Addiction Treatment Blog

Save for the occasional use of Cocaine he had no vices, and he only turned to the drug as a protest against the monotony of existence.

Dr. Watson describing Sherlock Holmes in ‘The Adventure of the Yellow Face’, Sir Arthur Conan Doyle, 1893.

When cocaine is taken, users hope to experience a 'rush' of exhilaration as the drug reaches the brain.

History

Cocaine occurs naturally in the leaves of the coca plant, Erythroxylum coca, and certain related species which originate from South America, especially Peru, Bolivia and Columbia. The Incas considered the plant a divine gift and reserved its use for the higher echelons of society. Conversely, all levels of society amongst the Andean Indians have used the leaves as a masticatory for thousands of years. The leaves are combined with slaked lime or plant ash to produce an alkaline medium which enables the cocaine base to form a solution in saliva and thus and the circulation. Chewing the leaves helps the Indians tolerate hunger, exposure and fatigue at high altitudes where the working environment can be hostile. Cocaine provides a stimulus to manual labour, therefore, as well as inducing feelings of pleasure. The leaves contain about 1 per cent cocaine.

In about 1860, cocaine was isolated and identified as the active constituent of the coca plant. It was subsequently employed medicinally as a local anaesthetic. Karl Koller was probably the first to use it in humans, when he performed eye surgery in 1884.

When recreational use of cocaine developed outside South America the form developed was a water-soluble extract: crystalline cocaine hydrochloride. This is still probably the form of drug most widely used; it is often mixed with a diluent powder on the street and in the UK is usually known as coke, snow or blow.

Until relatively recently, cocaine was viewed in the UK as an expensive drug, used more by the wealthier sections of the populations. However, the number of abusers at all levels of society has increased. This is probably because cocaine has a reputation as a ‘clean’ drug and the street price has decreased considerably. Other factors influencing the greater demand for the drug may include the increased availability of very pure forms of cocaine such as ‘crack’ and the fact that various forms of the drug can produce rapid-onset, short-lived but intense effects without the need for injection.

‘Crack‘ is a highly pure form of the free base of cocaine (i.e. it is not a salt of cocaine like cocaine hydrochloride). The name is thought to originate from the cracking noises that lumps of free base make when heated up. This noise is probably caused by impurities in the cocaine remaining from the extraction process (e.g. sodium bicarbonate, sodium chloride). ‘Crack’ began to be available on a large scale in the USA in the mid-1980s.

'Crack' cocaine.

Effects Shought

When a cocaine is injected or ‘crack cocaine‘ is smoked, users hope to experience a ‘rush’ of exhilaration as the drug reaches the brain. This is afforded by rapid access to the circulation. It is not a feature of nasal insufflation of the hydrochloride salt because absorption across the nasal mucous membranes is slow (it is probably further retarded by the vasoconstrictor actions of cocaine which restrict blood flow to the site). The desired effects of cocaine are heralded by a series of adrenaline like reactions due to stimulation of the sympathetic nervous system and release of adrenaline. Generally the mental effects produced  by cocaine are feelings of euphoria, alertness, excitement and rapid flow of thought. This may manifest as hyperactivity, increased confidence, talkativeness and sometimes emotional lability. When intoxicated, abusers may feel indifferent to matters which normally cause them great concern.

Cocaine is a stimulant; it helps to combat fatigue and subjectively there may be feelings of increased capacity to do work, great physical strength and mental supremacy.

Administration

The usual method of use for cocaine hydrochloride is to arrange the powder in a line on a flat surface and inhale it nasally via small tube (e.g. a drinking straw or rolled paper). This method of nasal insufflation is termed ’snorting’. Cocaine hydrochloride powder is illustrated in below.

