Cocaine has a damaging effect on the digestive system, immune system, cardiovascular system, and genitourinary system, especially as dose-dependent hepatic toxin, which can lead to hepatocyte necrosis.

However, unlike other drugs, a small amount of cocaine or cocaine-containing substances can actually eliminate fatigue and improve mood (the specific dose still has no accurate data and the interval fluctuates greatly).

Cocaine Effects

The study believes that it can block the nerve conduction of the human body, produce local anesthesia, and stimulate the cerebral cortex and excite the central nervous system by strengthening the activity of chemicals (such as dopamine) in the human body.

It shows that the mood is high, active, and even tends to attack. Further research has also confirmed that the structure and function of the corresponding brain regions will change after cocaine is used.

cocaine

It is important to emphasize that drug addicts have a relapse rate of more than 90% after drug withdrawal. Since the neural mechanism of relapse is unclear, no effective preventive drug or means have been developed in the world.

Physical and chemical properties

Cocaine Composition

Commercially available cocaine is mostly extracted directly from coca leaves and is generally not pure. Mainly containing benzoyl methyl.

cocaine composition

Angerine, ecgonine, benzoylecgonine (BZE), cinnamococaine, N-formaldehyde cocaine, 6-hydroxycocaine, 3,4,5-trimethoxycinnamoyl cocaine and 3,4,5-trimethoxycocaine and the like.

The cocaine ester bond is unstable and can be rapidly hydrolyzed to break the ester group by boiling in an alkaline, strong acid or aqueous solution.

The main metabolites are benzoylecgonine (about 29%-54% of the total), ecgonine methyl ester (EME, about 26% to 60%), in addition to norcocaine. (norcocaine), ethyl benzoquinone cocaethylene, meta-hydroxycocaine, p-hydroxycocaine, 3-hydroxy-4-methoxy cocaine, 4-hydroxy-3-methoxy cocaine.

Pure nature

The chemical name for pure cocaine is methyl 8-methyl-3-(benzoyloxy)-8-azabicyclo [3,2,1]octane-2-carboxylate. Molecular formula C17H21NO4 molecule.

cocaine

Amount 303. Pure product is white crystal, odorless, taste slightly bitter and hemp, insoluble in water (1:600), soluble in organic solvents such as chloroform (1:0.7), ether (1:3), ethanol (1:7) It is soluble in organic solvents such as acetone, benzene, ethyl acetate, carbonyl disulfide, and petroleum ether.

It exhibits monoclinic flaky crystals in ethanol. The melting point of 98° (90° or more can be slowly volatilized), specific optical rotation -16 ° (C=4, chloroform).

Its hydrochloride is white crystal or crystalline powder, very soluble in water, soluble in ethanol and chloroform, but insoluble in ether. The main metabolites of cocaine are benzoyl ecgonine and ecgonine methyl ester, which can be further hydrolyzed to form ecgonine.

Same series of compounds

Aigang Ning, a monoclinic columnar crystal, soluble in water, insoluble in ethanol, almost insoluble in other organic solvents, melting point 205 ° C. Acid-base, and

Both acid and base can be combined into a salt. Aigang Ning can be extracted from coca leaves or directly hydrolyzed by cocaine.

Cinnamyl Methyl Agony, also known as Cinnamococaine, is pure needle-like crystal, melting point 121 ° C, almost insoluble in water, soluble in organic solvents, long needle-like crystal.

Lidocaine is a white crystalline powder with a special odor. Stable in air, melting point 65 ~ 69 ° C. Almost insoluble in water, soluble in ethanol, chloroform, and ether.

Lidocaine

Due to the steric hindrance effect in the chemical structure, it is not easy to be hydrolyzed and is stable to both acid and alkali. This product hydrochloride, also known as xylocaine, is a colorless crystalline powder that is odorless and has a bitter taste. The temperature of 76 ~ 79 ° C. Very soluble in water (1:1) and ethanol (1:15), soluble in chloroform (1:40), insoluble Ether.

Classification

Common cocaines and preparations include:

(1) Coca leaf (the leaves of the coca bush, which is the raw material for refining cocaine, and a source of food containing trace amounts of cocaine in South America). The millennium history of South America has proved that chewing coca leaves will not Addictive, because the content of cocaine in the leaves is extremely low, according to the custom of Cusco in Peru, the daily intake does not exceed 0.5mg.

