Neuroplasticity

Neuroplasticity is the putative mechanism behind learning and memory. It involves physical changes in the synapses between two communicating neurons, characterized by increased gene expression, altered cell signaling, and the formation of new synapses between the communicating neurons. When addictive drugs are present in the system, they appear to hijack this mechanism in the reward system so that motivation is geared towards procuring the drug rather than natural rewards. Depending on the history of drug use, excitatory synapses in the nucleus accumbens(NAc) experience two types of neuroplasticity: long-term potentiation (LTP) and long-term depression (LTD). Using mice as a model, Kourrich et al. showed that chronic exposure to cocaine increases the strength of synapses in NAc after a 10-14 day withdrawal period, while strengthened synapses did not appear within a 24 hour withdrawal period after repeated cocaine exposure. A single dose of cocaine did not elicit any attributes of a strengthened synapse. When drug-experienced mice were challenged with one dose of cocaine, synaptic depression occurred. Therefore, it seems the history of cocaine exposure along with withdrawal times affects the direction of glutamatergic plasticity in the NAc.

Once a person has transitioned from drug use to addiction, behavior becomes completely geared towards seeking the drug, even though addicts report the euphoria is not as intense as it once was. Despite the differing actions of drugs during acute use, the final pathway of addiction is the same. Another aspect of drug addiction is a decreased response to normal biological stimuli, such as food, sex, and social interaction. Through functional brain imaging of patients addicted to cocaine, scientists have been able to visualize increased metabolic activity in the anterior cingulate and orbitofrontal cortex (areas of the prefrontal cortex) in the brain of these subjects. The hyperactivity of these areas of the brain in addicted subjects is involved in the more intense motivation to find the drug rather than seeking natural rewards, as well as an addict’s decreased ability to overcome this urge. Brain imaging has also shown cocaine-addicted subjects to have decreased activity, as compared to non-addicts, in their prefrontal cortex when presented with stimuli associated with natural rewards. The transition from recreational drug use to addiction occurs in gradual stages and is produced by the effect of the drug of choice on the neuroplasticity of the neurons found in the reward circuit. During events preceding addiction, cravings are produced by the release of DA in the prefrontal cortex. As a person transitions from drug use to addiction, the release of dopamine (DA) in the NAc becomes unnecessary to produce cravings; rather, DA transmission decreases while increased metabolic activity in the orbitofrontal cortex contributes to cravings. At this time a person may experience the signs of depression if cocaine is not used. Before a person becomes addicted and exhibits drug-seeking behavior, there is a time period in which the neuroplasticity is reversible. Addiction occurs when drug-seeking behavior is exhibited and the vulnerability to relapse persists, despite prolonged withdrawal; these behavioral attributes are the result of neuroplastic changes which are brought about by repeated exposure to drugs and are relatively permanent.

Treatment

Drug addiction is a complex but treatable brain disease. It is characterized by compulsive drug craving, seeking, and use that persist even in the face of severe adverse consequences. For most people, drug addiction becomes chronic, with relapses possible even after long periods of abstinence. As a chronic, recurring illness, addiction may require continued treatments to increase the intervals between relapses and diminish their intensity. Through treatment tailored to individual needs, people with drug addiction can recover and lead productive lives. The ultimate goal of drug addiction treatment is to enable an individual to achieve lasting abstinence, but the immediate goals are to reduce drug abuse, improve the patient's ability to function, and minimize the medical and social complications of drug abuse and addiction. Like people with diabetes or heart disease, people in treatment for drug addiction will need to change behavior to adopt a more healthful lifestyle. Treatments for drug addiction vary widely according to the types of drugs involved, amount of drugs used, duration of the drug addiction, medical complications and the social needs of the individual. Determining the best type of recovery program for an addicted person depends on a number of factors, including: personality, drug(s) of addiction, concept of spirituality or religion, mental or physical illness, and local availability and affordability of programs.

Many different ideas circulate regarding what is considered a "successful" outcome in the recovery from addiction. It is widely accepted that abstinence from addictive substances is a successful outcome. However, abstinence is difficult to achieve in practice. Programs that emphasize controlled drinking exist for alcohol addiction. Opiate replacement therapy has been a medical standard of treatment for opioid addiction for many years

Anti-addictive drugs

Treatments and attitudes toward drug addiction vary widely among different countries. In the USA and developing countries, the goal of treatment for drug dependence is generally total abstinence from all drugs. While ideal, this is in practice very difficult to achieve. Other countries, particularly in Europe, argue the aims of treatment for drug dependence are more complex, with treatment aims including reduction in use to the point that drug use no longer interferes with normal activities such as work and family commitments, shifts the addict away from more dangerous routes of drug administration such as injecting to safer routes such as oral administration, reduction in crime committed by drug addicts, and treatment of other comorbid conditions such as AIDS, hepatitis and mental health disorders. These kind of outcomes can be achieved without eliminating drug use completely. Drug treatment programs in Europe often report more favourable outcomes than those in the USA because the criteria for measuring success are functional rather than abstinence based. [17][18][19] The supporters of programs with total abstinence from drugs as a goal stress that enabling further drug use just means prolonged drug use and risks an increase in addiction and complications from addiction.

