Alleviate Withdrawal Symptoms Research Articles

Neuroadaptive changes associated with smoking: structural and functional neural changes in nicotine dependence.

Tobacco smoking is the most frequent form of substance abuse. We provide a review of the neuroadaptive changes evidenced in human smokers with regard to the current neurobiological models of addiction. Addiction is thought to result from an interplay between positive and negative reinforcement. Positive reinforcing effects of the drugs are mediated by striatal dopamine release, while negative reinforcement involves the relief of withdrawal symptoms and neurobiological stress systems. In addition, drug-related stimuli are attributed with excessive motivational value and are thought to exert a control on the behavior. This mechanism plays a central role in drug maintenance and relapse. Further neuroadaptive changes associated with chronic use of the drug consist of reduced responses to natural rewards and in the activation of an antireward system, related to neurobiological stress systems. Reduced inhibitory cognitive control is believed to support the development and the maintenance of addiction. The findings observed in human nicotine dependence are generally in line with these models. The current state of the research indicates specific neuroadaptive changes associated with nicotine addiction that need to be further elucidated with regard to their role in the treatment of nicotine dependence.

Nicotine Replacement Therapy Use at Home After Use During a Hospitalization

We assessed whether providing inpatient smokers with nicotine replacement therapy (NRT) to relieve withdrawal symptoms while hospitalized was associated with self-initiated NRT use soon after hospital discharge. We conducted an observational study of 1,895 cigarette smokers admitted to a large hospital over 24 months (July 2007 through June 2009) and seen by a tobacco counselor during hospitalization. Participants were surveyed at 2 weeks after discharge to assess postdischarge NRT use. We calculated adjusted rate ratios (ARRs) for the effect of NRT use in the hospital on the rate of NRT use after discharge, adjusting for gender, age, hospital service, intention to quit, baseline smoking level, length of stay, and counseling duration. 62 percent (1,166/1,895) of enrolled participants received NRT during hospitalization. The survey response rate was 72%. 42 percent (544/1,293) of survey respondents reported initiating postdischarge NRT use within 2 weeks of discharge. NRT use after discharge was more likely to be reported by those who used it in hospital whether they had ever used it prior to hospitalization (ARR: 5.64, 95% CI: 3.95-8.05) or had never used it before (ARR: 4.68, 95% CI: 3.25-6.73). Smokers who received NRT during a hospitalization were more likely to use it after discharge compared with those who did not use NRT in hospital. By encouraging use of this effective cessation aid, supplementing counseling with NRT for hospitalized smokers may promote smoking cessation efforts after discharge.

The Evidence Doesn’t Justify Steps By State Medicaid Programs To Restrict Opioid Addiction Treatment With Buprenorphine

Many state Medicaid programs restrict access to buprenorphine, a prescription medication that relieves withdrawal symptoms for people addicted to heroin or other opiates. The reason is that officials fear that the drug is costlier or less safe than other therapies such as methadone. To find out if this is true, we compared spending, the use of services related to drug-use relapses, and mortality for 33,923 Massachusetts Medicaid beneficiaries receiving either buprenorphine, methadone, drug-free treatment, or no treatment during the period 2003-07. Buprenorphine appears to have significantly expanded access to treatment because the drug can be prescribed by a physician and taken at home compared with methadone, which by law must be administered at an approved clinic. Buprenorphine was associated with more relapse-related services but $1,330 lower mean annual spending than methadone when used for maintenance treatment. Mortality rates were similar for buprenorphine and methadone. By contrast, mortality rates were 75 percent higher among those receiving drug-free treatment, and more than twice as high among those receiving no treatment, compared to those receiving buprenorphine. The evidence does not support rationing buprenorphine to save money or ensure safety.

