Dr. DeLuca's Addiction Website

http://www.doctordeluca.com/References/Nal_Crave.htm

Naltrexone and Craving references.
 

 See also:
Pharmacotherapy of Substance Use Disorders Collection
and:
Library and Resource Directory - Table of Contents


1
UI - 23
TI - Drug reduces alcohol craving [news]
MH - Alcohol Deterrents
MH - Alcoholism
MH - drug therapy
MH - Human
MH - Naltrexone
MH - Narcotic Antagonists
MH - nursing
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 99157642LA - EngRN - 0 (Alcohol Deterrents)RN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)PT - NEWSDA - 19990506IS - 0361-1817SB - MSB - NCY - UNITED STATESJC - OA1EM - 199907
UR - PM:0010048082
SO - Nurse Pract 1999 Feb ;24(2):104

2
UI - 45
AU - Anton RF
AU - Moak DH
AU - Latham PK
AD - Institute of Psychiatry, Medical University of South Carolina, Charleston, USA
TI - The obsessive compulsive drinking scale: A new method of assessing outcome in alcoholism treatment studies [published erratum appears in Arch Gen Psychiatry 1996 Jul;53(7):576]
AB - BACKGROUND: the 14-item Obsessive Compulsive Drinking Scale (OCDS) is a quick and reliable self-rating instrument that provides a total and two subscale scores that measure some cognitive aspects of alcohol "craving". This study validated further its utility as an alcoholism severity and treatment outcome instrument. METHODS: Alcoholism severity and analogue craving scales were administered at baseline, and the OCDS was given at baseline and weekly to 41 alcohol-dependent individuals who participated in a 12-week pharmacologic and cognitive-behavioral treatment trial. Repeated-measures analysis of variance was used to examine group differences in the OCDS scores of those individuals who remained abstinent or drank during the trial. RESULTS: At baseline, the OCDS was correlated with the alcohol composite score of the addiction severity index (r=.48), the alcohol dependence scale (r=.42), the analogue craving measures (range r=.40 to .57), and prestudy alcohol consumption (r=.60). Most importantly the OCDS total and subscale scores were significantly different between individuals who had relapse drinking, who had "slip" drinking, and who remained abstinent, with relapsers showing the highest scores. CONCLUSIONS: The OCDS scores appear to be sensitive to alcoholism severity and change during abstinence and relapse drinking. Since the shared variance with analogue craving measures is only about 20% to 30%, it appears to be measuring a largely independent dimension of alcohol dependence. Its ease of use (5 minutes per self-rating), reliability, validity, and analytic capabilities support its utility as a tool to measure severity and improvement during alcoholism treatment trials
MH - Adult
MH - Alcohol Drinking
MH - Alcoholism
MH - analysis
MH - Analysis of Variance
MH - Cognitive Therapy
MH - Combined Modality Therapy
MH - diagnosis
MH - Double-Blind Method
MH - drug therapy
MH - Female
MH - Human
MH - Male
MH - methods
MH - Middle Age
MH - Naltrexone
MH - Obsessive-Compulsive Disorder
MH - Personality Inventory
MH - Placebos
MH - Psychiatric Status Rating Scales
MH - psychology
MH - Psychometrics
MH - Reproducibility of Results
MH - statistics & numerical data
MH - Support,U.S.Gov't,P.H.S.
MH - Temperance
MH - therapeutic use
MH - therapy
MH - Treatment Outcome
RP - NOT IN FILE
NT - UI - 96183451LA - EngRN - 0 (Placebos)RN - 16590-41-3 (Naltrexone)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALID - RO1-AA09568/AA/NIAAADA - 19960528IS - 0003-990XSB - ASB - MCY - UNITED STATESJC - 72CAA - AuthorEM - 199608RO - M:MWS
UR - PM:0008611059
SO - Arch Gen Psychiatry 1996 Mar ;53(3):225-231

3
UI - 14
AU - Anton RF
AU - Moak DH
AU - Waid LR
AU - Latham PK
AU - Malcolm RJ
AU - Dias JK
AD - Alcohol Research Center, Medical University of South Carolina, Charleston 29425, USA
TI - Naltrexone and cognitive behavioral therapy for the treatment of outpatient alcoholics: results of a placebo-controlled trial
AB - OBJECTIVE: The opiate antagonist drug naltrexone has been shown in a few studies with limited sample sizes to be effective when combined with psychosocial therapies for the treatment of alcohol dependence. The goal of this study was to obtain additional information regarding its efficacy in pertinent alcoholic populations and with a well-defined therapy. METHOD: In this study, 131 recently abstinent alcohol- dependent outpatients were treated with 12 weekly sessions of manual- guided cognitive behavioral therapy and either 50 mg/day of naltrexone (N = 68) or placebo (N = 63) (with riboflavin added as a marker of compliance) in a double-blind, randomized clinical trial. Alcohol consumption, craving, adverse events, and urinary riboflavin levels were assessed weekly. Levels of blood markers of alcohol abuse were also ascertained during the trial. RESULTS: The study completion, therapy participation, and medication compliance rates in the trial were high, with no differences between treatment groups. Naltrexone- treated subjects drank less, took longer to relapse, and had more time between relapses. They also exhibited more resistance to and control over alcohol-related thoughts and urges, as measured by a subscale of the Obsessive Compulsive Drinking Scale. Over the study period, 62% of the naltrexone group did not relapse into heavy drinking, in comparison with 40% of the placebo group. CONCLUSIONS: Motivated individuals with moderate alcohol dependence can be treated with greater effectiveness when naltrexone is used in conjunction with weekly outpatient cognitive behavioral therapy. Naltrexone increases control over alcohol urges and improves cognitive resistance to thoughts about drinking. Thus, the therapeutic effects of cognitive behavioral therapy and naltrexone may be synergistic
MH - Adult
MH - Alcohol Drinking
MH - Alcoholism
MH - Ambulatory Care
MH - blood
MH - Cognitive Therapy
MH - Combined Modality Therapy
MH - drug therapy
MH - Female
MH - Human
MH - Male
MH - Naltrexone
MH - Narcotic Antagonists
MH - Patient Compliance
MH - Patient Selection
MH - Placebos
MH - psychology
MH - Recurrence
MH - Reproducibility of Results
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
MH - therapy
MH - Treatment Outcome
RP - NOT IN FILE
NT - UI - 20019168LA - EngRN - 0 (Narcotic Antagonists)RN - 0 (Placebos)RN - 16590-41-3 (Naltrexone)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALID - AA-09568/AA/NIAAADA - 19991116IS - 0002-953XSB - ASB - MCY - UNITED STATESJC - 3VGAA - AuthorEM - 200001
UR - PM:0010553740
SO - Am J Psychiatry 1999 Nov ;156(11):1758-1764

4
UI - 35
AU - Besson J
AD - Unite d'abus de substances, Departement universitaire de psychiatrie adulte, Lausanne
TI - [New drugs in the treatment of alcoholism]
AB - Pharmacotherapy of alcoholism is improving rapidly with the introduction of new agents. New knowledge about the neurobiology of alcoholism is necessary for the clinician, who has to establish the diagnosis. Useful pharmacological agents for the treatment of alcohol dependence can be classified into four groups: (1) agents for the treatment of the withdrawal syndrome, (2) aversive agents, (3) therapeutic agents for comorbidity, (4) new agents to reduce craving for alcohol or prevent relapse. These new agents derive from research in four directions, based on neurobiological hypotheses: (a) the glutamatergic hypothesis with acamprosate, (b) the opioid hypothesis with naltrexone, (c) the serotonergic hypothesis with the new antidepressants, and (d) other hypotheses, including dopaminergic, peptidic etc. Of these new agents, acamprosate has undergone most study in controlled clinical trials around Europe. Its efficacy has been demonstrated statistically, it is well tolerated and does not interact with alcohol. Acamprosate can be associated with disulfiram therapy. Future perspectives for treatment and research are discussed, in particular with regard to therapeutic associations
MH - adverse effects
MH - Alcohol Deterrents
MH - Alcohol Withdrawal Delirium
MH - Alcoholism
MH - analogs & derivatives
MH - Brain
MH - Controlled Clinical Trials
MH - diagnosis
MH - Disulfiram
MH - drug effects
MH - English Abstract
MH - Human
MH - Naltrexone
MH - Receptors,Neurotransmitter
MH - rehabilitation
MH - Taurine
MH - therapeutic use
MH - therapy
MH - Treatment Outcome
RP - NOT IN FILE
NT - UI - 97475600LA - FreRN - 0 (Alcohol Deterrents)RN - 0 (Receptors, Neurotransmitter)RN - 107-35-7 (Taurine)RN - 77337-76-9 (N-acetylhomotaurine)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19971222IS - 0036-7672SB - MCY - SWITZERLANDJC - UEIAA - AuthorEM - 199802
UR - PM:0009411716
SO - Schweiz Med Wochenschr 1997 Sep 20 ;127(38):1574-1578

5
UI - 19
AU - Brauer LH
AU - Behm FM
AU - Westman EC
AU - Patel P
AU - Rose JE
AD - Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA. lbrauer@acpub.duke.edu
TI - Naltrexone blockade of nicotine effects in cigarette smokers
AB - RATIONALE: The role of endogenous opiate systems in cigarette smoking remains unclear. In laboratory animals, opiate antagonists block many of the effects of nicotine, but in humans they do not consistently alter smoking behavior. OBJECTIVE: This study explored the effects of naltrexone, alone and in combination with nicotine, on smoking behavior. METHODS: In a double-blind, double-dummy, within-subjects design, 19 regular smokers received four treatments of 1 week duration: naltrexone tablet (50 mg) plus placebo skin patch, placebo tablet plus nicotine skin patch (21 mg/24 h), naltrexone tablet plus nicotine skin patch, and placebo tablet plus placebo skin patch. During each treatment, subjects rated their responses to nicotine-containing and denicotinized cigarettes in the laboratory, and to their own brand of cigarette smoked ad libitum outside the laboratory. RESULTS: Pretreatment with the nicotine patch attenuated smoking-induced decreases in craving, negative affect, and rates of ad lib smoking, and potentiated the aversiveness of a cigarette. Naltrexone reversed these effects of the nicotine patch, and produced negative effects on mood. CONCLUSIONS: The blockade of nicotine's effects by naltrexone supports a role for opioid mechanisms in cigarette smoking
MH - Adult
MH - Affect
MH - Analysis of Variance
MH - Animal
MH - antagonists & inhibitors
MH - blood
MH - Double-Blind Method
MH - drug effects
MH - etiology
MH - Female
MH - Human
MH - Male
MH - methods
MH - Middle Age
MH - Naltrexone
MH - Narcotic Antagonists
MH - Nicotine
MH - pharmacology
MH - physiopathology
MH - Placebos
MH - prevention & control
MH - psychology
MH - Questionnaires
MH - Smoking
MH - Substance Withdrawal Syndrome
MH - Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 99293970LA - EngRN - 0 (Narcotic Antagonists)RN - 0 (Placebos)RN - 16590-41-3 (Naltrexone)RN - 54-11-5 (Nicotine)PT - CLINICAL TRIALPT - CONTROLLED CLINICAL TRIALPT - JOURNAL ARTICLEDA - 19990805IS - 0033-3158SB - MCY - GERMANYJC - QGIAA - AuthorEM - 199910
UR - PM:0010367550
SO - Psychopharmacology (Berl) 1999 Apr ;143(4):339-346

6
UI - 25
AU - Catafau AM
AU - Etcheberrigaray A
AU - Perez de los CJ
AU - Estorch M
AU - Guardia J
AU - Flotats A
AU - Berna L
AU - Mari C
AU - Casas M
AU - Carrio I
AD - Nuclear Medicine Department, Hospital de Sant Pau, Barcelona, Spain
TI - Regional cerebral blood flow changes in chronic alcoholic patients induced by naltrexone challenge during detoxification
AB - The recent introduction of the opioid antagonist naltrexone for alcohol- dependence therapy has been mainly based on behavioral animal models that provide evidence of the involvement of the endogenous opioid system in alcohol drinking and dependence. However, the neurophysiological mechanisms of the effect of naltrexone in alcoholic patients remain unknown. This study investigates the effects of a naltrexone challenge on regional cerebral blood flow (rCBF) in chronic alcoholic patients during detoxification. METHODS: Sixteen alcoholic inpatients underwent two 99mTc-hexamethyl propyleneamine oxime (HMPAO) brain SPECTs: a basal SPECT on day 10 of abstinence and a second SPECT on day 12 of abstinence after oral administration of 150 mg naltrexone. Region-to-cerebellar ratios were obtained for the orbitary frontal, prefrontal, lateral temporal and mesial temporal regions, basal ganglia and thalamus in each hemisphere. A percentage of rCBF change between both SPECTs was calculated for each region as 100 x (naltrexone - baseline)/ baseline. Values from 13 brain SPECTs of age-matched normal volunteers including test-retest measurements were used for statistical comparison. RESULTS: In baseline conditions, alcoholics showed lower rCBF than controls in left orbitofrontal cortex (84.0+/-5.1 versus 89.8+/-5.0, P < 0.01) and prefrontal cortex (left hemisphere: 87.4+/- 5.2 versus 96.2+/-3.6, P < 0.001; right hemisphere: 87.0+/-4.9 versus 95.8+/-4.2, P< 0.001). After naltrexone, a significant rCBF decrease was found versus test-retest values in left basal ganglia (-3.3%+/-4.0% versus 1.5%+/-4.1%, P< 0.05), right basal ganglia (-4.2%+/-4.9% versus 0.6%+/-2.7%, P < 0.01) and left mesial temporal region (-4.5%+/-6.8% versus 2.2%+/-2.9%, P < 0.01). CONCLUSION: The rCBF decrease detected by SPECT after naltrexone challenge in structures rich in opioid receptors, such as the basal ganglia and the left mesial temporal region, may reflect a naltrexone-induced decreased metabolic activity in these areas. These results support the involvement of the opioid system in alcohol dependence. Furthermore, the localization of naltrexone-induced rCBF changes in mesial temporal structures and in basal ganglia supports the implication of emotional memory and obsessive-compulsive phenomena in craving
MH - Adult
MH - Alcohol Drinking
MH - Alcoholism
MH - Animal
MH - blood
MH - Brain
MH - Cerebrovascular Circulation
MH - diagnostic use
MH - drug effects
MH - Female
MH - Human
MH - Male
MH - methods
MH - Middle Age
MH - Naltrexone
MH - Narcotic Antagonists
MH - pharmacology
MH - physiopathology
MH - radionuclide imaging
MH - Radiopharmaceuticals
MH - Support,Non-U.S.Gov't
MH - Technetium Tc 99m Exametazime
MH - Temperance
MH - therapy
MH - Tomography,Emission-Computed,Single-Photon
RP - NOT IN FILE
NT - UI - 99131750LA - EngRN - 0 (Narcotic Antagonists)RN - 0 (Radiopharmaceuticals)RN - 0 (Technetium Tc 99m Exametazime)RN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEDA - 19990225IS - 0161-5505SB - MSB - XCY - UNITED STATESJC - JECAA - AuthorEM - 199904
UR - PM:0009935051
SO - J Nucl Med 1999 Jan ;40(1):19-24

7
UI - 2
AU - Chick J
AU - Anton R
AU - Checinski K
AU - Croop R
AU - Drummond DC
AU - Farmer R
AU - Labriola D
AU - Marshall J
AU - Moncrieff J
AU - Morgan MY
AU - Peters T
AU - Ritson B
AD - Department of Psychiatry, University of Edinburgh, University Department of Medicine, Royal Free Campus, The Royal Free and University College Medical School, London, St George's Hospital Medical School, London, King's College Hospita
TI - A multicentre, randomized, DOUBLE-BLIND, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse [In Process Citation]
AB - The opioid antagonist, naltrexone, is reported, in single centre studies, to improve the clinical outcome of individuals with alcohol dependence participating in outpatient psychosocial programmes. This is the first multicentre controlled study to evaluate the efficacy and safety of naltrexone as adjunctive treatment for alcohol dependence or abuse. Patients who met criteria for alcohol dependence (n = 169) or alcohol abuse (n = 6) were randomly assigned to receive double-blind oral naltrexone 50 mg daily (n = 90) or placebo (n = 85) for 12 weeks as an adjunct to psychosocial treatment. The primary efficacy variable was time to first episode of heavy drinking; secondary efficacy assessments included time to first drink, alcohol consumption, craving, and changes in the serum biological markers gamma-glutamyl transferase (GGT), and aspartate and alanine aminotransferases. Compliance was assessed by tablet counts and, in the naltrexone-treated group, by measurement of urinary concentrations of 6-ss-naltrexol. Forty-nine (58%) patients randomized to placebo and 53 (59%) randomized to naltrexone did not complete the study. In intention-to-treat analyses, there was no difference between groups on measures of drinking. The median reduction from baseline of serum GGT (P: < 0.05) and the reductions in alcohol craving (Obsessive and Compulsive Drinking Scale: OCDS) were greater in the naltrexone group (P: < 0.05), from approximately half-way through the study. Of 70 patients (35 placebo; 35 naltrexone) who met an a priori definition of compliance (80% tablet consumption, attendance at all follow-up appointments), those allocated to naltrexone reported consuming half the amount of alcohol (P: < 0.05), had greater median reduction in serum GGT activity (P: < 0.05), and greater reduction in alcohol craving (OCDS total score: P: < 0.05; Obsessive subscale score: P: < 0.05), compared to patients in the placebo group. Use of naltrexone raised no safety concerns. Naltrexone is effective in treating alcohol dependence/abuse in conjunction with psychosocial therapy, in patients who comply with treatment
RP - NOT IN FILE
NT - UI - 20547444LA - EngDA - 20001228IS - 0735-0414SB - MCY - ENGLANDJC - AALAA - AUTHORRO - O:099
UR - PM:0011093966
SO - Alcohol Alcohol 2000 Nov ;35(6):587-593

8
UI - 73
AU - Childress AR
AU - McLellan AT
AU - O'Brien CP
TI - Assessment and extinction of conditioned withdrawal-like responses in an integrated treatment for opiate dependence
AB - Recent data have generally been consistent with our pilot findings: a significant proportion--33 to 40%--of opiate-dependent patients show a time-linked decrease in skin-temperature in response to standard drug- related stimuli, suggestive of conditioned withdrawal. Patients' physiological changes are often accompanied by subjective craving and withdrawal, but the correlation among these measures is modest. Though craving seems to diminish with repeated exposure to drug-related stimuli, withdrawal-like symptoms are often persistent and slow to extinguish. Our current design initially assumed that most patients would show conditioned craving and withdrawal to our standard stimuli and that our current procedure would be adequate to produce complete extinction for these "responders.' As it turned out, not all patients respond to our standard stimuli, and our extinction procedure is not completely effective for those who do. Given these two findings, our current design does not permit the best test of the potential clinical benefits of extinction. Our rich experience during the first phase of this project has stimulated several procedural changes which should increase our accuracy in determining the incidence of these conditioned phenomena, our effectiveness in extinguishing them, and permit a better assessment of their potential clinical benefit. These are as follows: Individualize eliciting (drug-related) stimuli--We initially chose to use standard (the same for all patients) stimuli for practical and experimental reasons. However, their use may have resulted in an underestimate of the incidence of conditioned craving and withdrawal, and in less relevant extinction for many patients.(ABSTRACT TRUNCATED AT 250 WORDS)
MH - Adult
MH - Conditioning,Classical
MH - Emotions
MH - Extinction (Psychology)
MH - Female
MH - Human
MH - Male
MH - Naltrexone
MH - Opioid-Related Disorders
MH - psychology
MH - Skin Temperature
MH - Substance Withdrawal Syndrome
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
MH - therapy
MH - Time Factors
MH - United States
RP - NOT IN FILE
NT - UI - 86040354LA - EngRN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEID - DA03008/DA/NIDADA - 19851213IS - 1046-9516SB - MCY - UNITED STATESJC - NRMAA - AuthorEM - 198602
UR - PM:0006443380
SO - NIDA Res Monogr 1984 ;55():202-210