(2) Can be a paste: The granules are thick, moist and agglomerate, with a special odor; in fact, it is a coarse extract of cocaine, containing residuals and chemical products of hydrocarbons, which have certain addiction risk.

(3) Cocaine: the sample is a pure white to off-white powder with very little moisture and a special smell. The internationally smuggled cocaine purity is generally 80% to 90%.

In the process of smuggling and trafficking in developed countries, they are usually diluted two or three times to increase their weight. Also incorporate artificial synthetic anesthetics such as lidocaine, procaine or benzocaine.

Some also incorporate hydrocarbons such as mannitol, lactose or glucose, and the purity is generally around 30%. After purification, it can be made into finished products such as fastball and Klerk.

(4) Cocaine drink: which is the most important way to take cocaine in the early years. Later, it disappeared with the release of national bans. Due to the re-emergence of energy drinks, the main ingredient is a trace amount of cocaine hydrochloride.

Detection Method

The detection methods of cocaine mainly include high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and gas chromatography-mass spectrometry.

Usage (GC-MS), solvent microextraction – online back extraction – field amplification injection – capillary electrophoresis – ultraviolet detection (SME-OLBE-FASI-CE-UV) and direct real-time ionization time-of-flight mass spectrometry (DART-TOF- MS), etc., in which the detection of cocaine and its metabolites in urine is mainly by GC-MS.

cocaine

The chemical color development method and the thin layer chromatography detection method (TLC) are simple and convenient to operate but the sample amount is large, and the detection sensitivity and precision are not high.

Instrumental analysis methods are extremely sensitive and precise but require expensive instruments, equipment, and specially trained technicians to perform on-site inspections.

The immunoassay has the advantages of simple operation, high efficiency, sensitivity, specificity, and suitable for large-scale detection. However, to use this, it is necessary to obtain an antigen-active cocaine whole antigen.

Generally, a substance having a molecular weight of less than 1000 is not immunogenic, does not produce antibodies when it enters the body and must be coupled with a carrier protein to form a whole antigen in order to be immunogenic.

The active group contained in the carrier protein mainly has a carboxyl group, an amino group, a hydroxyl group, a thiol group and the like, whereby a carboxyl group is introduced into the cocaine molecular structure to react with an amino group in the protein to form a conjugate.

High-performance liquid chromatography, the principle of high-performance liquid chromatography, compared with gas chromatography, can separate and detect various drugs with thermal instability, non-volatile, and large molecular weight.

Commonly used detectors include UV detectors and diode array detectors. , fluorescence detectors, etc.

Chromatography/mass spectrometry, the identification of toxicants and drugs using GC/MS or HPLC/MS has become an internationally recognized standard method and a necessary condition for providing courts with identification results.

Biological Sample

There are many types of biological samples tested, and blood and urine samples are the most commonly used biological samples. The advantage of urine samples is that the concentrations of prodrugs and metabolites are higher.

After the biological samples are collected, they must be pretreated to extract and detect the target components. The blood sample can be used for extraction and detection by centrifugation, and the supernatant can be used for extraction and detection.

The urine sample needs to be acid-decomposed, enzymatically hydrolyzed, and free of the original substance or metabolite. The pretreatment of the hair is complicated, and the surface of the hair needs to be cleaned and adhered.

The substance is then hydrolyzed with a suitable acid, base, alcohol, and enzyme. In the establishment of immunoassay methods such as colloidal gold and ELISA detection methods, the commonly used protein carrier proteins are BSA, ovalbumin (OVA) and human serum albumin (HAS), and the most commonly used is BSA.

The reason is that its physicochemical properties are stable, not easy to be denatured, and can maintain a large solubility at different pH values ​​and different ionic strengths; a large number of reactive groups such as amino groups, carboxyl groups, etc., in an organic solvent state (pyridine, dimethylformamide) can be coupled to a hapten.

Toxicity

Abuse method

Cocaine abuse methods include nasal aspiration/spraying, smoking, and injection. Generally, the dose is used, and the nasal inhalation is 10-30 mg/time (individually reported to reach 50-200 mg, the typical user will inhale this dose separately with two nostrils).

If using the injection method 10-20 mg/time. The degree of action of these toxins into the human body is closely related to the way they enter.

The bioavailability of cocaine by intravenous injection (the amount of drug absorbed by the body) is 100%, oral administration is 20%-30%, and nasal suction is 20% – 30%, fuel absorption is 6%-32%.