The effects of galantamine on nicotine withdrawal-induced deficits in contextual fear conditioning in C57BL/6 mice

Current smoking cessation aids are relatively ineffective at maintaining abstinence during withdrawal. Nicotine withdrawal is associated with a variety of symptoms including cognitive deficits and targeting these deficits may be a useful strategy for maintaining abstinence. Galantamine is an acetylcholinesterase inhibitor and allosteric modulator of nicotinic acetylcholine receptors (nAChRs) with cognitive enhancing effects that may alleviate cognitive deficits associated with nicotine withdrawal. The effects of galantamine on nicotine withdrawal-induced deficits in contextual fear conditioning in C57BL/6 mice were examined. An initial acute dose–response experiment revealed that 0.5 and 1 mg/kg galantamine had no effect on fear conditioning. To determine if galantamine would reverse nicotine withdrawal-related deficits in contextual fear conditioning, mice were implanted with osmotic mini-pumps that delivered chronic saline or 6.3 mg/kg/d nicotine for 12 days and then pumps were removed. Training and testing of fear conditioning occurred 24 and 48 h later, respectively. Nicotine withdrawal disrupted contextual fear conditioning, which was reversed with 1 but not 0.5 mg/kg galantamine. Across all conditions in both studies 2 mg/kg galantamine led to high levels of freezing that were likely due to nonspecific effects. The ability of galantamine to reverse nicotine withdrawal-deficits in contextual conditioning is likely mediated through enhanced levels of acetylcholine via inhibition of acetylcholinesterase, potentiation of hippocampal α4β2* nAChRs, or both. The present study suggests that acetylcholinesterase inhibitors and/or drugs that act as allosteric modulators of nAChRs might be targets for smoking cessation aids because they may alleviate withdrawal symptoms such as cognitive deficits that can lead to relapse.

Acceptability and effectiveness for withdrawal symptom relief of a novel oral nicotine delivery device: a randomised crossover trial

Existing nicotine replacement therapies (NRT) improve the chances of smoking cessation but are limited by either relatively slow nicotine absorption rates or unpleasant side effects, leaving scope for the development of more effective and acceptable products. This study aimed to test the acceptability and effectiveness for withdrawal symptom relief of a novel nicotine delivery device, the 'Nicotine Cannon' (NC), compared with three existing, equivalent products: the nicotine lozenge, mini-lozenge and nicotine inhalator. A repeated-measures crossover trial where participants were randomised to one of two conditions (1- or 10-h abstinence) and in each condition to one of 24 possible sequence permutations to test each product for 10 min was carried out. Standard sociodemographic and smoking characteristics were assessed as well as withdrawal and NRT use symptoms before, during and after NRT use and product satisfaction after use. The results were similar across both durations of abstinence. The NC was significantly more effective than the inhalator in reducing withdrawal symptoms (F(3, 196)=3.5, p=0.015) and together with the mini-lozenge performed better than other NRT in alleviating urges to smoke (F(3, 563)=9.6, p<0.001) and desire for cigarettes within 10 min of use (F(3, 727)=26.1, p<0.001). The NC induced fewer adverse side effects than other NRT and was judged to be more enjoyable (F(3, 87)=13.56, p<0.001) and satisfying to use (F(3, 92)=12.35, p<0.001). The 'Nicotine Cannon' is at least as effective as equivalent NRT in reducing withdrawal symptoms and more acceptable to users, suggesting that it would be a useful addition to existing NRT. The acceptability profile could make it particularly useful as a 'harm reduction' tool.

Methylphenidate for treating tobacco dependence in non-attention deficit hyperactivity disorder smokers: A pilot randomized placebo-controlled trial

