Pyramid Science

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Monday, August 20, 2007

Avandia - Rosiglitazone

Cocaine Addiction

The parallel between cocaine and nicotine addiction and 'quitting' is remarkable, though not surprising. The physiological addiction may operate in a different way though the psychological one seems to be almost identical as the damaging health implications make little impact on quitting.

A possible biological explanation is that the 'normal state' of the brain is altered, making it difficult to quit.

There is an established sequence of events that defines addiction: first there is the euphoria effect produced, secondly tolerance develops (in time more and more drug is necessary to produce the euphoria) and lastly the physical dependence. Survival is dependent on the drug and addiction is complete.

In purely descriptive terms, nicotine can be substituted for cocaine as can alcohol in alcoholism.

Cocaine is associated to the nucleus accumbens - the brain's pleasure centre. The mesoaccumbens dopamine (DA) pathway (also linked to nicotine in a reinforcing effect when administered acutely) shows that pleasurable events and cocaine abuse are accompanied by large amounts of dopamine release in the nucleus accumbens and so initiating the action on the dopamenergic systems.

Dopamine is released by a transmitting neuron in the dopamine pathway in the non-addicted, normal, brain and binds to receptors in the postsynaptic neuron, propagating a signal. After binding, the dopamine reuptake transporters (DAT) remove any unused dopamine and take it back into the cell.


Cocaine inhibits the re-uptake of dopamine and so it remains in the synapse prolonging the pleasure effect

Cocaine also affects serotonin and norepinephrine reuptake transporters, intensifying the levels of these neurotransmitters in the cell. It is speculated that more than one neurotransmitter is responsible for the pleasurable feeling cocaine provides. The reinforcing effect.

Biological (physiological) effects on the brain create the dependency and the addiction to repeated euphoric responses. The overwhelming desire to re-experience the extreme euphoric effects of cocaine. Continuation in the abuse of cocaine becomes a necessity to restore the minimal normal level of dopamine: the inevitable, and very significant, low after a cocaine 'rush' requires more cocaine to be abused in the attempt to raise dopamine levels. Clearly, it's not a drug to allow personal control (like all drugs) and it's very much a dreadful downward spiral.

The brain is biologically altered in addicts

Tolerance or sensitisation can occur with this abuse. The number of receptors on the dendrites of neurons is reduced with chronic (long term) use, less stimulation of the nerves in the dopamine pathway being possible. Tolerance needs more of the drug for an equivalent earlier effect. Sensitisation is the opposite where an abuser will become more responsive to the same earlier dose. Whether a different brain make-up is responsible for one effect (tolerance) or the other (sensitisation), or even if its in the manner of administration, is not clear.

Quitting any addiction involves the psycho/social component and conditioning operates in the same way. The environment of administration has an important r├┤le to play. Place, act and effect become associated. The distortion of reality can promote an overdose where the environment becomes associated with reward and not necessarily the drug itself. The reward can be chased and too higher level of drug in the system can occur before it is cleared from the system. The accumulation of active grows to a fatally high level.

Like the interaction with cigarette smoke, the environment can act as the trigger. A major difficulty for quitting nicotine. Avoidance of the environment associated with smoking (and its rewards) is essential in breaking the nicotine 'habit'.

The marriage between the physiological
and psychological dependencies is made

It has been proposed at the National Institute On Drug Abuse that it is in the extended amygdala where memories relating to drug administration are converted into craving for that specific drug.