9
UI - 27
AU - Chow BL
AU - Sellers EM
AU - Tomkins DM
AD - Biobehavioural Research Department, Addiction Research Foundation, Toronto, Ontario, Canada
TI - Effect of naltrexone and its derivatives, nalmefene and naltrindole, on conditioned anticipatory behaviour and saccharin intake in rats
AB - Drug craving, the desire to re-experience the effects of a psychoactive substance, may be an important influence on drug-seeking and drug- taking behaviour. In rats, drug-seeking behaviour can be operationalized as conditioned anticipatory behaviour, evidenced by frequent visits to, and an increased time spent and distance travelled in, the drug administration area prior to the availability of the reinforcer. The effects of the opioid antagonist, naltrexone, and its derivatives, nalmefene and naltrindole, on conditioned anticipatory behaviour and drinking-associated behaviour and fluid intake during the access phase were examined. Male Wistar rats were trained to consume 0.1% saccharin and water in a distinct environment in a free-choice limited-access procedure. Naltrexone (0.3, 1 mg/kg) decreased conditioned anticipatory behaviour and drinking-associated behaviour in the saccharin zone without affecting the corresponding behaviour in the water zone. Its derivatives had different effects. Nalmefene (0.1 mg/kg) increased drinking-associated behaviour but not conditioned anticipatory behaviour, whereas naltrindole (1, 2 mg/kg) modestly decreased conditioned anticipatory behaviour but not drinking- associated behaviour. Naltrexone (0.3, 1 mg/kg) and naltrindole (1, 2 mg/kg), but not nalmefene, selectively decreased saccharin intake. These findings suggest that the blockade of selective opioid receptors may differentially alter conditioned anticipatory behaviour, drinking- associated behaviour and consumption levels, and that these behaviours can be modified separately
MH - analogs & derivatives
MH - Animal
MH - Conditioning,Operant
MH - Cues
MH - Dose-Response Relationship,Drug
MH - Drinking Behavior
MH - drug effects
MH - Male
MH - Naltrexone
MH - Narcotic Antagonists
MH - pharmacology
MH - Rats
MH - Rats,Wistar
MH - Saccharin
MH - Sweetening Agents
MH - Taste
RP - NOT IN FILE
NT - UI - 99050153LA - EngRN - 0 (Narcotic Antagonists)RN - 0 (Sweetening Agents)RN - 111555-53-4 (naltrindole)RN - 16590-41-3 (Naltrexone)RN - 55096-26-9 (nalmefene)RN - 81-07-2 (Saccharin)PT - JOURNAL ARTICLEDA - 19981229IS - 0955-8810SB - MCY - ENGLANDJC - CM8AA - AuthorEM - 199903
UR - PM:0009832959
SO - Behav Pharmacol 1997 Dec ;8(8):725-735

10
UI - 36
AU - Ciraulo AM
AU - Alpert N
AU - Franko KJ
AD - National Institute of Drug Abuse/Department of Veterans Affairs Medication Development Center, Boston, Massachusetts, USA
TI - Naltrexone for the treatment of alcoholism
AB - Naltrexone is a pure opioid antagonist that is an effective nonaversive pharmacologic treatment for alcohol dependence. The usual dosage is 50 mg per day. Side effects may include nausea, headache, dizziness and arthralgia. Naltrexone appears to exert its effect by decreasing the craving for alcohol. It has also been useful in allowing some patients to decrease their need for other medications, such as benzodiazepines and antihypertensives. Naltrexone should be used as an adjunct to a comprehensive alcohol treatment program that addresses concomitant medical problems and psychosocial concerns
MH - Alcoholism
MH - Case Report
MH - drug therapy
MH - Human
MH - Male
MH - Middle Age
MH - Naltrexone
MH - Narcotic Antagonists
MH - Physician's Role
MH - Primary Health Care
MH - Support,Non-U.S.Gov't
MH - Support,U.S.Gov't,Non-P.H.S.
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
MH - therapy
RP - NOT IN FILE
NT - UI - 97447122LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19971007IS - 0002-838XSB - ASB - MCY - UNITED STATESJC - 3BTAA - AuthorEM - 199712
UR - PM:0009301573
SO - Am Fam Physician 1997 Sep 1 ;56(3):803-806

11
UI - 4
AU - de Wit H
AD - Department of Psychiatry, University of Chicago 60637, USA
TI - Laboratory-based assessment of alcohol craving in social drinkers
AB - Subjective feelings of craving for drugs and alcohol are hallmark symptoms of substance abuse and dependence, and they are thought to play a pivotal role in relapse to drug use. However, relatively little is known about the relationship between craving and overt drug-seeking behavior or drug consumption. One way to investigate the relationship between self-report measures of craving and objective measures of drug- taking behavior is to investigate the degree to which they co-vary in laboratory studies. In particular it may be informative to examine the degree to which these measures co-vary after experimental manipulations that are expected to increase or decrease craving for, or use of, a drug. We review the results of several laboratory studies in which both self-report measures of craving or desire for alcohol and alcohol consumption were measured, using subjects who were non-problem social drinkers. The experimental manipulation used to increase craving and drug-taking was the administration of a priming dose of alcohol. The manipulation that was intended to decrease craving and drug-taking was administration of a dose of naltrexone, because of its use in the treatment for alcoholism. In most of these studies, self-reported ratings of desire for alcohol were positively associated with consumption of alcohol. However, there were also instances in which one measure varied independently of the other, indicating that under certain circumstances they are controlled by separate factors. Laboratory-based studies such as these may improve our understanding of how subjective reports of alcohol craving are related to objective measures of consumption
MH - administration & dosage
MH - Alcohol Drinking
MH - Behavior,Addictive
MH - Choice Behavior
MH - drug therapy
MH - Human
MH - Naltrexone
MH - Narcotic Antagonists
MH - psychology
MH - Self Disclosure
MH - Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 20458012LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALID - DA02812/DA/NIDAID - DA09133/DA/NIDADA - 20001005IS - 0965-2140CY - ENGLANDJC - BM3AA - AuthorEM - 200012
UR - PM:0011002911
SO - Addiction 2000 Aug ;95 Suppl 2():S165-S169

12
UI - 49
AU - Di Chiara G
AU - Acquas E
AU - Tanda G
AD - Department of Toxicology, University of Cagliari, Italy
TI - Ethanol as a neurochemical surrogate of conventional reinforcers: the dopamine-opioid link
AB - Various lines of evidence support the view that ethanol is a neurochemical surrogate of conventional reinforcers, such as food and sex. In fact, ethanol activates central neuronal systems that utilize dopamine, opioids, and gamma-aminobutyric acid (GABA) as neurotransmitters and also are activated by conventional reinforcers. These neurotransmitter systems are likely to mediate specific aspects of ethanol's reinforcing properties. Activation of the mesolimbic dopamine and endogenous opioid systems might be the substrate of the incentive and rewarding (ergotropic) properties of ethanol (arousal, euphoria, motor stimulation) and of the process of acquiring ethanol- related secondary reinforcers (incentive learning) and ethanol self- administration habits. Stimulation of the endogenous GABAergic system might mediate the sedative and drive-reducing (trophotropic) properties of ethanol. The dopamine and opioid systems are largely interconnected. Thus, pharmacological blockade of the endogenous opioid system by mu- or delta-opioid receptor antagonists prevents ethanol's activation of the dopamine system and reduces ethanol consumption. This interaction might contribute to naltrexone's effectiveness in reducing alcohol craving in humans
MH - Animal
MH - Dopamine
MH - Ethanol
MH - Human
MH - Naltrexone
MH - Narcotic Antagonists
MH - Neurotransmitters
MH - Opioid Peptides
MH - pharmacology
MH - physiology
MH - Self Administration
MH - Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 96435042LA - EngRN - 0 (Narcotic Antagonists)RN - 0 (Neurotransmitters)RN - 0 (Opioid Peptides)RN - 51-61-6 (Dopamine)RN - 64-17-5 (Ethanol)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19961202IS - 0741-8329SB - MCY - UNITED STATESJC - AG9AA - AuthorEM - 199702
UR - PM:0008837928
SO - Alcohol 1996 Jan ;13(1):13-17

13
UI - 1
AU - Elman I
AU - D'Ambra MN
AU - Krause S
AU - Breiter H
AU - Kane M
AU - Morris R
AU - Tuffy L
AU - Gastfriend DR
AD - Addiction Services, Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, WACC-812, 02114, Boston, MA, USA
TI - Ultrarapid opioid detoxification: effects on cardiopulmonary physiology, stress hormones and clinical outcomes
AB - This study explored the acute and long-term consequences of ultrarapid opioid detoxification (URD) in individuals with opioid dependence. In an open case series, seven patients underwent URD and subsequent treatment with daily naltrexone. Structured interviews, integrated rehabilitation and hair sampling were employed in the 12-week course of longitudinal follow-up. Cardiac and pulmonary physiology did not change significantly during the anesthesia phase of URD, but plasma ACTH and cortisol levels increased 15- and 13-fold, respectively. Marked withdrawal and tachypnea in all patients and respiratory distress in one patient occurred during the acute post-anesthesia phase. Withdrawal scores were significantly elevated for 3 weeks compared with baseline in the face of minimal self-reported craving for opioids. Anxiety, depression and vegetative symptoms improved gradually. Four patients remained abstinent of opioid use, two reported a brief period of opioid intake and one relapsed into daily opioid consumption. Given its effect on breathing and stress hormones, this procedure should be conducted by experienced anesthesiologists. The fact that URD and subsequent naltrexone treatment appears to cause a dissociation effect in the usual relationship between withdrawal and craving has implications for behavioral pharmacology. Further research is needed on the efficacy, safety, mechanisms and neurobiological sequelae of the procedure
RP - NOT IN FILE
NT - UI - 0LA - ENGPT - JOURNAL ARTICLEDA - 20010103IS - 0376-8716JC - EBS
UR - PM:0011137281
SO - Drug Alcohol Depend 2001 Jan 1 ;61(2):163-172

14
UI - 29
AU - Emanuele MA
AU - LaPaglia N
AU - Steiner J
AU - Jabamoni K
AU - Hansen M
AU - Kirsteins L
AU - Emanuele NV
AD - Department of Medicine, Loyola University Medical Center, Maywood, Illinois 60153, USA
TI - Reversal of ethanol-induced testosterone suppression in peripubertal male rats by opiate blockade
AB - Teenage drinking is a major problem in the United States, as well as abroad. Besides psychosocial implications, ethanol (EtOH) has detrimental effects on the reproductive system. Clinical problems associated with reduced reproductive hormones include osteoporosis, decreased muscle function, anemia, altered immune function, prostate involution, and decreased reproductive abilities. Education coupled with strategies aimed at preventing these deleterious consequences even in the face of continued EtOH intake is extremely important. We have tested the possibility that naltrexone, a drug currently used in patients to decrease alcohol craving, might also prevent the fall in the male hormone, testosterone, caused by EtOH exposure. Rats aged 35 days old (prepubertal), 45 days old (midpubertal), and 55 days old (late pubertal) were injected (intraperitoneally) with either saline, EtOH, naltrexone, or EtOH plus naltrexone. In the two older age groups, EtOH significantly suppressed testosterone, which was prevented by administration of naltrexone. In the youngest animals, there was no treatment effect presumably due to low basal levels of testosterone. EtOH similarly reduced luteinizing hormone (LH), but this suppression was not prevented by naltrexone. There was no consistent effect of any treatment on hypothalamic concentration of pro-LH releasing hormone (RH) (LHRH), LHRH, or on steady-state levels of LHRH mRNA. We conclude that, as animals progress through puberty, EtOH suppresses LH and testosterone. The testosterone decline can be prevented by opiate blockade with naltrexone, an effect primarily seen at gonadal level. Thus, naltrexone, a drug already used clinically to reduce EtOH intake, also has protective physiological effects on the endocrine system
MH - Aged
MH - Animal
MH - antagonists & inhibitors
MH - blood
MH - drug effects
MH - Ethanol
MH - Hypothalamus
MH - Lh
MH - Male
MH - Naltrexone
MH - Narcotic Antagonists
MH - pharmacology
MH - Rats
MH - Rats,Sprague-Dawley
MH - Sex Maturation
MH - Support,U.S.Gov't,P.H.S.
MH - Testosterone
MH - toxicity
RP - NOT IN FILE
NT - UI - 98427464LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)RN - 57-85-2 (Testosterone)RN - 64-17-5 (Ethanol)RN - 9002-67-9 (LH)PT - JOURNAL ARTICLEID - 2POAA08661-06DA - 19990104IS - 0145-6008SB - MCY - UNITED STATESJC - 35XAA - AuthorEM - 199903
UR - PM:0009756033
SO - Alcohol Clin Exp Res 1998 Sep ;22(6):1199-1204

15
UI - 24
AU - Emanuele NV
AU - LaPaglia N
AU - Steiner J
AU - Kirsteins L
AU - Emanuele MA
AD - Department of Medicine, Loyola University Medical Center, Maywood, Illinois 60153, USA
TI - Reversal of chronic ethanol-induced testosterone suppression in peripubertal male rats by opiate blockade
AB - Teenage drinking continues to be a significant problem in the U.S., as well as abroad. We have previously demonstrated that opiate blockade with naltrexone, a drug currently used in patients to diminish alcohol craving, prevented the fall in serum testosterone seen after acute ethanol (EtOH) exposure in young, peripubertal male rats. To follow-up on this reversal, a series of experiments was performed to determine if naltrexone would also prevent the testosterone suppression caused by chronic EtOH exposure. Peripubertal rats either 45 days old (mid- pubertal) or 55 days old (late pubertal) were fed an EtOH-containing liquid diet or pair-fed control diet for 14 days. Each animal was implanted with either a naltrexone containing or placebo pellet before starting the liquid diet. In each age group, EtOH alone significantly suppressed testosterone, whereas naltrexone prevented this fall, although it had no effect alone. Serum luteinizing hormone was also suppressed by EtOH; however, naltrexone did not abrogate this fall. In the 45-day-old animals, beta-luteinizing hormone mRNA levels rose significantly in the EtOH group, but not when naltrexone was coadministered with EtOH. There was no change in hypothalamic luteinizing hormone releasing hormone (LHRH) mRNA, pro-LHRH, or LHRH in any group at either age. Thus, naltrexone is able to partially prevent the EtOH-induced suppression of gonadal testosterone of young, adolescent male rats. This effect appears to be mediated directly at gonadal level, because hypothalamic and pituitary hormone changes were minor and nonsignificant
MH - Age Factors
MH - Animal
MH - blood
MH - Central Nervous System Depressants
MH - drug effects
MH - Eating
MH - Ethanol
MH - Gonadorelin
MH - Lh
MH - Male
MH - Naltrexone
MH - Narcotic Antagonists
MH - pharmacology
MH - Rats
MH - Rats,Sprague-Dawley
MH - Sex Maturation
MH - Support,U.S.Gov't,P.H.S.
MH - Testosterone
RP - NOT IN FILE
NT - UI - 99151662LA - EngRN - 0 (Central Nervous System Depressants)RN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)RN - 33515-09-2 (Gonadorelin)RN - 57-85-2 (Testosterone)RN - 64-17-5 (Ethanol)RN - 9002-67-9 (LH)PT - JOURNAL ARTICLEID - 2POAA08661-06DA - 19990601IS - 0145-6008SB - MCY - UNITED STATESJC - 35XAA - AuthorEM - 199908
UR - PM:0010029204
SO - Alcohol Clin Exp Res 1999 Jan ;23(1):60-66

16
UI - 17
AU - Flannery BA
AU - Volpicelli JR
AU - Pettinati HM
AD - Department of Psychiatry, University of Pennsylvania, Philadelphia 19104, USA. flannery_b@research.trc.upenn.edu
TI - Psychometric properties of the Penn Alcohol Craving Scale [see comments]
AB - BACKGROUND: This study introduces the Penn Alcohol Craving Scale (PACS), which has been used in several clinical trials at the University of Pennsylvania's Treatment Research Center. The PACS is a five-item, self-report measure that includes questions about the frequency, intensity, and duration of craving, the ability to resist drinking, and asks for an overall rating of craving for alcohol for the previous week. Each question is scaled from 0 to 6. METHODS: To examine the questionnaire's psychometric properties, we sampled responses from 147 individuals participating in a 9-month combined natrexone (100 mg/day)/psychotherapy trial. The psychotherapy consisted of weekly sessions of nurse-administered medication compliance and supportive treatment. RESULTS: The PACS proved to have excellent internal consistency. Predictive validity was demonstrated via a logistic regression analysis of craving during the 2nd week of the study on alcohol relapse during weeks 3-12 of the trial. Construct validity of the PACS was demonstrated via its convergence with two commonly used measures for assessing craving, the Obsessive Compulsive Drinking Scale and the Alcohol Urge Questionnaire. Lack of correlation between PACS scores and several other noncraving, self-report measures indicates that the PACS also had good discriminant validity. Additional analyses revealed that there were significant differences in craving scores during the initial 3 weeks of the trial among those who did and those who did not relapse during weeks 3-12. CONCLUSION: The PACS is a reliable and valid measure of alcohol craving and can predict which individuals are at risk for subsequent relapse
MH - Adult
MH - Aged
MH - Alcohol Deterrents
MH - Alcoholism
MH - Behavior,Addictive
MH - drug therapy
MH - Female
MH - Human
MH - Male
MH - methods
MH - Middle Age
MH - Naltrexone
MH - Narcotic Antagonists
MH - psychology
MH - Psychometrics
MH - Questionnaires
MH - Reproducibility of Results
MH - Severity of Illness Index
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 99397571LA - EngRN - 0 (Alcohol Deterrents)RN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEID - T32 DA07241/DA/NIDAID - R01AA-07517/AA/NIAAADA - 19991026IS - 0145-6008SB - MCY - UNITED STATESJC - 35XAA - AuthorEM - 200001
UR - PM:0010470970
SO - Alcohol Clin Exp Res 1999 Aug ;23(8):1289-1295

17
UI - 61
AU - Froehlich JC
AU - Li TK
AD - Department of Medicine, Indiana University School of Medicine, Indianapolis 46202
TI - Recent developments in alcoholism:opioid peptides
AB - A large body of evidence indicates that the endogenous opioid system plays an important role in maintaining alcohol drinking behavior. Research is reviewed indicating that the reinforcing properties of alcohol which lead to continued and repeated bouts of drinking are due, in part, to alcohol-induced activation of the endogenous opioid system. Opioid receptor antagonists decrease alcohol craving, alcohol consumption, and loss of control over drinking. The potential of opioid receptor antagonists to improve treatment outcome in comprehensive relapse prevention programs is discussed
MH - Alcohol Drinking
MH - Alcoholism
MH - Animal
MH - Brain
MH - Clinical Trials
MH - Drinking Behavior
MH - drug effects
MH - Endorphins
MH - Human
MH - Naltrexone
MH - Neurotransmitters
MH - physiology
MH - physiopathology
MH - psychology
MH - Receptors,Opioid
MH - rehabilitation
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
MH - Treatment Outcome
MH - United States
RP - NOT IN FILE
NT - UI - 94052853LA - EngRN - 0 (Endorphins)RN - 0 (Neurotransmitters)RN - 0 (Receptors, Opioid)RN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALID - AA07611/AA/NIAAAID - AA08312/AA/NIAAAID - AA08553/AA/NIAAADA - 19931206IS - 0738-422XSB - MCY - UNITED STATESJC - RDAAA - AuthorEM - 199402
UR - PM:0007901877
SO - Recent Dev Alcohol 1993 ;11():187-205

18
UI - 32
AU - Galarza NJ
AU - Diaz RD
AU - Guzman F
AU - Caballero JA
AU - Martinez AJ
AD - Department of Psychiatry, University of Puerto Rico, San Juan
TI - The use of naltrexone to treat ambulatory patients with alcohol dependence
AB - The purpose of this study is to evaluate the efficacy of Naltrexone in decreasing craving symptoms among Puerto Rican male veterans with alcohol dependence. METHOD: This is a double blind placebo control study with a convenience sample of eleven patients divided in two groups (placebo and Naltrexone). Scales consisting of Zung Depression, Zung Anxiety, MMSE, OCD Screener, Craving, and Somatization were administered at baseline, and weekly for four weeks as follow up. RESULTS: There were no statistically significant differences between the two groups on any of the outcome variables at baseline or follow up measurements. A statistical trend was noted toward a decrease in somatization. A decrease in craving symptoms was observed in the experimental group. CONCLUSIONS: Even though our results did not show evidence of the efficacy of Naltrexone in decreasing craving symptoms, a small number of patients did benefit from the medication. The results could have been affected by the small sample size
MH - Adult
MH - Aged
MH - Alcoholism
MH - Ambulatory Care
MH - Anxiety
MH - Cognition Disorders
MH - Depression
MH - Double-Blind Method
MH - drug therapy
MH - Human
MH - Male
MH - Middle Age
MH - Naltrexone
MH - Obsessive-Compulsive Disorder
MH - Pilot Projects
MH - Psychological Tests
MH - psychology
MH - Somatoform Disorders
MH - therapeutic use
MH - Treatment Outcome
RP - NOT IN FILE
NT - UI - 98237904LA - EngRN - 16590-41-3 (Naltrexone)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALDA - 19980625IS - 0004-4849CY - PUERTO RICOJC - AB4AA - AuthorEM - 199808
UR - PM:0009577049
SO - Bol Asoc Med P R 1997 Oct ;89(10-12):157-160