BackgroundMethylphenidate blocks the re-uptake of dopamine by binding to the dopamine transporter in the presynaptic cell membrane and increases extracellular dopamine levels. Similarities in neuropsychologic effects between nicotine and methylphenidate make it an intriguing potential therapeutic option. Previous research of methylphenidate in smokers has suggested a possible beneficial effect for the relief of nicotine withdrawal symptoms, but showed no efficacy in helping smokers with attention deficit hyperactivity disorder (ADHD) to stop smoking.MethodsTo investigate potential efficacy for relieving nicotine withdrawal symptoms and promoting smoking abstinence, we conducted a randomized, double-blind, placebo-controlled, phase II study of once-a-day osmotic-release oral system methylphenidate (OROS-MPH, Concerta®) at a target dose of 54-mg/day for 8 weeks compared with placebo in 80 adult cigarette smokers.ResultsOf the 80 randomized subjects and median smoking rate was 20 cigarettes per day. At the end of the medication phase, the biochemically confirmed 7-day point prevalence smoking abstinence was 10% (4/40) for the placebo group and 2.5% (1/40) for the OROS-MPH group.Nicotine withdrawal was not found to differ significantly between treatment groups during the first 14 days following the start of medication prior to the target quit date (p = 0.464) or during the first 14 days following the target quit date (p = 0.786).ConclusionWe observed no evidence of efficacy of OROS-MPH to aid smokers to stop smoking. Although there are biologically plausible hypotheses that support the use of OROS-MPH for treating tobacco dependence, we found no evidence to support such hypotheses. In addition to no increase in smoking abstinence, we saw no effect of OROS-MPH for tobacco withdrawal symptom relief and no change in smoking rates was observed in the OROS-MPH group compared to the placebo group.

Sodium oxybate in maintaining alcohol abstinence in alcoholic patients with and without psychiatric comorbidity

Sodium oxybate (SMO) is a GABA-ergic drug currently used for the treatment of alcohol-dependence in some European countries. In particular, clinical studies have shown a role of SMO in promoting alcohol abstinence, as well as in relieving withdrawal symptoms. The aim of this study was to describe alcohol abstinence and the onset of craving for and abuse of SMO in alcohol-dependent subjects with and without psychiatric co-morbidity. Forty-eight patients were enrolled and classified into two groups: group A (20 alcoholics without any psychiatric co-morbidity) and group B (28 alcoholics with a psychiatric co-morbidity). All patients were treated with oral SMO (50 mg/kg of body weight t.i.d.) for 12 weeks. Alcohol abstinence as well as alcohol drinking during the 12 weeks of treatment did not differ between the two groups at the end of treatment (p = 0.9). In addition, a reduction of alcohol intake in both groups has been observed (p < 0.0001). On the other hand, craving for SMO was significantly more frequent in group B than group A (p = 0.001). Cases of SMO abuse were observed in almost 10% of group B patients. In conclusion, alcohol abstinence achieved through SMO administration does not differ in patients with and without psychiatric co-morbidity. However, alcoholics with co-morbid borderline disorders appear to be at high risk of developing craving for and abuse of the drug; therefore, SMO may not be indicated in these patients.

Auricular Acupressure for Smoking Cessation: A Pilot Randomized Controlled Trial

Abstract Background: Many health hazards are related to smoking. Patients who wish to stop smoking often need assistance. Objective: To determine the effectiveness of auricular acupressure for smoking cessation and for the relief of withdrawal symptoms in habitual smokers. Design, Setting, Intervention, and Participants: A prospective, randomized, sham-controlled trial using auricular acupressure was conducted from November 2007 to March 2009 in 70 active smokers in Hong Kong. The active group (n = 38) used Shenmen, Lung, Mouth, and Brain acupoints for 3 weeks. The sham group (n = 32) used non-meridian points. The selected acupoints were stimulated with small hard beads fixed in place with adhesive tape. The enrolled participants were then followed up weekly for 3 weeks and for 3 months after acupressure treatment. Main Outcome Measures: Individual daily cigarette consumption, expiration test for carbon monoxide content, and cigarette withdrawal symptom scores were recorded. Results: At the end of the tre...

