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Background and objectives Substance use disorder (SUD) includes maladaptive patterns of substance use despite negative consequences. Previous structural neuroimaging studies showed some structural alterations in SUD, but it remains unknown whether these alterations are specifically associated with SUD or common comorbidities. This study attempts to validate the findings of structural differences between SUD, healthy controls (HC), and psychiatric controls (PC). Methods We used HC (N = 86) matched for demographics, and PC (N = 86) matched for demographics and psychiatric diagnoses to a group of SUD patients (N = 86). We assessed the group differences of subcortical volumes, cortical volumes, thickness, and surface areas between SUD and HC. We then analyzed the group differences between SUD and PC within regions showing differences between SUD and HC. Results SUD had smaller left nucleus accumbens, right thalamus, right hippocampus, left caudal anterior cingulate cortex (ACC) volume, and larger right caudal ACC volume, and right caudal ACC, right caudal middle frontal gyrus (MFG), and right posterior cingulate cortex (PCC) surface than HC. Increased right caudal ACC volume and right PCC surface in SUD were the only findings when compared with PC. Several areas showed thickness alterations between SUD and HC, but none survived multiple comparisons vs PC. Discussion and conclusions Our findings suggest that cingulate structures may be altered in SUD compared with both HC and PC. Scientific significance These results are among the first to indicate that some structural alterations may be SUD-specific, and highlight a cautionary note about using HC in psychiatric biomarker research. (Am J Addict 2020;00:00-00).

The gut microbiota has recently gained attention as a possible modulator of brain activity. A number of reports suggest that the microbiota may be associated with neuropsychiatric conditions such as major depressive disorder, autism and anxiety. The gut microbiota is thought to influence the brain via vagus nerve signalling, among other possible mechanisms. The insula processes and integrates these vagal signals. To determine if microbiota diversity and structure modulate brain activity, we collected faecal samples and examined insular function using resting state functional connectivity (RSFC). Thirty healthy participants (non-smokers, tobacco smokers and electronic cigarette users, n = 10 each) were studied. We found that the RSFC between the insula and several regions (frontal pole left, lateral occipital cortex right, lingual gyrus right and cerebellum 4, 5 and vermis 9) were associated with bacterial microbiota diversity and structure. In addition, two specific bacteria genera, Prevotella and Bacteroides, were specifically different in tobacco smokers and also associated with insular connectivity. In conclusion, we show that insular connectivity is associated with microbiome diversity, structure and at least two specific bateria genera. Furthemore, this association is potentially modulated by tobacco smoking, although the sample sizes for the different smoking groups were small and this result needs validation in a larger cohort. While replication is necessary, the microbiota is a readily accessible therapeutic target for modulating insular connectivity, which has previously been shown to be abnormal in anxiety and tobacco use disorders.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic and control measures may have increased the risk of abusing addictive substances as well as addictive behaviors. METHODS: We present an initial online survey in 6416 Chinese about the relation between the COVID-19 pandemic and addictive behavior in China. RESULTS: During the COVID-19 pandemic, 46.8% of the subjects reported increased dependence on internet use, and 16.6% had longer hours of internet use. The prevalence (4.3%) of severe internet dependence rose up to 23% than that (3.5%) before the COVID-19 pandemic occurred, and their dependence degree rose 20 times more often than being declined (60% vs 3%). Relapses to abuse from alcohol and smoking abstinence were relatively common at 19% and 25%, respectively. Similarly, 32% of regular alcohol drinkers and 20% of regular smokers increased their usage amount during the pandemic. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: These three coping behaviors (internet, alcohol, and smoking) during this COVID-19-related crisis appear to have increased the risk for substance use disorders and internet addiction. (Am J Addict 2020;00:00-00).

Background and objectives The opioid crisis has taken an immense toll in the United States. On average, five lives are lost to an opioid overdose every hour of the day; estimated costs associated with opioid misuse exceed $500 billion annually. Illicit opioid discontinuation is the first step in the treatment of opioid use disorder (OUD), and transition to an opioid agonist may initiate treatment. However, discontinuation to abstinence from either OUD directly or following agonist treatment results in severely distressing opioid withdrawal symptoms (OWS). Methods This review evaluated studies on the etiology, burden, and management of OWS. Results Noradrenergic hyperactivity generates many OWS. These OWS can cause patients to relapse during early opioid discontinuation. While agonist therapies are generally first-line for moderate or severe OUD and reduce OWS, prescribing restrictions can limit their availability. Discussion and conclusions Non-opioid medications to treat OWS provides a gateway into long-term treatment with naltrexone or psychosocial therapies. For opioid dependent patients without OUD, non-opioid treatments like α-2 adrenergic agonists can facilitate opioid tapering. Scientific significance For the millions who are physically dependent on opioids, new treatments for OWS can enhance recovery from OUD and prevent relapse. (© 2019 The Authors. The American Journal on Addictions Published by Wiley Periodicals, Inc.;XX:1-8).

