Cocaine is a crystalline tropane alkaloid extracted from the leaves of the coca plant. It is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI) and central nervous system (CNS) stimulant used recreationally for its euphoric effect and medically as a local anesthetic; it increases energy, mental alertness and suppresses appetite. Cocaine is highly addictive and has profound and dangerous physical and psychological effects.
Introduction to Cocaine
Cocaine is a crystalline tropane alkaloid extracted from the leaves of the coca plant. It is a serotonin-norepinephrine-dopamine reuptake inhibitor and central nervous system (CNS) stimulant, used recreactionally to increase energy and mental alertness, and medically as a topical anesthetic and appetite suppressant. Regular use of cocaine can lead to increased tolerance and dosing, and eventually addiction. Deaths related to cocaine abuse are often a result of cardiac arrest, seizures and respiratory failure, especially when used in conjunction with other CNS stimulants or depressants. Possession, cultivation, and distribution of cocaine is illegal for non-medicinal and non-government sanctioned purposes in virtually all parts of the world.
Using Cocaine
Ways of administration
Cocaine 's usual route of administration is insufflation (snorting). However, cocaine can also be wrapped in paper and ingested orally. Injection directly into the veins is yet another method. Some users also smoke salted cocaine. (Not to be confused with the freebase crack, this is still in the HCl form.)Effects of Cocaine
When cocaine is used it interferes with the re-absorption of dopamine, a brain chemical associated with pleasure and movement. Cocaine usually makes the user feel euphoric, energetic, talkative, and mentally alert, especially to the sensations of sight, sound, and touch. It can also temporarily decrease the need for food and sleep.
During the euphoric period after cocaine use, which can last up to an hour, user will experience hyper stimulation, reduced fatigue, and mental alertness. However, some users also experience restlessness, irritability, and anxiety.Combinations with Cocaine
Alcohol
Cocaine is often combined with alcohol. Alcohol metabolized by the liver may combine with the cocaine to form cocaethylene, a more cardiotoxic substance. This process is called transesterfication in which the ethyl group from the ethanol is substituted for cocaine's methyl.
Another danger in combining cocaine with alcohol is it reduces alcohol's depressant effects which might give one a false sense of sobriety and consume dangerous quantities of alcohol. As the effects of the cocaine wear off, alcohol could be at dangerous levels and without the stimulant effects of the cocaine could cause extreme impairment and even blackouts.
Additionally, alcohol will lower one's judgement and might result in the consumption of more cocaine than intended.
These two substances, while they may compliment each other in producing additional euphoria, are a dangerous combination due to three factors, cocaethylene, increased cocaine consumption and increased alcohol consumption.Different Uses for Cocaine
Cocaine is used by health care professionals to temporarily numb the lining of the mouth, nose, eyes, and throat (mucous membranes) before certain medical procedures (e.g., biopsy, stitches, wound cleaning). It is an anesthetic that works quickly to numb the area about 1-2 minutes after application. Cocaine also causes blood vessels to narrow, an effect that can decrease bleeding and swelling from the procedure.
Pharmacology of Cocaine
The pharmacology of cocaine involves a complex relationship between neurotransmitters, which must be understood in it's entirety if one is to explain all of the effects of cocaine in an accurate fashion.Take a look at a molecule of cocaine base, it's naturally occurring form:
The molecule contains two rings, a six-carbon phenyl ring and a nitrogen-containing ring.Both are necessary for the drug's pharmacological activity.Changes in other parts of the molecule can yield interesting compounds with increased (or decreased) pharmacological activity.
Most of the effects of cocaine can be attributed to it's blocking of the reuptake of 3 monoamine neurotransmitters: Dopamine, norepinephrine and serotonin.These neurotransmitters are usually cleared from the synaptic cleft by membrane proteins called transporters.Cocaine binds to these transporters, inhibiting their function, which naturally leads to an increase in the amount of these neurotransmitters in the synaptic cleft, with a corresponding increase in transmittion at the affected synapses.At higher concentrations, the voltage-gated Na channels are blocked, leading to it's local anesthetic effect.Cocaine's effects on the reuptake of dopamine are represented in figure 1.0:
Cocaine binds to the DA transporter, inhibiting it's reuptake and increasing it's levels in the synaptic cleft.