Brain β2*-nicotinic acetylcholine receptor occupancy after use of a nicotine inhaler

The Nicotrol® (Pfizer, USA) nicotine inhaler reduces craving by mimicking the behavioural component of cigarettes and delivering controlled doses of nicotine, which binds to the beta-2 subunit-containing nicotinic acetylcholine receptors (β2*-nAChRs). Previous studies examined β2*-nAChR occupancy after administration of regular and low-nicotine cigarettes. Here, we measured occupancy of β2*-nAChRs after administration of nicotine via inhaler, and the relationship between occupancy and changes in craving for tobacco smoking and withdrawal symptoms. Tobacco smokers participated in [123I]5-IA-85380 SPECT studies with either a nicotine inhaler (n=9) or tobacco cigarette (n=4) challenge. [123I]5-IA was administered as a bolus plus constant infusion. After equilibrium was achieved, three 30-min baseline scans were collected, and subjects either used the nicotine inhaler or a regular cigarette, and up to six additional scans were obtained. Receptor occupancy was determined based on the Lassen plot method. Craving for tobacco smoking and withdrawal symptoms were evaluated pre- and post-challenge. Use of the nicotine inhaler produced an average 55.9±6.4% occupancy of β2*-nAChRs 2-5 h post-challenge, whereas use of a cigarette produced significantly higher receptor occupancy (F=10.6, p=0.009) with an average 67.6±14.1% occupancy 1.5-5 h post-challenge. There was a significant decrease in withdrawal symptoms post-nicotine inhaler use (F=6.13, p=0.04). These results demonstrate significant differences in occupancy of β2*-nAChRs by nicotine after use of the inhaler vs. a cigarette and confirm the ability of the nicotine inhaler to relieve withdrawal symptoms.

Cannabis withdrawal symptoms in non-treatment-seeking adult cannabis smokers

Background Cannabis withdrawal is not recognized in DSM-IV because of doubts about its clinical significance. Objectives Assess the phenomenon of cannabis withdrawal and its relationship to relapse in non-treatment-seeking adults. Subjects Convenience sample of 469 adult cannabis smokers who had made a quit attempt while not in a controlled environment. Methods Subjects completed a 176-item Marijuana Quit Questionnaire collecting information on sociodemographic characteristics, cannabis use history, and their “most difficult” cannabis quit attempt. Results 42.4% of subjects had experienced a lifetime withdrawal syndrome, of whom 70.4% reported using cannabis in response to withdrawal. During the index quit attempt, 95.5% of subjects reported ≥1 individual withdrawal symptom (mean [SD] 9.5 [6.1], median 9.0); 43.1% reported ≥10. Number of withdrawal symptoms was significantly associated with greater frequency and amount of cannabis use, but symptoms occurred even in those using less than weekly. Symptoms were usually of ≥ moderate intensity and often prompted actions to relieve them. Alcohol (41.5%) and tobacco (48.2%) were used more often than cannabis (33.3%) for this purpose. There was little change during withdrawal in use of other legal or illegal substances. Conclusions Cannabis withdrawal is a common syndrome among adults not seeking treatment. The intention to relieve withdrawal symptoms can drive relapse during quit attempts, giving cannabis withdrawal clinical significance as a target of treatment.

Non Smoking for Successful Aging: Therapeutic Perspectives

The smoke of cigarettes represents an important accelerator of the aging process, and there is no doubt that smoke is an important risk factor for many diseases, in particular for cardiovascular, neoplastic and respiratory diseases. Smoking plays an important role also in the development of other pathological conditions being particularly frequent in geriatric ages, such as dementia, osteoporosis, diabetes, erectile dysfunction, senile macular degeneration, nuclear cataract and alterations of skin. This means that smoke compromises not only life expectancy, but also the quality of the life, favoring the occurrence of non-autonomy. Non-smokers have a much higher life expectancy than smokers, and the suspension of smoking is accompanied, even in the elderly, by an increase in the survival time due to the reduction of smoke-induced biological damage. The first requirement of stopping smoking certainly is the motivation of the smoker himself to do this, since without this motivation any attempt is futile. Today numerous quitting strategies exist, either of pharmacological or non-pharmacological type, which are also advantageous for the elderly person. Approved pharmacological treatments include nicotine replacement therapies, bupropion, drugs targeting cannabinoid receptors and newer pharmacological approaches including the selective nicotinic partial agonists. Varenicline, an alpha4 beta2 nicotinic acetylcoline receptor partial agonist, is the most recently agent approved for smoking cessation. This drug works by reducing the strength of the smoker's urge to smoke and by relieving withdrawal symptoms. The most effective smoking cessation programs involve a combination of pharmacotherapy and behavioural and/or cognitive counselling to improve abstinence rates.

