Cocaine dependence

Cocaine dependence (or addiction) is a psychological desire to use cocaine regularly. Cocaine overdose may result in cardiovascular and brain damage such as constricting blood vessels in the brain, causing strokes and constricting arteries in the heart, causing heart attacks ^[1] specifically in the central nervous system.

The use of cocaine creates euphoria and high amounts of energy much like caffeine. If taken in large unsafe doses, it is possible to cause mood swings, paranoia, insomnia, psychosis, high blood pressure, tachycardia, panic attacks, cognitive impairments and drastic changes in personality.

The symptoms of cocaine withdrawal (also known as comedown or crash) range from moderate to severe: dysphoria, depression, anxiety, psychological and physical weakness, pain and compulsive craving.

Historically, the addiction was known as cocainism.^[2]

Signs and symptoms

Cocaine is a powerful stimulant known to make users feel energetic, happy, talkative, etc. In time, negative side effects include increased body temperature, irregular or rapid heart rate, high blood pressure, increased risk of heart attacks, strokes and even sudden death from cardiac arrest.^[3] Many habitual abusers develop a transient manic-like condition similar to amphetamine psychosis and schizophrenia, whose symptoms include aggression, severe paranoia, and tactile hallucinations including the feeling of insects under the skin (formication), also known as "coke bugs", during binges.^[4]

Risk

According to a study of 1081 US residents aged over 11 years who had used cocaine for the first time within 24 months prior to assessment, the risk of becoming cocaine-dependent within 2 years of first use (recent-onset) is 5-6%; after 10 years, it increases to 15-16%. These are the aggregate rates for all types of use considered, i.e., smoking, snorting, injecting. Among recent-onset users, the relative rates are higher for smoking (3.4 times) and much higher for injecting. They also vary, based on other characteristics, such as sex: among recent-onset users, women are 3.3 times more likely to become addicted, compared with men; age: among recent-onset users, those who started using at ages 12 or 13 were 4 times as likely to become addicted, compared with those who started between ages 18 and 20.^[5]

However, a study of non-deviant^{[nb 1]} users in Amsterdam found "relative absence of destructive and compulsive use patterns over a ten year period" and concluded that cocaine users can and do exercise control. "Our respondents applied two basic types of controls to themselves: 1) restricting use to certain situations and to emotional states in which cocaine's effects would be most positive, and 2) limiting mode of ingestion to snorting of modest amounts of cocaine, staying below 2.5 grams a week for some, and below 0.5 grams a week for most. Nevertheless, those whose use level exceeded 2.5 grams a week all returned to lower levels."^[6]

Mechanism of dependence

It is speculated that cocaine's intense addictive properties stem partially from its DAT-blocking effects (in particular, increasing the dopaminergic transmission from ventral tegmental area neurons). However, a study has shown that mice with no dopamine transporters still exhibit the rewarding effects of cocaine administration.^[7] Later work demonstrated that a combined DAT/SERT knockout eliminated the rewarding effects.^[8] The rewarding effects of cocaine are influenced by circadian rhythms,^[9] possibly by involving a set of genes termed "clock genes".^[10]

There is a correlation between a variant of the CAMK4 gene and cocaine addiction; a German study found that addicts were 25% more likely to have a variant of the gene than people who did not use cocaine.^[11][12]

However, chronic cocaine addiction is not solely due to cocaine reward. Chronic repeated use is needed to produce cocaine-induced changes in brain reward centers and consequent chronic dysphoria. Dysphoria magnifies craving for cocaine because cocaine reward rapidly, albeit transiently, improves mood. This contributes to continued use and a self-perpetuating, worsening condition, since those addicted usually cannot appreciate that long-term effects are opposite those occurring immediately after use.

