produce ethanol. :C₁₂H₂₂O₁₁ → C₆H₁₂O₆ + C₆H₁₂O₆ :Invertase → glucose + fructose :C₆H₁₂O₆ + H₂O → C₂H₅OH + CO₂ :Glucose → zymase + ethanol
- Direct hydration: using ethene or other alkenes from cracking of fractions of distilled crude oil. Uses a catalyst of phosphoric acid under high temperature and pressure.
- Methanol from water gas: It is manufactured from synthesis gas, where CO + 2 H₂ are combined to produce methanol using a Cu, ZnO and Al₂O₃ catalyst at 250°C and a pressure of 50-100 atm. :[CO + H₂] + H₂O (g) → CH₃OH

Reactions

See the physical and chemical properties section above for a general overview.

Deprotonation

Alcohols can behave as weak acids, undergoing deprotonation. The deprotonation reaction to produce an alkoxide salt is either performed with a strong base such as sodium hydride or n-butyllithium, or with sodium or potassium metal. : 2 R-OH + 2 NaH → 2 R-O^-Na⁺ + H₂↑ : 2 R-OH + 2Na → 2R-O⁻Na⁺ : e.g. 2 CH₃CH₂-OH + 2 Na → 2 CH₃-CH₂-O⁻Na⁺ Water is similar in pK_a to many alcohols, so with sodium hydroxide there is an equilibrium set up which usually lies to the left: : R-OH + NaOH <=> R-O^-Na⁺ + H₂O (equilibrium to the left)

Nucleophilic substitution

The OH group is not a good leaving group in nucleophilic substitution reactions, so neutral alcohols do not react in such reactions. However if the oxygen is first protonated to give R−OH₂⁺, the leaving group (water) is much more stable, and nucleophilic substitution can take place. For instance, tertiary alcohols react with hydrochloric acid to produce tertiary alkyl halides, where the hydroxyl group is replaced by a chlorine atom. If primary or secondary alcohols are to be reacted with hydrochloric acid, an activator such as zinc chloride is needed. Alternatively the conversion may be performed directly using thionyl chloride.^[1] thionyl chloride Alcohols may likewise be converted to alkyl bromides using hydrobromic acid or phosphorus tribromide, for example: : 3 R-OH + PBr₃ → 3 RBr + H₃PO₃ In the Barton-McCombie deoxygenation an alcohol is deoxygenated to an alkane with tributyltin hydride or a trimethylborane-water complex in a radical substitution reaction.

Dehydration

Alcohols are themselves nucleophilic, so R−OH₂⁺ can react with ROH to produce ethers and water, although this reaction is rarely used except in the manufacture of diethyl ether. More useful is the E1 elimination reaction of alcohols to produce alkenes. The reaction generally obeys Zaitsev's Rule, which states that the most stable (usually the most substituted) alkene is formed. Tertiary alcohols eliminate easily at just above room temperature, but primary alcohols requre a higher temperature. This is a diagram of acid catalysed dehydration of ethanol to produce ethene: 550px

Esterification

To form an ester from an alcohol and a carboxylic acid the reaction, known as "Fischer esterification", is usually performed at reflux with a catalyst of concentrated sulfuric acid: : R-OH + R'-COOH

\Leftrightarrow

R'-COOR + H₂O In order to drive the equilibrium to the right and produce a good yield of ester, water is usually removed, either by an excess of H₂SO₄ or by using a Dean-Stark apparatus. Esters may also be prepared by reaction of the alcohol with an acid chloride in the presence of a base such as pyridine. Other types of ester are prepared similarly- for example p-toluenesulfonate (tosylate) esters are made by reaction of the alcohol with p-toluenesulfonyl chloride in pyridine.

Oxidation

Primary alcohols generally give aldehydes or carboxylic acids upon oxidation, while secondary alcohols give ketones. Traditionally strong oxidants such as the dichromate ion or potassium permanganate are used, under acidic conditions, for example: :3 CH₃-CH(-OH)-CH₃ + K₂Cr₂O₇ + 4 H₂SO₄ → 3 CH₃-C(=O)-CH₃ + Cr₂(SO₄)₃ + K₂SO₄ + 7 H₂O Frequently in aldehyde preparations these reagents cause a problem of over-oxidation to the carboxylic acid. To avoid this, other reagents such as PCC, Dess-Martin periodinane, IBX acid, TPAP or methods such as Swern oxidation are now preferred. Alcohols with a methyl group attached to the alcohol carbon can also undergo a haloform reaction (such as the iodoform reaction) in the presence of the halogen and a base such as sodium hydroxide. Tertiary alcohols resist oxidation, but can be oxidised by reagents such as 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.

External links

- [http://www.french-paradox.net/fpbksb1.html What Is Alcohol, Anyway?] Interesting information about alcohols.
- Category:Drugs Category:Antiseptics Category:Arabic words Category:functional groups ja:アルコール simple:Alcohol

Barbiturate

Barbiturates are drugs that act as central nervous system (CNS) depressants, and by virtue of this they produce a wide spectrum of effects, from mild sedation to anesthesia. Some are also used as anticonvulsants. Barbiturates are derivatives of barbituric acid. barbituric acid

Medical uses

Today barbiturates are infrequently used as anticonvulsants and for the induction of anesthesia. Benzodiazepines were made as barbiturate alternatives and as such are more widely used and prescribed today than the barbiturate drugs. These barbiturates are available in the U.S.:
- Amobarbital (Sodium Amytal; hypnotics)
- Aprobarbital (hypnotic)
- Butabarbital (hypnotics)
- Butalbital (Fiorinal; sedative)
- Hexobarbital (Sombulex; hypnotic/anesthetic)
- Mephobarbital (antianxiety)
- Pentobarbital (Nembutal; hypnotic)
- Phenobarbital (Luminal; hypnotic, sedative, anticonvulsant)
- Secobarbital (Seconal; hypnotic)
- Sodium thiopental
- Talbutal (Lotusate; hypnotic)
- Thiobarbital (anesthetic) Sometimes two or more barbiturates are combined in a single tablet or capsule; perhaps the most well-known of these combinations is Tuinal, which consists of amobarbital and secobarbital in equal proportions.