The hydrochloride salt has a high melting point (197 °C) and it is not very stable when heated to high temperature. It is therefore costly and wasteful to smoke because large amounts need to be used. The free base form of cocaine has greater thermal stability and a lower melting point (98°C), making it a more suitable preparation to smoke. The method of production involves treating cocaine hydrochloride with alkali, followed by the heating of the precipitate in a glass pipe. The alkaloid base vapour then inhaled. This technique is called ‘freebasing‘.

Cocaine hydrochloride powder.

‘Crack’ cocaine is ready-made free base cocaine which has been prepared on a large scale and sold on the street. ‘Crack’ may be smoked in a pipe, heated on foil and the vapour inhaled, or smoked with tobacco in a cigarette.

Injection of cocaine is less popular method of abuse than smoking or insufflation. The hydrochloride is generally used because it is much more water-soluble than ‘crack’. However, in one study over 20 per cent of ‘crack’ users were found to be attempting injection of the free base. The time to onset of action and peak effects are similar to those seen with ‘crack’ smoking. A ‘speedball‘ is a mixed injection of heroin and cocaine favoured by some abusers.

Cocaine is active when taken orally but is not commonly taken by this route because the onset of action is too slow and the effects are much less intense.

When an abuser ‘freebases’, smokes ‘crack’ or injects cocaine hydrochloride, the psychoactive effects begin within seconds but peak after a few minutes. To maintain the desired euphoria the process must be repeated frequently. Repeated use of drug in this way is described as a ‘run‘ or a ‘binge‘. It may continue until the individual is exhausted or until the supply of drug runs out. The peak effects from nasal insufflation or oral administration take longer to develop: 15 to 30 minutes for nasal insufflation, up to an hour when taken orally. Hence abuse via these routes is likely to be associated with a ‘run’. After a ‘run’ or a single dose, an individual may ‘crash’, i.e. experience post-cocaine dysphoria.

Pharmacokinetics and Pharmacology

The half life of cocaine varies from 45 to 90 minutes. The average is probably about 60 minutes. There may be a moderate increase in half-life as the dose increases. The psychotropic effects of the drug last for varying lengths of time depending on the method of administration. These differences are summarised in the table below.

The majority of a cocaine dose (about 90 per cent) is metabolised by hydrolysis. Plasma and liver pseudocholinesterases convert cocaine to metabolites which may have some action on the sympathetic nervous system but which are not thought to be psychoactive. The three major metabolites are ecgonine methyl ester, benzoylecgonine and ecgonine. These are excreted in urine. The remaining proportion which is not  hydrolysed is metabolised in the liver by N-demethylation. The ultimate product of this metabolic pathway, norcocaine nitroxide, has been proposed as the cause of cocaine-induced hepatotoxicity (but see below).

Cocaine inhibitis reuptake of dopamine, noradrenaline and serotonin in central and peripheral nerve synapses and so effectively prolongs and augments their effects. It seems particularly to increase the concentration of neurotransmitters in dopaminergic areas of the brain. The inhibition of dopamine reuptake is believed to cause euphoria and this is the main reason why users continue to take the drug. Mice which have been genetically manipulated so that they lack a central dopamine reuptake mechanism at synapses and stimulate the release of adrenaline from the adrenals.

In the laboratory setting many experienced abusers, given unidentified drugs to inject, cannot distinguish between the effects of cocaine and those of amphetamine. This is not surprising as they produce similar net effects at the synapse level but by different mechanisms. Both drugs increase the activity of similar central nervous system (CNS) neurotransmitters, have stimulant properties and enhance the peripheral sympathetic nervous system. Their similarity is further supported by study of side effect profiles which are remarkably alike.

Time Course of Psychoactive Effects of Cocaine

Cocaine is a dangerous drug which may cause adverse physical and psychological effects.

Adverse Effects of Cocaine

As with many drugs of abuse, the most serious side effects are often a consequence of acute overdosage or chronic use of high doses. Potential acute adverse reactions, occurring within a few hours of taking cocaine are summarised in the table below. There is no specific treatment for cocaine intoxication per se.