BACKGROUND AND OBJECTIVE Methamphetamine (MA) substance use disorder (SUD) does not have an efficacious pharmacotherapy. We developed a MA vaccine and investigated its potential to attenuate MA induced responses. METHODS We examined a novel adjuvant, E6020, a Toll-like receptor-4 (TLR-4) agonist combined with tetanus-toxoid conjugated to succinyl-methamphetamine (TT-SMA) adsorbed on aluminum hydroxide (alum). Adult BALB/c female mice received the vaccine and booster injections at weeks 0, 3, and 6. The efficacy of the vaccine was assessed by the level and affinity of anti-MA antibodies elicited, its ability to attenuate MA induced locomotor activation and its reduction in the amount of MA entering the brains of vaccinated mice. RESULTS The TT-SMA vaccine containing alum and E6020 adjuvant produced anti-MA antibodies with nanomolar affinities and showed threefold greater peak titer levels than without E6020 (700 vs 250 μg/ml). These antibodies significantly decreased MA-induced locomotor activation (p

BACKGROUND AND OBJECTIVES The core pharmacological treatment of Post-Traumatic Stress Disorder (PTSD) is selective serotonin reuptake inhibitors (SSRIs), although remission is only around 30% with them. Many patients will self-treat with opioids and due to the opiate system involvement in dysphoric mood and anxiety/stress responses, it is likely that antagonism of the kappa opioid receptor (KOR) system represents a potential target for treatment of PTSD. The aim of this study is to compare response of PTSD symptoms when antagonizing KOR via buprenorphine/naloxone compared to SSRIs or opioid therapy. METHODS A retrospective chart review of patients in the MEDVAMC between June 1, 2010 and June 30, 2016 was conducted. Inclusion criteria included patients with a documented diagnosis of PTSD with at least two documented PTSD scores (either PCLC or PC-PTSD). Exclusion criteria included patients not prescribed one of the study medications (ie, buprenorphine, SSRI, or opiate for chronic pain), and patients not on the study medication for at least 30 days. RESULTS Buprenorphine patients exhibited the lowest final average PTSD score (2.47) and the largest change from baseline (-24.0%) compared to opioids (-16.1%) or SSRIs (1.16%). The average buprenorphine dose was 23.3 mg/day, and the average length of therapy was 860 days. CONCLUSIONS Buprenorphine may help decrease PTSD symptoms more than SSRIs or opioids alone. Prospective studies are needed to determine whether these effects are reproducible. SCIENTIFIC SIGNIFICANCE Pharmacotherapy advancements in PTSD treatment have been limited and the kappa opioid receptor system presents a new target that warrants further research. (Am J Addict 2019;XX:1-6).

BACKGROUND AND OBJECTIVES The endogenous cannabinoid anandamide (AEA), an agonist at type-1 cannabinoid (CB1) receptors, is metabolized by fatty acid amide hydrolase (FAAH). The common variant rs324420 C->A within the FAAH gene on chromosome 1 codes for a missense substitution (Pro129Thr), resulting in decreased FAAH activity and increased endocannabinoid potentiation. This FAAH variant has been linked to alterations in mood and stress reactivity, as well as being independently linked to increased risk for addiction. We hypothesized that cocaine use disordered (CUD) participants with the FAAH Pro129 Thr variant would exhibit a distinct profile of cocaine-induced subjective effects in the laboratory. METHODS A total of 70 CUD participants received intravenous doses of saline (placebo, 0 mg) and cocaine (20, 40 mg) in a lab-controlled setting and rated 10 subjective effect measures prior to and following saline and cocaine administration, using a Visual Analog Scale (VAS). RESULTS The variant allele was associated with increased cocaine-induced subjective ratings for "Drug Effect," "High," and "Depressed." The prevalence of the variant allele A and the AA genotypes were greater in our CUD group than in the general population (A allele: 47% vs. 34%; AA genotype: 30% vs. 13%; p