Residential drug treatment can be broadly divided into two camps: 12 step programs or Therapeutic Communities. 12 step programs have the advantage of coming with an instant social support network though some find the spiritual context not to their taste. In the UK drug treatment is generally moving towards a more integrated approach with rehabs offering a variety of approaches. These other programs may use Cognitive-Behavioral Therapy an approach that looks at the relationship between thoughts feelings and behaviors, recognizing that a change in any of these areas can affect the whole. CBT sees addiction as a behavior rather than a disease and subsequently curable, or rather, unlearnable. CBT programs recognize that for some individuals controlled use is a more realistic possibility.

Step program

One of many recovery methods is the 12 step recovery program, with prominent examples including Alcoholics Anonymous and Narcotics Anonymous. They are commonly known and used for a variety of addictions for the individual addicted and the family of the individual. Substance-abuse rehabilitation (or "rehab") centers frequently offer a residential treatment program for the seriously addicted in order to isolate the patient from drugs and interactions with other users and dealers. Outpatient clinics usually offer a combination of individual counseling and group counseling. Frequently a physician or psychiatrist will assist with prescriptions the side effects of the addiction (the most common side effect that the medications can help is anxiety).

Other forms of treatment include replacement drugs such as methadone or buprenorphine, used as a substitute for illicit opiate drugs.Although these drugs are themselves addictive, opioid dependency is so severe that a way to stabilize opioid use is required. Once stabilized, treatment enters maintenance or tapering phases. In the United States, opiate replacement therapy is tightly regulated in methadone clinics and under the DATA 2000 legislation. In some countries, other opioid derivatives such as levomethadyl acetate, dihydrocodeine, dihydroetorphine and even heroin are used as substitute drugs for illegal street opiates, with different drugs being used depending on the needs of the individual patient.

Amphetamine addiction

Substitute drugs for other forms of drug dependence have historically been less successful than opioid substitute treatment, but some limited success has been seen with drugs such as dexamphetamine to treat stimulant addiction, and clomethiazole to treat alcohol addiction. Bromocriptine and desipramine have been reported to be effective for treatment of cocaine but not amphetamine addiction.

Other pharmacological treatments for alcohol addiction include drugs like naltrexone, disulfiram, acamprosate and topiramate, but rather than substituting for alcohol, these drugs are intended to reduce the desire to drink, either by directly reducing cravings as with acamprosate and topiramate, or by producing unpleasant effects when alcohol is consumed, as with disulfiram. These drugs can be effective if treatment is maintained, but compliance can be an issue as alcoholic patients often forget to take their medication, or discontinue use because of excessive side effects. Additional drugs acting on glutamate neurotransmission such as modafinil, lamotrigine, gabapentin and memantine have also been proposed for use in treating addiction to alcohol and other drugs.

Opioid antagonists such as naltrexone and nalmefene have also been used successfully in the treatment of alcohol addiction, which is often particularly challenging to treat. These drugs have also been used to a lesser extent for long-term maintenance treatment of former opiate addicts, but cannot be started until the patient has been abstinent for an extended period, otherwise they can trigger acute opioid withdrawal symptoms.

Alternative therapies

Treatment of stimulant addiction can often be difficult, with substitute drugs often being ineffective, although newer drugs such as nocaine, vanoxerine and modafinil may have more promise in this area, as well as the GABAB agonist baclofen.Another strategy that has recently been successfully trialled used a combination of the benzodiazepine antagonist flumazenil with hydroxyzine and gabapentin for the treatment of methamphetamine addiction.

Another area in which drug treatment has been widely used is in the treatment of nicotine addiction. Various drugs have been used for this purpose such as bupropion, mecamylamine and the more recently developed varenicline. The cannaboinoid antagonist rimonabant has also been trialled for treatment of nicotine addiction but has not been widely adopted for this purpose. Ibogaine is a psychoactive drug that specifically interrupts the addictive response, and is currently being studied for its effects upon cocaine, heroin, nicotine, and SSRI addicts. Alternative medicine clinics offering ibogaine treatment have appeared along the U.S. border. A synthetic analogue of ibogaine, 18-methoxycoronaridine has also been developed which has similar efficacy but less side effects, however this drug is still being tested in animals and human trials have not yet been carried out.

Medical definitions

Alternative therapies, such as acupuncture, are used by some practitioners to alleviate the symptoms of drug addiction. In 1997, the American Medical Association (AMA) adopted as policy the following statement after a report on a number of alternative therapies including acupuncture:

There is little evidence to confirm the safety or efficacy of most alternative therapies. Much of the information currently known about these therapies makes it clear that many have not been shown to be efficacious. Well-designed, stringently controlled research should be done to evaluate the efficacy of alternative therapies. Acupuncture has been shown to be no more effective than control treatments in the treatment of opiate dependence.Acupuncture, acupressure, laser therapy and electrostimulation have no demonstrated efficacy for smoking cessation. The terms abuse and addiction have been defined and re-defined over the years. The 1957 World Health Organization (WHO) Expert Committee on Addiction-Producing Drugs defined addiction and habituation as components of drug abuse: Drug addiction is a state of periodic or chronic intoxication produced by the repeated consumption of a drug (natural or synthetic).