19
UI - 21
AU - Garbutt JC
AU - West SL
AU - Carey TS
AU - Lohr KN
AU - Crews FT
AD - Department of Psychiatry, Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, USA
TI - Pharmacological treatment of alcohol dependence: a review of the evidence [see comments]
AB - CONTEXT: Alcoholism affects approximately 10% of Americans at some time in their lives. Treatment consists of psychosocial interventions, pharmacological interventions, or both, but which drugs are most effective at enhancing abstinence and preventing relapse has not been systematically reviewed. OBJECTIVE: To evaluate the efficacy of 5 categories of drugs used to treat alcohol dependence--disulfiram, the opioid antagonists naltrexone and nalmefene, acamprosate, various serotonergic agents (including selective serotonergic reuptake inhibitors), and lithium. DATA SOURCES: Reports of randomized controlled trials, nonrandomized trials, and other study designs in English, French, and German identified from multiple searches of MEDLINE, EMBASE, and specialized databases; hand searching bibliographies of review articles; searches for unpublished literature; and discussions with investigators in the field. STUDY SELECTION: We included all studies on alcohol-dependent human subjects aged 18 years or older from all inpatient and outpatient settings between 1966 and December 1997 that met our inclusion criteria. DATA EXTRACTION: We abstracted the following information: study design and blinding, diagnostic instrument and severity assessment, drug interventions and cointerventions, demographic and comorbidity details about patients, compliance, and numerous outcome measures (eg, relapse, return to drinking, drinking or nondrinking days, time to first drink, alcohol consumed per unit of time, craving). We graded quality of the individual articles (scale, 0-100) independently from the strength of evidence for each drug class (A, strong and consistent evidence of efficacy in studies of large size and/or high quality; B, mixed evidence of efficacy; C, evidence of lack of efficacy; and I, insufficient evidence). DATA SYNTHESIS: Of 375 articles evaluated, we abstracted and analyzed data from 41 studies and 11 follow-up or subgroup studies. Naltrexone (grade A) reduces the risk of relapse to heavy drinking and the frequency of drinking compared with placebo but does not substantially enhance abstinence, ie, avoidance of any alcohol consumption. Acamprosate (grade A, from large-scale studies in Europe) reduces drinking frequency, although its effects on enhancing abstinence or reducing time to first drink are less clear. Controlled studies of disulfiram (grade B) reveal a mixed outcome pattern--some evidence that drinking frequency is reduced but minimal evidence to support improved continuous abstinence rates. The limited data on serotonergic agents were not very promising (grade I), although most studies were confounded by high rates of comorbid mood disorders. Lithium lacks efficacy (grade C) in the treatment of primary alcohol dependence. CONCLUSIONS: Recent reports documenting that naltrexone and acamprosate are more effective than placebo in the treatment of alcoholism justify clinical interest in use of these medications for alcohol-dependent patients. Use of disulfiram is widespread but less clearly supported by the clinical trial evidence; however, targeted studies on supervised administration of disulfiram may be warranted. Use of existing serotonergic agents or lithium for patients with primary alcohol dependence does not appear to be supported by the efficacy data available at this time; these medications may still have a positive effect in patients with coexisting psychiatric disorders
MH - Adult
MH - Affect
MH - Aged
MH - Alcohol Deterrents
MH - Alcoholism
MH - analogs & derivatives
MH - Disulfiram
MH - drug therapy
MH - Human
MH - Lithium
MH - Naltrexone
MH - Narcotic Antagonists
MH - Serotonin Agents
MH - Support,U.S.Gov't,P.H.S.
MH - Taurine
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 99222829LA - EngRN - 0 (Alcohol Deterrents)RN - 0 (Narcotic Antagonists)RN - 0 (Serotonin Agents)RN - 107-35-7 (Taurine)RN - 16590-41-3 (Naltrexone)RN - 55096-26-9 (nalmefene)RN - 7439-93-2 (Lithium)RN - 77337-76-9 (N-acetylhomotaurine)RN - 97-77-8 (Disulfiram)PT - JOURNAL ARTICLEPT - META-ANALYSISID - 290-97-0011DA - 19990422IS - 0098-7484SB - ASB - MSB - XCY - UNITED STATESJC - KFRAA - AuthorEM - 199906RO - M:CNR
UR - PM:0010208148
SO - JAMA 1999 Apr 14 ;281(14):1318-1325

20
UI - 28
AU - Gatch MB
AU - Lal H
AD - Department of Pharmacology, University of North Texas Health Science Center, Fort Worth, USA
TI - Pharmacological treatment of alcoholism
AB - 1. Pharmacological treatments are effective as part of a treatment plan that includes substantial education, psychological therapy and social support. This paper reviews recent literature on animal models of and treatment for alcohol abuse under seven categories: agents to block craving or reduce alcohol intake, agents to induce aversion to alcohol, agents to treat acute alcohol withdrawal, agents to treat protracted alcohol withdrawal, agents to diminish drinking by treating associated psychiatric pathology, agents to decrease drinking by treating associated drug abuse, and agents to induce sobriety in intoxicated individuals. 2. The benzodiazepines provide safe and effective treatment for detoxification, although current research focuses on finding drugs with a smaller likelihood of dependence. As yet, there are no drugs that effectively reverse the intoxicating effects of alcohol. 3. Currently, only two major groups of drugs that are relatively safe have shown any effect at reducing alcohol consumption: aversives such as disulfiram, and opioid antagonists such as naltrexone. 4. Finally, it is important to customize therapy for each patient rather than putting everyone through a standard treatment plan, especially in regards to the use of antidepressant or antipsychotic medications. Tailoring the program to the patient's needs dramatically improves the outcome of therapy and reduces the risk of adverse effects
MH - adverse effects
MH - Alcohol Drinking
MH - Alcoholism
MH - Animal
MH - Disease Models,Animal
MH - Disulfiram
MH - drug therapy
MH - Human
MH - Naltrexone
MH - pharmacology
MH - therapy
RP - NOT IN FILE
NT - UI - 99006307LA - EngPT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19990105IS - 0278-5846SB - MCY - ENGLANDJC - Q45AA - AuthorEM - 199903
UR - PM:0009789878
SO - Prog Neuropsychopharmacol Biol Psychiatry 1998 Aug ;22(6):917-944

21
UI - 50
AU - Gerra G
AU - Fertonani G
AU - Zaimovic A
AU - Rota-Graziosi I
AU - Avanzini P
AU - Caccavari R
AU - Delsignore R
AU - Lucchini A
AD - Addiction Research Center, Ser.T.-A.U.S.L. Parma, Italy
TI - Hostility in heroin abusers subtypes: fluoxetine and naltrexone treatment
AB - 1. Substance abusers subtypes have been identified considering underlying psychobiological disorder, familial factors, age of onset, legal problems and drug of choice. 2. In the present study the authors submitted 98 male heroin addicted individuals (age 19-28 y) to the Buss Durkee Hostility Inventory (Italian version) and a structured interview concerning social and clinical history; legal problems, age of onset of drug abuse, drug of choice. 3. Serotonergic system sensitivity was evaluated with fenfluramine challenge for PRL assay. 4. Thirty two patients (group A) showed high score for resentment and guilt at BDHI (hostility in), low rate of legal problems, late age of onset, preference for heroin and alcohol. Twenty nine patients (group B) showed high score for assault and irritability at BDHI (hostility out), high rate of legal problems, early age of onset, preference for heroin and cocaine. The other 37 patients (group C) showed aggression score in the normal range at BDHI, no legal problems, late onset of substance abuse, preference for heroin only. 5. PRL responses was blunted in group A (p < 0.001) and significantly decreased in group B (p < 0.05). PRL plasma levels were inversely correlated with HRSD scores. 6. All the patients were included in a treatment protocol with fluoxetine and naltrexone or placebo and naltrexone for 6 months. 7. The treatment was effective in group A with a significant improvement of BDHI results and decrease of craving score, lower level of drop out, lower level of positive urine controls. No significant differences between fluoxetine and placebo effects have been evidenced in patients of group B and C. The present findings suggest that psychopharmacological approach to addiction needs a diagnostic screening for specific subtypes
MH - Adult
MH - Aggression
MH - Antidepressive Agents,Second-Generation
MH - Cocaine
MH - diagnostic use
MH - drug effects
MH - drug therapy
MH - Fenfluramine
MH - Fluoxetine
MH - Heroin Dependence
MH - Hostility
MH - Human
MH - Male
MH - Naltrexone
MH - Narcotic Antagonists
MH - Neurosecretory Systems
MH - pharmacokinetics
MH - physiology
MH - Psychiatric Status Rating Scales
MH - psychology
MH - therapeutic use
MH - Treatment Outcome
MH - urine
RP - NOT IN FILE
NT - UI - 97021845LA - EngRN - 0 (Antidepressive Agents, Second-Generation)RN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)RN - 458-24-2 (Fenfluramine)RN - 54910-89-3 (Fluoxetine)PT - CLINICAL TRIALPT - CONTROLLED CLINICAL TRIALPT - JOURNAL ARTICLEDA - 19961115IS - 0278-5846SB - MCY - ENGLANDJC - Q45AA - AuthorEM - 199701RO - M:RCT
UR - PM:0008868205
SO - Prog Neuropsychopharmacol Biol Psychiatry 1995 Dec ;19(8):1225-1237

22
UI - 11
AU - Gerra G
AU - Zaimovic A
AU - Rustichelli P
AU - Fontanesi B
AU - Zambelli U
AU - Timpano M
AU - Bocchi C
AU - Delsignore R
AD - Centro Studi Farmacotossicodipendenze-Servizio Tossicodipendenze, Az. USL di Parma, Italy
TI - Rapid opiate detoxication in outpatient treatment: relationship with naltrexone compliance
AB - A variety of detoxification methods have been utilized for the treatment of heroin withdrawal before individuals begin long-term opiate-free and naltrexone programs. While methadone in decreasing doses is still widely used for detoxication procedures, rapid and ultrarapid protocols including clonidine and opiate receptors antagonists have been proposed. This study compares the efficacy of different detoxification methods and investigates possible changes in naltrexone compliance. Ninety-eight heroin-addicted individuals were studied to evaluate withdrawal symptoms, craving, mood, urine toxicologic screens, and drop-out rate during therapy with: Group A: clonidine only (5 days); Group B: clonidine, oxazepam, baclofen, and ketoprofene with naloxone and naltrexone (2 days); and Group C: methadone in decreasing doses (10 days). Naltrexone compliance and relapse rates were evaluated during a 6-month follow-up period. Rapid detoxification with opiate antagonists (Group B) induced slight and transient withdrawal symptoms, and resulted in a significantly lower percentage of heroin catabolites in urine controls during the detoxification procedure, lower negative and positive craving, less mood problems, and higher compliance in extended naltrexone treatment. In comparison with clonidine only (Group A) and methadone (Group C), the early use of naltrexone during detoxification in combination with benzodiazepines and clonidine facilitated extended naltrexone acceptance and improved the recovery outcome in outpatients
MH - administration & dosage
MH - Adolescence
MH - Adrenergic alpha-Agonists
MH - Adult
MH - Anti-Inflammatory Agents,Non-Steroidal
MH - Baclofen
MH - Clonidine
MH - Dose-Response Relationship,Drug
MH - drug therapy
MH - Drug Therapy,Combination
MH - Female
MH - Gaba Agents
MH - Heroin Dependence
MH - Human
MH - Ketoprofen
MH - Male
MH - Metabolic Detoxication,Drug
MH - Methadone
MH - Naloxone
MH - Naltrexone
MH - Narcotic Antagonists
MH - Narcotics
MH - Oxazepam
MH - Patient Compliance
MH - prevention & control
MH - Substance Withdrawal Syndrome
MH - therapy
MH - Treatment Outcome
MH - urine
RP - NOT IN FILE
NT - UI - 20178846LA - EngRN - 0 (Adrenergic alpha-Agonists)RN - 0 (Anti-Inflammatory Agents, Non-Steroidal)RN - 0 (GABA Agents)RN - 0 (Narcotic Antagonists)RN - 0 (Narcotics)RN - 1134-47-0 (Baclofen)RN - 16590-41-3 (Naltrexone)RN - 22071-15-4 (Ketoprofen)RN - 4205-90-7 (Clonidine)RN - 465-65-6 (Naloxone)RN - 604-75-1 (Oxazepam)RN - 76-99-3 (Methadone)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALDA - 20000419IS - 0740-5472SB - MCY - UNITED STATESJC - KAIAA - AuthorEM - 200006
UR - PM:0010716102
SO - J Subst Abuse Treat 2000 Mar ;18(2):185-191

23
UI - 70
AU - Gonzalez JP
AU - Brogden RN
AD - ADIS Drug Information Services, Manchester
TI - Naltrexone. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of opioid dependence
AB - Naltrexone is a long acting competitive antagonist at opioid receptors which blocks the subjective and objective responses produced by intravenous opioid challenge. It is suitable for oral administration, and has been studied as an adjunct for use in opioid addiction management programmes. In non-comparative clinical trials involving detoxified patients, oral naltrexone reduced heroin craving and between 23 and 62% of patients remained in treatment after 3 to 4 weeks. However, in two studies 32 to 58% of patients who continued in treatment were opioid-free between 6 and 12 months after stopping naltrexone. As might be expected studies involving highly motivated patients have shown this type of patient group to achieve greater treatment success rates during naltrexone therapy, and remain opioid- free longer than other groups of apparently less motivated patients. In addition, when naltrexone is combined with family support, psychotherapy and counselling, patients are more likely to remain opioid-free. Naltrexone produces a low incidence of side effects, with gastrointestinal effects being the most commonly reported symptoms. Thus, despite the overall high attrition rates from trials, in selected patient groups and in combination with appropriate support mechanisms and psychotherapy, naltrexone represents a useful adjunct for the maintenance of abstinence in the detoxified opioid addict
MH - adverse effects
MH - Animal
MH - antagonists & inhibitors
MH - Clinical Trials
MH - drug effects
MH - drug therapy
MH - Family
MH - Heroin
MH - Heroin Dependence
MH - Human
MH - Naltrexone
MH - Narcotic Antagonists
MH - Opioid-Related Disorders
MH - pharmacokinetics
MH - pharmacology
MH - Psychotherapy
MH - Receptors,Opioid
MH - therapeutic use
MH - therapy
RP - NOT IN FILE
NT - UI - 88224717LA - EngRN - 0 (Narcotic Antagonists)RN - 0 (Receptors, Opioid)RN - 16590-41-3 (Naltrexone)RN - 561-27-3 (Heroin)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19880629IS - 0012-6667SB - MCY - NEW ZEALANDJC - EC2AA - AuthorEM - 198809
UR - PM:0002836152
SO - Drugs 1988 Mar ;35(3):192-213

24
UI - 71
AU - Greenstein RA
AU - Resnick RB
AU - Resnick E
TI - Methadone and naltrexone in the treatment of heroin dependence
AB - Over the past 20 years, methadone maintenance has been shown to be a safe, effective treatment for large numbers of heroin addicts. The majority of patients derive major benefits while in treatment, most measurably in the areas of decreased use of illicit opiates, diminished criminality, increased levels of employment and more stable interpersonal relationships. An advantage of methadone maintenance over other treatments is that it attracts and retains a relatively large segment of the addict population and is reasonably cost-effective. Naltrexone is well suited as a transitional treatment for individuals who have progressed using methadone maintenance. Patients completing a course of methadone maintenance should be encouraged to use naltrexone during the postmethadone period, when symptoms of protracted abstinence often lead them to reinitiate use of heroin. Those with stable family relationships, good jobs, minimal antisocial behavior, and low drug- craving before beginning a course of naltrexone appear to benefit most from the treatment. Rates of retention improve when naltrexone is used within a comprehensive rehabilitation program. Although addicted individuals are often stereotyped, they are, in fact, a heterogeneous group representing a range of psychopathologies and life situations. Thus, within any one facility, a variety of modalities should be available to allow treatment to be tailored to the individual. No single treatment is best for all patients, and, moreover, the preferred modality for any one individual may change over time as a result of progress in treatment or varying life circumstances. Multimodality programs that include methadone and naltrexone enable the maximal number of individuals to benefit from treatment
MH - administration & dosage
MH - analogs & derivatives
MH - drug therapy
MH - Family
MH - Heroin
MH - Heroin Dependence
MH - Human
MH - Methadone
MH - Naloxone
MH - Naltrexone
MH - pharmacology
MH - psychology
MH - Psychotherapy
MH - rehabilitation
MH - Substance Withdrawal Syndrome
MH - therapeutic use
MH - therapy
MH - Time Factors
MH - United States
RP - NOT IN FILE
NT - UI - 85112905LA - EngRN - 16590-41-3 (Naltrexone)RN - 465-65-6 (Naloxone)RN - 76-99-3 (Methadone)PT - JOURNAL ARTICLEDA - 19850315IS - 0193-953XSB - MCY - UNITED STATESJC - PBNAA - AuthorEM - 198505
UR - PM:0006522309
SO - Psychiatr Clin North Am 1984 Dec ;7(4):671-679

25
UI - 68
AU - Guthrie SK
AD - College of Pharmacy, University of Michigan, Ann Arbor 48109
TI - Pharmacologic interventions for the treatment of opioid dependence and withdrawal
AB - This article discusses current pharmacologic methods in the treatment of heroin dependence and withdrawal. Methadone hydrochloride, the most commonly used opiate agonist, is used for both withdrawal and maintenance therapy. However, it produces dependence and withdrawal results upon abrupt discontinuation. Other opiate agonists including L- alpha acetyl methadyl (LAAM) and propoxyphene napsylate have been used for both withdrawal and maintenance therapy. LAAM is currently available only as an investigational agent and propoxyphene is easily accessible but has been associated with hallucinations and dysphoria at high doses. Alpha 2-adrenergic agonists decrease opiate withdrawal symptoms by decreasing the central adrenergic hyperarousal that is associated with withdrawal. Clonidine effectively attenuates but does not totally eliminate withdrawal symptoms. Other alpha 2-adrenergic agonists (e.g., lofexidine hydrochloride, guanfacine hydrochloride, and guanabenz) have undergone only preliminary investigations. Although alpha 2 agonists effectively decrease most withdrawal symptoms they often cause hypotension. Buprenorphine hydrochloride is a partial opiate agonist that shows some promise in the treatment of the heroin- dependent population. It attenuates opiate craving and causes only minimal withdrawal upon abrupt discontinuation. Because it is well accepted by the heroin-dependent population, however, it may ultimately become an abused substance. Naltrexone is a potent, orally acting opiate antagonist that blocks all opiate-agonist effects and causes no euphoria. Unfortunately, it has not been well accepted by the heroin- dependent population. Scant research has been conducted concerning the use of adjunctive medications during opioid withdrawal
MH - agonists
MH - Buprenorphine
MH - Clonidine
MH - drug therapy
MH - Heroin Dependence
MH - Human
MH - Methadone
MH - methods
MH - Naltrexone
MH - Opioid-Related Disorders
MH - Substance Withdrawal Syndrome
MH - therapy
MH - United States
RP - NOT IN FILE
NT - UI - 90327807LA - EngPT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19900830IS - 1042-9611SB - MCY - UNITED STATESJC - XS4AA - AuthorEM - 199011
UR - PM:0002197814
SO - DICP 1990 Jul ;24(7-8):721-734

