Treating the rush, stress and aversion pathways
Addicts suffer from the negative symptoms associated with stress and anxiety. Cocaine temporarily alleviates that stress, and this is the cause of the addiction. It is a form of inappropriate self-medication. It is the return of the negative symptoms that are the major cause of relapse in addicts who are attempting to quit. Researchers have found that over several years, excessive and prolonged cocaine use changes the point at which this euphoria is achieved, at least in part by activating these stress/aversive systems in the brain. Over time, it takes more of the drug to achieve the same effect, and after cocaine use is stopped, stress and aversion remains elevated.
When cocaine is snorted or smoked, it enters the 
bloodstream and crosses the blood–brain barrier, accumulating rapidly in areas linked to the so-called motivational/pleasure circuits of the brain. Here, the cocaine molecules interfere with the normal regulation of dopamine (a neurotransmitter) by binding and blocking the dopamine transporters. This leads to the build-up of dopamine in the brain's motivational systems, which produces a feeling of euphoria, a quick rush that hits seconds after the user takes the drug and lasts several minutes. This physiological action triggers opposing actions in the brain, one of which is an increase in a neuropeptide known as dynorphin that produces stress/aversive like effects (effectively an opposing process).
Combined drugs
A new study explores how combined drugs can restore the brain’s reward and stress/aversive systems to normal. Naltrexone is already approved by the USA Food and Drug Administration (FDA) for treating alcohol and tobacco addiction.
Buprenorphine is an opiate painkiller and is known to be effective at helping people, who are addicted to both heroin and cocaine, kick their combined drug habits because it moderately produces the pleasurable effects of opioids and reverses the stress/aversive-like effects of opioid withdrawal.
The danger is that treating cocaine addiction with buprenorphine would merely substitute one dependence for another, causing people to suffer from buprenorphine withdrawal instead of cocaine withdrawal. The Scripps Research Institute in the USA has found a way around this problem, however, by combining buprenorphine with a low dose of naltrexone.
Research for the Scripps article was supported by National Institute on Drug Abuse of the National Institutes of Health.