Barbiturate abuse

Barbiturates were very popular in the first half of the 20th century. In moderate amounts, these drugs produce a state of intoxication that is remarkably similar to alcohol intoxication. Symptoms include slurred speech, loss of motor coordination, and impaired judgment. Depending on the dose, frequency, and duration of use, one can rapidly develop tolerance, physical dependence, and psychological dependence on barbiturates. With the development of tolerance, the margin of safety between the effective dose and the lethal dose becomes very narrow. That is, in order to obtain the same level of intoxication, the tolerant abuser may raise his or her dose to a level that may result in coma or death. Although many individuals have taken barbiturates therapeutically without harm, concern about the addiction potential (withdrawal symptoms can include tonic-clonic or grand mal seizures potentially leading to permanent disability or even death) of barbiturates and the ever-increasing number of fatalities associated with them led to the development of alternative medications, namely benzodiazepines. Today, fewer than 10 percent of all sedative/hypnotic prescriptions in the United States are for barbiturates.

History

- Dec 4, 1863 Barbituric acid is discovered by German researcher Adolf von Baeyer. His discovery came on the day of St. Barbara, so he chose the name "barbiturate" as a combination of St. Barbara and "urea". Another possible explanation is that he named the substance after his girlfriend Barbara.
- 1903 Barbital, the first medicinal barbiturate, is synthesized from barbituric acid by German scientists Emil Hermann Fischer and Joseph von Mering. It was marketed under the trade name Veronal.
- 1912 Phenobarbital is introduced under the trade name Luminal as a sedative-hypnotic.
- 1950s - 1960s Reports increase about side effects and dependence related to barbiturates.
- 1970 Pentobarbital (II), secobarbital (II), amobarbital (II), butabarbital (III), phenobarbital (IV), and barbital (IV) are all scheduled with the passage of the U.S. Drug Abuse Regulation and Control Act of 1970.
- 1971 Convention on Psychotropic Substances is signed in Vienna. Designed to regulate amphetamines, barbiturates, and other synthetics, the treaty today regulates amobarbital (III), butalbital (III), cyclobarbital (III), pentobarbital (III), allobarbital (IV), methylphenobarbital (IV), phenobarbital (IV), secbutabarbital (IV), and vinylbital (IV) as scheduled substances.

Other non-therapeutical use

Barbiturates in high doses are used for physician-assisted suicide (PAS), and, in combination with a muscle relaxant, for euthanasia and for capital punishment by lethal injection.

Trivia

- Marilyn Monroe died from an overdose of barbiturates, as did George Sanders and also Jean Seberg.
- Judy Garland (Dorothy from the Wizard of Oz) also died from (accidental) barbiturate overdose.
- Michael Rabin, one of the most prodigious violinists America has ever had, became dependent on barbiturates and his death was partially linked to abuse of this drug.
- Jimi Hendrix's death was a combination of barbiturate overdose and vomit inhalation.

References

- Text partially derived from public domain text from [http://www.usdoj.gov/dea/concern/depressants.html U.S. Drug Enforcement Agency].
- http://www.erowid.org/chemicals/barbiturates/barbiturates.shtml
- http://www.ch.ic.ac.uk/rzepa/mim/drugs/html/barbiturate_text.htm Category:Barbiturates Category:Anticonvulsants

Caffeine

Caffeine, also known as trimethylxanthine, coffeine, theine, mateine, guaranine, methyltheobromine and 1,3,7-trimethylxanthine, is a xanthine alkaloid found naturally in such foods as coffee beans, tea, kola nuts, Yerba mate, guarana berries, and (in small amounts) cacao beans and Yaupon Holly. For the plant, caffeine acts as a natural pesticide since it paralyzes and kills some of the insects that attempt to feed on the plant. Caffeine-containing beverages, such as coffee, enjoy great popularity. Additionally, it is occasionally used medically in the formulation of some analgesics. Caffeine's main pharmacological properties are: a stimulant action on the central nervous system with psychotropic effects and stimulation of respiration, a stimulation of the heart rate, and a mild diuretic effect.

Chemical properties

Caffeine is an alkaloid of the methylxanthine family, which also includes the similar compounds theophylline and theobromine. In its pure state it is an intensely bitter white powder. Its chemical formula is C₈H₁₀N₄O₂, its systematic name is 1,3,7-trimethyl xanthine or 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione, and its structure is shown above. Its International Chemical Identifier is InChI=1/C8H10N4O2/c1-10-4-9-6-5(10)7(13)12(3)8(14)11(6)2/h4H,1-3H3.

Physical properties

Pure caffeine occurs as odorless, white, fleecy masses, glistening needles or powder.
- Melting point: 238 °C
- Boiling point: 178 °C (sublimes)
- Density: 1.2 g/cm³
- Volatility: 0.5%
- Vapor pressure: 101 kPa @ 178 °C
- pH: 6.9 (1% solution)
- Solubility in water: 2.17%
- Vapor density: 6.7 g/m³
- Molecular weight: 194.19 g/mol

Caffeine extraction

It is very difficult to know the exact amount of caffeine in a particular drink that is not automatically prepared. The amount of caffeine in a single serving of coffee varies considerably due to many variables. Concentration can vary from bean to bean within a given bush; preparation of the raw bean will affect concentration, as well as multiple variables involved in brewing. To extract caffeine takes some time (about two hours) and requires chemicals unavailable for everyday use and a nice system of distillation and sublimation. To extract caffeine, one must take the beverage one wants to extract the caffeine from and mix it with a solvent with a finer affiliation to the caffeine and a different density. Chloroform is known to possess both these properties. Caffeine will go in the solvent it is the most soluble in, and it is more soluble in chloroform than water. Using a separating funnel, one should take about 30 ml of chloroform and 200 ml of the beverage one wants to extract the caffeine from and agitate for about two minutes. The bottom phase will be the chloroform and the caffeine, so one will keep this phase. Repeating this step about five times should ensure extraction of most of the caffeine. The next step is a distillation using a standard distillation column where one gets rid of most of the chloroform. Finally, one has to sublimate the caffeine under vacuum. If the result is a fine white powder, one's extraction has succeeded.