26
UI - 38
AU - Hartmann PM
AD - York Hospital, Pennsylvania, USA
TI - Naltrexone in alcohol dependence
AB - Naltrexone is a narcotic antagonist that has been shown to reduce alcohol craving and alcohol use in patients with alcohol dependence. It should not be used as exclusive treatment but only as an adjunct to a comprehensive program that includes psychologic and social treatment approaches such as those in Alcoholics Anonymous or professional programs. The two most serious complications of naltrexone therapy are the precipitation of narcotic withdrawal in patients taking narcotics, and hepatotoxicity. The latter complication occurs only at dosages much higher than the 50 mg per day recommended for treatment of alcohol dependence. Alcohol is known to enhance opioid receptors. Evidently, naltrexone blockade of these receptors results in reduced craving for alcohol, less of a "high" while drinking and less alcohol use
MH - Alcoholism
MH - complications
MH - drug therapy
MH - Human
MH - Naltrexone
MH - Narcotic Antagonists
MH - Narcotics
MH - pharmacology
MH - therapeutic use
MH - therapy
RP - NOT IN FILE
NT - UI - 97259075LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19970429IS - 0002-838XSB - ASB - MCY - UNITED STATESJC - 3BTAA - AuthorEM - 199707
UR - PM:0009105212
SO - Am Fam Physician 1997 Apr ;55(5):1877-4

27
UI - 18
AU - Holter SM
AU - Spanagel R
AD - Max Planck Institute of Psychiatry, Kraepelinstrasse 2, D-80804 Munich, Germany. hoelter@mpipsykl.mpg.de
TI - Effects of opiate antagonist treatment on the alcohol deprivation effect in long-term ethanol-experienced rats
AB - RATIONALE: Opiate antagonists are promising pharmacotherapeutic agents for the treatment of alcohol dependence, reducing craving and relapse rates in weaned alcoholics. However, preclinical findings indicate that they can also increase ethanol consumption and preference in animals with a strong liking for ethanol, depending on the dose and treatment regimen. OBJECTIVE: The present study examined the effects of chronic, intermittent and acute opiate antagonist treatment on the alcohol deprivation effect (ADE) in long-term ethanol- experienced rats, which is an animal model of craving and relapse. METHODS: Long-term ethanol- experienced rats were either implanted with mini-osmotic pumps delivering 0, 0.5 or 1 mg/kg per hour naloxone (chronic treatment) or received intermittent naltrexone injections (2x5 mg/kg per day SC). Effects of chronic and intermittent treatment on the ADE were studied in a four-bottle home cage drinking paradigm. In a second experiment, long-term ethanol-experienced rats trained in an operant ethanol self- administration paradigm received acute naltrexone treatment (0, 0.1, 1 or 10 mg/kg SC) before a 23-h session either during basal drinking or during the ADE. RESULTS: Chronic naloxone treatment increased ethanol preference during the ADE. Intermittent naltrexone treatment at a dose comparable to the lower dose of chronic treatment moderately attenuated the ADE. Acute naltrexone treatment selectively reduced lever pressing for ethanol both during the ADE and during basal drinking only at the lowest dose, whereas higher doses also suppressed water intake. The ethanol-specific suppressant effect on the ADE was long lasting. Concerning basal drinking, however, naltrexone had a long lasting reductive effect only on lever pressing for water. CONCLUSIONS: A low dose of naltrexone and an intermittent treatment regimen seem to be necessary to maintain a specific reduction in ethanol intake in individuals with a high motivation to consume ethanol. These findings are consistent with the notion that, at low doses, opiate antagonists reduce the reward value of reinforcers
MH - administration & dosage
MH - Alcoholism
MH - Animal
MH - drug therapy
MH - Ethanol
MH - Male
MH - methods
MH - Motivation
MH - Naloxone
MH - Naltrexone
MH - Narcotic Antagonists
MH - pharmacology
MH - Rats
MH - Rats,Wistar
MH - Self Administration
MH - Support,Non-U.S.Gov't
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 99389953LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)RN - 465-65-6 (Naloxone)RN - 64-17-5 (Ethanol)PT - JOURNAL ARTICLEDA - 19991019IS - 0033-3158SB - MCY - GERMANYJC - QGIAA - AuthorEM - 199912
UR - PM:0010460312
SO - Psychopharmacology (Berl) 1999 Aug ;145(4):360-369

28
UI - 41
AU - Jaffe AJ
AU - Rounsaville B
AU - Chang G
AU - Schottenfeld RS
AU - Meyer RE
AU - O'Malley SS
AD - Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511, USA
TI - Naltrexone, relapse prevention, and supportive therapy with alcoholics: an analysis of patient treatment matching
AB - Alcohol-dependent patients (N = 97) were randomly assigned to receive either naltrexone or placebo and either relapse prevention therapy or supportive therapy. The present report explored the hypothesis that patients could be matched to the above treatments on the basis of specific pretreatment characteristics. Treatment matching variables explored included craving, alcohol dependence severity, and cognitive measures of learning and memory. Results of linear regression analyses tentatively suggest that patients experiencing higher levels of craving and poorer cognitive functioning may derive the greatest benefit from naltrexone versus placebo. For psychotherapy, lower levels of verbal learning were associated with poorer drinking outcomes for relapse prevention therapy but not for supportive therapy. Conversely, higher levels of verbal learning were associated with better outcomes for relapse prevention therapy but not for supportive therapy
MH - Adolescence
MH - Adult
MH - adverse effects
MH - Aged
MH - Alcohol Drinking
MH - Alcoholism
MH - Cognitive Therapy
MH - Combined Modality Therapy
MH - Comparative Study
MH - drug effects
MH - Female
MH - Human
MH - Male
MH - Middle Age
MH - Naltrexone
MH - Narcotic Antagonists
MH - Personality Assessment
MH - prevention & control
MH - psychology
MH - Psychotherapy
MH - Recurrence
MH - rehabilitation
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
MH - therapy
MH - Treatment Outcome
MH - Verbal Learning
RP - NOT IN FILE
NT - UI - 97074086LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALID - AA-P50-03-510/AA/NIAAAID - AA-08033/AA/NIAAAID - AA-07080/AA/NIAAAID - +DA - 19970106IS - 0022-006XCY - UNITED STATESJC - HW3AA - AuthorEM - 199703
UR - PM:0008916634
SO - J Consult Clin Psychol 1996 Oct ;64(5):1044-1053

29
UI - 9
AU - Johnson BA
AU - Ait-Daoud N
AD - University of Texas Health Sciences Center, San Antonio, USA
TI - Medications to treat alcoholism
AB - Advances in neurobiology support the development of medications to treat alcoholism by modifying the activity of specific chemical messengers (i.e., neurotransmitters) in the brain. Among the most promising new medications is acamprosate, which appears to decrease the intensity of craving after a person has stopped drinking. Naltrexone (ReVia) has been shown to decrease alcohol consumption, although its practical effectiveness may be compromised by poor patient compliance and other factors. Ondansetron shows promise for decreasing drinking and increasing abstinence rates among early onset alcoholics, who respond poorly to psychosocial treatment alone. Researchers are investigating whether the use of specific medications in combination can further enhance their effectiveness. Additional research is needed to determine how medications interact with different psychosocial factors and treatments
MH - Alcohol Deterrents
MH - Alcoholism
MH - analogs & derivatives
MH - Calcium Channel Blockers
MH - Dopamine Antagonists
MH - drug therapy
MH - Drug Therapy,Combination
MH - Excitatory Amino Acid Antagonists
MH - Human
MH - Naltrexone
MH - Narcotic Antagonists
MH - Serotonin Uptake Inhibitors
MH - Support,U.S.Gov't,P.H.S.
MH - Taurine
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 20343247LA - EngRN - 0 (Alcohol Deterrents)RN - 0 (Calcium Channel Blockers)RN - 0 (Dopamine Antagonists)RN - 0 (Excitatory Amino Acid Antagonists)RN - 0 (Narcotic Antagonists)RN - 0 (Serotonin Uptake Inhibitors)RN - 107-35-7 (Taurine)RN - 77337-76-9 (N-acetylhomotaurine)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW LITERATUREID - AA10522-05/AA/NIAAAID - AA10522-0551/AA/NIAAADA - 20000814CY - UNITED STATESJC - DKHAA - AuthorEM - 200010
UR - PM:0010890803
SO - Alcohol Res Health 1999 ;23(2):99-106

30
UI - 74
AU - Judson BA
AU - Carney TM
AU - Goldstein A
TI - Naltrexone treatment of heroin addiction: efficacy and safety in a double-blind dosage comparison
AB - The goals of this study were two-fold: (1) to test the hypothesis that retention of patients in naltrexone treatment could be improved by educating and preparing them for it while enrolled in a LAAM (l-alpha- acetylmethadol) detoxification program; and (2) to compare the safety and efficacy of 60 mg vs. 120 mg administered thrice weekly in a double- blind, sequential trial design. Patients were allowed a maximum of 365 days on naltrexone, and a maximum of four admissions; 119 patients received at least one dose of naltrexone. We found no clinically important differences between the two dosages, and retention in treatment was similar to that reported in earlier clinical trials. Slightly more than half the patients ever used heroin while receiving naltrexone, and only 9% of all urine tests were positive for opiates. Craving for heroin decreased dramatically by the end of the first week. We found no side-effect or toxicity due to naltrexone
MH - Adolescence
MH - Adult
MH - adverse effects
MH - analogs & derivatives
MH - Clinical Trials
MH - Dose-Response Relationship,Drug
MH - Double-Blind Method
MH - Female
MH - Heroin
MH - Heroin Dependence
MH - Human
MH - Male
MH - Middle Age
MH - Naloxone
MH - Naltrexone
MH - rehabilitation
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
MH - toxicity
MH - urine
RP - NOT IN FILE
NT - UI - 82003796LA - EngRN - 16590-41-3 (Naltrexone)RN - 465-65-6 (Naloxone)PT - CLINICAL TRIALPT - JOURNAL ARTICLEID - DA-923/DA/NIDAID - DA-1199/DA/NIDADA - 19811118IS - 0376-8716SB - MCY - SWITZERLANDJC - EBSAA - AuthorEM - 198201
UR - PM:0007023894
SO - Drug Alcohol Depend 1981 Jul ;7(4):325-346

31
UI - 22
AU - Katner SN
AU - Magalong JG
AU - Weiss F
AD - Scripps Research Institute, Department of Neuropharmacology, La Jolla, California 92037, USA
TI - Reinstatement of alcohol-seeking behavior by drug-associated discriminative stimuli after prolonged extinction in the rat
AB - Clinical observations suggest that stimuli associated with the availability or consumption of ethanol can evoke subjective feelings of craving and trigger episodes of relapse in abstinent alcoholics. To study the motivational significance of alcohol-related environmental cues experimentally, the effects of discriminative stimuli previously predictive of alcohol availability on the reinstatement of ethanol- seeking behavior were examined. Wistar rats were trained to lever-press for 10% (w/v) ethanol or water in the presence of distinct auditory cues. The rats were then subjected to an extinction phase where lever presses had no scheduled consequences. After extinction, the animals were exposed to the respective auditory cues without the availability of ethanol or water. Neither the ethanol (SA+) nor water-associated (SA- ) auditory cue increased responding over extinction levels. In contrast, subsequent presentation of an olfactory cue associated with ethanol (SO+), but not a water-associated (SO-) cue significantly reinstated lever pressing behavior in the absence of the primary reinforcer. Moreover, responding elicited by the concurrent presentation of the SO+ and SA+ was selectively attenuated by the opiate antagonist naltrexone (0.25 mg/kg; s.c.). The results suggest that ethanol-associated cues can reinstate extinguished ethanol-seeking behavior in rats, but that the efficacy of these stimuli may be modality-specific. In addition, the present procedures may be useful for studying neurobiological mechanisms of alcohol-seeking behavior and relapse
MH - Acoustic Stimulation
MH - Alcohol Drinking
MH - Animal
MH - Cues
MH - Discrimination (Psychology)
MH - Discrimination Learning
MH - drug effects
MH - Ethanol
MH - Extinction (Psychology)
MH - Male
MH - Naltrexone
MH - Narcotic Antagonists
MH - pharmacology
MH - physiology
MH - psychology
MH - Rats
MH - Rats,Wistar
MH - Self Administration
MH - Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 99208907LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEID - AA 10531/AA/NIAAADA - 19990609IS - 0893-133XSB - MCY - UNITED STATESJC - ADQAA - AuthorEM - 199908
UR - PM:0010192827
SO - Neuropsychopharmacology 1999 May ;20(5):471-479

32
UI - 7
AU - King AC
AU - Meyer PJ
AD - The University of Chicago, Department of Psychiatry, Chicago, IL 60637, USA
TI - Naltrexone alteration of acute smoking response in nicotine-dependent subjects
AB - There are mixed results on the effects of opioid antagonists on acute nicotine response in humans. The present study examined the effects of a single dose of 50 mg oral naltrexone relative to placebo on smoking response in 22 chronic smokers during short-term nicotine abstinence, after acute smoking and subsequent smoking deprivation, and on smoking behavior in a choice paradigm. The results showed that naltrexone significantly reduced immediate postcigarette ratings of smoking craving and desire to smoke and increased light-headedness, dizziness, and head rush (ps < 0.05). Reductions in craving and smoking desire persisted during a subsequent 1 h nonsmoking interval. Naltrexone also was found to significantly reduce the total number of cigarettes smoked in the choice interval, which was supported by objective measures of both reduced CO and plasma nicotine levels (ps < 0.01). Exploratory analyses on potential individual difference factors revealed that smokers with the highest levels of craving during abstinence showed the most pronounced naltrexone attenuation of smoking response. The results support the continued exploration of naltrexone as an adjunct to smoking cessation, especially in identified smoker subgroups most sensitive to the effects of opioid antagonism
MH - Adult
MH - Affect
MH - blood
MH - drug effects
MH - drug therapy
MH - Female
MH - Human
MH - Male
MH - Middle Age
MH - Naltrexone
MH - Narcotic Antagonists
MH - Nicotine
MH - psychology
MH - Smoking
MH - Smoking Cessation
MH - Substance Withdrawal Syndrome
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
MH - Tobacco Use Disorder
RP - NOT IN FILE
NT - UI - 20359652LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)RN - 54-11-5 (Nicotine)PT - CLINICAL TRIALPT - CONTROLLED CLINICAL TRIALPT - JOURNAL ARTICLEID - M01RR00055/RR/NCRRID - M01RR00109/RR/NCRRID - R03AA11133/AA/NIAAADA - 20001005IS - 0091-3057SB - MCY - UNITED STATESJC - P3QAA - AuthorEM - 200012
UR - PM:0010899371
SO - Pharmacol Biochem Behav 2000 Jul ;66(3):563-572

33
UI - 72
AU - Kleber HD
AU - Kosten TR
TI - Naltrexone induction: psychologic and pharmacologic strategies
AB - Attempts ot improve naltrexone retention during the induction and stabilization phases of treatment are described. During induction, street addicts appear to do better than postmethadone patients and to benefit more from counseling. Inpatient withdrawal and induction appear to be more successful than outpatient, but use of new techniques such as clonidine and clonidine/naltrexone may improve results in outpatients. Prolonged withdrawal symptoms and drug craving appear to contribute to the high dropout rate during stabilization. Pharmacologic and psychological methods of treatment, and future research strategies for these first two parts of naltrexone treatment, are summarized
MH - administration & dosage
MH - Ambulatory Care
MH - analogs & derivatives
MH - Behavior Therapy
MH - Clonidine
MH - Counseling
MH - Drug Administration Schedule
MH - drug therapy
MH - Drug Therapy,Combination
MH - Family Therapy
MH - Hospitalization
MH - Human
MH - Injections,Intramuscular
MH - methods
MH - Naloxone
MH - Naltrexone
MH - Opioid-Related Disorders
MH - Patient Dropouts
MH - rehabilitation
MH - Research Design
MH - Street Drugs
MH - therapeutic use
MH - therapy
MH - United States
RP - NOT IN FILE
NT - UI - 84289322LA - EngRN - 0 (Street Drugs)RN - 16590-41-3 (Naltrexone)RN - 4205-90-7 (Clonidine)RN - 465-65-6 (Naloxone)PT - JOURNAL ARTICLEDA - 19841022IS - 0160-6689SB - MCY - UNITED STATESJC - HICAA - AuthorEM - 198412
UR - PM:0006469934
SO - J Clin Psychiatry 1984 Sep ;45(9 Pt 2):29-38

34
UI - 12
AU - Knox PC
AU - Donovan DM
AD - Detoxification Services, Central Seattle Recovery Center, Washington, USA
TI - Using naltrexone in inpatient alcoholism treatment
AB - Naltrexone has been used successfully in outpatient settings as an adjunct to alcoholism treatment. This study examines the efficacy of using naltrexone in an inpatient treatment setting. Sixty-three alcohol- dependent patients who volunteered for a double-blind, placebo- controlled study were followed over the course of their 20 days in treatment and six months follow-up. A comparison group of 59 patients who did not volunteer were also studied over the same period of time. Patients in the study group were randomly assigned to receive naltrexone or placebo. Information was gathered daily on alcohol craving, drug craving and moods on self-reporting forms from the naltrexone and placebo groups, and from the comparison group. Follow-up data was gathered through self-report and through Washington State's TARGET management information system. No significant differences were found in craving scores while in treatment, nor in recidivism after treatment
MH - Adolescence
MH - Adult
MH - adverse effects
MH - Affect
MH - Aged
MH - Alcoholism
MH - Behavior,Addictive
MH - Double-Blind Method
MH - drug effects
MH - drug therapy
MH - Female
MH - Follow-Up Studies
MH - Hospitalization
MH - Human
MH - Male
MH - Middle Age
MH - Naltrexone
MH - Narcotic Antagonists
MH - psychology
MH - Questionnaires
MH - therapeutic use
MH - Treatment Outcome
RP - NOT IN FILE
NT - UI - 20143339LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALDA - 20000324IS - 0279-1072SB - MCY - UNITED STATESJC - JLPAA - AuthorEM - 200006RO - M:CNR
UR - PM:0010681104
SO - J Psychoactive Drugs 1999 Oct ;31(4):373-388

35
UI - 5
AU - Koob GF
AD - Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA
TI - Animal models of craving for ethanol
AB - Craving has various meanings but can be defined generally in terms of a desire for the previously experienced effects of ethanol. Animal models provide a means by which to study the underlying mechanisms associated with craving and are most useful when they fulfill the requirements for predictive validity and reliability. Craving is a key part of the process of addiction that can lead to relapse and is conceptualized as having at least three components: preoccupation/anticipation, binge/intoxication and withdrawal/negative affect. Animal models of craving are hypothesized at this time to involve three domains of motivation to take drugs: excessive drinking, negative affective states and conditioned reinforcement. Excessive drinking includes the alcohol deprivation effect, drinking during withdrawal and drinking after a history of dependence. Models of the negative affective state include increases in brain reward thresholds, and conditioned reinforcement models include cue-induced resistance to extinction or cue-induced reinstatement. Experimental psychology is a rich resource of sensitive behavioral techniques by which to measure hypothetical constructs associated with the motivation to drink ethanol. Rigorous tests of predictive validity and reliability will be necessary to make them useful for understanding the neurobiology of craving and for the development of new medications for treating craving
MH - Alcohol Deterrents
MH - Alcohol Drinking
MH - analogs & derivatives
MH - Animal
MH - Behavior,Addictive
MH - Conditioning,Operant
MH - Disease Models,Animal
MH - drug therapy
MH - Drug Tolerance
MH - Motivation
MH - Naltrexone
MH - Narcotic Antagonists
MH - Predictive Value of Tests
MH - psychology
MH - Rats
MH - Reinforcement (Psychology)
MH - Reproducibility of Results
MH - Substance Withdrawal Syndrome
MH - Support,U.S.Gov't,P.H.S.
MH - Taurine
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 20458005LA - EngRN - 0 (Alcohol Deterrents)RN - 0 (Narcotic Antagonists)RN - 107-35-7 (Taurine)RN - 16590-41-3 (Naltrexone)RN - 77337-76-9 (N-acetylhomotaurine)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALID - AA06420/AA/NIAAAID - AA08459/AA/NIAAADA - 20001005IS - 0965-2140CY - ENGLANDJC - BM3AA - AuthorEM - 200012
UR - PM:0011002904
SO - Addiction 2000 Aug ;95 Suppl 2():S73-S81