Background and objectives Opioid use disorder (OUD) is a chronic condition with potentially severe health and social consequences. Many who develop moderate to severe OUD will repeatedly seek treatment or interact with medical care via emergency department visits or hospitalizations. Thus, there is an urgent need to develop feasible and effective approaches to help persons with OUD achieve and maintain abstinence from opioids. Treatment that includes one of the three FDA-approved medications is an evidence-based strategy to manage OUD. The purpose of this review is to address practices for managing persons with moderate to severe OUD with a focus on opioid withdrawal and naltrexone-based relapse-prevention treatment. Methods Literature available on PubMed was used to review the evolution of treatment strategies from the 1960s onward to manage opioid withdrawal and initiate treatment with naltrexone. Results Emerging practices for extended-release naltrexone induction include the use of agonist tapers and adjuvant medications. Clinical challenges frequently encountered when initiating this therapy include managing withdrawal and ongoing opioid use during treatment. Clinical factors may inform decisions regarding patient selection and length of naltrexone treatment, such as recent opioid use and patient preferences. Conclusions and scientific significance Treatment strategies to manage opioid withdrawal have evolved, but many patients with OUD do not receive medication for the prevention of relapse. Clinical strategies for induction onto extended-release naltrexone are now available and can be safely and effectively implemented in specialty and select primary care settings. (© 2018 The Authors. The American Journal on Addictions Published by Wiley Periodicals, Inc. on behalf of The American Academy of Addiction Psychiatry (AAAP);27:177-187).

Background and Objectives Moderators of treatment response to serotonin reuptake inhibitor sertraline (SRT) for cocaine dependence were assessed in two randomized, double blind, placebo-controlled clinical trials. Methods Generalized estimating equation modeling was performed on data from cocaine-dependent volunteers randomized to receive SRT or placebo (N = 126) who completed >2-week drug-free residential portions of the 12-week trials, in which subsequent outpatient treatment (weeks 3–12) included weekly cognitive behavioral therapy and thrice-weekly supervised urine toxicology. Primary Outcome Measure: Relapse (2 consecutive cocaine-positive or missing urines) following residential stay. Potential moderators included treatment, sex, age, race, depression measures, baseline cocaine urine result, and alcohol dependence diagnosis (ADDx). Results Odds ratios (OR) for relapse showed placebo-treated participants were significantly more likely to relapse than SRT participants. Regardless of treatment condition, participants more likely to relapse were male, and those with lower Hamilton depression ratings, or baseline cocaine-negative urines. Older subjects or those with current ADDx had higher relapse risk than those without ADDx; however, treating older or ADDx participants with SRT reduced cocaine relapse more than placebo. Discussion and Conclusions Women or those with more severe cocaine use or depressive symptoms may have fewer cocaine relapses regardless of medication treatment. SRT at 200 mg reduced cocaine relapse more than placebo, especially in older participants or in those with comorbid ADDx. Scientific Significance SRT may be efficacious to support relapse prevention among cocaine-dependent patients in the context of brief residential followed by outpatient treatment, especially in older participants or those with comorbid alcohol/cocaine dependence. (Am J Addict 2017;XX:1–8)

Background and objectives Opioid use disorder (OUD) is a chronic disorder with relapse based on both desire for reinforcement (craving) and avoidance of withdrawal. The aversive aspect of dependence and relapse has been associated with a small brain structure called the habenula, which expresses large numbers of both opioid and nicotinic receptors. Additionally, opioid withdrawal symptoms can be induced in opioid-treated rodents by blocking not only opioid, but also nicotinic receptors. This receptor co-localization and cross-induction of withdrawal therefore might lead to genetic variation in the nicotinic receptor influencing development of human opioid dependence through its impact on the aversive components of opioid dependence. Methods We studied habenular resting state functional connectivity with related brain structures, specifically the striatum. We compared abstinent psychiatric patients who use opioids (N = 51) to psychiatric patients who do not (N = 254) to identify an endophenotype of opioid use that focused on withdrawal avoidance and aversion rather than the more commonly examined craving aspects of relapse. Results We found that habenula-striatal connectivity was stronger in opioid-using patients. Increased habenula-striatum connectivity was observed in opioid-using patients with the low risk rs16969968 GG genotype, but not in patients carrying the high risk AG or AA genotypes. Conclusions We propose that increased habenula-striatum functional connectivity may be modulated by the nicotinic receptor variant rs16969968 and may lead to increased opioid use. Scientific significance Our data uncovered a promising brain target for development of novel anti-addiction therapies and may help the development of personalized therapies against opioid abuse. (Am J Addict 2017;26:751-759).

