Use of selective chloride channel modulators to treat alcohol and/or stimulant substance abuse

Abstract

The invention relates to methods of and treatments for using pharmaceutical compositions from a class of compounds that directly or indirectly selectively modulates GABA_A chloride channel activity to treat alcohol and/or stimulant substance abuse. The present invention also relates to methods of, and protocols for, relieving symptoms associated with alcohol and/or stimulant substance abuse in a comprehensive treatment plan. More specifically, the present invention relates to the use of a selective chloride channel modulator, such as flumazenil, to treat alcohol and/or psychostimulant dependency, the withdrawal symptoms associated therewith, and the cravings associated therewith.

Description

CROSS REFERENCE [0001] The present invention is a continuation in part of U.S. patent application Ser. No. 10 / 621,229, entitled “Use of flumazenil in the production of a drug for the treatment of alcohol dependency”, filed on Jul. 15, 2003.FIELD OF THE INVENTION [0002] The invention relates to methods of, and methodologies for, using pharmaceutical compositions from a class of compounds that directly or indirectly selectively modulates GABAA chloride channel activity to treat alcohol and / or psychostimulant substance abuse, including, but not limited to, the various physical and psychological states that manifest an individual's impaired control over substance use, addiction, continued substance use despite harm, compulsive substance use, cravings, psychological dependence, physical dependence, tolerance, a maladaptive pattern of substance use, preoccupation with substance use, and / or the prevalence of withdrawal symptoms upon cessation of use. The present invention also relates to m...

AI Technical Summary

Benefits of technology

[0026] It is another object of the present invention to provide for methods and protocols that reduce cravings and withdrawal symptoms from addiction to alcohol and/or psychostimulants that includes administration, to a patient in need of said treatment, of a therapeutically effective quantity of a compound that directly or indirectly selectively modulates chloride channel activity, administered in multiple doses at a predetermined rate, until said therapeutically effective quantity administration reduces cravings and withdrawal symptoms from addiction to alcohol and/or psychostimulants.

[0027] It is another object of the present invention to provide a methodology for controlling cravings, reducing withdrawal symptoms and treating addiction to alcohol and/or psychostimulants. It is yet another object of the present invention to administer a compound that directly or indirectly selectively modulates chloride channel activity, such as, but not limited to flumazenil, in a th...

Problems solved by technology

Alcohol and stimulant substance abuse disorders have a devastating economic and societal impact on the United States population.

First, a reduction in the ability of natural rewards to activate the reward pathways leads to depressed motivation and mood, and increased compulsion to take more drugs.

For many individuals, an innate neurochemical anomaly renders them susceptible to substance dependency or addictive behavior, even before any long-term effects of alcohol on neurological processing are evident.

It is clear, however, that excessive drinking over time can lead to the impairment of brain function and result in structural brain changes in frontal and prefrontal areas of the brain, which are associated with cognition.

Repeated exposure results in cross-tolerance and cross-dependence between alcohol and benzodiazepines.

Consequently, an alcohol dependent person experiences stress, a down regulation of GABAA and an increase in the severity of withdrawal symptoms when he or she attempts to withdraw.

Therefore, when an alcoholic attempts to initiate abstinence or stop consuming alcohol, he or she may experience withdrawal symptoms, including cravings, which often result in a failure to stop consuming alcohol.

In some cases, withdrawal symptoms may be more severe and result in complications, including seizures, hallucinosis, hallucinations with severe tremors (or “delirium tremens”, DTs) and difficulty regulating body temperature.

These complications may often be fatal.

Stimulants affect a number of neurological circuits, including dopaminergic, beta-adrenergic, serotonergic, glutamatergic, GABAergic circuits, and ultimately results in impaired dopamine function.

GABAA functionality is eventually impaired.

As dosing increases, a person starts to experience tremors, emotional instability, restlessness, irritability, and feelings of paranoia and panic.

A return of “normal” mood and the ability to experience pleasure may take a significant amount of time due to the depletion or modification of neurotransmitters.

Alcohol and psychostimulant substance abuse are often associated with changes in food selection and intake that lead to calorie and protein malnutrition and disruption of energy expenditure.

The resulting malnutrition is related to deficient food intake, malabsorption, increased protein turnover, liver disease, intensity of drug addiction, anorexia, and poor food and drink consumption.

Furthermore, the disturbance of social and familial links can itself result in poor nutrition.

Malnutrition, in turn, is associated with impairment of immune function.

Detoxification can take 3-5 days, in...

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