A narrative review on the management of medication overuse headache: the steep road from experience to evidence

The management of medication overuse headache (MOH) is based essentially on the withdrawal of the overused drug(s). Drug withdrawal is performed according to widely differing protocols, both within and across countries; therefore, therapeutic recommendations for the acute phase of detoxification vary considerably among studies. Basically, the aims of MOH management are: (a) to withdraw the overused drug(s); (b) to alleviate withdrawal symptoms by means of a bridge therapy, which includes pharmacological and non-pharmacological support, designed to help the patient to tolerate the withdrawal process; (c) to prevent relapse. Today, there is extensive debate over the best strategies for achieving these goals and the different aspects of this debate are discussed in this review. The authors searched for the best available evidence relating to the following questions: should medication withdrawal be abrupt or gradual? Should patients receive replacement therapy? What are the most effective therapeutic programmes for controlling withdrawal symptoms? Should replacement therapy be administered routinely or as rescue therapy? Should preventive treatment be started before, during or after withdrawal? What are the most effective preventive treatments? Should patients be managed through inpatient or outpatient withdrawal programmes? What is the best approach to adopt in preventing relapses? Treatment of MOH is a difficult challenge, but may be very rewarding. Although there is still a lack of high-quality studies providing evidence-based answers to the many specific questions it raises, neurologists need to know that the combination of education with a rational use of selected therapeutic strategies may be beneficial to people with chronic headache and help to relieve their suffering.

α2-Receptor Agonists for Treatment and Prevention of Iatrogenic Opioid Abstinence Syndrome in Critically Ill Patients

To review the literature regarding the use of alpha(2)-agonists in the treatment and prevention of iatrogenic opioid abstinence syndrome (IOAS) in critically ill patients. Primary literature was identified through a search of MEDLINE (1950-June 2009), EMBASE (1988-June 2009), International Pharmaceutical Abstracts (1970-June 2009), and the Cochrane Library (1996-June 2009), using the names of individual alpha(2)-agonists and the following key words: children, opioid withdrawal, opioid, and adult. Relevant abstracts from the Society of Critical Care Medicine, reference citations from selected articles, and manufacturers' product information were also reviewed. All English-language articles identified from the data sources were evaluated. Three retrospective studies and 6 case reports/series representing 44 patients were included for analysis. Central alpha(2)-agonists are thought to minimize symptoms of IOAS by decreasing presynaptic outflow of catecholamines. Successful use of clonidine and dexmedetomidine for management of IOAS has been reported. Lofexidine, an alpha(2)-agonist not yet approved in the US, may offer similar withdrawal symptom relief but has yet to be studied in the intensive care setting. Although the quality of studies identified was limited, preliminary evidence does provide some support for the use of transdermal clonidine and injectable dexmedetomidine in the treatment and prevention of IOAS. These agents were shown to facilitate discontinuation of opioids and to minimize withdrawal symptoms with few reported adverse events. Central alpha(2)-agonists appear to be effective and safe second-line agents for treatment and prevention of IOAS. Further studies should be conducted to determine their role in the therapy of patients with IOAS.