Sources

One common source of caffeine is the coffee plant, the beans of which are used to make coffee. Caffeine content varies substantially between Arabica and Robusta species and to a lesser degree between varieties of each species. One 'shot' of coffee contains about 40 mg of caffeine. Thus, a "double shot" espresso contains about 80 mg. A single serving (6 fl oz / 150 ml) of strong drip coffee or one-half caffeine tablet would deliver about 100 mg. However, there is a large variation in the amount of caffeine per serve, ranging from about 40 mg to 120 mg. Such variability was shown to be even higher in a study conducted in 2005 by Ben Desbrow, a dietitian of Griffith University. His survey of 99 short blacks found caffeine content ranging from 25 mg to 214 mg. Generally, dark roast coffee has less caffeine than lighter roasts since the roasting process reduces caffeine content of the bean. Tea is another common source of caffeine in many cultures. Tea contains somewhat less caffeine per serving than coffee, (usually about half as much, depending on the strength of the brew), though certain types of tea, such as black and oolong, contain more caffeine. Caffeine is also common in soft drinks such as cola. Such drinks typically contain about 15 mg to 40 mg of caffeine per serving. Most energy drinks such as Red Bull contain 80 mg. Mateine and guaranine are other names for caffeine. The names come from yerba maté and guarana respectively, caffeine-containing plants used for tea and other things. Many yerba maté enthusiasts insist that mateine is a stereoisomer of caffeine and thus a different substance altogether. However, this is impossible; caffeine is an achiral molecule with no stereogenic centers (also known as a chiral centers), and therefore has no stereoisomers. Similar claims are sometimes made of guaranine. Caffeine is sometimes called theine when it is found in tea, as the caffeine in tea was once thought to be a separate compound to the caffeine found in coffee. But tea does contain another xanthine, theophylline whose chemical formula is C₇H₈N₄O₂ compared to caffeine's C₈H₁₀N₄O₂.

Coffee

All fluid ounces are U.S. fluid ounces.
- Coffee, brewed (drip) - 4 to 20 mg/floz (130 to 680 mg/litre) (20 to 100 mg/5 floz)
- Coffee, decaffeinated - 0.4 to 0.6 mg/floz (13 to 20 mg/litre)
- Coffee, instant - 4 to 12 mg/floz (130 to 400 mg/litre)
- Espresso Arabica - ~40 mg/floz (1.36 g/litre)
- Espresso Robusta - ~100 mg/floz (3.4 g/litre)

Teas and other infusions

- Black tea, brewed (USA) - 2.5 to 11 mg/floz (85 to 370 mg per litre)
- Black tea, brewed (other) - 3 to 14 mg/floz (100 to 470 mg/litre)
- Black tea, canned iced - 2 to 3 mg/floz (70 to 100 mg/litre)
- Black tea, instant - 3.5 mg/floz (120 mg/litre)
- Oolong, 3.75 mg/floz (120 mg per litre) (12 to 55 mg per tea bag, i.e. one serving)
- Green tea, 2.5 mg/floz (85 mg/litre) (8 to 30 mg per tea bag, i.e. one serving)
- White tea, 2.0 mg/floz (68 mg/litre) (6 to 25 mg per tea bag, i.e. one serving)
- Decaf, 0.5 mg/oz (17 mg/litre) (1 to 4 mg per tea bag, i.e. one serving)
- Tisanes (i.e. Herbal teas) - caffeine content depends on the herb, e.g. Chamomile and Rooibos "teas" have no caffeine while Yerba mate and Guarana do contain varying quantities. Many tea drinkers characterise herbal tea simply as that which, unlike black or green tea, contains no caffeine.

Chocolate

Chocolate is a weak stimulant due to content of theobromine, theophylline, and caffeine.[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15549276] However, chocolate contains too little of these compounds for a reasonable serving to create effects in humans that are on par with coffee.

Other sources

- Energy drink - 10 mg/floz (340 mg/litre). Some countries limit the caffeine content at 135 mg/litre.
- Soft drink (caffeinated) - 3 to 8 mg/floz (100 to 270 mg/litre, some countries limit the caffeine content in cola drinks to 200 mg/l)
- Pill (caffeine) - 200 mg (100 mg in Canada and many countries within EU)
- Buckfast Tonic Wine - 375 mg/litre (0.05% of caffeine by weight)
- Jolt Gum - 45 mg/piece
- Bawls - 67mg per 10oz, 80 per 12oz

Equivalents to 200 mg of caffeine

- One caffeine pill (Two in some countries where these are 100 mg)
- ~2 shots of espresso from robusta beans (2 floz)
- ~2 "5 floz containers" of regular coffee (10 floz)
- ~1.3 L soft drink (these can vary widely in content)
- ~5 cups (8 floz) of black tea or ~10 cups (8 floz) of green tea
- ~5 cans of soda (these can vary widely in content) In the European Union, a warning must be placed on packaging if the caffeine content of any beverage exceeds 150 mg per litre. This includes caffeine from any source (including guarana, which is often found in energy drinks). In many countries, caffeine is classified as a flavouring.

History

Although tea consumption in China began thousands of years ago, the first documented use of caffeine in a beverage for its pharmacological effect was by the sufis of Yemen, who used coffee to stay awake during prayers in the 15th century. In the 16th century there were coffeehouses in Cairo and Mecca. Coffeehouses opened in Europe in the 17th century. Caffeine was isolated by the German chemist Friedrich Ferdinand Runge in 1819. According to the legend, he did this at the instigation of Johann Wolfgang von Goethe (Weinberg & Bealer 2001).

Mechanism of Action

Caffeine is thought to act by blocking adenosine receptors on the surface of cells. This thereby blocks a pathway leading to breakdown of cyclic adenosine monophosphate (cAMP). The usual effect of adenosine in nerve cells is to inhibit nerve conduction by inhibiting post-synaptic potentials. The caffeine molecule, being structurally similar to adenosine, binds to the same receptors but does not stimulate them, thereby decreasing the adenosine action. The resulting increased nerve activity causes the release of the hormone epinephrine (adrenaline), which in turn leads to several effects such as higher heart rate, increased blood pressure, increased blood flow to muscles, decreased blood flow to the skin and inner organs, and release of glucose by the liver. It also increases the levels of the neurotransmitter dopamine in the brain, similar to amphetamines. Other purported mechanisms of action of caffeine include mobilisation of intracellular calcium and inhibition of specific phosphodiesterases, however these only occur at high non-physiological concentrations.