Cocaine has different affinities to each transporter, having the highest affinity for the serotonin (5-HT) transporter, followed by the dopamine and norepinephrine transporters.Although it has the highest affinity for the 5HT transporter, it is it's blockeade of dopamine reuptake that is most important for cocaine's euphoric, stimulating and addictive propieties.Nevertheless, blockeade of the DA transporter isn't enough to explain all of cocaine's effects, and so norepinephrine and serotonin must also be taken into account.
The mesolimbic DA pathway to the nucleus accumbens plays a key role in the reinforcing effects of cocaine.Thus, lesions to the nucleus accumbens reduce the reinforcing propieties of systemically administered cocaine.
One interesting paradox however, is that although rats will self-administer amphetamine directly into the nucleus accumbens, they will not self-administer cocaine into the same area.One difference between the two is that amphetamine not only blocks dopamine reauptake, but stimulates it's release.However, it's unknown if this difference can explain the lack of self-administration into the nucleus accumbens.
The rewarding effects of cocaine, however, can differ given various factors, of which three are most important: Dopamine transporter (DAT) occupancy, baseline level of DA activity in the mesolimbic pathway and the rate at which the dopamine transporters are blocked after administration of the drug.
Once DAT occupancy reaches a certain minumum (40%-60%), a drug-induced high may be experienced.
Secondly, although it is still unclear why, the faster the rate at which the dopamine transporter is blocked, the more intense the "rush" will be.It is well-known that the faster the route of administration gets the drug to the brain, the stronger the high.This is quite clear when one looks at the reinforcing and addictive qualities of insufflated powdered cocaine vs. crack cocaine, which is smoked.
Laslty, the higher the baseline level of DA in the synaptic cleft, the stronger the effect of cocaine.This makes sense when one considers that cocaine is only a dopamine reuptake inhibitor and does not induce the release of dopamine.Therefore, the higher the initial concentration of DA, the more drastic the effect of blocking it's reuptake.
LD50 (mg/kg) (as the freebase) [1] :
Rat : 17.5 intravenously
Chemistry of Cocaine
Cocaine is actually benzoylmethyl ecgonine. It is an ester of benzoic acid and a nitrogenated base which may be considered as a tertiary amine to which it owes its local anesthetic properties. The fundamental structure can be viewed as formed by three portions: Lipophilic group, Hydrophilic group, and the Aliphatic group which joins the first two groups.
[1]
Column 1 Column 2 Systematic (IUPAC) name: methyl (1R,2R,3S,5S)-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate Synonyms: (1R,2R,3S,5S)-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid methyl ester, 3[beta]-hydroxy-1[alpha]H,5[alpha]H-tropane-2[beta]-carboxylic acid methyl ester benzoate, 2[beta]-carbomethoxy-3[beta]-benzoxytropane, ecgonine methyl ester benzoate, l-cocaine, [beta]-cocaine, benzoylmethylecgonine; cocaine muriate (hydrochloride) Molecular Formula: C17H21NO4, C17H21NO4.HCl (hydrochloride) Molar mass: 303.36 g/mol, 339.82 g/mol (hydrochloride) CAS Registry Number: 50-36-2, 53-21-4 (hydrochloride) Melting Point: 98°C, ~ 195°C (hydrochloride) Boiling Point: 187-188°C @ 0.1 mmHg Flash Point: no data Solubility: Freebase : 1 g dissolves in 600 mL water, 270 mL water (80°C), 6.5 mL alcohol, 0.7 mL chloroform, 3.5 mL ether, 12 mL oil turpentine, 12 mL olive oil, 30-50 mL liquid petrolatum (vaseline oil ?); soluble in acetone, ethyl acetate, carbon disulfide; sparingly soluble in mineral oil. Hydrochloride : 1 g dissolve in 0.4 mL water, 3.2 mL cold alcohol, 2 mL hot alcohol, 12.5 mL chloroform; also soluble in glycerol, acetone; insoluble in ether or oils Additionnal data: pKa 8.61 Notes: Freebase aspect : monoclinic tablets; crystallyzed from alcohol; volatile, especially above 90°C. Hydrochloride aspect : colorless to white crystals or white crystalline powder; saline, slightly bitter taste, numbs tongue and lips; solution prone to decomposition (hydrolysis of ester) upon heating; store in well-closed, light-resistant containers
The dangers of Cocaine
Effect on the Body
Cocaine has a number of side effects: constricts the blood vessels, dilates pupils, raises body temperature, increases heart rate, and blood pressure. Those are the virtually guaranteed symptoms, but it can also produce headaches and gastrointestinal issues like stomach cramping, diarrhea, and abdominal pain.
