Track topics on Twitter Track topics that are important to you
Human Laboratory Trial of Doxazosin for Cocaine Dependence: Accumulating evidence implicates noradrenergic (NE) systems in mediating the effects of stimulants (1-8). Mice lacking NE £\ -1 receptor mice show reduced sensitivity to cocaine and amphetamine (8, 9). Local depletion of prefrontal cortex (PFC) NE reduced rewarding effects of amphetamine and reduced amphetamine-induced dopamine (DA) release in the PFC and accumbens (7), suggesting that PFC NE contributes to the rewarding effects of stimulants. Treatment with the NE ƒÑ-1 antagonist prazosin has been shown to antagonize a variety of effects produced by cocaine and amphetamine. In rats, prazosin (1-2 mg/kg) significantly attenuated the locomotor activating effects produced by cocaine (10-12) and for amphetamine (4, 13, 14). Similar findings have been observed for the discriminative stimulus effects produced by cocaine and amphetamine in mice (15) and for food-maintained responding in pigeons (16). More recently, prazosin (0.3 mg/kg) reduced reinstatement of extinguished cocaine-seeking behavior in rats without affecting responding for food, suggesting that prazosin my blunt the motivational effects of drug cues (5). Clinical Experience with Alpha-1 Adrenergic Antagonists: Prazosin is a prototypical antagonist at NE £\-1 receptors. When first released the medication was thought to produce relaxation of smooth muscles in the vasculature. Since then however it has been determined that prazosin antagonizes norepinephrine and this mediates the antihypertensive effect (17). The medication has been assessed extensively for the treatment of hypertension (18). The initial dose is 1mg two or three times per day. The usual dose range is 6mg/day to 15mg/day, with some patients requiring up to 40mg/day in divided doses. The most common side effects are: dizziness 10.3%, headache 7.8%, drowsiness 7.6%, lack of energy 6.9%, weakness 6.5%, palpitations 5.3%, and nausea 4.9%. In most instances side effects have disappeared with continued therapy or have been tolerated with no decrease in dose of drug. More recently, prazosin has been successfully used to treat post traumatic stress disorder (19, 20). For this indication, prazosin was initiated at 1mg at bedtime and increased as needed to control symptoms to up to 15mg at bedtime by day 28. This approach resulted in no change in systolic and diastolic blood pressure compared to pretreatment measurements. Several subjects reported transient dizziness upon standing (9/14 in the prazosin group and 6/15 in the placebo group), but none reported syncope. Prazosin has a relatively short elimination half-life of 3.5 h (21). Longer-lasting cogeners (e.g. terazosin and doxazosin) are available, but there is no experience using these medications as treatments for cocaine dependence. The purpose of this study is to evaluate the effects of doxazosin on the cardiovascular and subjective effects of cocaine in a human laboratory study. Doxazosin was selected because it has a longer elimination half-life (22h) compared to terazosin (12h). The side-effect profile of doxazosin closely resembles that of prazosin.
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Health Services Research
Sugar Pill, Doxazosin
Michael Debakey VA Medical Center
National Institute on Drug Abuse (NIDA)
Published on BioPortfolio: 2014-08-27T03:16:08-0400
Cocaine use disorders affect approximately 1.5 million Americans annually. Currently, there are no US Food and Drug Administration approved medications for treatment of cocaine dependence;...
The investigators will assess the impact of treatment with doxazosin and modafinil, alone and in combination, on the subjective and reinforcing effects of cocaine in non-treatment-seeking,...
Cocaine addiction continues to be an important public health problem in the US with a significant cost to the individual and society. Among substance abusers, cocaine use has been recogniz...
The purpose of the study is to asses the potential interactions between methamphetamine and doxazosin in methamphetamine-dependent volunteers who are not seeking treatment. The study will ...
This study aims at testing for the impact of glutamatergic changes on drug craving in cocaine addiction, and to evaluate the effects of n-acetylcysteine (n-AC) on both glutamate homeostasi...
Many studies have investigated how cognitive control may be compromised in cocaine addiction. Here, we extend this literature by employing spatial Independent Component Analysis (ICA) to describe circ...
Clinical guidelines recommend psychosocial interventions for cocaine and/or amphetamine addiction as first-line treatment, but it is still unclear which intervention, if any, should be offered first. ...
There is evidence that dopamine receptors D2 (DRD2) and D4 (DRD4) polymorphisms may influence substance use disorders (SUD) susceptibility both individually and through their influence in the formatio...
In rats, continuous cocaine access during long self-administration sessions (6 versus 1-2 hours) promotes the development of behavioral symptoms of addiction. This has led to the assumption that taki...
Cocaine use disorder is characterized by compulsive drug-seeking that persists long into abstinence. Work using rodent models of cocaine addiction has found evidence for reversal learning deficits 21 ...
The purified, alkaloidal, extra-potent form of cocaine. It is smoked (free-based), injected intravenously, and orally ingested. Use of crack results in alterations in function of the cardiovascular system, the autonomic nervous system, the central nervous system, and the gastrointestinal system. The slang term "crack" was derived from the crackling sound made upon igniting of this form of cocaine for smoking.
SMOKING of COCAINE.
Disorders related or resulting from use of cocaine.
An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.
A selective alpha-1-adrenergic blocker that lowers serum CHOLESTEROL. It is also effective in the treatment of HYPERTENSION.
Food is any substance consumed to provide nutritional support for the body. It is usually of plant or animal origin, and contains essential nutrients, such as carbohydrates, fats, proteins, vitamins, or minerals. The substance is ingested by an organism ...
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...