Metabolism and toxicology

Caffeine is completely absorbed from the stomach and small intestine, within 45 minutes of ingestion. It is widely distributed in total body water and is eliminated by apparent first-order kinetics that can be described by a one-compartment open-model system. Caffeine is metabolized in the liver by the cytochrome P-450 enzyme system. The first metabolic products of caffeine are three dimethylxanthines: paraxanthine (84%), theobromine (12%) and theophylline (4%). Paraxanthine increases lipolysis, leading to elevated glycerol and free fatty acid levels in the blood plasma. Theobromine, the principal alkaloid in cocoa (chocolate), can dilate blood vessels and increase urine volume. Theophylline relaxes smooth muscles of the bronchi and is used to treat asthma. However, the therapeutic dose is many time greater than the levels achieved from caffeine metabolism. Each of these metabolites is further metabolised and then excreted in the urine. Caffeine is quickly and completely removed from the brain, and, unlike other CNS stimulants or alcohol, its effects are short-lived. In many people, caffeine does not negatively affect concentration or higher mental functions, and hence caffeinated drinks are often consumed in the course of work. Continued consumption of caffeine can lead to tolerance. Upon withdrawal, the body becomes oversensitive to adenosine, causing the blood pressure to drop dramatically, leading to headache and other symptoms. Any accumulated sleep debt will be fully felt on withdrawal as well. Intravenous caffeine (in the form of caffeine benzoate 500 mg over 1 hour) is occasionally used medically to treat post-lumbar puncture ("spinal tap") headache[http://www.emedicine.com/neuro/topic557.htm]. Although caffeine solutions are often used as a chemical standard for bitterness, caffeine is added to some soft drinks such as colas, Irn-Bru and Mountain Dew ostensibly for its taste. Mountain Dew While safe for humans, caffeine and its related compounds theobromine and theophylline are considerably more toxic to some other animals such as dogs, horses and parrots due to a much poorer ability to metabolize these compounds. Caffeine does more damage to spiders than most drugs.

Toxicity

Too much caffeine can lead to caffeine intoxication. The symptoms of this disorder are restlessness, nervousness, excitement, insomnia, flushed face, diuresis, gastrointestinal complaints, even hallucinations. They can occur in some people after as little as 250 mg per day. More than 1,000 mg per day may result in muscle twitching, rambling flow of thought and speech, cardiac arrhythmia or tachycardia, and psychomotor agitation. Caffeine intoxication can lead to symptoms similar to those of panic disorder and generalized anxiety disorder. The minimum lethal dose ever reported is 3,200 mg, intravenously. The LD₅₀ of caffeine is estimated between 13 and 19 grams for oral administration for an average adult. The LD₅₀ of caffeine is dependent on weight and estimated to be about 150 to 200 mg per kg of body mass, roughly 140 to 180 cups of coffee for an average adult taken within a limited timeframe that is dependent on half-life. The half-life, or time it takes for the amount of caffeine in the blood to decrease by 50%, ranges from 3.5 to 10 hours. In adults the half-life is generally around 5 hours. However contraceptive pills increase this to around 12 hours, and, for women over 3 months pregnant, it varies from 10 to 18 hours. In infants and young children, the half-life may be longer than in adults. With common coffee and a very rare half-life of 100 hours, it would require 3 cups of coffee every hour for 100 hours just to reach LD₅₀. Though achieving lethal dose with coffee would be exceptionally difficult, there have been many reported deaths from intentional overdosing on caffeine pills. Studies in humans have shown that caffeine may cause miscarriage or may slow the growth of a developing fetus when given in doses greater than 300 mg (an amount equal to three cups of coffee) a day. In addition, use of large amounts of caffeine by the mother during pregnancy may cause problems with the heart rhythm of the fetus. Excessive ingestion of caffeine can result in increased blood pressure and pulse, increased urine production, vasoconstriction (tightening or constricting of superficial blood vessels) sometimes resulting in cold hands or fingers, increased amounts of fatty acids in the blood, and increased production of gastric acid. Those suffering from overdose should seek medical attention. If medical care is not possible, they should find a quiet place to rest. Within an hour after the effects first arise, peak influence on the body should occur, with a 15-30 minute plateau, after which the effects should abate and the sufferer can return to normal activity.

Withdrawal

Caffeine withdrawal usually manifests itself in long drawn-out headaches. A feeling of "pressure" is created and the sufferer has difficulty concentrating and maintaining a train of thought. Unless the user can identify the fact that they are going into caffeine withdrawal, usually they regard it as a common or garden headache. The feeling is sometimes described as similar to dehydration, but can be recognized by the fact that from soon after they get up (assuming morning usage) the feeling slowly comes on then stays steady. Although painkillers such as asprin can relieve symptoms, often a small dose of caffeine does the best job. A cup of white or black tea relieves the symptoms quite well and almost instantly.

Abuse

Caffeine, in its many forms, has been used for its stimulating effects. In modern times, though, the substance can be produced in much higher quantities, and has found its way into many products. Purer forms, such as those in caffeine pills, are easily available. These pills are sometimes used by college students and shift workers to last an entire night without sleep. Caffeine pills have been under media fire for recent and past deaths of students, usually take on the form of a caffeine overdose. One such example of this was the death of a North Carolina student, Jason Allen. He swallowed most of a bottle of 90 such pills [http://www.collegepublisher.com/media/paper87/DFPArchive/science/1103981.html]. This was the equivalent of about 250 cups of coffee (or, alternatively, a gallon and a half (5 liters) of espresso, or 22 gallons (~85 liters) of caffeinated Mountain Dew (this soft drink is not available in caffeinated form in all areas). Allen probably ingested about 18 grams of caffeine, since caffeine pills are restricted to 200 milligrams or less in the U.S., and most manufacturers make them in that size. A few other deaths by caffeine overdose have been known, almost always in the case of massive pill consumption. Long periods of abuse can lead to detrimental effects on the esophagus; persons who consume high amounts of caffeine may have a risk for higher incidents of peptic ulcers, erosive esophagitis, and gastroesophageal reflux disease. They may also have heart problems, insomnia, chronic muscle tension, and nervousness. The term caffeinism has been coined to mean addiction to (or debilitating dependence on) caffeine.

References

- Weinberg BA, Bealer BK. The world of caffeine. New York & London: Routledge, 2001. ISBN 0-415-92722-6.
- Noever, R., J. Cronise, and R. A. Relwani. 1995. Using spider-web patterns to determine toxicity. NASA Tech Briefs 19(4):82. Published in New Scientist magazine, 27 April 1995.