36
UI - 66
AU - Kreek MJ
AD - Rockefeller University, New York, New York 10021
TI - Rationale for maintenance pharmacotherapy of opiate dependence
AB - At this time, 27 years after the initial studies on development of methadone for the maintenance treatment of opiate addiction were begun, it has been shown that [table; see text] methadone meets most criteria for a pharmacologic agent for chronic treatment of an addiction. It is effective after oral dosing: it has a long biological half-life in humans, it causes minimal side effects when used in chronic treatment, and it has no true toxic effects or serious side effects. Also methadone has been shown to be very effective when appropriately used in programs which combine pharmacotherapy with the best elements of "drug free" treatment, that is, counseling and psychological support. In addition to pharmacological treatment, there should be access to, if not on-site, medical and behavioral care as needed, as well as linkage to resources for various aspects of rehabilitation. At this time many of the actions, as well as the specific sites of action, and mechanisms of actions of methadone as used in chronic treatment of opiate addiction have been defined by scientific experimentation, both at the preclinical and clinical levels. It is known that methadone prevents abstinence symptoms, prevents drug hunger or craving, blocks euphorogenic effects of other opiates, and prevents relapse to illicit use of opiates. It is known that the site of action of methadone is at specific opioid receptors. Research to date suggests that there is no demonstrable down-regulation or up-regulation of opioid receptors during chronic opioid agonist perfusion, although chronic administration of the opioid antagonist naltrexone does appear to up- regulate opioid receptors. Clinical studies show that chronic use of methadone allows normalization of release and peripheral levels of one of the classes of endogenous opioids, beta-endorphin, and the related peptides derived from POMC released and processed from the anterior pituitary in humans. Also levels of beta-endorphin in cerebrospinal fluid become normal during chronic maintenance treatment, reflecting apparently normal processing and release of beta-endorphin at brain or hypothalamic sites of POMC production. Available data from studies of beta-endorphin indicate that there is a [table; see text] normalization, rather than disruption, of the endogenous opioid system in general during steady state administration of methadone, as contrasted with intermittent dosing and then abrupt withdrawal of short- acting opiates such as heroin. Although there is still much to be learned about the neurobiology of opiate addiction, at this time we do know a great deal about the effects of opiates and opioids.(ABSTRACT TRUNCATED AT 400 WORDS)
MH - beta-Endorphin
MH - Brain
MH - Combined Modality Therapy
MH - drug effects
MH - Heroin Dependence
MH - Human
MH - Methadone
MH - Naltrexone
MH - Neurotransmitters
MH - Opioid-Related Disorders
MH - physiology
MH - physiopathology
MH - psychology
MH - Receptors,Neurotransmitter
MH - rehabilitation
MH - Substance Abuse,Intravenous
MH - Support,Non-U.S.Gov't
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
MH - United States
RP - NOT IN FILE
NT - UI - 92159518LA - EngRN - 0 (Neurotransmitters)RN - 0 (Receptors, Neurotransmitter)RN - 76-99-3 (Methadone)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALID - 1-P50-DA05130/DA/NIDAID - DA-00049/DA/NIDAID - M01-RR00102/RR/NCRRDA - 19920326IS - 0091-7443SB - MCY - UNITED STATESJC - R6PAA - AuthorEM - 199205
UR - PM:0001346939
SO - Res Publ Assoc Res Nerv Ment Dis 1992 ;70():205-230

37
UI - 65
AU - Lerner A
AU - Sigal M
AU - Bacalu A
AU - Shiff R
AU - Burganski I
AU - Gelkopf M
AD - Pardessia Governmental Mental Health Center, Netanya, Israel
TI - A naltrexone double blind placebo controlled study in Israel
AB - In a double blind study, out of 31 newly abstinent patients who underwent opioid free detoxification, 15 were started on the opiate antagonist Naltrexone for 2 months, and 16 were put on placebo for the same period. Given Naltrexone's known efficacy in blocking euphorigenic effects of opioid intake, and in decreasing cravings for the drug, the authors have tried to assess eventual drug taking, specifically in the context of suburban housing projects, and evaluate the rate of retention in a rehabilitative program for both the Naltrexone and placebo groups. An Opioid free condition was followed up for a year, also respecting double blind conditions. Naltrexone did not appear to be superior to the placebo with regards to retention rate. In the Naltrexone group (n = 15), 9 finished the two-month treatment, and 8 remained opioid-free for a year. In the placebo group (n = 16), 8 finished the 2 month trial and 6 remained opioid-free for a year. Naltrexone blocked opioid-induced euphoria and decreased the craving for opium, but it did not inhibit drug usage. The retention rate registered during the course of the study, as well as an opioid-free condition in the follow-up year, correlated with a patient profile defined by good social functioning and stable relationships. The inherent methodological limitations of this study did not allow for the discrimination of the role of non-pharmacological factors, such as psychotherapy, supportive family framework, community assistance, and staff motivation, concerning the clinical results. Further investigation of Naltrexone in larger samples is needed
MH - Adult
MH - Ambulatory Care
MH - Double-Blind Method
MH - Family
MH - Female
MH - Follow-Up Studies
MH - Human
MH - Israel
MH - Male
MH - Motivation
MH - Naltrexone
MH - Opioid-Related Disorders
MH - Placebos
MH - psychology
MH - Psychotherapy
MH - rehabilitation
MH - Social Adjustment
MH - Social Support
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 92234740LA - EngRN - 0 (Placebos)RN - 16590-41-3 (Naltrexone)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALDA - 19920528IS - 0333-7308CY - ISRAELJC - GYEAA - AuthorEM - 199207
UR - PM:0001568861
SO - Isr J Psychiatry Relat Sci 1992 ;29(1):36-43

38
UI - 57
AU - Mason BJ
AU - Ritvo EC
AU - Morgan RO
AU - Salvato FR
AU - Goldberg G
AU - Welch B
AU - Mantero-Atienza E
AD - Department of Psychiatry, University of Miami School of Medicine, FL 33136
TI - A double-blind, placebo-controlled pilot study to evaluate the efficacy and safety of oral nalmefene HCl for alcohol dependence
AB - A dozen studies have been published showing that opiate antagonists suppress alcohol drinking in animals, and two independent placebo- controlled, double-blind clinical trials of naltrexone found this agent was associated with decreased alcohol craving and consumption in alcohol-dependent patients. Nalmefene is a newer opiate antagonist that has a number of potential advantages over naltrexone in the treatment of alcoholism, including no dose-dependent association with liver toxicity and more effective binding to central opiate receptors. Consequently, a double-blind pilot study was conducted to gather preliminary data on the safety and efficacy of nalmefene for reducing alcohol consumption in alcohol-dependent subjects. Twenty-one alcohol- dependent subjects meeting admission criteria were randomly assigned to 12 weeks of double-blind treatment with 40 mg nalmefene, 10 mg nalmefene, or placebo, resulting in 7 patients/treatment group. Nalmefene was well tolerated, with no serious adverse drug reactions. The 40 mg group had a significantly lower rate of relapse (p < or = 0.05), and a greater increase in the number of abstinent days/week (p < or = 0.09), than the other treatment groups. A significant decrease in the number of drinks/drinking day was noted for both nalmefene groups (p < or = 0.04), but not for placebo. These results were supported by parallel decreases in ALT. These pilot data provide preliminary support for the hypotheses that nalmefene can be safely given to alcoholics, and that nalmefene may have a role in reducing alcohol consumption and preventing relapse, particularly at the 40 mg level. A full-scale study is underway to confirm these preliminary findings
MH - administration & dosage
MH - adverse effects
MH - Alcohol Drinking
MH - Alcoholism
MH - analogs & derivatives
MH - Animal
MH - Body Weight
MH - chemically induced
MH - Clinical Trials
MH - Comparative Study
MH - Depression
MH - Dose-Response Relationship,Drug
MH - Double-Blind Method
MH - Drug Administration Schedule
MH - drug effects
MH - Human
MH - Naltrexone
MH - Narcotic Antagonists
MH - Patient Admission
MH - Pilot Projects
MH - psychology
MH - rehabilitation
MH - toxicity
MH - Treatment Outcome
MH - United States
RP - NOT IN FILE
NT - UI - 95150264LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)RN - 55096-26-9 (nalmefene)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALDA - 19950308IS - 0145-6008SB - MCY - UNITED STATESJC - 35XAA - AuthorEM - 199505
UR - PM:0007847600
SO - Alcohol Clin Exp Res 1994 Oct ;18(5):1162-1167

39
UI - 42
AU - Mason BJ
AD - Alcohol Disorders Research Unit, University of Miami School of Medicine, FL 33136, USA
TI - Dosing issues in the pharmacotherapy of alcoholism
AB - Pharmacological treatments for alcohol dependence have focused increasingly on agents that reduce alcohol craving and consumption or that treat psychiatric disorders associated with drinking relapse. Clinicians who treat alcohol-dependent patients must find the optimal dose of these agents to maximize response. Determining the best dosing strategy has been the goal of recent treatment studies with alcohol- dependent patients. One study, for example, showed that an opiate antagonist medication had a dose-dependent relationship with patient outcome and retention in treatment. Another dosing consideration involves the effect of long-term alcohol abuse on drug metabolism (e.g., when treating alcohol-dependent patients for comorbid psychiatric disorders). This was demonstrated in a study of recently abstinent patients who were taking the antidepressant desipramine for major depression. Alcohol-dependent patients had higher hepatic enzyme activities and lower plasma levels of desipramine relative to oral dose than did a comparison group of depressed patients without an alcohol use disorder
MH - administration & dosage
MH - Administration,Oral
MH - Adult
MH - adverse effects
MH - Alcoholism
MH - analogs & derivatives
MH - Antidepressive Agents,Tricyclic
MH - Comorbidity
MH - Depression
MH - Depressive Disorder
MH - Dose-Response Relationship,Drug
MH - Female
MH - Human
MH - Imipramine
MH - Male
MH - metabolism
MH - Middle Age
MH - Naltrexone
MH - Narcotic Antagonists
MH - pharmacokinetics
MH - psychology
MH - Randomized Controlled Trials
MH - rehabilitation
MH - Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 97060943LA - EngRN - 0 (Antidepressive Agents, Tricyclic)RN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)RN - 50-49-7 (Imipramine)RN - 55096-26-9 (nalmefene)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALID - AA09560/AA/NIAAAID - AA08111/AA/NIAAADA - 19970221IS - 0145-6008SB - MCY - UNITED STATESJC - 35XAA - AuthorEM - 199705
UR - PM:0008904989
SO - Alcohol Clin Exp Res 1996 Oct ;20(7 Suppl):10A-16A

40
UI - 34
AU - Modesto-Lowe V
AU - Burleson JA
AU - Hersh D
AU - Bauer LO
AU - Kranzler HR
AD - Alcohol Research Center, University of Connecticut Health Center, Farmington 06030, USA
TI - Effects of naltrexone on cue-elicited craving for alcohol and cocaine
AB - This study examined the effects of naltrexone (50 mg/day) on mood and self-reported desire for alcohol and cocaine in 26 patients with comorbid alcohol and cocaine abuse/dependence. Two laboratory sessions were conducted, separated by 1 week. During the sessions, subjects viewed 5-min films containing either cocaine, alcohol, or neutral cues. The first session occurred prior to random assignment to medication group and the second session was held after 1 week of double-blind treatment with either naltrexone or placebo. The cocaine-related film induced a greater desire to use cocaine than the desire for alcohol that was induced by the alcohol-related film. This finding was observed using both a simple, one-item analog scale administered during the films and more complex craving questionnaires administered immediately after the films. Collectively, the alcohol and cocaine-related films evoked greater levels of self-reported anxiety and elation, and lower levels of concentration, than the neutral film. Naltrexone did not differ from placebo in reducing the desire to use either cocaine or alcohol
MH - Adolescence
MH - Adult
MH - Affect
MH - Alcoholism
MH - Anxiety
MH - Cocaine-Related Disorders
MH - Comparative Study
MH - complications
MH - Cues
MH - diagnosis
MH - Double-Blind Method
MH - drug effects
MH - drug therapy
MH - Female
MH - Human
MH - Male
MH - Middle Age
MH - Naltrexone
MH - Narcotic Antagonists
MH - pharmacology
MH - physiology
MH - Psychiatric Status Rating Scales
MH - Questionnaires
MH - Severity of Illness Index
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
MH - Time Factors
MH - Visual Perception
RP - NOT IN FILE
NT - UI - 98135561LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALID - P50-DA04060/DA/NIDAID - P50-AA03510/AA/NIAAAID - T32-AA07290/AA/NIAAAID - +DA - 19980518IS - 0376-8716SB - MCY - IRELANDJC - EBSAA - AuthorEM - 199807
UR - PM:0009476694
SO - Drug Alcohol Depend 1997 Dec ;49(1):9-16

41
UI - 16
AU - Monti PM
AU - Rohsenow DJ
AU - Hutchison KE
AU - Swift RM
AU - Mueller TI
AU - Colby SM
AU - Brown RA
AU - Gulliver SB
AU - Gordon A
AU - Abrams DB
AD - Providence VA Medical Center, Brown University, Rhode Island 02912, USA. Peter_Monti@Brown.edu
TI - Naltrexone's effect on cue-elicited craving among alcoholics in treatment
AB - BACKGROUND: Advancing knowledge of biobehavioral effects of interventions can result in improved treatments. Thus, a standardized laboratory cue reactivity assessment has been developed and validated to assess the cognitive and psychophysiological responses to a simulated high-risk situation: alcohol cues. The present study investigates the effects of a pharmacotherapy (naltrexone) on a laboratory-based, cue-elicited urge to drink among abstinent alcoholics in treatment. METHODS: Alcohol-dependent subjects were randomized to 12 weeks of naltrexone or placebo after completing a partial hospital program. After approximately 1 week on medication, all received cue reactivity assessment. RESULTS: Significantly fewer patients taking naltrexone reported any urge to drink during alcohol exposure than did those on placebo. Those with any urges reported no decrement in level of the urges. Mean arterial pressure decreased significantly for those on placebo, but not for those on naltrexone, whereas cue-elicited decreases in heart rate were not affected by the medication. CONCLUSIONS: The results have implications for models of relapse and naltrexone's effects. Cue reactivity methodology has utility for investigating hypothesized mediators of therapeutic effects of pharmacotherapies as well as behavioral treatments
MH - Adult
MH - Alcoholism
MH - Analysis of Variance
MH - Behavior,Addictive
MH - Blood Pressure
MH - Cues
MH - Double-Blind Method
MH - drug effects
MH - drug therapy
MH - Female
MH - Heart Rate
MH - Human
MH - Male
MH - methods
MH - Middle Age
MH - Naltrexone
MH - Narcotic Antagonists
MH - physiology
MH - Salivation
MH - Support,Non-U.S.Gov't
MH - Support,U.S.Gov't,Non-P.H.S.
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 99397583LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALID - 2R01 AA07850/AA/NIAAAID - AA07459/AA/NIAAADA - 19991026IS - 0145-6008SB - MCY - UNITED STATESJC - 35XAA - AuthorEM - 200001
UR - PM:0010470982
SO - Alcohol Clin Exp Res 1999 Aug ;23(8):1386-1394

42
UI - 3
AU - Monti PM
AU - Rohsenow DJ
AU - Hutchison KE
AD - Providence VA Medical Center/Brown University, USA
TI - Toward bridging the gap between biological, psychobiological and psychosocial models of alcohol craving
AB - Urge to drink ("craving") has been a central focus of many theories and treatments, but some researchers question the importance of urges during recovery. Several studies assessed reactions to the presence of beverage alcohol (cue-reactivity) or to simulated high-risk situations (role plays). Higher urges in response to role plays predicted more drinking during the 6 months after treatment. However, urges in response to beverage cues were inconsistently predictive of outcome while measures of awareness or attention to cues predicted less drinking. Urge to drink might reflect a conflict between motivation to drink and awareness of danger. Whether urges predict increased risk of drinking should be a function of factors that affect motivation to drink, awareness of risk and effectiveness of coping. Cue-reactivity assessment has recently been used to bridge the gap between psychosocial and biomedical approaches in several ways: (1) salivation to cues predicts increased drinking independent of urge or attention, showing the value of including both physiological and psychosocial measures; (2) naltrexone has been shown to decrease cue-elicited urge to drink, illustrating the value of this assessment methodology for medications evaluation and (3) pre-pulse inhibition of startle response is being used to investigate the role of dopaminergic pathways in cue- elicited urge. Thus, this laboratory based program of research has the potential to add to knowledge of both biomedical and psychosocial mechanisms involved in urge and relapse, leading to greater integration of models
MH - Alcohol-Related Disorders
MH - Behavior,Addictive
MH - Conditioning,Classical
MH - Cues
MH - drug effects
MH - drug therapy
MH - Human
MH - Models,Biological
MH - Models,Psychological
MH - Motivation
MH - Naltrexone
MH - Narcotic Antagonists
MH - Predictive Value of Tests
MH - psychology
MH - rehabilitation
MH - Startle Reaction
MH - Support,U.S.Gov't,Non-P.H.S.
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
MH - Treatment Outcome
RP - NOT IN FILE
NT - UI - 20458018LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALID - 2R01 AA07850/AA/NIAAAID - AA07459/AA/NIAAADA - 20001005IS - 0965-2140CY - ENGLANDJC - BM3AA - AuthorEM - 200012
UR - PM:0011002917
SO - Addiction 2000 Aug ;95 Suppl 2():S229-S236

43
UI - 43
AU - Myers RD
AD - Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27858, USA
TI - Tetrahydroisoquinolines and alcoholism: where are we today?
AB - The present status of research on the tetrahydroisoquinoline (THIQ) family of compounds and other aldehyde metabolites in the field of alcoholism is described. A brief history of the background of experimental studies on the actions of the THIQ's and beta-carbolines on alcohol drinking is presented. A computer data base search of articles published in this field reveals that both the historical and current research trends have waxed and waned since the 1960s. The clinical utility of naltrexone in terms of the cerebral function of opioid compounds in drinking behavior and alcoholism is likewise considered. Finally, the residual controversy concerning the significance of multiple intermediary metabolites in alcohol dependence and craving should ultimately be resolved in the future by broad-based investigations which employ state-of-the-art experimental approaches
MH - Alcohol Drinking
MH - Alcoholism
MH - Animal
MH - Brain
MH - Drinking Behavior
MH - Human
MH - Isoquinolines
MH - metabolism
MH - Naltrexone
MH - Opioid Peptides
MH - pharmacology
MH - physiology
MH - physiopathology
MH - rehabilitation
RP - NOT IN FILE
NT - UI - 96330467LA - EngRN - 0 (Isoquinolines)RN - 0 (Opioid Peptides)RN - 91-21-4 (1,2,3,4-tetrahydroisoquinoline)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19961107IS - 0145-6008SB - MCY - UNITED STATESJC - 35XAA - AuthorEM - 199701
UR - PM:0008727243
SO - Alcohol Clin Exp Res 1996 May ;20(3):498-500

44
UI - 56
AU - O'Brien CP
AD - University of Pennsylvania/VA Medical Center, Philadelphia 19104-6178
TI - Treatment of alcoholism as a chronic disorder
AB - Alcoholism is a common disorder that tends to be chronic and relapsing. Although there is clear evidence that treatment can be expected to induce a period of remission or at least decreased symptoms, treatment of alcoholism is generally regarded as unsuccessful. Alcoholism should be approached as a chronic medical disorder such as diabetes or arthritis. Complete abstinence is the preferred goal, but "cures" or permanent abstinence from alcohol are rare. In this model, treatment benefits may be measured by length of remission, reduction in alcohol use, improvement in health and enhancement of social functioning. Treatment continues over a period of years, mainly on an outpatient basis with increasing intensity if symptoms recur. Medications that reduce craving for alcohol or diminish the euphoric effects of alcohol would be very helpful in the management of this chronic disorder. Preclinical studies have produced evidence for involvement of the endogenous opioid system in the reinforcing effects of alcohol. Recent controlled clinical trials of the opiate receptor antagonist naltrexone suggest that medications of this type may improve the results of treatment for alcoholism
MH - Alcoholism
MH - antagonists & inhibitors
MH - Clinical Trials
MH - Controlled Clinical Trials
MH - drug therapy
MH - Human
MH - Naltrexone
MH - Opioid Peptides
MH - physiology
MH - Recurrence
MH - Support,U.S.Gov't,Non-P.H.S.
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
MH - United States
RP - NOT IN FILE
NT - UI - 95169280LA - EngRN - 0 (Opioid Peptides)RN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALID - DA 05186/DA/NIDADA - 19950324IS - 0741-8329SB - MCY - UNITED STATESJC - AG9AA - AuthorEM - 199506
UR - PM:0007865139
SO - Alcohol 1994 Nov ;11(6):433-437