The cardiac toxicity of cocaine has been studied in some detail because many deaths have been attributed to this adverse effect. The effects upon the heart in any one person are unpredictable but cocaine has been reported to cause a variety of cardiac adverse effects, of which myocardial infarction (MI) is the most serious MI has been documented in numerous case reports and the likelihood of infarction does not seem to be related to duration of use, frequency of use or method of administration.

In patients with pre-existing ischaemic heart disease, cocaine can have apparently sympathometic effect on the heart, increasing myocardial oxygen demands to the extent that angina pains occur and sometimes myocardial infection. However, the majority of patients who have suffered a heart attack as a result of taking cocaine do not have pre-existing symptomatic heart disease and a thrombus is often absent at post-mortem. Research has shown that cocaine can cause coronary vasospasm. The exact mechanism of this is uncertain, but it could be a direct vasoconstriction caused by cocaine itself or the catecholamines that it can release. Cocaine abuse can cause endothelial damage, and vasospasm could consequently be at least partly due to a reduction in the synthesis of endothelium-derived vasodilators such as nitric oxide or prostacyclin. However, it seems unlikely that coronary vasospasm alone would be sufficient to trigger a fatal infarction. The effect may be augmented by formation of a thrombus which lyses before post-mortem (platelet aggregation being triggered by the aforementioned damage to the endothelium) and catecholamine-induced increase in myocardical oxygen requirement.

In one study, coronary vasospasm closely mirrored the time course of cocaine plasma levels. But spasm also occurred when there was a later peak in cocaine metabolites, so these may also be important in the aetiology of cocaine cardiotoxicity.

Arrhythmias produced by cocaine may simply be secondary to the adrenergic effects of the drug. However, arrhythmias could arise as a result of the adverse cardiac effects of cocaine (MI, myocarditis or the reperfusion after coronary artery spasm). Cocaine as a local anaesthetic also has a direct membrane stabilising effects on the myocardium itself and can be demonstrated to prolong the QT interval on an electrocardiogram (ECG).

Chest pain is quite a common complaint. A study of 217 chronic ‘crack’ smokers showed that 39 per cent suffered pains in the chest within an hour of smoking cocaine; 64 per cent reported a pain that was made worse by taking a deep breath. The cause of the pain is unclear; there may be more than one kind of pain and therefore a variety of causes. The pain is generally short-lived. It can be due to cocaine-induced MI or cardiac ischaemia but when a series of 100 chest pain patients were given an ECG, only 8 per cent had a trace typical of an MI. Researchers have suggested inflammation of pleural membranes as a cause because of the pain on inspiration. Thoracic muscle rhabdomyolysis has also been suggested and this is consistent with the high creatinine kinase levels observed in such patients. Involvement of pectoral or intercostal muscles would explain why the pain can be more intense on inspiration. In those taking amphetamine derivatives similar pains have been attributed to spasm of the intercostal muscles. It is not known how cocaine could be toxic to skeletal muscle. If it is capable of causing prolonged spasm this could give rise to rhabdomyolysis, although why thoracic muscles alone should be specifically involved is not understood.

Cocaine ‘snorting‘ or smoking can exacerbate asthma. Rubin and Neugarten described six asthmatics who suffered severe or life-threatening bronchopasm after using cocaine. Wheezing has been described six asthmatics who suffered severe or life-threatening bronchospasm after using cocaine. Wheezing has been described in up to a third of free base smokers. A US study of 217 chronic smokers of the free base revealed that 44 per cent of subjects had reported coughing up black sputum within 12 hours of use and that 6 per cent had coughed up blood. Other pulmonary complications appear to be very rare but include pulmonary oedema, pneumomediastinum, pneumothorax and bronchiolitis.

Stroke is rare in patients under 45 years of age but the taking of cocaine is associated with an increased risk. Haemorrhagic stroke is more likely than thrombotic or embolic types.