External links

- [http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202105.html US National Library of Medicine: MedlinePlus® Drug Information: Caffeine]
- [http://www.erowid.org/chemicals/caffeine/caffeine.shtml Erowid Caffeine Vault]
- [http://www.mrkland.com/fun/xocoatl/caffeine.htm Caffeine in chocolate?]
- [http://chemistry.about.com/od/moleculescompounds/a/caffeine.htm Caffeine Chemistry]
- [http://www.CaffeineWeb.com Site dedicated to "Caffeinism's Mimicry of Mental Illness"]
- [http://www.thenakedscientists.com/html/columnists/dalyacolumn2.htm Why do plants make caffeine?]
- [http://www.cspinet.org/new/cafchart.htm Caffeine Content of Foods]
- [http://www.benbest.com/health/caffeine.html Is Caffeine a Health Hazard?]
- [http://www.coffeefaq.com/caffaq.html The Caffeine FAQ]
- [http://www.compchemwiki.org/index.php?title=Caffeine Computational Chemistry Wiki]
- [http://www.energyfiend.com/death-by-caffeine/ Death by Caffeine Calculator (humor)]
- [http://www.energyfiend.com/the-caffeine-database/ Caffeine content of drinks, mints, chocolates, and pills]
- [http://www.nescafe.com/ Nescafe - Coffee company] Category:Xanthines Category:Coffee ms:Kafeina ja:カフェイン simple:Caffeine th:คาเฟอีน

Cocaine

:This article is about the drug Cocaine. For the blues song by J.J. Cale (later covered by Eric Clapton) see Cocaine (song) Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. It is a stimulant of the central nervous system and an appetite suppressant, creating what has been described as a euphoric sense of happiness and increased energy. Though most often used recreationally for this effect, cocaine is also a topical anesthetic that was used in eye and throat surgery in the 19th and early 20th centuries. Cocaine is an addictive substance, and its possession, cultivation, and distribution is illegal for non-medicinal / non-government sanctioned purposes in virtually all of the world.

History

The coca leaf

For thousands of years and still today, South American indigenous peoples have chewed the coca leaf (Erythroxylon coca), a plant which contains vital nutrients as well as numerous alkaloids, including cocaine. The leaf was and is chewed almost universally by some indigenous communities, but there is no evidence that its habitual use ever led to any of the negative consequences generally associated with habitual cocaine use today. It is an important source of nutrition and energy in a region that is lacking in other food sources and oxygen; the vitamins and protein present in the leaves, as well as the cocaine alkaloid, helps provide the energy and strength necessary for steep walks in this mountainous area and days without eating. indigenous communities When the Spaniards conquered South America, they at first ignored Aboriginal claims that the leaf gave them strength and energy, and declared the practice of chewing it the work of the Devil. But after discovering that these claims were true, they legalized and taxed the leaf, taking 10% of the value of each crop. These taxes were for a time the main source of support for the Roman Catholic Church in the region. In 1609 Padre Blas Valera wrote:

Coca protects the body from many ailments, and our doctors use it in powdered form to reduce the swelling of wounds, to strengthen broken bones, to expel cold from the body or prevent it from entering, and to cure rotten wounds or sores that are full of maggots. And if it does so much for outward ailments, will not its singular virtue have even greater effect in the entrails of those who eat it?

Isolation

Although the stimulant and hunger-suppressant properties of coca had been known for many centuries, the isolation of the cocaine alkaloid was not achieved until 1855. Although many scientists had attempted to isolate cocaine, no one had been successful for two reasons: the knowledge of chemistry required was insufficient at the time, and coca does not grow in Europe and is easily ruined during travel. The cocaine alkaloid was first isolated by the German chemist Friedrich Gaedcke in 1855. Gaedcke named the alkaloid “erythroxyline”, and published a description in the journal Archives de Pharmacie. In 1856 Friederich Wöhler asked Dr. Carl Scherzer, a scientist aboard the Novara (an Austrian frigate sent by Emperor Franz Joseph to circle the globe), to bring him a large amount of coca leaves from South America. In 1859 the ship finished its travels and Wöhler received a trunk full of coca. Wöhler passed on the leaves to Albert Niemann, a Ph.D. student at the University of Göttingen in Germany, who then developed an improved purification process. Niemann described every step he took to isolate cocaine in his dissertation entitled On a New Organic Base in the Coca Leaves, which was published in 1860 — it also earned him his Ph.D. and is now in the British Library. He wrote of the alkaloid's “colourless transparent prisms” and said that, “Its solutions have an alkaline reaction, a bitter taste, promote the flow of saliva and leave a peculiar numbness, followed by a sense of cold when applied to the tongue.” Niemann named the alkaloid “cocaine” — as with other alkaloids its name carried the “-ine” suffix (from Latin -ina).

Popularization

In 1859 an Italian doctor Paolo Mantegazza returned from Peru, where he had witnessed first-hand the use of coca by the natives. He proceeded to experiment on himself and upon his return to Milan he wrote a paper in which he described the effects. In this paper he declared coca and cocaine (at the time they were assumed to be the same) as being useful medicinally, in the treatment of “a furred tongue in the morning, flatulence, [and] whitening of the teeth.” flatulence gold medal to Angelo Mariani.]] A chemist named Angelo Mariani who read Mantegaza’s paper became immediately intrigued with coca, and its economic potential. In 1863 Mariani started marketing a wine called Vin Mariani which had been treated with coca leaves. The ethanol in the wine acted as a solvent and extracted the cocaine from the coca leaves, altering the drink’s effect. It contained 6 mg cocaine per ounce of wine, but Vin Mariani which was to be exported contained 7.2 mg per ounce in order to compete with the higher cocaine content of similar drinks in the United States. A “pinch of coca leaves” was included in John Styth Pemberton's original 1886 recipe for Coca-Cola, though the company began using decocainized leaves in 1906 when the Pure Food and Drug Act was passed. The only known measure of the amount of cocaine in Coca-Cola was determined in 1902 as being as little as 1/400 of a grain (0.2 mg) per ounce of syrup. (6 ppm.) The actual amount of cocaine that Coca-Cola contained during the first twenty years of its production is impossible to determine. In 1879 cocaine began to be used to treat morphine addiction. Cocaine was introduced into clinical use as a local anaesthetic in Germany in 1884, about the same time as Sigmund Freud published his work Über Coca, in which he wrote that cocaine causes:

...exhilaration and lasting euphoria, which in no way differs from the normal euphoria of the healthy person...You perceive an increase of self-control and possess more vitality and capacity for work....In other words, you are simply normal, and it is soon hard to believe you are under the influence of any drug....Long intensive physical work is performed without any fatigue...This result is enjoyed without any of the unpleasant after-effects that follow exhilaration brought about by alcohol....Absolutely no craving for the further use of cocaine appears after the first, or even after repeated taking of the drug...