45
UI - 58
AU - O'Brien CP
AD - University of Pennsylvania/VA Medical Center, Philadelphia 19104-6178
TI - Treatment of alcoholism as a chronic disorder
AB - Alcoholism is a common disorder that tends to be chronic and relapsing. Although there is clear evidence that treatment can be expected to induce a period of remission or at least decreased symptoms, treatment of alcoholism is generally regarded as unsuccessful. Alcoholism should be approached as a chronic medical disorder such as diabetes or arthritis. Complete abstinence is the preferred goal, but "cures" or permanent abstinence from alcohol are rare. In this model, treatment benefits may be measured by length of remission, reduction in alcohol use, improvement in health and enhancement of social functioning. Treatment continues over a period of years, mainly on an outpatient basis with increasing intensity if symptoms recur. Medications that reduce craving for alcohol or diminish the euphoric effects of alcohol would be very helpful in the management of this chronic disorder. Pre- clinical studies have produced evidence for involvement of the endogenous opioid system in the reinforcing effects of alcohol. Recent controlled clinical trials of the opiate receptor antagonist naltrexone suggest that medications of this type may improve the results of treatment for alcoholism
MH - Adult
MH - Alcoholism
MH - Animal
MH - Chronic Disease
MH - Clinical Trials
MH - Controlled Clinical Trials
MH - drug therapy
MH - Endorphins
MH - Human
MH - Naltrexone
MH - Patient Compliance
MH - physiology
MH - physiopathology
MH - Recurrence
MH - rehabilitation
MH - Support,U.S.Gov't,Non-P.H.S.
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 94305301LA - EngRN - 0 (Endorphins)RN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALID - DA 05186/DA/NIDADA - 19940812SB - MCY - SWITZERLANDJC - BFZAA - AuthorEM - 199410
UR - PM:0008032166
SO - EXS 1994 ;71():349-359

46
UI - 47
AU - O'Brien CP
AU - Volpicelli LA
AU - Volpicelli JR
AD - Center for the Study of Addiction, University of Pennsylvania, Philadelphia 19104-6178, USA
TI - Naltrexone in the treatment of alcoholism: a clinical review
AB - The pooled results from our Veterans Affairs studies are presented for 99 men. The naltrexone-treated subjects reported a reduction in alcohol craving and drinking, as well as less euphoria when they ingested alcohol. Relapse rates were significantly lower for the naltrexone- treated subjects than they were for placebo-treated subjects. Together with the consistent results from other double-blind trials of naltrexone, we conclude that naltrexone is a safe and useful adjunct in the rehabilitation of alcohol-dependent patients. Although administration of naltrexone was shown to improve treatment outcome, subjects who attended all 12 research visits demonstrated larger treatment effects. These data suggest that the use of naltrexone as a pharmacological adjunct to psychosocial intervention is an effective treatment for alcohol dependence. The effectiveness of naltrexone may be improved by designing a treatment program that enhances compliance with the medication
MH - Adult
MH - Alcoholism
MH - drug therapy
MH - Human
MH - Male
MH - Middle Age
MH - Naltrexone
MH - Narcotic Antagonists
MH - Psychotherapy
MH - Randomized Controlled Trials
MH - Recurrence
MH - rehabilitation
MH - Support,U.S.Gov't,Non-P.H.S.
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
MH - therapy
MH - Treatment Outcome
RP - NOT IN FILE
NT - UI - 96435046LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALID - AA-07517/AA/NIAAAID - DA-05186/DA/NIDADA - 19961202IS - 0741-8329SB - MCY - UNITED STATESJC - AG9AA - AuthorEM - 199702
UR - PM:0008837932
SO - Alcohol 1996 Jan ;13(1):35-39

47
UI - 63
AU - O'Connor PG
AU - Waugh ME
AU - Schottenfeld RS
AU - Diakogiannis IA
AU - Rounsaville BJ
AD - Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510
TI - Ambulatory opiate detoxification and primary care: a role for the primary care physician [see comments]
AB - To determine the feasibility of primary care-based ambulatory opiate detoxification (AOD) and an optimal regimen, the authors conducted a pilot study of AOD in a medical clinic comparing two regimens: clonidine and clonidine plus naltrexone. Sixty-two opiate addicts who had been referred for AOD had the following features: mean age was 34 years, 75% were male, 74% used cocaine, and 64% shared needles. Initially, 40 patients selected clonidine, 22 clonidine/naltrexone. The groups (clonidine and clonidine/naltrexone) were similar in baseline features, including: craving scores (44/100 vs. 42/100) and withdrawal scores (20/72 vs. 17/72). Overall, 61% (38/62) of initial AODs were successful, including 43% (17/40) of those using clonidine and 95% (21/22) of those using clonidine/naltrexone (p less than 0.0001). Of 45 patients who ultimately completed AOD, 78% (35/45) remained in treatment for at least one month
MH - Adult
MH - adverse effects
MH - Clonidine
MH - Cocaine
MH - Comparative Study
MH - drug therapy
MH - Drug Therapy,Combination
MH - Feasibility Studies
MH - Female
MH - Human
MH - Male
MH - Metabolic Detoxication,Drug
MH - metabolism
MH - Naltrexone
MH - Narcotics
MH - Opioid-Related Disorders
MH - pharmacokinetics
MH - Physician's Role
MH - Pilot Projects
MH - Primary Health Care
MH - Substance Withdrawal Syndrome
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
MH - Treatment Outcome
MH - United States
RP - NOT IN FILE
NT - UI - 93019668LA - EngRN - 0 (Narcotics)RN - 16590-41-3 (Naltrexone)RN - 4205-90-7 (Clonidine)PT - JOURNAL ARTICLEID - 5R18DA05758/DA/NIDADA - 19921104IS - 0884-8734SB - MCY - UNITED STATESJC - JGIAA - AuthorEM - 199301RO - M:CNRRO - M:LC1
UR - PM:0001403211
SO - J Gen Intern Med 1992 Sep ;7(5):532-534

48
UI - 52
AU - O'Connor PG
AU - Waugh ME
AU - Carroll KM
AU - Rounsaville BJ
AU - Diagkogiannis IA
AU - Schottenfeld RS
AD - Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8025, USA
TI - Primary care-based ambulatory opioid detoxification: the results of a clinical trial
AB - OBJECTIVE: To determine the feasibility of primary care-based ambulatory opioid detoxification (AOD) using two protocols: clonidine and clonidine plus naltrexone. SETTING: The Central Medical Unit (CMU)-- a freestanding primary care medical clinic staffed by physicians and nurse practitioners. PATIENTS: Injection drug users (IDUs) seeking substance abuse treatment between the ages of 18 and 50 years who were addicted to opioids (e.g., heroin) and not currently in drug treatment. INTERVENTIONS: In the clonidine protocol, clonidine was administered every 4 hours "as needed" for up to 12 days. In the clonidine plus naltrexone protocol, clonidine was administered and naltrexone was administered in increasing doses over five days. Both protocols included "adjuvant" medications for muscle cramps, insomnia, and vomiting. Successfully detoxified patients were referred to ongoing drug treatment. DESIGN: A prospective nonrandomized clinical trial. MEASUREMENTS AND MAIN RESULTS: One hundred forty opioid-addicted IDUs were referred to the medical clinic for AOD. Among the 125 patients who enrolled in the study, 57 selected clonidine and 68 selected clonidine/naltrexone. The treatment groups (clonidine vs clonidine/naltrexone) were similar at baseline with respect to: age at first heroin use (21 years vs 23 years), mean admission opioid craving score (45/100 vs 49/100), and withdrawal symptom score (19/72 vs 18/72). Overall, 70% (88/125) of the AODs were successful, including 42% (24/57) for clonidine and 94% (64/68) for clonidine/naltrexone (p < 0.001). CONCLUSIONS: This study suggests that primary care-based AOD can be safely and effectively carried out by primary care providers and that clonidine/naltrexone may be more effective in this setting than is clonidine alone. Ambulatory opioid detoxification can give internists a larger role in initiating drug treatment for IDUs who are addicted to opioids
MH - administration & dosage
MH - Adolescence
MH - Adult
MH - Ambulatory Care
MH - Chi-Square Distribution
MH - Clonidine
MH - Cohort Studies
MH - Comparative Study
MH - Drug Administration Schedule
MH - drug therapy
MH - Drug Therapy,Combination
MH - Feasibility Studies
MH - Female
MH - Human
MH - Male
MH - Middle Age
MH - Naltrexone
MH - Opioid-Related Disorders
MH - Pilot Projects
MH - Primary Health Care
MH - Prospective Studies
MH - therapeutic use
MH - Treatment Outcome
RP - NOT IN FILE
NT - UI - 95341424LA - EngRN - 16590-41-3 (Naltrexone)RN - 4205-90-7 (Clonidine)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALDA - 19950822IS - 0884-8734SB - MCY - UNITED STATESJC - JGIAA - AuthorEM - 199510RO - M:RCT
UR - PM:0007616334
SO - J Gen Intern Med 1995 May ;10(5):255-260

49
UI - 26
AU - O'Malley SS
AD - Department of Psychiatry, School of Medicine, Yale University, New Haven, CT 06511, USA
TI - Opioid antagonists in the treatment of alcohol dependence: clinical efficacy and prevention of relapse
AB - Placebo-controlled studies have demonstrated that patients treated with opioid antagonists had fewer drinking days, lower rates of resumed heavy drinking, and reduced alcohol craving, when compared with placebo- treated patients. Patients who received an opioid antagonist were also less likely to drink heavily if they sampled alcohol during treatment. One study also demonstrated that patients who were treated with the opioid antagonist naltrexone had lower serum aspartate aminotransferase and alanine aminotransferase levels than placebo-treated patients. This is consistent with self-reported decreases in alcohol consumption. These patients also had less severe alcohol-related problems than placebo-treated patients, as indicated by the Addiction Severity Index. Opioid antagonists might act by reducing the reinforcing effects of alcohol and the incentive to drink. These agents, when combined with comprehensive treatment programmes, are an effective adjunctive treatment for alcohol-dependent patients
MH - Alcoholism
MH - Controlled Clinical Trials
MH - drug therapy
MH - Human
MH - Naltrexone
MH - Narcotic Antagonists
MH - psychology
MH - Recurrence
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 99059175LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19990225IS - 1358-6173SB - MCY - ENGLANDJC - AAPAA - AuthorEM - 199904
UR - PM:0009845042
SO - Alcohol Alcohol Suppl 1996 Mar ;1():77-81

50
UI - 44
AU - O'Malley SS
AD - Department of Psychiatry, School of Medicine, Yale University, New Haven, CT 06511, USA
TI - Opioid antagonists in the treatment of alcohol dependence: clinical efficacy and prevention of relapse
AB - Placebo-controlled studies have demonstrated that patients treated with opioid antagonists had fewer drinking days, lower rates of resumed heavy drinking, and reduced alcohol craving, when compared with placebo- treated patients. Patients who received an opioid antagonist were also less likely to drink heavily if they sampled alcohol during treatment. One study also demonstrated that patients who were treated with the opioid antagonist naltrexone had lower serum aspartate aminotransferase and alanine aminotransferase levels than placebo-treated patients. This is consistent with self-reported decreases in alcohol consumption. These patients also had less severe alcohol-related problems than placebo-treated patients, as indicated by the Addiction Severity Index. Opioid antagonists might act by reducing the reinforcing effects of alcohol and the incentive to drink. These agents, when combined with comprehensive treatment programmes, are an effective adjunctive treatment for alcohol-dependent patients
MH - adverse effects
MH - Alcoholism
MH - analysis
MH - Biological Markers
MH - drug effects
MH - Human
MH - Motivation
MH - Naltrexone
MH - Narcotic Antagonists
MH - Neurologic Examination
MH - Opioid Peptides
MH - physiology
MH - physiopathology
MH - psychology
MH - Randomized Controlled Trials
MH - Recurrence
MH - rehabilitation
MH - therapeutic use
MH - Treatment Outcome
RP - NOT IN FILE
NT - UI - 96346233LA - EngRN - 0 (Biological Markers)RN - 0 (Narcotic Antagonists)RN - 0 (Opioid Peptides)RN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19961107IS - 0735-0414SB - MCY - ENGLANDJC - AALAA - AuthorEM - 199701
UR - PM:0008737005
SO - Alcohol Alcohol 1996 Mar ;31 Suppl 1():77-81

51
UI - 46
AU - O'Malley SS
AU - Jaffe AJ
AU - Rode S
AU - Rounsaville BJ
AD - Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA
TI - Experience of a "slip" among alcoholics treated with naltrexone or placebo
AB - OBJECTIVE: This study tested the hypothesis that naltrexone reduces relapse rates among alcoholics by modifying the reinforcing effects of initial alcohol consumption and alcohol-induced craving. METHOD: Sixteen alcoholic patients treated with naltrexone and 27 treated with placebo who participated in a 12-week clinical trial reported retrospectively on their subjective responses to their first episode of a lapse into alcohol consumption and on their reasons for terminating the drinking episode. RESULTS: Compared to the subjects who received placebo, the subjects who received naltrexone reported lower levels of craving for alcohol and were more likely to give reasons for terminating drinking that were consistent with decreased incentive to drink. CONCLUSIONS: These findings support the hypothesis that a central effect of naltrexone is the modification of alcohol-induced craving
MH - Alcohol Drinking
MH - Alcoholic Intoxication
MH - Alcoholism
MH - drug effects
MH - drug therapy
MH - Emotions
MH - epidemiology
MH - Human
MH - Naltrexone
MH - pharmacology
MH - Placebos
MH - psychology
MH - Recurrence
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 96155946LA - EngRN - 0 (Placebos)RN - 16590-41-3 (Naltrexone)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALID - AA-00171/AA/NIAAAID - AA-09538/AA/NIAAAID - AA-03510/AA/NIAAADA - 19960223IS - 0002-953XSB - ASB - MCY - UNITED STATESJC - 3VGAA - AuthorEM - 199605
UR - PM:0008561215
SO - Am J Psychiatry 1996 Feb ;153(2):281-283

52
UI - 15
AU - Palfai T
AU - Davidson D
AU - Swift R
AD - Department of Psychology, Boston University, Massachusetts 02215, USA. palfai@bu.edu
TI - Influence of naltrexone on cue-elicited craving among hazardous drinkers: the moderational role of positive outcome expectancies
AB - This study was designed to elucidate mechanisms by which naltrexone (NTX) influences drinking among hazardous drinkers. Thirty-six hazardous drinkers received 50 mg NTX or placebo on 2 separate occasions before participation in a taste test procedure with low- alcohol beer. Urges to drink before consumption, beer volume consumed, and perceived stimulation and sedation after consumption were assessed. Although NTX did not influence beer consumption, hazardous drinkers who reported high positive reinforcement expectancies rated their urges to drink as significantly lower when they were on NTX compared with placebo. Positive outcome expectancies also moderated the effects of NTX on subjective reports of stimulation following drinking. These findings suggest that naltrexone may be particularly effective at reducing alcohol cue-elicited positive reinforcement for those with high positive alcohol outcome expectancies
MH - Adult
MH - Alcoholism
MH - Beer
MH - Cross-Over Studies
MH - Cues
MH - drug effects
MH - drug therapy
MH - Human
MH - Male
MH - Middle Age
MH - Naltrexone
MH - Narcotic Antagonists
MH - psychology
MH - Reinforcement (Psychology)
MH - Taste
MH - therapeutic use
MH - Time Factors
MH - Treatment Outcome
RP - NOT IN FILE
NT - UI - 99401735LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALDA - 19991019IS - 1064-1297SB - MCY - UNITED STATESJC - CWBAA - AuthorEM - 199912
UR - PM:0010472515
SO - Exp Clin Psychopharmacol 1999 Aug ;7(3):266-273

53
UI - 37
AU - Phillips TJ
AU - Wenger CD
AU - Dorow JD
AD - Veterans Affairs Medical Center, Portland, OR 97201, USA
TI - Naltrexone effects on ethanol drinking acquisition and on established ethanol consumption in C57BL/6J mice
AB - Naltrexone's success as a treatment agent for alcoholism seems to be due to its ability to reduce craving in abstinent, dependent individuals and to reduce the pleasure associated with subsequent intake. However, more study is needed to establish the optimal amount of time that naltrexone treatment should be continued. Little information seems to have been collected regarding the most effective dosing regimen for reducing alcohol craving and consumption, and the usefulness of opiate antagonists in the prevention of alcohol dependence in nonaddicts, rather than just as a treatment agent in addicted individuals, also deserves further study. The alcohol- preferring C57BL/6J (B6) mice were used to: (1) study naltrexone effects on consumption in established drinkers using an increasing dosing regimen, (2) study naltrexone effects on the acquisition of ethanol drinking, and (3) study the effects of chronic naltrexone from timed-release pellets on drinking in alcohol-naive mice. Naltrexone reduced ethanol preference in established drinkers, but its effects waned at increasing doses. Naltrexone slowed the acquisition of ethanol drinking, but was ineffective when readministered after a phase when ethanol was offered in the absence of naltrexone. Mice with chronic naltrexone pellets consumed greater amounts of ethanol and showed higher ethanol preference than did placebo-pelleted animals. The observed reduced efficacy of naltrexone with increasing dosage and chronic treatment may have been due to naltrexone-induced opiate receptor changes. Such changes are presumably more likely to occur when naltrexone doses remain high or perhaps accumulate. Thus, dose and frequency of administration may be important factors in determining naltrexone's effectiveness in treating alcohol dependence
MH - Alcohol Drinking
MH - Alcoholism
MH - Animal
MH - Brain
MH - Dose-Response Relationship,Drug
MH - drug effects
MH - Drug Implants
MH - Ethanol
MH - Female
MH - Mice
MH - Mice,Inbred C57BL
MH - Motivation
MH - Naltrexone
MH - Narcotic Antagonists
MH - Opioid Peptides
MH - pharmacology
MH - physiology
MH - physiopathology
MH - Receptors,Opioid
MH - Support,Non-U.S.Gov't
MH - Support,U.S.Gov't,Non-P.H.S.
MH - Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 97338366LA - EngRN - 0 (Drug Implants)RN - 0 (Narcotic Antagonists)RN - 0 (Opioid Peptides)RN - 0 (Receptors, Opioid)RN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEID - P01-AA08621/AA/NIAAAID - P50-AA10760/AA/NIAAADA - 19970820IS - 0145-6008SB - MCY - UNITED STATESJC - 35XAA - AuthorEM - 199710
UR - PM:0009194926
SO - Alcohol Clin Exp Res 1997 Jun ;21(4):691-702

54
UI - 33
AU - Salloum IM
AU - Cornelius JR
AU - Thase ME
AU - Daley DC
AU - Kirisci L
AU - Spotts C
AD - Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, PA 15213, USA
TI - Naltrexone utility in depressed alcoholics
AB - The aim of this open-label pilot study was to evaluate the utility of naltrexone (50 mg per day) in decreasing alcohol use and to examine its impact on depressive symptoms among depressed alcoholics who have failed to abstain from alcohol use despite treatment with a selective serotonin reuptake inhibitor (SSRI). Fourteen ambulatory care patients, aged 18 to 65 years, with DSM-III-R comorbid diagnoses of alcohol dependence and major depressive disorder, who failed to abstain despite treatment with an antidepressant medication were enrolled in the study. Patients were followed for 12 weeks with weekly assessment of drinking behavior, depressive symptoms, functioning, alcohol craving, and side effects. The results of this study indicated a significant decrease in alcohol use and in urges to drink alcohol in the presence of the usual triggers. There was also a trend suggesting improvement in depressive symptoms and overall functioning. Naltrexone was well tolerated, with mild side effects reported at the onset of treatment
MH - Adult
MH - Aged
MH - Alcoholism
MH - Ambulatory Care
MH - complications
MH - Depressive Disorder
MH - Drinking Behavior
MH - drug therapy
MH - Female
MH - Human
MH - Male
MH - Naltrexone
MH - Narcotic Antagonists
MH - Pilot Projects
MH - Support,Non-U.S.Gov't
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 98225368LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)PT - CLINICAL TRIALPT - JOURNAL ARTICLEID - AA-10523/AA/NIAAAID - AA-09127/AA/NIAAADA - 19980521IS - 0048-5764CY - UNITED STATESJC - QG1AA - AuthorEM - 199807
UR - PM:0009564207
SO - Psychopharmacol Bull 1998 ;34(1):111-115