Convulsions are probably more common when high doses, or long ‘runs’ of cocaine are used. Fitting can occur with any mode of administration and seems to resolve without leaving a permanent propensity to seizures, whether treated with anticonvulsants or not.

Acute Adverse Reactions to Cocaine

• Adrenaline-like effects such as tachycardia, mydriasis, sweating, tremor, flushing, reduced appetite, headaches
• Nausea and vomiting
• Chest pain, black sputum, wheeziness, shortness of breath, respiratory arrest
• Hypertension, palpitations, tachyarrhythmias, myocarditis, cardiomyopathy, cardiac arrest, sudden death
• Stroke, convulsions
• Rhabdomyolysis, with or without hyperpyrexia, and sequelae
• Anxiety, paranoia, hallucinations (visual, auditory, tactile) after large doses. Acute psychotic reactions, panic reactions, violence
• Cocaine may induce heightened sexual interest; this may result in acquisition of sexually transmitted diseases or unwanted pregnancies
• Intoxication may facilitate accidents or participation in risk taking behaviour
• After a ‘run’ there is frequently a ‘crash’, characterised by dysphoria, depression, irritability and craving for the drug; this is often followed by fatigue and sleep.

Long-term Use

Panic attacks are a common acute psychiatric problem. But chronic cocaine abuse may cause a range of psychiatric problems which may be acute or chronic. Anxiety, nervousness, depression, exhaustion, mania and paranoid psychosis have all been attributed to frequent cocaine use. Persistent anhedonia or dysphoria can also develop. Subjects may find it difficult to concentrate, suffer from memory loss and become antisocial. The anorexic properties of the drug frequently give rise to weight loss.

Perforation of the nasal septum and rhinorrhoea commonly result from regular ’snorting’ of cocaine. However, the effects on the rest of the respiratory tract are less clear. Chronic abusers often have a cough and may suffer from bouts of wheeziness or a hoarse voice. Measurements of lung function can reveal a deterioration in the gaseous exchange capacity of the alveoli but the implications of this for long-term health are not understood.

Dental erosions have been reported in those who draw snorted cocaine through the nose and then into the mouth, thus partly relying on buccal absorption. This is more likely to occur in those with a perforated nasal septum. The hugh salivary pH caused by cocaine is thought to be responsible for the resulting damage to teeth.

Despite cocaine being a dose-dependent hepatotoxin in mice, it is unclear weather the drug has similar effect in humans. A review by Farrell highlighted that, in all reported cases of alleged cocaine-induced liver damage, more obvious well-established causes of liver failure were either present or had not been excluded. Farrell suggested that hepatic ischaemia caused by shock and hypotension were more likely mechanisms by which cocaine could derange liver function than a direct hepatotoxic action of cocaine or its metabolite norcocaine nitroxide.

Limited studies suggest that cocaine may accelerate the process of atheroma formation and cases of thrombocytopenia occurring up to three weeks after use have also been reported.

Cocaine Dependence

Cocaine can produce both physical and psychological dependence but the dependence potential of cocaine may vary according to the method of administration. ‘Snorting’ cocaine hydrochloride has a lower dependence potential than smoking the free base (’crack’) or injecting the hydrochloride. This is probably because these latter two methods cause such an intense and short lived exhilaration. In animal studies, cocaine possesses very potent ‘reinforcing properties’, i.e. animals will more quickly adopt a certain pattern of behaviour if cocaine is offered as a reward. In humans, this is manifested as a ‘craving’ for the drug. The individual has a strong desire to experience again the euphoric effects of the drug (positive reinforcement) and may also be driven by the desire to reserve the dysphoric aftermath (negative reinforcement). Positive reinforcement is probably the dominant drive to continued use. ‘Crack’ cocaine has been associated with a particularly strong craving heavy users may go without food or sleep for long periods in order to continue to use the drug.