Frequent cocaine use leads to many adverse effects on the body. Regular insufflation (snorting) of cocaine can make you lose your sense of smell, cause nose bleeds, break down the membranes in the nasal passages (this can make it difficult to impossible to dive/swim as the pressure cannot be maintained outside the face.) Problems swallowing, sore throat, and chronic runny nose are possible.
Extended or frequent ingesting of cocaine orally can cause severe gangrene in the bowel or other digestive tissue from the constant constricting of blood vessels leading to tissue death.
Injecting cocaine has all of the risks associated with IV drug use, like abscesses, risk of blood borne disease if sharing needles. It also can give you a massive dose very quickly increasing the risk of cardiomyopathy.Cardiovascular Risks
In addition to all of the other effects, cocaine has a very serious issue: cardiomyopathy. This is concisely defined as a measurable decrease in heart muscle strength. You are most likely to have a cardiac "Acute myocardial infarction" (AMI) within the first hour after use, but this can occur up to a week later, possibly due to slower acting metabolites produced as byproducts.Stroke
Cocaine can also lead to an ischemic stroke. These are seen with the highest frequency in cocaine users 1 hour after use but the risk persists for a week or more. It is thought to be probably caused by a thrombogenic effect associated with platelet activation.Heart Palpitations
While not necessarily life-threatening, heart palpitations occur frequently during cocaine use and are a clear indicator of the stress that is being placed on the heart muscle. If you are particularly susceptible to these palpitations, you may be better suited reconsidering use of cocaine.
History of Cocaine
Cocaine has a very long, interesting and obscure history that begins with the coca shrub, which has been used around the Andes mountains for at least 3000 years [1].
Coca was very important to religious occasions in the Incan civilization and it's use was reserved to the ruling classes., up until the Spanish conquest.
After the fall of the Incan empire, coca chewing became commonplace and was even used as a medium of exchange.But soon Spanish missionaries began to argue that coca interfered with the conversion of these natives to Catholicism and the practice became discouraged and banned in many areas.But the Spanish soon realized that, without this powerful stimulant, the natives were much less productive, and couldn't work as long in the mines and coca chewing was once again allowed by the Spanish rulers and the church.
Cocaine, in the form of coca chewing, never gained popularity in Europe in part because of it's degradation on the long voyage, although this was about to change;
In 1863, Angelo Mariani, a french chemist who became interested in coca after reading a paper on the subject by Paolo Mantegazza, and went on to create the first widely sold coca extract: Vin Mariani.It used alcohol as a solvent (in the form of wine) to make a cocaine solution from the coca leaves which contained aproximately 6-7mg of cocaine per bottle.
Vin Mariani was extremely popular, and soon, poeple like Queen Victoria of Great Britain and Ireland, Pope Leo XIII and Thomas Edison were endorsing it to the public, with numerous copycat cocaine beverages coming to the market soon after, the most notable of them being Coca-Cola.
In 1859, Albert Niemann isolated cocaine, and soon numerous doctors began to promote the use of the drug for all kinds of ailments, including depression, pain, indigestion, and child birth with it's use as a local anesthetic being discovered later on [2] [3] .The most notable of these physicians was Dr Sigmound Freud, who in the spring of 1884 wrote his “Über Coca”, known as the best medical and experimental analysis of the drug at the time [4]. It was also frequently supplied to slaves and railroad workers as a way to increase their productivity.
Pharmaceutical companies such as Merck rushed to produce cocaine on an industrial scale, and this marked the beginning of cocaine's bittersweet relationship with man and society, that hasn't been over to this day, nor will it likely ever end.
By the beginning of the 20th century, the problems of addiction, violence and rising crime were apparent, and this, combined with the widespread belief that cocaine incited African-Americans to commit rape and murder, led in part to the 1914 Harisson tax act, which required cocaine and opioids to be dispensed only with a doctor's order [6]
Ever since, cocaine suffered increasing amounts of control, and is today a schedule II substance, almost exclusively used as a local anesthetic in dentistry [7].