Incarceration and Opioid Withdrawal: The Experiences of Methadone Patients and Out-of-Treatment Heroin Users

Both heroin-addicted individuals and methadone maintenance patients are likely to face untreated opioid withdrawal while incarcerated. Limited research exists concerning the withdrawal experiences of addicted inmates and their impact on individuals' attitudes and plans concerning drug abuse treatment. In the present study, 53 opioid dependent adults (32 in methadone treatment and 21 out of treatment) were interviewed in an ethnographic investigation of withdrawal experiences during incarceration. When treatment for opioid withdrawal was unavailable, detoxification experiences were usually described as negative and were often associated with a variety of unhealthy behaviors designed to relieve withdrawal symptoms. Negative methadone withdrawal experiences also negatively influenced participants' receptivity to seeking methadone treatment upon release. A minority of participants took a positive view of their withdrawal experience and saw it as an opportunity to detox from heroin or discontinue methadone. Findings support the importance of providing appropriate opioid detoxification and/or maintenance therapy to opioid-dependent inmates.

Smoking Cessation with Varenicline: A Suicidal Fatality

The most effective smoking cessation programs involve a combination of pharmacotherapy and behavioral and/or cognitive counseling to improve abstinence rates. Varenicline (Champix in France and the U.K.), the most recently approved agent for tobacco cessation, is the first drug in a new class (alpha4beta2 partial agonist) that binds to the nicotinic receptors to release dopamine and alleviate withdrawal symptoms. As the literature reports psychiatric disorders being linked to varenicline as an issue, we describe the case of a man who committed suicide while receiving therapy with this drug. The deceased (a 39-year-old man) was found dead at his home address with slash wounds to his wrist. The deceased had been prescribed varenicline for several months at a dose of 1 tablet (1 mg) twice daily. The lab received a blood specimen to perform a screening for unknown drugs, including varenicline. Because of its selectivity and sensitivity, liquid chromatography coupled to tandem mass spectrometry was chosen as the best approach to develop a procedure for varenicline. One milliliter of blood was extracted with 5 mL of a mixture of dichloromethane/isopropanol/n-heptane (25:10:65) at pH 9.5 (phosphate buffer) in the presence of diazepam-d(5), which was used as an internal standard (IS). The resultant blood extract was separated on an XTerra MS C18 column using a gradient of acetonitrile and formic acid in water. Drugs were identified by three or two transitions (m/z 212 > 169, 212 > 183, and 212 > 195 and 290 > 154 and 290 > 198 for varenicline and IS, respectively). The limit of quantitation of varenicline was 1 ng/mL. The concentration of varenicline in the blood was determined to be 10 ng/mL. This concentration could not be compared with therapeutic levels, as there are no therapeutic concentrations reported in the literature. Because of its potential effects on behavior, the influence of the drug on the mental functioning of the user should be considered in cases of suicide.

Caffeine reinforces flavor preference and behavior in moderate users but not in low caffeine users

The study examined the role of caffeine consumption in caffeine reinforcement. Previous findings have shown that caffeine reinforced flavor preference in moderate caffeine consumers who are caffeine deprived. However, most of these studies have employed rating procedures only, and have not shown the effectiveness of caffeine to reinforce behaviors other than through subjective ratings. Twenty-five participants (15 low caffeine consumers, and 10 moderate caffeine consumers) were each given three exposures to a caffeinated drink, and three exposures to a non-caffeinated drink. Each drink was associated with a particular color. At each session, they were asked to rate the pleasantness of the drink, and choose from distinctively colored sweets. The results showed an increase in the rating of pleasantness for the caffeinated drink in moderate caffeine consumers, but a decrease in rated pleasantness for low caffeine consumers. The opposite effect was seen for the non-caffeinated drink. There was an increase in consumption of the number of sweets with the same color as that of the caffeine-paired drink in the moderate caffeine consumers. These findings suggest that caffeine may serve as a negative reinforcer, and that the alleviation of withdrawal symptoms may be associated with the flavor and appearance of the caffeinated drink.

Cannabis reinforcement and dependence: role of the cannabinoid CB1 receptor.

