A Neuroendocrinological Hypothesis on Gender Effects of Naltrexone in Relapse Prevention Treatment
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Abstract:
The ability of naltrexone to increase hypothalamo-pituitary-adrenocortical (HPA)-axis activity was recently reported to be associated with its effects on the reduction of craving for alcohol. We now present data showing naltrexone to be more efficacious in female alcoholics. Since HPA-axis might be interpreted as a key mechanism of action that could explain the observed gender differences in the abstinence maintenance treatment of alcohol addiction.Keywords:
Alcohol Dependence
Relapse prevention
The authors administered a five‐item craving questionnaire daily to 86 outpatients to determine whether initial craving scores predicted the likelihood of initiation of abstinence within a 30‐day period. Patients with higher mean craving scores during the first 3 days of the study were less likely to initiate abstinence. However the relationship between craving and abstinence initiation was not linear. Rather, patients in the top quartile of craving scores were significantly less likely to abstain than were patients in the lower three quartiles. The findings suggest that this rapid, easily administered craving questionnaire may have short‐term predictive validity.
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Time-dependent increases in cue-induced nicotine and methamphetamine craving during abstinence were recently reported in human drug-dependent individuals. In the present study, we sought to determine whether this 'incubation of craving' phenomenon also occurs in alcoholics. Four groups of 80 inpatient adult male alcoholics were assessed in a single session (between-group design) for cue-induced alcohol craving at 7, 14, 30 and 60 days of abstinence. Another group that included 19 patients was repeatedly tested for cue-induced alcohol craving at the same abstinence days as above. Other psychological and physiological measures were assessed at the four abstinence timepoints. Cue-induced alcohol craving measured with visual analogue scales was the highest at 60 days of abstinence both between and within groups. However, heart rate, blood pressure and skin conductance responses did not differ between abstinent groups. These results provide evidence of the incubation of alcohol craving in humans, extending previous reports with smokers and methamphetamine addicts.
Cue reactivity
Methamphetamine
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The role of craving for alcohol as a response to alcohol treatment is not well understood. We examined daily diary ratings of craving over the course of 28 days among individuals participating in an inpatient substance abuse treatment program. Participants were alcohol dependent patients (n = 100) in the Hazelden residential treatment program who were offered and agreed to take naltrexone and an age- and gender-matched comparison group (n = 100) of alcohol-dependent patients in the same program who declined the offer of treatment with naltrexone. Changes in craving over time were compared between the two groups. The naltrexone-treated group reported a more rapid decrease in craving than the usual care group. The change in the trajectory of craving is consistent with prior reports suggesting that craving reduction is a mechanism of naltrexone's efficacy in treating alcohol dependence. Providing naltrexone to individuals seeking treatment for alcohol dependence may accelerate a reduction in their craving, consistent with a primary target of many addiction treatment programs. Craving ratings by 100 residential patients taking naltrexone for alcohol dependence were compared to ratings by 100 patients who did not take naltrexone. Craving for alcohol decreased more rapidly in the patients taking naltrexone. Providing naltrexone to individuals seeking treatment for alcohol dependence may accelerate a reduction in craving, which may benefit treatment efforts.
Alcohol Dependence
Relapse prevention
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ABSTRACT Naltrexone blocks the opioid receptors that modulate the release of dopamine in the brain reward system and therefore blocks the rewarding effects of heroin and alcohol. It is generally assumed that naltrexone leads to reduction of craving, but few studies have been performed to prove this. The purpose of the present study was to examine the effect of the administration of naltrexone on craving level after rapid opioid detoxification induced by naltrexone. A naturalistic study was carried out in which patients were followed during 10 months after rapid detoxification. Data about abstinence, relapse, and naltrexone use were collected by means of urine specimens. Craving was measured by the visual analogue scale craving, the Obsessive Compulsive Drug Use Scale, and the Desires for Drug Questionnaire. Results showed that patients who relapsed in opioid use experienced obviously more craving than abstinent people. Patients who took naltrexone did not experience significant less craving than those who did not. These results suggest that the use of opioids is associated with increased craving and that abstinence for opioids is associated with less craving, independent of the use of naltrexone. This is in contrast to the general opinion. Because of the naturalistic design of the study, no firm conclusions can be drawn, but the results grounded the needs of an experimental study.