Craving may persist for weeks after cessation of chronic administration and is the most prominent feature of withdrawal. Sometimes other symptoms of withdrawal are seen including irritability, depression, anxiety, insomnia and dysphoria. Craving encourages the subject to continue the abuse but, unlike opioid withdrawal, there seem to be no physiological signs necessitating a gradual reduction in the dose of the drug.

Cocaine Treatment

Pharmacologically, a variety of drugs have been used in an attempt to reduce cocaine use, decrease craving and alleviate dependence or symptoms of withdrawal. Research has concentrated mainly on two approaches. In the first, antidepressants have been used because cocaine abstinence produces symptoms similar to depression. The second popular approach has been to employ drugs which interact with dopamine because this neurotransmitter is known to have a key role in the positive reinforcement produced by cocaine. Other pharmacological approaches have involved drugs which affect neurotransmitters which may be involved in the neurochemical effects of cocaione (e.g. serotonin, opioids) and symptomatic treatment of underlying mental illness. Non-pharmacological approaches are important and include counselling, behavioural therapy and psychotherapy.

Tricyclic antidepressants, particularly desipramine, seem to facilitate an initial abstinence from cocaine and this initial success may be independent of whether the individual suffers from depression or not. However, the continued success of treatment may be related to the existence of underlying depression. It has been suggested that tricyclics only be used for six to ten weeks in those without depression because otherwise side effects such as jitteriness and stimulation may act as cues for cocaine craving. In those who do suffer from depression, it may be beneficial to continue tricyclics in order to prevent recurrence of depression which could otherwise encourage a desire for the mood-elevating effects of cocaine. Identifying depression in drug abusers can be difficult, not least because cocaine itself can be a cause of depression. Despramine is more successful in cocaine abusers than in chronic cocaine dependents.

Patients with schizophrenia who abuse cocaine may need bigger doses of existing treatment or a complete reappraisal of neuroleptic therapy if cocaine has exacerbated psychosis. Alternatively, such patients may require specific treatment for neuroleptic adverse effects. This may necessitate reduced doses of existing treatment, a change in neuroleptic or an additional drug (e.g. antimuscarinic). If cocaine is being taken simply as a mood enhancer, an antidepressant may help (as above).

Studies have suggested that buprenorphine may reduce cocaine use. This effect could be because central opioid pathways may help mediate cocaine dependence but also because many cocaine abusers use, or are dependent upon, opioids at the same time. Bromocriptine may decrease craving and dysphoria in some individuals but side effects are troublesome. Carbamazepine and fluoxetine have been studied but are probably ineffective.

Social and environmental ‘cues’ are important in triggering craving for cocaine; at the physiological level dopamine may be the neuro-transmitter involved in this effect. A recent small study of 20 patients suggested that a dopamine antagonist such as haloperidol 4mg daily could reduce craving. This is important because cue-elicited craving is one of the main reasons for recidivism in cocaine dependents seeking abstinence.

Recent work in animals has suggested that stimulation of post-synaptic dopamine D1 receptors can prevent or alleviate craving for cocaine whereas stimulation of D2 receptors may actually increase craving. A highly specific D1 agonist that has no activity at other dopamine receptors could therefore be very helpful therapeutically. In 1995, a team of researchers showed that it was possible to vaccinate against the action of cocaine in rats such that CNS concentrations and response to the drug were markedly reduced.

For cocaine abusers and dependents there are no universally applicable pharmacological interventions which will aid abstinence, prevent craving or treat withdrawal. Most users of cocaine seeking abstinence simply stop taking the drug abruptly, with or without counselling or other non-pharmacological support. There is no necessity to medicate the immediate withdrawal period, but drugs such as desipramine may make it easier for some, unless there is a treatable ‘reason’ for abuse (e.g. depression), there are no drugs to stop the chronic compulsion to take cocaine. Hence the chronic abuser must unfortunately rely largely on ‘will power’ to prevent recidivism.

Are You Addicted to Cocaine and In Need of Help?

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