Über CocaIn 1885 the U.S. manufacturer Parke-Davis sold cocaine in various forms, including cigarettes, powder, and even a cocaine mixture that could be injected directly into the user’s veins with the included needle. The company promised that its cocaine products would “supply the place of food, make the coward brave, the silent eloquent and ... render the sufferer insensitive to pain.” By late Victorian era cocaine use had appeared as a vice in literature, for example as the cucaine injected by Arthur Conan Doyle’s fictional Sherlock Holmes. In 1909 Ernest Shackleton took “Forced March” brand cocaine tablets to Antarctica, as did Captain Scott a year later on his ill-fated journey to the south pole.

Prohibition

By the turn of the twentieth century, the addictive properties of cocaine had become clear to many, and the problem of cocaine abuse began to capture public attention in the United States. The dangers of cocaine abuse became part of a moral panic that was tied to the dominant racial and social anxieties of the day. In 1903 the American Journal of Pharmacy stressed that most cocaine abusers were “bohemians, gamblers, high- and low-class prostitutes, night porters, bell boys, burglars, racketeers, pimps, and casual laborers.” In 1914 Dr. Christopher Koch of Pennsylvania’s State Pharmacy Board made the racial innuendo explicit, testifying that, “Most of the attacks upon the white women of the South are the direct result of a cocaine-crazed Negro brain.” Mass media manufactured an epidemic of cocaine use amongst African-Americans in the Southern United States, although there is little evidence that such an epidemic actually took place, to play upon racial prejudices of the era. In the same year, the Harrison Narcotics Tax Act banned the nonprescription use of cocaine-containing products, and it was officially outlawed as a narcotic in 1922.

Modern usage

In most Western countries, cocaine, also known as "coke", "stardust", "snow", "white", and "blow", is a popular recreational drug. In the United States, the introduction of "crack" cocaine introduced it to a generally poorer inner-city market. Use of the powder form has stayed relatively constant, experiencing a new height of use during the late 1990s and early 2000s in the USA, and has become much more popular in the last few years in the UK. Cocaine use is prevalent across all socioeconomic strata, including age, demographics, economic, social, political, religious, and livelihood. Cocaine in its various forms comes in second only to cannabis as the most popular illegal recreational drug in the United States, and is number one in street value sold each year. The estimated U.S. cocaine market exceeded $35 billion in street value for the year 2003, exceeding revenues by corporations such as AT&T and Starbucks. There is a tremendous demand for cocaine in the U.S. market, particularly among those who are making incomes affording luxury spending, such as single adults and various professionals. Cocaine’s status as a club drug shows its immense popularity among the “party crowd”. Cocaine’s high revenues may be due to the drug’s psychologically addictive nature, which makes the cessation of use quite difficult when compared to less addictive drugs such as marijuana. It has become much more popular as a middle class drug in the United Kingdom in recent years.

Pharmacology

Appearance

United Kingdom Cocaine in its purest form is an off-white or pink chunky product. Cocaine appearing in powder form is a salt, typically cocaine hydrochloride (CAS 53-21-4). Cocaine is frequently adulterated or “cut” with various powdery fillers to increase its volume; the substances most commonly used in this process are baking soda, sugars, such as lactose, inositol, and mannitol, and local anesthetics, such as lidocaine. Adulterated cocaine is often a white or off-white powder. The color of “crack” cocaine depends upon several factors including the origin of the cocaine used, the method of preparation — with ammonia or sodium bicarbonate, and the presence of impurities, but will generally range from a light brown to a pale brown. Its texture will also depend on the factors which affect color, but will range from a crumbly texture, which is usually the lighter variety, to hard, almost crystalline nature, which is usually the darker variety.

Forms of cocaine

Cocaine sulfate

Cocaine sulfate is produced by macerating coca leaves along with water that has been acidulated with sulfuric acid. This is often accomplished by putting the ingredients into a vat and stamping on it, in a manner not dissimilar to the traditional method for crushing grapes. After the cocaine is extracted, the water is evaporated to yield a pastey mass of impure cocaine sulfate. The sulfate itself is an intermediate step to producing cocaine hydrochloride. In South America it is commonly smoked along with tobacco, and is known as pasta, basuco, basa, pitillo, or simply paste.

Freebase

As the name implies, “freebase” is the base form of cocaine, as opposed to the salt form of cocaine hydrochloride. Whereas cocaine hydrochloride is extremely soluble in water, cocaine base is insoluble in water and is therefore not suitable for drinking, snorting or injecting. Cocaine hydrochloride is not well-suited for smoking because the temperature at which it vaporizes is very high, and close to the temperature at which it burns; however, cocaine base vaporizes at a low temperature, which makes it suitable for inhalation. Smoking freebase is preferred by many users because the cocaine is absorbed immediately into blood via the lungs, where it reaches the brain in about five seconds. The rush is much more intense than sniffing the same amount of cocaine nasally, but the effects do not last as long. The peak of the freebase rush is over almost as soon as the user exhales the vapor, but the high typically lasts 5–10 minutes afterwards. What makes freebase a particularly dangerous drug is that users typically don't wait that long for their next hit and will continue to smoke freebase until none is left. These effects are similar to those that can be achieved by injecting or “slamming” cocaine hydrochloride, but without the risks associated with intravenous drug use (although there are other serious risks associated with smoking freebase). Freebase cocaine is produced by first dissolving cocaine hydrochloride in water. Once dissolved in water, cocaine hydrochloride (Coc HCl) disassociates into protonated cocaine ion (CocH⁺) and chloride ion (Cl^-). Any solids that remain in the solution are not cocaine (they are part of the cut) and are removed by filtering. A base, typically ammonia (NH₃), is added to the solution to remove the extra proton from the cocaine. The following net chemical reaction takes place:

NH₃ + CocH⁺ + Cl^- → NH₄Cl + Coc

As freebase cocaine (Coc) is insoluble in water, it precipitates and the solution becomes cloudy. To recover the freebase, diethyl ether is added to the solution: Since freebase is highly soluble in ether, a vigorous shaking of the mixture results in the freebase being dissolved in the ether. As ether is insoluble in water, it can be siphoned off. The ether is then left to evaporate, leaving behind the nearly pure freebase. This procedure is dangerous because of the hazards of handling diethyl ether: it is extremely flammable, its vapors are heavier than air and can “creep” from an open bottle, and in the presence of oxygen it can form peroxides which can spontaneously combust. Demonstrative of the dangers of the practice, the famous comedian Richard Pryor used to perform a well known skit in which he pokes fun at himself during a 1980 incident in which he caused an explosion and set himself on fire while attempting to smoke “freebase”, presumably still wet with ether.