Background and Objectives Driving while intoxicated (DWI) represents an area of grave concern in China, yet little research has focused on it or on the personality traits and psychiatric disorders among these drivers. Methods We enrolled 325 of 382 residents charged with DWI in a compulsory detention center in Beijing, China. And 351 male drivers who had never had any alcohol arrests as control participants. All were screened for Axis I disorders using the Chinese version of the Structured Clinical Interview for the Diagnostic Statistical Manual of Mental Disorders IV-TR (SCID), the Minnesota Multiphasic Personality Inventory (MMPI-2), and the Sixteen Personality Factor Questionnaire (16PF). Results The subjects were all males with a mean (±SD) age of 34.41 ± 8.48 years, and almost 30% met DSM-IV criteria for alcohol abuse or dependence (n = 92). Compared to normal controls they showed greater Social Boldness, Abstractedness, Apprehension, Liveliness and Tension, and poorer Reasoning, Vigilance, Openness to Change, and Self-reliance. On the MMPI-2, DWI subjects showed greater Hypochondriasis, Psychopathic Deviate, Paranoia, Psychasthenia, Schizophrenia and Hypomania; and lower Social introversion. Conclusions and Scientific Significance Severe alcohol problems are more common in Beijing's drunk drivers than in the Chinese general population. These DWI drivers also have a broad variety of traits that increase their tendency to be venturesome and socially bold while enjoying excitement and risk-taking. (Am J Addict 2017;XX:1–5)

Background and Objectives Tobacco use is a significant public health issue on a global scale. Prevalence of daily tobacco smoking for men in China is much higher than in the United States. Although prevailing literature suggests a negative relationship between smoking and quality of life, this pilot study sought to evaluate whether smoking reduction/cessation impacted on the perception of quality of life in an in-patient population in China. Methods Twenty Chinese patients meeting DSM-IV criteria for schizophrenia were recruited from Beijing Hui-Long-Guan Hospital, an in-patient facility in Beijing, China, for participation in this 4-week study. Seventeen participants with schizophrenia completed the study and were included in the final analysis. Cigarette consumption was recorded daily and the World Health Organization Quality of Life-BREF (WHOQOL-BREF) was completed at baseline and at week 4. The relationships between smoking and perceived quality of life were evaluated using correlations between changes in WHOQOL-BREF and changes in cigarettes consumed as measured from baseline to week 4. Results We found an increase in perceived quality of life in the social relationships domain with increased cigarette consumption in contrast to a decrease in this domain with decreased consumption. However, decreased cigarette consumption was associated with an increase in the psychological domain compared to the social domain. Conclusions and Scientific Significance These associations suggest a need for interventions to improve the social relationship perceptions with any successful reduction in cigarette consumption among Chinese schizophrenics in order to match their perceived psychological improvement. (Am J Addict 2016;25:86–90)

BACKGROUND AND OBJECTIVES: Post-traumatic Stress Disorder (PTSD) and substance use disorders (SUD) frequently co-occur, and their combination can increase poor health outcomes as well as mortality. METHODS: Using PUBMED and the list of references from key publications, this review article covered the epidemiology, neurobiology and pharmacotherapy of PTSD with comorbid alcohol, opiate, and cannabis use disorders. These SUD represent two with and one without FDA approved pharmacotherapies. RESULTS: SUD is two to three times more likely among individuals with lifetime PTSD, and suicide, which is made more likely by both of these disorders, appears to be additively increased by having this comorbidity of SUD and PTSD. The shared neurobiological features of these two illnesses include amygdalar hyperactivity with hippocampal, medial prefrontal and anterior cingulate cortex dysfunction. Medications for comorbid PTSD and SUD include the PTSD treatment sertraline, often used in combination with anticonvulsants, antipsychotics, and adrenergic blockers. When PTSD is comorbid with alcohol use disorder (AUD), naltrexone, acamprosate or disulfiram may be combined with PTSD treatments. Disulfiram alone may treat both PTSD and AUD. For PTSD combined with opiate use disorder methadone or buprenorphine are most commonly used with sertraline. Marijuana use has been considered by some to be a treatment for PTSD, but no FDA treatment for this addiction is approved. Pregabalin and D-cycloserine are two innovations in pharmacotherapy for PTSD and SUD. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Comorbid PTSD and SUD amplifies their lethality and treatment complexity. Although they share important neurobiology, these patients uncommonly respond to a single pharmacotherapy such as sertraline or disulfiram and more typically require medication combinations and consideration of the specific type of SUD. (Am J Addict 2015;XX:1-8). Language: en