55
UI - 75
AU - Sideroff SI
AU - Charuvastra VC
AU - Jarvik ME
TI - Craving in heroin addicts maintained on the opiate antagonist naltrexone
AB - The level of heroin craving was monitored in patiens receiving naltrexone on a regular basis. Meetings and interviews conducted twice weekly attested to a pattern of craving reduction in most but not all the addicts. It was also found that it usually took 3 to 5 weeks for this effect to occur. The possible relationship between drug craving and participation in the naltrexone program is discussed
MH - analogs & derivatives
MH - Heroin
MH - Heroin Dependence
MH - Human
MH - Naloxone
MH - Naltrexone
MH - Patient Dropouts
MH - psychology
MH - rehabilitation
MH - therapeutic use
MH - United States
RP - NOT IN FILE
NT - UI - 80017510LA - EngPT - JOURNAL ARTICLEDA - 19791129IS - 0095-2990SB - MCY - UNITED STATESJC - 3GWAA - AuthorEM - 198001
UR - PM:0000755381
SO - Am J Drug Alcohol Abuse 1978 ;5(4):415-423

56
UI - 69
AU - Sinclair JD
AD - Research Laboratories, Alko Ltd, Helsinki, Finland
TI - Drugs to decrease alcohol drinking
AB - A wide variety of drugs have been tested in experimental animals and several have been found that reduce voluntary alcohol drinking. The available evidence suggested that the same drugs also reduce alcohol drinking in alcoholics. Various factors limited or prevented the clinical use of the these drugs. Our working hypothesis has been that alcohol drinking is a learned response, reinforced primarily from alcohol in the brain, and that an alcoholic is a person in which this response and the related craving have become so strong that they dominate the behaviour and interfere with normal functioning. Learned responses are extinguished if they are made repeatedly while the reinforcement is blocked, and opiate antagonists appear to block the reinforcement from alcohol. A series of experiments support the hypothesis that drinking alcohol while an antagonist is present extinguishes the alcohol-drinking response in rats. The antagonists are non-addictive and at least naloxone appears to be safe. Clinical trials are now needed, but the present results suggest that this extinction procedure might be a useful adjunct to the treatment of alcoholism
MH - Alcohol Drinking
MH - Alcoholism
MH - Animal
MH - Brain
MH - Clinical Trials
MH - drug therapy
MH - Extinction (Psychology)
MH - Male
MH - Naloxone
MH - Naltrexone
MH - Narcotic Antagonists
MH - Opioid-Related Disorders
MH - pharmacology
MH - Rats
MH - Rats,Inbred Strains
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 91151694LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)RN - 465-65-6 (Naloxone)PT - JOURNAL ARTICLEDA - 19910410IS - 0785-3890SB - MCY - FINLANDJC - AMDAA - AuthorEM - 199106
UR - PM:0002291844
SO - Ann Med 1990 ;22(5):357-362

57
UI - 20
AU - Sinha R
AU - O'Malley SS
AD - Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA
TI - Craving for alcohol: findings from the clinic and the laboratory
AB - This paper presents a review of the current status of empirical research in the area of alcohol craving. After an introduction on the origins of the construct of craving, we first present clinical studies that have examined craving as a hallmark symptom of alcohol dependence and demonstrated its sensitivity as an outcome measure in assessing change in pharmacotherapy trials of alcohol dependence. There is also discussion regarding new multifactorial self-report instruments of alcohol craving with good reliability and predictive validity, that may be sensitive to detecting alcohol craving and assessing change in craving as it relates to relapse during treatment. Next, we examine the experimental paradigms that have been used to induce alcohol craving in the laboratory. Further, the methodological issues affecting laboratory- based paradigms are presented, while also elucidating the potential use of effective laboratory-based craving induction paradigms, both in clinical studies as well as in laboratory studies that examine the brain mechanisms associated with the concept of craving. Finally, directions for future research on craving in the laboratory and the clinic are presented in the context of developing more effective treatments for different phases of recovery from alcohol dependence
MH - Alcoholism
MH - Behavior,Addictive
MH - drug therapy
MH - Human
MH - Naltrexone
MH - Narcotic Antagonists
MH - physiopathology
MH - psychology
MH - Stress
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 99274579LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW LITERATUREID - P50-1103510ID - K02-110171DA - 19990707IS - 0735-0414SB - MCY - ENGLANDJC - AALAA - AuthorEM - 199909
UR - PM:0010344782
SO - Alcohol Alcohol 1999 Mar ;34(2):223-230

58
UI - 40
AU - Spanagel R
AU - Zieglgansberger W
AD - Drug Abuse Group, Max Planck Institute of Psychiatry, Munich, Germany
TI - Anti-craving compounds for ethanol: new pharmacological tools to study addictive processes
AB - Anti-craving compounds have recently been registered for relapse prophylaxis in weaned alcoholics in various European countries (acamprosate), and in the United States (naltrexone). Acamprosate, the Ca(2+)-salt of N-acetyl-homotaurinate, interacts with NMDA receptor- mediated glutamatergic neurotransmission in various brain regions and reduces Ca2+ fluxes through voltage-operated channels. The opioid receptor antagonist naltrexone most likely interferes with alcohol- induced reinforcement via the block of opioid receptors. In this article Rainer Spanagel and Walter Zieglgansberger discuss the pivotal role of incremental neuroadaptation to alcohol and alcohol-associated stimuli for craving, and the possible mechanisms of action underlying the anti-craving properties of acamprosate and naltrexone
MH - administration & dosage
MH - Alcoholism
MH - analogs & derivatives
MH - Animal
MH - antagonists & inhibitors
MH - Behavior,Animal
MH - Brain
MH - Calcium Channels
MH - cytology
MH - Disease Models,Animal
MH - drug effects
MH - drug therapy
MH - Ethanol
MH - Human
MH - Naltrexone
MH - Narcotic Antagonists
MH - Neurons
MH - pharmacology
MH - Rats
MH - Receptors,N-Methyl-D-Aspartate
MH - Receptors,Opioid
MH - Recurrence
MH - Substance Withdrawal Syndrome
MH - Support,Non-U.S.Gov't
MH - Synaptic Transmission
MH - Taurine
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 97245643LA - EngRN - 0 (Calcium Channels)RN - 0 (Narcotic Antagonists)RN - 0 (Receptors, N-Methyl-D-Aspartate)RN - 0 (Receptors, Opioid)RN - 107-35-7 (Taurine)RN - 16590-41-3 (Naltrexone)RN - 77337-76-9 (N-acetylhomotaurine)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19970513IS - 0165-6147CY - ENGLANDJC - WFTAA - AuthorEM - 199707
UR - PM:0009090311
SO - Trends Pharmacol Sci 1997 Feb ;18(2):54-59

59
UI - 6
AU - Spanagel R
AU - Holter SM
AD - Max Planck Institute of Psychiatry, Munich, Federal Republic of Germany
TI - Pharmacological validation of a new animal model of alcoholism [In Process Citation]
AB - A new animal model of alcoholism has been developed. Rats derived from this model show certain characteristics: (i) they have an incentive demand to consume alcohol, (ii) they exhibit relapse-like drinking even after a very long time of abstinence, (iii) they show tolerance to alcohol and have mild signs of physical withdrawal during the onset of abstinence, and (iv) during abstinence they also exhibit a psychological withdrawal syndrome consisting of enhanced anxiety- related behaviour and hyperreactivity to stressful situations. Anti- craving drugs such as acamprosate and naltrexone which proved to be effective in human alcoholics to prevent relapse were also effective in our animal model. Thus, both compounds suppressed the alcohol deprivation effect which is used as a measure for craving and relapse. It is concluded that this pharmacological validation of our model demonstrates the predictive value of our model and enables us to further characterize putative anti-craving drugs and neurobiological mechanisms of addictive behaviour
MH - Animal
MH - Human
MH - Naltrexone
MH - Rats
RP - NOT IN FILE
NT - UI - 20397823LA - EngDA - 20000812SB - MCY - AUSTRIAJC - CIJAA - AUTHORRO - O:099
UR - PM:0010943907
SO - J Neural Transm 2000 ;107(6):669-680

60
UI - 67
AU - Stevens KE
AU - Shiotsu G
AU - Stein L
AD - Department of Pharmacology, College of Medicine, University of California, Irvine 92717
TI - Hippocampal mu-receptors mediate opioid reinforcement in the CA3 region
AB - Dependence on reinforcing chemicals is manifested when drug-seeking and drug-taking behaviors come to dominate the response repertoire. Clinical observations suggest that the craving and compulsive drug- seeking that characterize drug dependence are aroused by memories of the reinforcing drug experience. If so, a brain structure intimately associated with memory--the hippocampus--would be a plausible substrate for drug reinforcement effects. We report here that drug-naive rats rapidly learn to self-administer the opioid peptide dynorphin A in the CA3 region of hippocampus, and that this behavior is blocked by co- administration of the non-selective opiate antagonist naloxone. Subsequent studies demonstrated that coadministration of mu-, but not kappa- or delta-opioid antagonists also blocked self-administration behavior. We conclude that mu-receptors in the CA3 region of hippocampus may be important target sites for opioid dependence
MH - administration & dosage
MH - analogs & derivatives
MH - Animal
MH - Brain
MH - drug effects
MH - Dynorphins
MH - Enkephalin,Leucine
MH - Hippocampus
MH - Kinetics
MH - Male
MH - Memory
MH - Naloxone
MH - Naltrexone
MH - Narcotic Antagonists
MH - pharmacology
MH - physiology
MH - Pyramidal Tracts
MH - Rats
MH - Rats,Inbred Strains
MH - Receptors,Opioid
MH - Reference Values
MH - Reinforcement (Psychology)
MH - Self Administration
MH - Support,Non-U.S.Gov't
MH - Support,U.S.Gov't,Non-P.H.S.
MH - Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 91316608LA - EngRN - 0 (Narcotic Antagonists)RN - 0 (Receptors, Opioid)RN - 0 (Receptors, Opioid, mu)RN - 105618-26-6 (norbinaltorphimine)RN - 16590-41-3 (Naltrexone)RN - 465-65-6 (Naloxone)RN - 58822-25-6 (Enkephalin, Leucine)RN - 72782-05-9 (beta-funaltrexamine)RN - 74913-18-1 (Dynorphins)RN - 89352-67-0 (ICI 174864)PT - JOURNAL ARTICLEID - 05107ID - 1 F31 DA05288/DA/NIDADA - 19910830IS - 0006-8993SB - MCY - NETHERLANDSJC - B5LAA - AuthorEM - 199111
UR - PM:0001677606
SO - Brain Res 1991 Apr 5 ;545(1-2):8-16

61
UI - 8
AU - Swift RM
AD - Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island, USA
TI - Medications and alcohol craving
AB - The use of medications as an adjunct to alcoholism treatment is based on the premise that craving and other manifestations of alcoholism are mediated by neurobiological mechanisms. Three of the four medications approved in the United States or Europe for treating alcoholism are reported to reduce craving; these include naltrexone (ReVia), acamprosate, and tiapride. The remaining medication, disulfiram (Antabuse), may also possess some anticraving activity. Additional medications that have been investigated include ritanserin, which has not been shown to decrease craving or drinking levels in humans, and ondansetron, which shows promise for treating early onset alcoholics, who generally respond poorly to psychosocial treatment alone. Use of anticraving medications in combination (e.g., naltrexone plus acamprosate) may enhance their effectiveness. Future studies should address such issues as optimal dosing regimens and the development of strategies to enhance patient compliance
MH - Alcohol Deterrents
MH - Alcoholism
MH - Behavior,Addictive
MH - drug therapy
MH - Human
MH - Naltrexone
MH - physiopathology
MH - psychology
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 20343260LA - EngRN - 0 (Alcohol Deterrents)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW LITERATUREDA - 20000810CY - UNITED STATESJC - DKHAA - AuthorEM - 200010
UR - PM:0010890816
SO - Alcohol Res Health 1999 ;23(3):207-213

62
UI - 31
AU - Terenius L
AD - Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. Lars.Terenius@cmm.ki.se
TI - Rational treatment of addiction
AB - Treatment of alcohol and drug addictions, which has been neglected medically for a long time, is currently sparked with optimism. Craving for alcohol can be treated with two newly registered drugs: naltrexone and acamprosate. New approaches to symptom relief during detoxification or during maintenance therapies are rationally based on experimental and clinical work. It is now clear that addictive drugs are surrogates of natural substances involved in the 'reward system'
MH - agonists
MH - Alcohol Deterrents
MH - Alcoholism
MH - Animal
MH - Attitude
MH - Disulfiram
MH - drug therapy
MH - Human
MH - Naltrexone
MH - Narcotic Antagonists
MH - Narcotics
MH - Reward
MH - Substance Withdrawal Syndrome
MH - Substance-Related Disorders
MH - therapeutic use
MH - therapy
RP - NOT IN FILE
NT - UI - 98408136LA - EngRN - 0 (Alcohol Deterrents)RN - 0 (Narcotic Antagonists)RN - 0 (Narcotics)RN - 97-77-8 (Disulfiram)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19981118IS - 1367-5931SB - MCY - ENGLANDJC - C4UAA - AuthorEM - 199901
UR - PM:0009736929
SO - Curr Opin Chem Biol 1998 Aug ;2(4):541-547

63
UI - 60
AU - Thomas JM
AU - Hoffman BB
AD - Department of Medicine, Stanford University School of Medicine, Palo Alto, California
TI - Buprenorphine prevents and reverses the expression of chronic etorphine- induced sensitization of adenylyl cyclase in SK-N-SH human neuroblastoma cells
AB - Buprenorphine is an opiate drug with a mixed agonist-antagonist profile and has therapeutic efficacy in attenuating drug craving and addiction. Because the adenylyl cyclase system has been implicated in the biochemical basis of opiate withdrawal phenomena, we have compared the acute and chronic effects of buprenorphine with the full opiate agonist etorphine on cyclic AMP (cAMP) synthesis in the human neuroblastoma cell SK-N-SH. Both drugs acutely inhibited prostaglandin (PG)E1- stimulated cAMP accumulation; the inhibition caused by either drug was prevented by pretreatment with the opiate antagonist naltrexone or with pertussis toxin. Chronic treatment of the cells with etorphine induced an increase in PGE1-stimulated cAMP synthesis which was observed after withdrawal of the inhibitory drug. Chronic treatment with buprenorphine appeared to have the opposite effect, resulting in an attenuated PGE1 stimulation; additionally, buprenorphine prevented the etorphine- induced enhancement in cAMP synthesis, whether administered before or after prolonged incubation of the cells with etorphine. The attenuating effect of buprenorphine occurred within 5 min and was prevented by a prior application of naltrexone, but could not be reversed by a subsequent treatment with antagonist. These findings suggest that buprenorphine was binding (pseudo)irreversibly to the opiate receptor, resulting in a persistent inhibition of cAMP synthesis which masks the etorphine-induced enhancement of adenylyl cyclase activity. This hypothesis was confirmed by experiments demonstrating that treatment of the cells with buprenorphine significantly reduced available opiate receptor binding sites despite extensive washing of the cells to remove unbound buprenorphine. These pharmacodynamic actions of buprenorphine may be relevant to its therapeutic efficacy in treating drug abuse and addiction
MH - Adenylate Cyclase
MH - Alprostadil
MH - biosynthesis
MH - Buprenorphine
MH - Cell Differentiation
MH - Comparative Study
MH - Cyclic AMP
MH - drug effects
MH - Drug Interactions
MH - enzymology
MH - Etorphine
MH - Human
MH - metabolism
MH - Naltrexone
MH - Neuroblastoma
MH - pharmacology
MH - physiology
MH - Receptors,Opioid,mu
MH - Sensitivity and Specificity
MH - Stimulation,Chemical
MH - Support,U.S.Gov't,Non-P.H.S.
MH - Support,U.S.Gov't,P.H.S.
MH - Time Factors
MH - Tretinoin
MH - Tumor Cells,Cultured
MH - United States
RP - NOT IN FILE
NT - UI - 93140026LA - EngRN - EC 4.6.1.1 (Adenylate Cyclase)RN - 0 (Receptors, Opioid, mu)RN - 14521-96-1 (Etorphine)RN - 302-79-4 (Tretinoin)RN - 52485-79-7 (Buprenorphine)RN - 60-92-4 (Cyclic AMP)RN - 745-65-3 (Alprostadil)PT - JOURNAL ARTICLEID - AG09597/AG/NIADA - 19930223IS - 0022-3565SB - MCY - UNITED STATESJC - JP3AA - AuthorEM - 199304
UR - PM:0008380866
SO - J Pharmacol Exp Ther 1993 Jan ;264(1):368-374

64
UI - 30
AU - Tinsley JA
AU - Finlayson RE
AU - Morse RM
AD - Department of Psychiatry and Psychology, Mayo Clinic Rochester, Minnesota 55905, USA
TI - Developments in the treatment of alcoholism
AB - The treatment of alcoholism has changed during the past 2 decades. Notable developments have occurred in pharmacotherapy, psychotherapy, and health-care delivery. A better understanding of the biologic basis for addiction has led to clinical trials of medications that target neuroreceptors. One such medication is the opiate antagonist naltrexone, which decreases the craving for alcohol. Psychosocial interventions continue to be the mainstay of alcohol treatment programs. The efficacy of three different therapies was demonstrated in a study called Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity). This study, however, did not prove the patient- treatment "matching" hypothesis. In addition to therapies provided by addiction specialists, interest is growing in the use of brief motivational techniques in primary-care settings. As the field of addiction responds to an unfolding health-care delivery system, a broader range of treatment options in conjunction with a greater opportunity to individualize patient care is evolving
MH - Alcohol Deterrents
MH - Alcoholism
MH - Anti-Anxiety Agents,Benzodiazepine
MH - Continuity of Patient Care
MH - Disulfiram
MH - drug therapy
MH - Human
MH - methods
MH - Naltrexone
MH - Narcotic Antagonists
MH - psychology
MH - Psychotherapy
MH - therapeutic use
MH - therapy
RP - NOT IN FILE
NT - UI - 98407240LA - EngRN - 0 (Alcohol Deterrents)RN - 0 (Anti-Anxiety Agents, Benzodiazepine)RN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)RN - 97-77-8 (Disulfiram)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19980923IS - 0025-6196SB - ASB - MCY - UNITED STATESJC - LLYAA - AuthorEM - 199811
UR - PM:0009737222
SO - Mayo Clin Proc 1998 Sep ;73(9):857-863

65
UI - 59
AU - Van Ree JM
AU - Kornet M
AU - Goosen C
AD - Department of Pharmacology, Rudolf Magnus Institute, Utrecht University, The Netherlands
TI - Neuropeptides and alcohol addiction in monkeys
AB - Neuropeptides have been implicated in experimental drug addiction. Desglycinamide (Arg8) vasopressin (DGAVP) attenuates heroin and cocaine intake during initiation of drug self-administration in rats. beta- Endorphin is self-administered in rats and a role of endogenous opioids in cocaine reward has been proposed. The present studies deal with voluntary alcohol consumption in monkeys under free choice conditions. Monkeys initiated alcohol drinking within a few days and after a stable drinking pattern was acquired increased their ethanol consumption during a short period following interruption of the alcohol supply (relapse). The alcohol drinking behavior seems under the control of reinforcement principles. DGAVP reduced the acquisition of alcohol drinking in the majority of treated monkeys. Initiation of alcohol drinking induced modifications in neuroendocrine homeostasis e.g. an increased plasma beta-endorphin. Both the opioid antagonist naltrexone and the opioid agonist morphine dose-dependently decreased alcohol intake during continuous supply and after imposed abstinence. The monkeys were more sensitive to both drugs after imposed abstinence. The effects are interpreted in the context of the endorphin compensation hypothesis of addictive behavior. It is suggested that endorphins may be particularly implicated in craving for addictive drugs and in relapse of addictive behavior
MH - administration & dosage
MH - Alcohol Drinking
MH - Alcoholism
MH - Animal
MH - beta-Endorphin
MH - blood
MH - Cocaine
MH - Drinking Behavior
MH - Endorphins
MH - Ethanol
MH - Human
MH - Macaca mulatta
MH - Male
MH - Morphine
MH - Naltrexone
MH - Neuropeptides
MH - pharmacology
MH - physiology
MH - physiopathology
MH - prevention & control
MH - psychology
MH - Rats
MH - Reinforcement (Psychology)
MH - Reward
MH - Self Administration
RP - NOT IN FILE
NT - UI - 94305281LA - EngRN - 0 (Neuropeptides)RN - 16590-41-3 (Naltrexone)RN - 57-27-2 (Morphine)RN - 60617-12-1 (beta-Endorphin)RN - 64-17-5 (Ethanol)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19940812SB - MCY - SWITZERLANDJC - BFZAA - AuthorEM - 199410
UR - PM:0008032147
SO - EXS 1994 ;71():165-174