Awareness of cannabis dependence as a clinically relevant issue has grown in recent years. Clinical and laboratory studies demonstrate that chronic marijuana smokers can experience withdrawal symptoms upon cessation of marijuana smoking and have difficulty abstaining from marijuana use. This paper will review data implicating the cannabinoid CB1 receptor in regulating the behavioral effects of Delta(9)-tetrahydrocannobinol (THC), the primary psychoactive component of cannabis, across a range of species. The behavioral effects that will be discussed include those that directly contribute to the maintenance of chronic marijuana smoking, such as reward, subjective effects, and the positive and negative reinforcing effects of marijuana, THC and synthetic cannabinoids. The role of the CB1 receptor in the development of marijuana dependence and expression of withdrawal will also be discussed. Lastly, treatment options that may alleviate withdrawal symptoms and promote marijuana abstinence will be considered.

Treatment of Tobacco Dependence

Cigarette smoking continues to cause substantial death and disability, but more than 1 in 5 adults smoke despite the desire among most smokers to stop and the availability of effective treatments. A systematic process to identify all smokers is crucial. Because tobacco dependence is characterized by relapses and remissions, clinicians should be ready to engage smokers and reengage relapsed smokers with options for new medication strategies and additional counseling resources.

Venlafaxine for Acute Heroin Detoxification

Dissatisfaction with current available heroin detoxification regimens has led to the search for alternatives. Evidences have shown that several neurotransmission systems, including serotonin, are involved in opioid withdrawal. This study investigated the efficacy and tolerability of venlafaxine, a serotonin-norepinephrine reuptake inhibitor, in managing heroin withdrawal symptoms. This was a randomized, double-blind, and placebo-controlled 7-day trial. Thirty-four heroin-dependent inpatients seeking detoxification were enrolled and assigned to either the venlafaxine (n = 15) or the placebo group (n = 19). The subjects received either venlafaxine 300 mg/d or placebo as their treatment regimen. Outcome measures were Objective Opioid Withdrawal Scale, total sleeping time, visual analog scale for subjective withdrawal severity, Clinical Global Impression scores on discharge, patient's impression of treatment, and amount of ancillary medications used. Data of outcome measures were analyzed by generalized estimating equation model. We analyzed the data from 20 subjects (8 in venlafaxine group and 12 in placebo group) who remained in the study after the fifth day of the trial. Objective Opioid Withdrawal Scale, visual analog scale, and total sleeping time demonstrated a significant efficacy of venlafaxine compared with the placebo group (P < 0.0001, P = 0.0195, and P < 0.0001, respectively). There was no difference in Clinical Global Impression and patient's impression of treatment between the 2 groups, although the placebo group needed more ancillary medications. Despite the small sample size, this study showed that venlafaxine is effective in alleviating withdrawal symptoms of heroin with good tolerability and safety.

Clinical Pharmacology of Nicotine: Implications for Understanding, Preventing, and Treating Tobacco Addiction

Understanding the basic and clinical pharmacology of nicotine provides a basis for improved prevention and treatment of tobacco addiction. Nicotine acts on nicotinic cholinergic receptors in the brain to release dopamine and other neurotransmitters that sustain addiction. Neuroadaptation and tolerance involve changes in both nicotinic receptors and neural plasticity. Nicotine addiction can occur in the context of physical dependence characterized by self-medication to modulate negative affect and/or to relieve withdrawal symptoms, as well as, in light or occasional smokers, primarily for positive reinforcement in specific situations. Nicotine is metabolized primarily by CYP2A6. Its clearance exhibits considerable individual variability that is determined by genetic, racial, and hormonal (sex) factors. Genetically slow metabolism of nicotine appears to be associated with a lower level of dependence. Nicotine dependence is highly heritable and appears to be influenced by genes coding for some nicotine receptor subtypes, some neurotransmitter genes, and genes involved in neural connectivity. Novel pharmacotherapies for nicotine dependence include partial agonists for nicotinic receptors and nicotine vaccines. Pharmacogenetic studies suggest various candidate genes and a nicotine metabolism phenotype that influence outcome. Human pharmacology studies of nicotine and smoking behavior also provide a basis for assessing the benefits and risks of long-term nicotine use for harm reduction and for a potential cigarette regulatory strategy that includes reducing nicotine content of cigarettes to nonaddictive levels.