Background and Objectives We previously reported that an anti-methamphetamine (MA) vaccine attenuated drug-conditioned effects in mice, but it used a carrier protein and adjuvant not available for clinical use. Here we produced a vaccine with the same hapten (succinyl-methamphetamine, SMA) but attached to tetanus toxoid (SMA-TT) and adsorbed to aluminum hydroxide, components approved for use in humans. We then assessed the vaccine's ability to generate anti-MA antibodies, alter acquisition and reinstatement of MA place conditioning, and prevent MA brain penetration. Methods Mice were administered SMA-TT at weeks 0 and 3 and non-vaccinated mice received saline. Anti-MA antibody concentrations were determined at 8 and 12 weeks. Place conditioning began during week 9 in which vaccinated and non-vaccinated mice were divided into groups and conditioned with .5, or 2.0 mg/kg MA. Following acquisition training, mice were extinguished and then a reinstatement test was performed in which mice were administered their original training dose of MA. Separate groups of non-vaccinated and vaccinated mice were administered .5 and 2.0 mg/kg MA and brain MA levels determined. Results and Conclusions Anti-MA antibody levels were elevated at week 8 and remained so through week 12. The SMA-TT vaccine attenuated acquisition and reinstatement of MA place conditioning. Significantly greater proportions of vaccinated mice during acquisition and reinstatement tests showed conditioned place aversion. Moreover, MA brain levels were decreased in vaccinated mice following administration of both doses of MA. Scientific Significance Results support further development of anti-MA vaccines using components approved for use in humans. (Am J Addict 2015;XX:XX--XX)

Background/Objectives Certain medical consequences seem unique to synthetic cannabinoid (SC) and not cannabis use. We report the case of an adolescent, whose drug expectancies appear to minimize the severity of SC-related adverse events. Methods/Results An 18-year-old male presented with altered mental status and seizure, complicated by respiratory failure. He was stabilized and on discharge, despite counseling on the harms of SC usage, the patient planned to resume use, insisting that the hospitalization was “just one bad high”. Discussion/Conclusions/Scientific Significance Diminished negative expectancies related to SC use among adolescents may reflect generalizations from cannabis. Effective interventions should counter cannabis-related expectancies of minimal harm. (Am J Addict 2016;XX:1–3)

Background and Objectives Immunotherapy for drug addiction is being investigated in several laboratories but most studies are conducted in animals of one sex. Yet, women show heightened immune responses and are more likely to develop autoimmune diseases than men. The purpose of this study was to compare the effects of an active anti-cocaine vaccine, succinyl-norcocaine conjugated to keyhole limpet hemocyanin, for its ability to elicit antibodies and alter cocaine-induced ambulatory activity in male versus female mice. Methods Male and female BALB/c mice were vaccinated (n = 44) or served as non-vaccinated controls (n = 34). Three weeks after initial vaccination, a booster was given. Ambulatory activity induced by cocaine (20 mg/kg) was assessed at 7 weeks and plasma obtained at 8 weeks to assess antibody levels. Results High antibody titers were produced in mice of both sexes. The vaccine reduced ambulatory activity cocaine-induced but this effect was greater in female compared to male mice. Discussion and Conclusions The efficacy of this anti-cocaine vaccine is demonstrated in mice of both sexes but its functional consequences are greater in females than males. Scientific Significance Results point to the importance of testing animals of both sexes in studies of immunotherapies for addiction. (Am J Addict 2014;23:604–607)