66
UI - 48
AU - Van Ree JM
AD - Department of Pharmacology, Rudolf Magnus Institute for Neurosciences, University of Utrecht, Netherlands
TI - Endorphins and experimental addiction
AB - Animal studies suggest that the endogenous opioid systems in the brain play an important role in the initiation and maintenance of drug dependence. Opioids in the ventral tegmental area (VTA) may be involved in rewarded behaviors and, consequently, in the initiation of drug self- administration that may be associated with addiction proneness. Opioids in the limbic forebrain are particularly implicated in subsequent drug self-administration, which may be associated with craving, maintenance, and relapse. Alcohol intake in monkeys is reduced after treatment with naltrexone in a graded, dose-dependent manner. Naltrexone also is associated with a greater decrease in alcohol consumption after imposed abstinence. These findings support the idea that endorphins play a role in alcohol-drinking behavior, particularly after a period of abstinence during the so-called catch-up phenomenon. Recent studies of recovering alcoholic patients provide evidence that opiate antagonists attenuate the craving for alcohol and decrease and/or postpone relapse into addictive behavior
MH - administration & dosage
MH - Alcohol Drinking
MH - Animal
MH - Brain
MH - Cocaine
MH - Disease Models,Animal
MH - Endorphins
MH - Macaca mulatta
MH - Male
MH - metabolism
MH - Naltrexone
MH - Narcotic Antagonists
MH - pharmacology
MH - physiology
MH - Rats
MH - Self Administration
MH - Substance-Related Disorders
RP - NOT IN FILE
NT - UI - 96435044LA - EngRN - 0 (Endorphins)RN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)RN - 50-36-2 (Cocaine)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19961202IS - 0741-8329SB - MCY - UNITED STATESJC - AG9AA - AuthorEM - 199702
UR - PM:0008837930
SO - Alcohol 1996 Jan ;13(1):25-30

67
UI - 62
AU - Volpicelli JR
AU - Alterman AI
AU - Hayashida M
AU - O'Brien CP
AD - Department of Psychiatry, University of Pennsylvania, Philadelphia
TI - Naltrexone in the treatment of alcohol dependence [see comments]
AB - Seventy male alcohol-dependent patients participated in a 12-week, double-blind, placebo-controlled trial of naltrexone hydrochloride (50 mg/d) as an adjunct to treatment following alcohol detoxification. Subjects taking naltrexone reported significantly less alcohol craving and days in which any alcohol was consumed. During the 12-week study, only 23% of the naltrexone-treated subjects met the criteria for a relapse, whereas 54.3% of the placebo-treated subjects relapsed. The primary effect of naltrexone was seen in patients who drank any alcohol while attending outpatient treatment. Nineteen (95%) of the 20 placebo- treated patients relapsed after they sampled alcohol, while only eight (50%) of 16 naltrexone-treated patients exposed to alcohol met relapse criteria. Naltrexone was not associated with mood changes or other psychiatric symptoms. Significant side effects (nausea) occurred in two naltrexone-treated subjects, and one naltrexone-treated subject complained of increased pain from arthritis. These results suggest that naltrexone may be a safe and effective adjunct to treatment in alcohol- dependent subjects, particularly in preventing alcohol relapse
MH - Adult
MH - adverse effects
MH - Alcohol Drinking
MH - Alcoholism
MH - Ambulatory Care
MH - chemically induced
MH - Combined Modality Therapy
MH - Double-Blind Method
MH - drug therapy
MH - Human
MH - Male
MH - Naltrexone
MH - Nausea
MH - Patient Dropouts
MH - Placebos
MH - Psychiatric Status Rating Scales
MH - psychology
MH - Psychotherapy
MH - Recurrence
MH - Severity of Illness Index
MH - Support,Non-U.S.Gov't
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
MH - therapy
MH - Treatment Outcome
MH - United States
RP - NOT IN FILE
NT - UI - 93074283LA - EngRN - 0 (Placebos)RN - 16590-41-3 (Naltrexone)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALID - AA0751701A1/AA/NIAAAID - DA05186/DA/NIDADA - 19921203IS - 0003-990XSB - ASB - MCY - UNITED STATESJC - 72CAA - AuthorEM - 199302RO - M:LC2
UR - PM:0001345133
SO - Arch Gen Psychiatry 1992 Nov ;49(11):876-880

68
UI - 51
AU - Volpicelli JR
AU - Volpicelli LA
AU - O'Brien CP
AD - Department of Psychiatry and Psychology, University of Pennsylvania, Philadelphia 19104, USA
TI - Medical management of alcohol dependence: clinical use and limitations of naltrexone treatment
AB - Historically, pharmacological and psychosocial treatments for alcohol dependence have demonstrated only modest effectiveness in reducing alcohol drinking. However, the recent US Food and Drug Administration approval of naltrexone for the treatment of alcohol dependence offers a new, safe and effective medication to reduce relapse following alcohol detoxification. This paper reviews the various psychosocial and pharmacological treatments currently available and the effectiveness of these treatments. This paper also reviews preclinical research which demonstrates the involvement of the opioid system in the reinforcing effects of alcohol. This research led to clinical trials on the use of the opioid antagonist, naltrexone, to reduce alcohol's pleasurable effects and enhance the effectiveness of psychosocial therapy. In two randomized clinical trials, naltrexone treatment reduced rates of alcohol relapse, number of drinking days and alcohol craving. The clinical efficacy of all pharmacological treatments for substance abuse are limited by compliance with taking the medication. Also, pharmacological treatment does not address the psychosocial complications which often result from chronic alcohol dependence. Therefore, the integration of medications such as naltrexone and psychosocial therapies may offer the best treatment. The further development and investigation of new pharmacological agents will enable matching of patient populations with specific treatments, offering more successful treatment outcomes
MH - Alcohol Drinking
MH - Alcoholism
MH - Combined Modality Therapy
MH - complications
MH - drug therapy
MH - Human
MH - Naltrexone
MH - Narcotic Antagonists
MH - psychology
MH - Psychotherapy
MH - Randomized Controlled Trials
MH - Recurrence
MH - Support,U.S.Gov't,Non-P.H.S.
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
MH - therapy
MH - Time Factors
MH - Treatment Outcome
RP - NOT IN FILE
NT - UI - 96286408LA - EngRN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALID - AA-07517/AA/NIAAAID - DA-05186/DA/NIDADA - 19960822IS - 0735-0414SB - MCY - ENGLANDJC - AALAA - AuthorEM - 199610
UR - PM:0008679021
SO - Alcohol Alcohol 1995 Nov ;30(6):789-798

69
UI - 53
AU - Volpicelli JR
AU - Watson NT
AU - King AC
AU - Sherman CE
AU - O'Brien CP
AD - Department of Psychiatry, University of Pennsylvania, Philadelphia 19104
TI - Effect of naltrexone on alcohol "high" in alcoholics
AB - OBJECTIVE: Subjective effects of alcohol in alcoholics treated with naltrexone or placebo were compared. METHOD: In a previously reported double-blind clinical trial of 50 mg/day of naltrexone or placebo for treatment of alcoholism, 36 of 70 detoxified male veterans deviated from abstinence. Of these 36, 29 subsequently reported on the subjective effects of drinking during the trial. RESULTS: A larger proportion of naltrexone-treated subjects (seven of 12) than placebo- treated subjects (two of 17) reported that the "high" produced by alcohol during the study was significantly less than usual. The naltrexone-treated subjects also drank less alcohol than the placebo- treated subjects during the first drinking episode. There was no difference between groups in reported intoxication, craving, memory, or loss of temper. CONCLUSIONS: The lower alcohol consumption by the naltrexone-treated subjects may have resulted from naltrexone's blockage of the pleasure produced by alcohol
MH - Alcohol Drinking
MH - Alcoholic Intoxication
MH - Alcoholism
MH - Double-Blind Method
MH - drug effects
MH - drug therapy
MH - Emotions
MH - Human
MH - Male
MH - Memory
MH - Naltrexone
MH - pharmacology
MH - Placebos
MH - psychology
MH - rehabilitation
MH - Support,U.S.Gov't,P.H.S.
MH - Temperance
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 95208925LA - EngRN - 0 (Placebos)RN - 16590-41-3 (Naltrexone)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALID - AA-07517/AA/NIAAAID - DA-05186/DA/NIDADA - 19950425IS - 0002-953XSB - ASB - MCY - UNITED STATESJC - 3VGAA - AuthorEM - 199506
UR - PM:0007694913
SO - Am J Psychiatry 1995 Apr ;152(4):613-615

70
UI - 55
AU - Volpicelli JR
AU - Clay KL
AU - Watson NT
AU - O'Brien CP
AD - Department of Psychiatry and Psychology, University of Pennsylvania, Philadelphia, USA
TI - Naltrexone in the treatment of alcoholism: predicting response to naltrexone
AB - The pooled results of 99 subjects from our Veterans Affairs population show that naltrexone-treated subjects had a greater reduction in alcohol craving, number of drinking days, and alcoholic relapse rates when compared with placebo-treated subjects. Based on our findings and results from other double-blind trials of naltrexone, we conclude that naltrexone is a safe and useful adjunct in the rehabilitation of alcohol-dependent patients. Increased baseline levels of psychological distress and craving as well as higher levels of somatic distress, anxiety, phobic anxiety, and obsessive-compulsive symptoms predicted an increased number of drinking days during the study. Significant interactions between naltrexone treatment, initial craving, and somatic distress suggest that naltrexone may be useful for subjects who present with high levels of craving and somatic symptoms
MH - Adult
MH - Aged
MH - Alcohol Drinking
MH - Alcoholism
MH - Ambulatory Care
MH - Anxiety
MH - Combined Modality Therapy
MH - drug therapy
MH - Human
MH - Male
MH - Middle Age
MH - Naltrexone
MH - Personality Inventory
MH - Placebos
MH - prevention & control
MH - Probability
MH - psychology
MH - rehabilitation
MH - Support,U.S.Gov't,P.H.S.
MH - therapeutic use
MH - Treatment Outcome
MH - United States
RP - NOT IN FILE
NT - UI - 95403301LA - EngRN - 0 (Placebos)RN - 16590-41-3 (Naltrexone)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALID - AA-07517/AA/NIAAAID - DA-05186/DA/NIDADA - 19951017IS - 0160-6689SB - MCY - UNITED STATESJC - HICAA - AuthorEM - 199512
UR - PM:0007673104
SO - J Clin Psychiatry 1995 ;56 Suppl 7():39-44

71
UI - 10
AU - Walsh K
AU - Alexander G
AD - Department of Medicine, University of Cambridge, Box 157, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
TI - Alcoholic liver disease
AB - Alcohol is a major cause of liver cirrhosis in the Western world and accounts for the majority of cases of liver cirrhosis seen in district general hospitals in the UK. The three most widely recognised forms of alcoholic liver disease are alcoholic fatty liver (steatosis), acute alcoholic hepatitis, and alcoholic cirrhosis. The exact pathogenesis of alcoholic liver injury is still not clear but immune mediated and free radical hepatic injury are thought to be important. There is increasing interest in genetic factors predisposing to hepatic injury in susceptible individuals. Diagnosis is based on accurate history, raised serum markers such as gamma-glutamyltransferase, mean corpuscular volume, and IgA and liver histology when obtainable. Abstinence is the most important aspect of treatment. Newer drugs such as acamprosate and naltrexone are used to reduce alcohol craving. Vitamin supplements and nutrition are vital while corticosteroids have a role in acute alcoholic hepatitis where there is no evidence of gastrointestinal haemorrhage or sepsis. Liver transplantation has excellent results in abstinent patients with end stage liver disease but there are concerns about recidivism after transplant
MH - Cytokines
MH - diagnosis
MH - etiology
MH - Female
MH - Human
MH - Liver Diseases,Alcoholic
MH - Male
MH - metabolism
MH - Naltrexone
MH - Risk Factors
MH - therapy
RP - NOT IN FILE
NT - UI - 20237870LA - EngRN - 0 (Cytokines)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 20000612IS - 0032-5473SB - MCY - ENGLANDJC - PFXAA - AuthorEM - 200008
UR - PM:0010775280
SO - Postgrad Med J 2000 May ;76(895):280-286

72
UI - 54
AU - Wirschubsky ZG
TI - [USA approves of a new drug that decreases the craving for alcohol]
MH - Alcoholism
MH - Drug Approval
MH - drug therapy
MH - Human
MH - Naltrexone
MH - prevention & control
MH - Substance Withdrawal Syndrome
MH - therapeutic use
MH - United States
RP - NOT IN FILE
NT - UI - 95191229LA - SweRN - 16590-41-3 (Naltrexone)PT - JOURNAL ARTICLEDA - 19950412IS - 0023-7205CY - SWEDENJC - L0NEM - 199506
UR - PM:0007885084
SO - Lakartidningen 1995 Mar 8 ;92(10):1005

73
UI - 13
AU - Wong GY
AU - Wolter TD
AU - Croghan GA
AU - Croghan IT
AU - Offord KP
AU - Hurt RD
AD - Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA
TI - A randomized trial of naltrexone for smoking cessation
AB - AIMS: To evaluate the efficacy and safety of orally administered naltrexone, alone or in combination with nicotine patches, as a treatment for cigarette smoking. DESIGN: Randomized, partially-blinded, 2 x 2 factorial trial using naltrexone (active vs. placebo) and nicotine patches (active vs. none). PARTICIPANTS: One hundred cigarette smokers. INTERVENTION: Twelve weeks of either placebo-only, naltrexone- only, placebo with nicotine patches or naltrexone with nicotine patches. The naltrexone dose was 50 mg taken once daily, and the nicotine patch dose was 21 mg/24-hour for the first 8 weeks and 14 mg/24-hour for the remaining 4 weeks. Brief behavioral intervention was provided at each visit. MEASUREMENTS: One-week point-prevalence smoking abstinence rates confirmed by an expired air carbon monoxide level of 8 parts per million (ppm) or less, daily cigarette smoking and cigarette craving. FINDINGS: At the end of treatment, there was no effect of naltrexone on smoking abstinence. The smoking abstinence rates were 19% and 22% for the placebo only and naltrexone only treatment groups, respectively, and 48% and 46% for the placebo with nicotine patch and naltrexone with nicotine patch groups, respectively. However, the effect of the nicotine patch at this time was significant (p = 0.006), but not at the 6-month follow-up. No significant effect of naltrexone was observed on daily cigarette smoking on cigarette craving during the study. CONCLUSIONS: The opioid antagonist naltrexone was not found to be effective for smoking cessation and had no significant effect on daily cigarette consumption or craving. The results of the present study provide no support for the use of naltrexone, alone or in combination with nicotine patches, as a therapeutic treatment for smoking cessation
MH - administration & dosage
MH - Administration,Cutaneous
MH - Administration,Oral
MH - Adolescence
MH - Adult
MH - Aged
MH - Drug Therapy,Combination
MH - Female
MH - Human
MH - Male
MH - methods
MH - Middle Age
MH - Naltrexone
MH - Narcotic Antagonists
MH - Nicotine
MH - Nicotinic Agonists
MH - Smoking
MH - Smoking Cessation
MH - Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 20082600LA - EngRN - 0 (Narcotic Antagonists)RN - 0 (Nicotinic Agonists)RN - 16590-41-3 (Naltrexone)RN - 54-11-5 (Nicotine)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALDA - 20000207IS - 0965-2140CY - ENGLANDJC - BM3AA - AuthorEM - 200004
UR - PM:0010615738
SO - Addiction 1999 Aug ;94(8):1227-1237

74
UI - 64
AU - Yanagita T
AD - Preclinical Research Division, Central Institute for Experimental Animals, Kawasaki, Japan
TI - [Overview of the progress in drug dependence studies--mainly focussing on psychic dependence]
AB - The technical term 'drug dependence' was officially adopted by WHO's Expert Committee on Addiction in 1964. Until this, to describe a state of dependence, terms such as 'poisoning', 'habit', 'ism', and 'addiction' had been used from time to time. Until the 1950's, investigators were mainly focussed on the phenomena of physical dependence. However, once the concept of psychic dependence had been introduced, behavioral and neuropharmacological studies on the modes of drug action that produce psychic dependence were activated and have progressed in the last two decades, and among the points clarified by these studies are the following: 1. The critical drug properties that produce psychic dependence are those of rewarding subjective and reinforcing effects of drugs but these effects are not the properties that produce physical dependence, although the development of physical dependence on particular drugs such as opiates may substantially enhance craving for the drugs. 2. The mesolimbic and mesocortical dopamine systems in the brain and also the N. Accumbens play a primary or at least a partial role in producing the subjective and reinforcing effects of major dependence-producing drugs such as cocaine, opiates, barbiturates, benzodiazepines, and ethanol. 3. Many drugs such as naltrexone, methadone, and some dopamine antagonists and serotonin reuptake inhibitors or antagonists were found to be effective in the pharmacotherapy of the dependence on opiates, cocaine, or ethanol
MH - Animal
MH - Benzodiazepines
MH - Brain
MH - Cocaine
MH - Dopamine
MH - Dopamine Antagonists
MH - drug therapy
MH - English Abstract
MH - Ethanol
MH - Haloperidol
MH - Human
MH - Limbic System
MH - Methadone
MH - Naloxone
MH - Naltrexone
MH - physiology
MH - psychology
MH - Receptors,Dopamine
MH - Substance-Related Disorders
MH - therapeutic use
RP - NOT IN FILE
NT - UI - 93051822LA - JpnRN - 0 (Benzodiazepines)RN - 0 (Receptors, Dopamine)RN - 465-65-6 (Naloxone)RN - 52-86-8 (Haloperidol)RN - 76-99-3 (Methadone)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19921211IS - 0015-5691SB - MCY - JAPANJC - F2XAA - AuthorEM - 199302
UR - PM:0001427500
SO - Nippon Yakurigaku Zasshi 1992 Aug ;100(2):97-107

75
UI - 39
AU - Zimmermann U
AU - Rechlin T
AU - Plaskacewicz GJ
AU - Barocka A
AU - Wildt L
AU - Kaschka WP
AD - Department of Psychiatry, University of Erlangen-Nuremberg, Germany
TI - Effect of naltrexone on weight gain and food craving induced by tricyclic antidepressants and lithium: an open study
MH - Adult
MH - adverse effects
MH - Antidepressive Agents,Tricyclic
MH - Appetite
MH - complications
MH - Depressive Disorder
MH - drug effects
MH - drug therapy
MH - Female
MH - Human
MH - Lithium
MH - Middle Age
MH - Naltrexone
MH - Narcotic Antagonists
MH - pharmacology
MH - Psychiatric Status Rating Scales
MH - psychology
MH - Weight Gain
RP - NOT IN FILE
NT - UI - 97219716LA - EngRN - 0 (Antidepressive Agents, Tricyclic)RN - 0 (Narcotic Antagonists)RN - 16590-41-3 (Naltrexone)RN - 7439-93-2 (Lithium)PT - CLINICAL TRIALPT - JOURNAL ARTICLEDA - 19970529IS - 0006-3223SB - MCY - UNITED STATESJC - A3SEM - 199707
UR - PM:0009067000
SO - Biol Psychiatry 1997 Mar 15 ;41(6):747-749

 

Alexander DeLuca, M.D., FASAM.
Copyright 1999. All rights reserved.                       [Top of Page]
Revised: October 29, 2004.
Dr. DeLuca's Addiction Website