Crack cocaine

Richard Pryor Because of the dangers of using ether to produce pure freebase cocaine, cocaine producers began to omit the step of removing the freebase cocaine precipitate from the ammonia mixture. Typically, filtration processes are also omitted. The end result of this process is that the cut, in addition to the ammonium salt (NH₄Cl), remains in the freebase cocaine after the mixture is evaporated. The “rock” which is thus formed also contains a small amount of water. When the rock is heated this water boils, making a crackling sound (hence the name “crack”). Baking soda is now most often used as a base rather than ammonia for reasons of lowered stench and toxicity; however, any weak base can be used to make crack cocaine. Strong bases, such as sodium hydroxide, tend to hydrolyze some of the cocaine into useless ecgonine. The net reaction when using baking soda (also called sodium bicarbonate, with a chemical formula of NaHCO₃) is:

CocH⁺ + Cl^- + NaHCO₃ → Coc + H₂O + CO₂ + NaCl

Crack is unique because it offers a strong cocaine experience in small, low-priced packages. In the United States, crack cocaine is often sold in small, inexpensive dosage units frequently known as “nickels” or “nickel rocks” (referring to the price of $5.00), and also “dimes” or “dime rocks” ($10.00) and sometimes as “twenties” or “solids”, and “forties”. The quantity provided by such a purchase varies depending upon many factors, such as local availability, which is affected by geographic location. A twenty may yield a quarter gram or half gram on average, yielding 30 minutes to an hour of effect if hits are taken every few minutes. After the $20 or $40 mark, crack and powder cocaine are sold in grams or fractions of ounces. Many inner-city addicts with a regular dealer will “work a corner”, taking money from anyone who wants crack, making a buy from the dealer, then delivering part of the product while keeping some for themselves. Although consisting of the same active drug as powder cocaine, crack cocaine in the United States is seen as a drug primarily by and for the inner city poor (the stereotypical "crack head" is a poor, urban, usually homeless person of color). While insufflated powder cocaine has an associated glamour attributed to its popularity among mostly middle and upper class whites (as well as musicians and entertainers), crack is perceived as a skid row drug of squalor and desperation. In many jurisdictions in the US, possession or sale of crack cocaine carries a harsher penalty than an equivalent amount of powder cocaine. Street names for crack include “Devil’s dandruff”, “Devilsmoke”, “Devil drug”, "Devil's Candy", “hard”, “dope”, “work”, “smoke”, “yoda”, “yayo”, “yay”, “bones”, “yola”, "candy", “matter”, "boy", and “food”; but most commonly, it is simply called “rock”. Crack cocaine was extremely popular in the mid- and late 1980s, especially in inner cities, although its popularity declined through the 1990s. In 1998, Gary Webb's book Dark Alliance: The CIA, the Contras, and the Crack Cocaine Explosion linked the “crack explosion” to the CIA funding of the anti-communism Contras fighting against sandinistas in Nicaragua.

Methods of administration

Chewed/eaten

The simplest way to administer cocaine is to chew on the leaves of the plant. Physical restrictions mean when taken this way, only small amounts of cocaine make it into the bloodstream and the effect is that of a mild stimulant. Mate de coca or coca-leaf tea is also a traditional method of consumption and is often recommended to treat altitude sickness. In 1986 an article in the Journal of the American Medical Association revealed that health food stores were selling coca-leaf tea as “Health Inca Tea”. While the packaging claimed it had been “decocainized”, no such process had taken place—they were selling a controlled substance off the shelves. The article stated that drinking two cups of the tea per day gave a mild stimulation, increased heart rate, and mood elevation, and the tea was essentially harmless. Despite this, the DEA seized several shipments in Hawaii, Chicago, Illinois, Georgia, and several locations on the East Coast of the United States, and the product was removed from the shelves.

Insufflation

Insufflation (known colloquially as “snorting” or “sniffing”) is the most common method of ingestion of recreational powder cocaine in the Western world. Contrary to widespread belief, cocaine is not actually inhaled using this method; rather the drug coats and is absorbed through the mucous membranes lining the sinuses. When insufflating cocaine, absorption through the nasal membranes is approximately 80%. Any material not directly absorbed through the mucous membranes is collected in mucous and swallowed. Chronic use results in ongoing rhinitis and necrosis of the nasal membranes. Cellulose granulomas from adulterants have also been found in the lungs of recreational “sniffers”. Prior to insufflation cocaine powder must be divided into very fine particles. Cocaine of high purity breaks into smallest dust very easily, except when it's moist(not well stored) and forms “chunks”, which reduce the efficiency of nasal absorption. Rolled up paper currency, hollowed-out pens and cut straws are often used to insufflate cocaine. Such devices are often referred to as 'tooters' by users. The cocaine typically is poured onto a flat, hard surface (such as a mirror) and divided into "lines" (usually with a razor blade or credit card) which are then insufflated. The amount of cocaine in a line varies widely from person to person and occassion to occassion (the purity of the cocaine is also a factor), but one line is generally considered to be a single dose.

Injected

The intravenous route of administration provides the highest blood levels of drug in the shortest time. It can get to the brain within 15 seconds. Injection of cocaine produces an exhilarating rush so intense that often the user may vomit uncontrollably, although the euphoria passes quickly as the liver rapidly metabolizes the drug. Aside from the toxic effects of cocaine, there is also danger of circulatory emboli from the insoluble substances that may be used to cut the drug. Obviously, there is also a risk of serious infection associated with the use of contaminated needles. An injected mixture of cocaine and heroin, known as “speedball” or “moonrock”, is a particularly popular and dangerous combination, as the converse effects of the drugs actually complement each other, but may also mask the symptoms of an overdose. It has been responsible for numerous deaths, particularly in and around Los Angeles, including celebrities such as John Belushi and Chris Farley. Experimentally, cocaine injections can be delivered to animals such as fruit flies [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15262059&query_hl=21] to study the mechanisms of cocaine addiction.