Research has shown that chronic cocaine use reduces the expression of a protein, called Rac1, known to regulate brain plasticity, producing a greater sensitivity to the rewarding effects of cocaine. This results in large increase in the number of physical protrusions or spines that grow out from the neurons in the reward center of the brain.^[13]

Treatment

A study published in May 2008, in the journal Molecular Psychiatry, detailed the effect of long-term cocaine intake on the amount and activity of thousands of proteins in monkeys. The researchers used "proteomic" technology, which enables the simultaneous analysis of thousands of proteins, to compare the "proteome" (all proteins expressed at a given time) between a group of monkeys that self-administered cocaine and a group that did not receive the drug. The study provides a comprehensive assessment of biochemical changes occurring in the cocaine-addicted brain. The profound changes in structure, metabolism and signaling of neurons may explain why relapse occurs and why it is difficult to reverse these changes after the drug use is discontinued.^[14]

On February 14, 2011, two Swiss psychologists, Dr. Francois Crespo and Dr. Sylvie Petitjean, published two years of trials and research which demonstrates that gambling along with psychotherapy is the best method to break the cocaine addiction cycle. According to Dr. Crespo - "After cocaine is used, it activates the reward center inside the brain. The brain released euphoric hormones and neurotransmitters such as dopamine, oxytocin and adrenaline which act as a mood enhancer. The same occurs with gambling: the brain perceives a reward from winning or the potential of a reward. The reward causes intense moments of happiness, which compensate for the desire to use cocaine". Further research is being conducted on long term relapse rates.^[15][16]

Withdrawal symptoms

After taking cocaine on a regular basis, some users will become addicted. When the drug is discontinued immediately, the user will experience what has come to be known as a "crash" along with a number of other cocaine withdrawal symptoms, including paranoia, depression, exhaustion, anxiety, itching, mood swings, irritability, fatigue, insomnia, an intense craving for more cocaine, and in some cases nausea and vomiting. Some cocaine users also report having similar symptoms to schizophrenia patients and feel that their mind is lost. Some users also report formication: a feeling of a crawling sensation on the skin also known as "coke bugs". These symptoms can last for weeks or, in some cases, months. Even after most withdrawal symptoms dissipate most users feel the need to continue using the drug; this feeling can last for years and may peak during times of stress. About 30-40% of cocaine addicts will turn to other substances such as medication and alcohol after giving up cocaine. There are various medications on the market to ease cocaine withdrawal symptoms.^[17]

Therapy

Twelve-step programs such as Cocaine Anonymous (modeled on Alcoholics Anonymous) have been widely used to help those with cocaine addiction. Cognitive Behavioral Therapy (CBT) combined with Motivational Therapy (MT) have proven to be more helpful than 12 step programs in treating cocaine dependency.^[18] However, both these approaches have a fairly low success rate. Cocaine vaccines are in clinical trials that will limit the rewarding effects from cocaine.^[19] The National Institutes of Health of US, particularly National Institute on Drug Abuse (NIDA) is researching modafinil, a narcolepsy drug and mild stimulant, as a potential cocaine treatment. Ibogaine has been under investigation as a treatment for cocaine dependency-and is used in clinics in Mexico, the Netherlands and Canada, but cannot be used legally in the USA. Non pharmacological treatments such as acupuncture^[20][21] and hypnosis^[22][23] have been explored, but without conclusive results. Cocaine addiction continues to be the most difficult to manage behind heroin, and according to some scientists, addiction to cocaine may be almost impossible to stop.^[24][25]

Medications

Medications that have been investigated include acetylcysteine,^[26][27][28] baclofen,^[29][30] bupropion,^[31] vanoxerine,^[32] and vigabatrin.^[29] Kim Janda has been working for years on a vaccination that would cure cocaine addiction.^[33]

Epidemiology

In the United States, cocaine use results in about 5,000 to 6,000 deaths annually^[34] while alcohol has been shown to cause on average 75,000 a year.^[35]

See also

• SB-277011-A - a dopamine D3 receptor antagonist, used in the study of cocaine addiction. Where cocaine reduces the threshold for brain electrical self-stimulation in rats, an indication of cocaine's rewarding effects, SB-277011-A completely reverses this effect.

Notes

1. ↑ The study's authors stated that they wanted to know which effects and consequences of cocaine use would become visible with persons who are mainstream citizens or as close to that social stratum as possible

References