Among them, the most common route is nasal inhalation, one nostril is blocked, and the other nostril is used to inhale cocaine crystal powder.

The cocaine powder is divided into a plurality of rows or columns by sharps such as razors, and one gram of cocaine can be divided into about 25-50 rows, each of which acts 3-5 cm, and contains about 25-30 mg of commercially available cocaine.

This medicine is then inhaled through a straw that is rolled up with US dollar bills or by means of a cocaine “spoon”. In this way, the drug is actually absorbed through the mucosa, and the peak plasma concentration can be reached in about 15 minutes, but the clinical onset time is very fast. Intravenous use of cocaine hydrochloride for approximately 3-5 minutes.

If you use the most popular free cocaine in the black market, you can have a strong euphoria in 1min when inhaled for 5-10min. Its half-life is also different.

The average half-life of intravenous injection was 45 min, the oral half-life was 48 min, and the half-life from nasal inhalation was 75 min. The lethal dose is 0.5~1g orally, 30mg for allergy, 30mg for intramuscular or mucosal administration, and lethal blood concentration are 0.9-21mg/L.

Cocaine can be absorbed quickly regardless of the way it enters the body. The difference is only the length of time and the strength of utility.

Its metabolism is mainly achieved through liver tissue and plasma. Cocaine is excreted in the urine by 1% of the amount in the body. The amount of 25%-40% is converted to benzoyl ingonine from the urine, 18%- 20% became Egonin methyl ester, 2%-3% became Egonin, and it was also excreted in the urine.

Abuse performance

Acute poisoning caused by cocaine abuse is extremely irritating, disturbed, mentally abnormal, unclear vision, tremor of the extremities, and severe cases can induce heart rhythm disorder, generalized convulsions, respiratory failure, and death.

Suckers often show symptoms such as anxiety, burnout and extreme excitement, which are similar to delusional schizophrenia.

Because cocaine is highly toxic to the central nervous system, it can stimulate the cerebral cortex and produce hallucinations such as sight, hearing, and touch. As a result, their sense of touch is especially strong.

It seems that there are always insects on the skin, resulting in self-harm, often psychological horror, always suspected of being monitored and tracked.

Chronic poisoning caused by long-term low-dose abuse generally affects only the individual’s eating and sleeping, and produces mild abnormalities such as irritability and distraction, mainly psychologically dependent reactions, and physiological dependence is very light.

Both acute and chronic poisoning can cause severe neurological and psychiatric injuries and neurological complications including ischemic stroke, subarachnoid hemorrhage and cerebral hemorrhage, headache, syncope, seizures, and death.

First aid

Mainly to remove poisons, especially shortly after medication. If it is inhaled, the drug should be removed from the nostrils, and gastric lavage should be given after using activated carbon.

If the liver and kidney function is normal, an acidic diuretic (ammonium chloride) is given, but there is a risk of causing renal failure. In addition, the need to effectively control excitement can reduce other symptoms of the patient, such as high blood pressure and tachycardia.

Cover the body with a hail full body or cool blanket and give benzodiazepines to calm. Patients with convulsions should be given 5-10mg of diazepam slowly, repeated every 5min, until the total amount reaches 30mg, but antipsychotic drugs may cause severe fever, prolong the duration of convulsions, preferably only for the treatment of only psychiatric symptoms By.

The main cause of death from acute cocaine poisoning is respiratory failure caused by a high degree of inhibition of the respiratory center. Naloxone hydrochloride has a specific antagonistic effect on respiratory depression caused by anesthesia analgesics.

Using a method of administration once every 30 minutes, naloxone maintains a high concentration level in the plasma, and the patient’s consciousness, breathing, and the like are restored as soon as possible. At the same time, the specific antagonist naloxone is used as soon as possible to maintain the patient’s blood pressure, respiratory and other vital signs.

Addiction mechanism

Drug dependence (drug addiction) is a special psychological state produced by the interaction between drugs and the body, including physiological state. The study found that both physical and mental dependence have their physiological basis. After the use of drugs such as cocaine, the structure and function of the corresponding brain regions will change.

Therefore, drug dependence can be considered to be a chronic recurrent brain disease to some extent. The National Institute of Drug Abuse, through research on the brain of cocaine-addicted mice, also found that neurons in a region of the prefrontal cortex of the brain were significantly weaker.