Smoked

(see also: Crack cocaine above) Smoking freebase or crack cocaine is most often accomplished using a pipe made from a small glass tube about one quarter-inch (about 6 mm) in diameter and up to several inches long. These are sometimes called “straight shooters”; readily available in convenience stores or smoke shops. They will sometimes contain a small paper flower and are promoted as a romantic gift. Buyers usually ask for a “rose” or a “flower”. An alternate method is to use a small length of a radio antenna or similar metal tube. To avoid burning the user’s fingers and lips on the metal pipe, a small piece of paper or cardboard (such as a piece torn from a matchbook cover) is wrapped around one end of the pipe and held in place with either a rubber band or a piece of adhesive tape. A small piece of steel or copper scouring pad—often called a “brillo” or “chore”, from the scouring pads of the same name—is placed into one end of the tube after having the soapy cleanser coating burned off the metal. It then serves as a crude filter in which the “rock” can melt and boil to vapor. The “rock” is placed at the end of the pipe closest to the filter and the other end of the pipe is placed in the mouth. A flame from a cigarette lighter or handheld torch is then held under the rock. As the rock is heated, it melts and burns away to vapor which the user inhales as smoke. The effects are felt almost immediately after smoking, are very intense, and do not last long — usually five to fifteen minutes. Most users will want more after this time, especially frequent users. “Crack houses” depend on these cravings by providing users a place to smoke, and a ready supply of small bags for sale. A heavily used crackpipe tends to fracture at the end from overheating with the flame used to heat the crack as the user obsessively attempts to inhale every bit of the drug on the metal wool filter. The end is often broken further as the user “pushes” the pipe. “Pushing” is a technique used to partially recover crack which hardens on the inside wall of the pipe as the pipe cools. The user pushes the metal wool filter through the pipe from one end to the other to collect the build-up inside the pipe. The ends of the pipe can be broken by the object used to push the filter, frequently a small screwdriver or stiff piece of wire. The user will often remove the most jagged edges and continue using the pipe until it becomes so short that it burns the lips and fingers. To continue using the pipe, the user will sometimes wrap a small piece of paper or cardboard around one end and hold it in place with a rubber band or adhesive tape. Of course, not all people who smoke crack cocaine will let it get that short, and will get a new or different pipe. The tell-tale signs of a used crack pipe are a glass tube with burn marks at one or both ends and a clump of metal wool inside. When smoked, cocaine is sometimes combined with other drugs, such as cannabis; often rolled into a joint or blunt. This combination is known as “primo”, “hype”, B-151er or a “woo”. Crack smokers who are being drug tested may also make their “primo” with cigarette tobacco instead of cannabis, since a crack smoker can test clean within 2 to 3 days of use, if only urine (and not hair) is being tested.

Mechanism of action

Cocaine is a potent blocker of the dopamine transporter (DAT) and a less potent blocker of the norepinephrine transporter (NET) and serotonin transporter (SERT). Cocaine also blocks sodium channels, thereby interfering with the propagation of action potentials; thus, like lidocaine and novocaine, it acts as a local anesthetic. The locomotor enhancing properties of cocaine may be attributable to its enhancement of dopaminergic transmission from the substantia nigra. Recent research points to an important role of circadian mechanisms [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12865893&query_hl=16] and clock genes [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15967985&query_hl=18] in behavioral actions of cocaine. After cocaine is introduced to the body it travels to reward areas of the brain: the ventral tegmental area (VTA), the nucleus accumbens and the prefrontal cortex. These areas are saturated with dopamine synapses. Normally, after dopamine is released in the synaptic cleft, it binds to the dopamine receptors; reuptake sites (protein transported structures) will utilize the rest of the neurotransmitter (dopamine). In the presence of cocaine the normal process of reuptaking is breached. Cocaine binds to the uptake sites, which leaves a higher concentration of dopamine in the synaptic cleft. The higher activation of dopamine receptors in the post-synaptic cell causes various intracellular changes, which ultimately lead to changes in firing patterns. Since nicotine increases the levels of dopamine in the brain, many cocaine users find that consumption of tobacco products during cocaine use enhances the euphoria. This, however, may have undesirable consequences, such as uncontrollable chain smoking during cocaine use (even users who don't normally smoke cigarettes have been known to chain smoke when using cocaine), in addition to the detrimental health effects and the additional strain on the cardiovascular system caused by tobacco.

Metabolism and excretion

Cocaine is extensively metabolized, primarily in the liver, with only about 1% excreted unchanged in the urine. It is mostly eliminated as benzoylecgonine, the major metabolite of cocaine, and is also excreted in lesser amounts as ecgonine methyl ester and ecgonine. If taken with alcohol, cocaine combines with the ethanol in the liver to form cocaethylene, which is both more euphorigenic and has higher cardiovascular toxicity than cocaine by itself. Cocaine metabolites are detectable in urine for up to four days after cocaine is used. Benzoylecgonine can be detected in urine within four hours after cocaine inhalation and remains detectable in concentrations greater than 1000 ng/ml for as long as 48 hours. Detection in hair is possible in regular users until the sections of hair grown during use are cut or fall out.

Effects and health issues

Cocaine is a potent central nervous system stimulant. Its effects can last from 20 minutes to several hours, depending upon the dosage of cocaine taken and its purity. The initial signs of stimulation are hyperactivity, restlessness, increased blood pressure, increased heart rate and euphoria. The euphoria is sometimes followed by feelings of discomfort and depression and a craving to re-experience the drug. Side effects can include twitching and paranoia, which usually increase with frequent usage. With excessive dosage the drug can produce hallucinations, paranoid delusions, tachycardia, itching, and delusional parasitosis . Overdose causes tachyarrhythmias and a marked elevation of blood pressure. These can be life threatening, especially if the user has existing cardiac problems. Cocaine consumed by “snorting” very rarely causes overdose. Cocaine raises the amount of dopamine and serotonin in the nucleus accumbens; the "crash" experienced after the initial high is marked by an undershooting of normal levels afterwards. This is because neurons run out of dopamine and serotonin neurotransmittors. Receptors disappear as a response mechanism to too much neurotransmitter. This contributes to the rise in an abuser's tolerance thus requiring a larger dosage to achieve the same effect. The lack of normal amounts of serotonin and dopamine in the brain is the cause of the dysphoria and depression felt after the initial high. The diagnostic crite

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