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Peak provoked craving (PPC) is an alternative approach to cue-induced craving that focuses on the highest craving level experienced during the exposure to drug-related cues. The main objective of this study was to assess the effect of abstinence on PPC in smokers and to determine whether PPC is altered by continuous abstinence. Results showed reductions on PPC levels only 24 hours after achieving abstinence and craving levels remain significantly lower after 7 days of abstinence.
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Rationale
Decreasing withdrawal and craving during smoking cessation is a major aim of cessation medications. Prior studies have shown that Nicotine Replacement Therapy (NRT) decreases withdrawal symptom severity but have relied on retrospective reports and lacked robust measures of baseline symptoms or symptoms during unmedicated abstinence.
Objectives and methods
We tested the effect of high-dose (35 mg) nicotine patch on withdrawal and craving during abstinence using real-time assessment with electronic diaries during ad libitum smoking, a brief period of experimentally directed trial abstinence, and the first 3 days of cessation. Subjects were 324 smokers randomized to high-dose nicotine patches or placebo.
Results
Treatment with active patches reduced withdrawal and craving during cessation and completely eliminated deprivation-related changes in affect or concentration.
Conclusion
High-dose NRT reduces withdrawal symptoms and craving and can eliminate some symptoms entirely.
Nicotine withdrawal
Nicotine patch
Nicotine replacement therapy
Nicotine gum
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Cue reactivity
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Adolescent alcohol use is associated with myriad adverse consequences and contributes to the leading causes of mortality among youth. Despite the magnitude of this public health problem, evidenced-based treatment initiatives for alcohol use disorders in youth remain inadequate. Identifying promising pharmacological approaches may improve treatment options. Naltrexone is an opiate receptor antagonist that is efficacious for reducing drinking in adults by attenuating craving and the rewarding effects of alcohol. Implications of these findings for adolescents are unclear; however, given that randomized trials of naltrexone with youth are non-existent. We conducted a randomized, double-blinded, placebo-controlled cross-over study, comparing naltrexone (50 mg/daily) and placebo in 22 adolescent problem drinkers aged 15-19 years (M = 18.36, standard deviation = 0.95; 12 women). The primary outcome measures were alcohol use, subjective responses to alcohol consumption, and alcohol-cue-elicited craving assessed in the natural environment using ecological momentary assessment methods, and craving and physiological reactivity assessed using standard alcohol cue reactivity procedures. Results showed that naltrexone reduced the likelihood of drinking and heavy drinking (P's ≤ 0.03), blunted craving in the laboratory and in the natural environment (P's ≤ 0.04), and altered subjective responses to alcohol consumption (P's ≤ 0.01). Naltrexone was generally well tolerated by participants. This study provides the first experimentally controlled evidence that naltrexone reduces drinking and craving, and alters subjective responses to alcohol in a sample of adolescent problem drinkers, and suggests larger clinical trials with long-term follow-ups are warranted.
Cue reactivity
Alcohol Dependence
Alcohol use disorder
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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.
Opiate
Heroin dependence
Narcotic antagonists
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The authors administered a five-item craving questionnaire daily to 86 outpatients to determine whether initial craving scores predicted the likelihood of initiation of abstinence within a 30-day period. Patients with higher mean craving scores during the first 3 days of the study were less likely to initiate abstinence. However the relationship between craving and abstinence initiation was not linear. Rather, patients in the top quartile of craving scores were significantly less likely to abstain than were patients in the lower three quartiles. The findings suggest that this rapid, easily administered craving questionnaire may have short-term predictive validity.
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