Background and Objectives Amphetamine-type stimulants (ATS) have quickly spread and been widely abused in many parts of the world, particularly in China. This review focuses on and describes the epidemiological trends and the advances of treatments of ATS in China. Methods A descriptive study based on literature identified from searches of the China National Knowledge Infrastructure (1979–2013), PubMed databases, hand-picked references, and online references with emphasis on epidemiology, treatment and traditional Chinese medicine. This review covers some traditional Chinese treatments and their complementary Western approaches. Results and Conclusions The epidemiological trends of ATS in China have led to its being 2.2 times the rate of morphine abuse and second only to marijuana abuse. The treatment programs in China have used traditional herbal approaches as well as acupuncture, often in combination with Western medications such as fluoxetine for depression associated with ATS abuse. Other herbal treatments have reversed the cardiac arrhythmias associated with ATS intoxication, and acupuncture has been used successfully for the protracted depressive and somatic symptoms of ATS withdrawal over a period of 3 months. Scientific Significance These traditional Chinese treatments may be increasingly available to the world, but will remain a consistent complementary therapy for ATS in China and the Far East, where ATS has become such a prevalent problem. (Am J Addict 2013;XX:000–000)

While the worldwide prevalence of cocaine use remains significant, medications, or small molecule approaches, to treat drug addictions have met with limited success. Anti-addiction vaccines, on the other hand, have demonstrated great potential for treating drug abuse using a distinctly different mechanism of eliciting an antibody response that blocks the pharmacological effects of drugs. We provide a review of vaccine-based approaches to treating stimulant addictions; specifically and cocaine addictions. This selective review article focuses on the one cocaine vaccine that has been into clinical trials and presents new data related to pre-clinical development of a methamphetamine (MA) vaccine. We also review the mechanism of action for vaccine induced antibodies to abused drugs, which involves kinetic slowing of brain entry as well as simple blocking properties. We present pre-clinical innovations for MA vaccines including hapten design, linkage to carrier proteins and new adjuvants beyond alum. We provide some new information on hapten structures and linkers and variations in protein carriers. We consider a carrier, outer membrance polysaccharide coat protein (OMPC), that provides some self-adjuvant through lipopolysaccharide components and provide new results with a monophosopholipid adjuvant for the more standard carrier proteins with cocaine and MA. The review then covers the clinical trials with the cocaine vaccine TA-CD. The clinical prospects for advances in this field over the next few years include a multi-site cocaine vaccine clinical trial to be reported in 2013 and phase 1 clinical trials of a MA vaccine in 2014.

Background and Objectives In cocaine vaccine studies, only a minority of subjects made strong antibody responses. To investigate this issue, IgG and IgM antibody responses to cocaine and to cholera toxin B (CTB—the carrier protein used to enhance immune responses to cocaine) were measured in sera from the 55 actively vaccinated subjects in a Phase IIb randomized double-blind placebo-controlled trial (TA-CD 109). Methods Isotype specific ELISAs were used to measure IgG and IgM anti-cocaine and anti-CTB antibody in serial samples collected prior to and at intervals after immunization. We assessed IgG anti-cocaine responses of patients with pre-vaccination IgM anti-cocaine antibodies. Competitive inhibition ELISA was used to evaluate antibody specificity. Results and Conclusions Before immunization, 36/55 subjects had detectable IgM antibodies to cocaine, and 9 had IgM levels above the 95% confidence limit of 11 μg/ml. These nine had significantly reduced peak IgG anti-cocaine responses at 16 weeks, and all were below the concentration (40 μg/ml) considered necessary to discourage recreational cocaine use. The IgG anti-CTB responses of these same subjects were also reduced. Scientific Significance Subjects who develop an IgM antibody response to cocaine in the course of repeated recreational exposure to this drug are significantly less likely to produce high levels of IgG antibodies from the cocaine conjugate vaccine. The failure may be due to recreational cocaine exposure induction of a type 2 T-cell independent immune response. Such individuals will require improved vaccines and are poor candidates for the currently available vaccine. (Am J Addict 2013;22:169-174)

Background The co-occurrence of schizophrenia and type 2 diabetes mellitus (T2DM) has been well documented. Recent genome-wide association studies and meta-analyses have shown robust associations of the solute carrier family 30 member 8 (SLC30A8) gene variants with T2DM in various populations. We examined the involvement of the SLC30A8 in the susceptibility to schizophrenia in a Han Chinese population. Methods The SLC30A8 rs13266634 gene polymorphism was genotyped in 837 chronic schizophrenic and 1109 unrelated healthy controls by using a case control design. We also assessed clinical symptoms. Results There were no significant differences in the rs13266634 genotype (χ2 = 1.95, df = 2, p = 0.38) and allele (χ2 = 0.47, df = 1, p = 0.50) distributions between the patient and control groups. There was no association between rs13266634 and clinical symptoms. Conclusion The SLC30A8 gene variation does not appear to contribute a genetic basis for the co-occurrence of schizophrenia and T2DM. Copyright © 2012 John Wiley & Sons, Ltd.