It has been previously found that the corresponding areas in the human brain are associated with behavioral control, and those with damaged or defective areas are more likely to be addicted to cocaine and more difficult to quit the addiction.

In the experiment, the researchers used optogenetic techniques to stimulate this region of the brain in the addicted experimental mice and found that the behavior of these experimental mice seeking cocaine was reduced.

Conversely, if the activity of neurons in this region is inhibited, the experimental mice show signs of increased drug addiction.

Dopamine mechanism

Addictive drugs such as cocaine are characterized by both a rewarding effect and a reinforcing effect on the nervous system.

The reward of the nervous system is a positive stimulus that the brain sees as intrinsic and sometimes must be obtained, and reinforcement can be considered as a stimulus that causes repeated repetition of related behaviors.

The neural basis of positive reinforcement is a multitude of interconnected forebrain structures, often referred to as the brain’s reward pathway.

The reward pathways include nucleus accumbens (NAc), basal forebrain, and medial prefrontal cortex, which accept dopamine (DA) in the ventral tegmental area (VTA) of the midbrain. ) can be introduced into nerve fibers.

Activation of the midbrain marginal system the dopamine system is the neurobiological basis for cocaine addiction.

Experiments have shown that under the action of cocaine, the discharge activity of dopamine neurons in VTA is enhanced, resulting in enhanced release of dopamine from NAc and other neurons.

Cocaine damage to the central nervous system is associated with the dopamine (DA) pathway in the midbrain limbic system. The ventral side of the midbrain

The covered area is projected to the nucleus accumbens of the ventral striatum and a portion of the limbic system, such as the septum, the almond complex, and the piriform cortex.

The dopamine transporter (DAT) is a membrane protein located in the presynaptic membrane of dopamine neurons. Its main function is to reuptake DA in the synaptic cleft. Cocaine limits DA by inhibiting DAT on the presynaptic membrane.

The time, extent, and extent of action with its receptor. In turn, the regulation of mental and emotional activities can be achieved, and the intensifying effect of Cain addiction can be achieved.

Under normal physiological conditions, DA and Na + bind to the corresponding sites on the presynaptic membrane DAT, and then Cl- binds to its own site. Finally, DAT transports DA from the synaptic gap to the intracellular storage.

The binding sites of cocaine and Na + on DAT are the same. When cocaine is present, it competes with Na + for the same site, so that DAT cannot normally bind to DA, resulting in accumulation of DA in synaptic space, making nerve fiber persistent. Excited, so that users have a thrill.

Studies of DAT-deficient mice have found that cocaine does not exert an addictive effect on mice that do not express DAT, suggesting that DAT plays an important role in cocaine addiction.

There are also studies on serotonin (5-HT) transporters, norepinephrine transporters, neuronal adaptation of glutamate transport in the nucleus accumbens, caudate nucleus dominated by cholinergic neurons, hippocampus, and ventral side Changes in the rate of acetylcholine renewal in the brain regions such as caps, and changes in certain enzyme activities, such as kinases, phosphatases, phospholipase A2, and PCCT (the rate-limiting enzyme for phosphatidylcholine synthesis), are also present in cocaine addiction.

Both the 5-HT/DA antagonist clozapine and the 5-HT receptor antagonist attenuated cocaine self-administration and cocaine-induced animal psychomotor stimulating behavior and cocaine reward effects. But DAT dominates it.

Treatment

There are three main treatment mechanisms: one is to act as a substitute for cocaine, to produce a similar dopamine effect; the other is to act as a cocaine

The antagonist acts to block the binding of cocaine to the dopamine transporter; the third is to regulate the cocaine effect by acting on other cocaine binding sites. It is important to emphasize that drug addicts have a relapse rate of more than 90% after drug withdrawal.

Since the neural mechanism of relapse is unclear, no effective preventive drug or means have been developed in the world. Some studies have shown that most people in the three months have a relapse or similar reactions.

The fundamental of alternatives lies in the reward effect. The rewarding effect of addictive drugs is the direct cause of drug addiction. The commonly used means of evaluating drug reward effects are mainly conditioned place preference (CPP) experiments and self-administration.

Experiment. Known treatments for cocaine addiction do not play a fundamental role, and most of them are in the laboratory stage, and the more prominent are cocaine-catalyzed antibodies and cocaine vaccines.