Stimulus functions of drugs and the assessment of abuse liability

The development of a unifying framework for conceptualizing the commonalities in various forms of substance abuse must encompass the data base focused upon the stimulus functions of drugs. In the first instance, for example, the research on drug self-administration has provided convincing evidence of a remarkable concordance between laboratory animals and human substance abusers in the reinforcing stimulus functions of a range of chemical agents. The recognition of these cross-species and cross-drug generalities has radically changed conceptualizations of substance abuse from a reactive to a more active process and has encouraged the kind of functional analysis of drug-seeking and drug-taking that has proven productive and useful in the study of other behavioral interactions. In this regard as well, recent refinements in the analysis of the discriminative stimulus functions of drugs have provided a more comprehensive basis for characterizing a chemical agent's spectrum of action and evaluating its abuse liability. While the correlation between the discriminative stimulus functions and the reinforcing stimulus functions is remarkably high for some drug classes, there are notable exceptions. Finally, the assessment of abuse liability requires an analysis of the eliciting stimulus functions of drugs as reflected by the physiological and behavioral changes, both acute and chronic, that follow drug administration. The methods used to evaluate both physiological dependence and behavioral toxicity in relationship to sensory and motor effects for a range of abused drugs have depended heavily upon an assessment of the eliciting stimulus functions of such compounds.     

Patterns of Cocaine Use Among Cocaine-Dependent Outpatients

The authors systematically evaluated the frequency patterns of cocaine use in 85 cocaine-dependent outpatients and found four patterns of use: continuous (27%), intermittent patterned (35%), intermittent nonpatterned (25%), and occasional (13%). Few subjects reported consistent cycling between binges and crashes. There were no significant differences in patterns of use associated with gender, race, educational level, route of administration, or recency of heroin use. Continuous users and occasional users were older than intermittent users. Because different contingencies may control patterned vs. nonpatterned cocaine use, pattern of use may have implications for treatment, even in individuals reporting similar amounts of cocaine use.     

Symptomatic and Clinical Improvement in Morbidly Obese Patients with Gastroesophageal Reflux Disease Following Roux-en-Y Gastric Bypass

Background: Patients who suffer with gastroesophageal reflux Disease (GERD) endure a worsening of symptoms as their weight increases. When medical treatment of this condition in the morbidly obese patients fails, surgical intervention may be indicated. Choosing a procedure which not only helps achieve weight control but which also relieves symptoms and complications of GERD is the goal. We present a review of patients who have undergone Roux-en-Y Gastric Bypass (RYGBP) and related procedures for this disease. Methods: One hundred eighty-eight patients undergoing surgery for morbid obesity and for GERD in 1992-1996 were contacted by mail or phone. All of these patients had undergone preoperative esophagogastroduodenoscopy to grade the severity of their disease. Their preoperative symptoms were compared to those experienced postoperatively. Results: One hundred thirty patients underwent a RYGBP with modified Hill fundopexy, 22 patients underwent a distal gastrectomy with modified Hill fundopexy, 8 patients underwent distal gastrectomy alone and 28 patients underwent RYGBP alone. There have been no deaths. There were nine surgical complications, eight early and one at 2.5 years postoperation. Follow-up is 4-48 months. The average BMI dropped from 43 to 30.2 kg/m². Whereas all patients were on some form of medical therapy before surgery, only 14 reported the need for medication postoperatively. Conclusions: Surgical intervention for weight control and treatment of GERD has been highly successful in our experience both with respect to weight control and to the reduction of reflux symptoms. Depending upon endoscopic and operative findings a RYGBP with or without an antireflux procedure can provide dramatic improvement. Gastrectomy with antireflux modifications is appropriate in selected cases.     

Comparison of the Permeability Characteristics of a Human Colonic Epithelial (Caco-2) Cell Line to Colon of Rabbit,Monkey, and Dog Intestine and Human Drug Absorption

The in vitro permeabilities of Caco-2 monolayers and permeabilities in tissue sections from colon of monkey, rabbit, and dog were compared using a series of compounds. The selected compounds differed in their physicochemical properties, such as octanol/water partition coefficient, water solubility, and molecular weight. Their structure included steroids, carboxylic acids, xanthins, alcohols, and polyethylene glycols. A linear permeability relationship was established between Caco-2 and colon tissue from both rabbit and monkey. The results suggest that Caco-2 is twice as permeable as rabbit and five times as permeable as monkey colon. However, no clear relationship could be established between Caco-2 monolayers and dog colon permeability. A relationship between permeability in Caco-2 monolayers and human absorption was found. The results suggest that within certain limits, permeability of Caco-2 monolayers may be used as a predictive tool to estimate human drug absorption.     

Acute psychoses: A proposed diagnosis for ICD-11 and DSM-V

This paper concerns the diagnostic classification of nonaffective acute remitting psychosis (NARP), which we also term acute brief psychosis. We argue that NARP can be delineated from both schizophrenia and the affective psychoses and considered as a single diagnosis. As indicated by the term NARP, four criteria would be central to the diagnosis: 1. nonaffective, 2. acute onset (over less than two weeks), 3. recovery within a brief duration (less than six months), and 4. psychosis broadly defined. We review the rationale and the empirical evidence for this proposed classification.