Aims Whether the selective serotonin reuptake inhibitor sertraline at 200 mg/day delays relapse in recently abstinent cocaine dependent individuals

We surveyed 205 Veterans Affairs (VA) staff on treatment of posttraumatic stress disorder (PTSD), substance use disorder (SUD), and the combination (PTSD/SUD). The survey was anonymous and VA-wide. PTSD/SUD was perceived as more difficult to treat than either disorder alone; gratification in the work was stronger than difficulty (for PTSD, SUD, and PTSD/SUD); and difficulty and gratification appeared separate constructs. Respondents endorsed views that represent expert treatment for the comorbidity; however, there was also endorsement of "myths." Thus, there is a need for more training, policy clarifications, service integration, and adaptations for veterans returning from Iraq and Afghanistan. Limitations are described.

In this double-blind, placebo-controlled trial, bupropion (BUPRO, 300 mg/day) was compared to placebo (PBO) for the concurrent treatment of opioid and tobacco addiction in 40 opioid-dependent smokers stabilized on buprenorphine (BUPRE, 24 mg/day). Participants received contingent, monetary reinforcement for abstinence from smoking, illicit opioids, and cocaine. Significant differences in treatment retention were observed (BUPRE+BUPRO, 58%; BUPRE+PBO, 90%). BUPRO treatment was not more effective than placebo for abstinence from tobacco, opioids, or cocaine in BUPRE-stabilized patients. These preliminary findings do not support the efficacy of BUPRO, in combination with BUPRE, for the concurrent treatment of opioid and tobacco addiction.

Despite the success of opiate-agonist therapies such as methadone for the treatment of opiate addiction, treatment response is not complete. This study evaluates the efficacy of citalopram augmented with bupropion in the treatment of illicit opiate use in a methadone-stabilized population. We conducted a 12-week randomized, double-blind, outpatient clinical trial in which 60 subjects were randomized into one of three treatment groups: placebo, citalopram (40 mg/day) plus placebo, or citalopram (40 mg/day) plus bupropion (50 mg/day). The results indicate that neither citalopram nor citalopram augmented with bupropion were more effective than placebo in the treatment of opioid abuse.

This issue of the American Journal on Addictions has a review of prescribing heroin in Great Britain, where a recent government commission considered its limits. The review is written by one of the commission members who supports its conclusion that ‘‘if diamorphine treatment could be offered to all problematic users who do not successfully access other treatments, we believe it could play a useful part in managing the social problems generated by this group of people.’’ 1 As Dr. Carnwath indicates, this was a controversial conclusion and was based on several studies that have been criticized for their outcome measures (self reports rather than urine toxicologies), lack of blinding in assessments, drug diversion, and incomplete followup. 2–17 A separate concern has been that the cost-benefit of this intervention, particularly if implemented on a larger scale than these small, geographically restricted studies, would be unsupportive. Although prescribing injectable heroin to heroin addicts is unlikely to find community and legal support in the United States, another harm reduction strategy—needle exchange—has broad public health support in the addictions field, and new freedoms are available for buprenorphine prescribing in an office-based setting with significant latitude in take-home medication. Both of these U.S. programs have raised some issues among regulatory agencies and some citizens about the role of these treatment modalities for ‘‘managing the social problems generated by this group of people,’’ as stated in the British Commission report. Medically based harm reduction strategies that do not involve prescribing heroin or decriminalization of all abused substances

Background and Purpose. Cerebral perfusion abnormalities and neuropsychological impairment are common sequelae of chronic cocaine abuse. While perfusion abnormalities have been shown to relate to cognitive deficits in this substance abuse population, the relationship between cognitive performance and the magnitude of perfusion abnormality has yet to be fully determined. Methods. Thirty-seven abstinent cocaine abusers and 13 normal controls were administered resting 99m-Tc-HMPAO single photon emission computed tomography (SPECT) scans followed by a neuropsychological assessment battery tapping executive skills, attention, memory, and motor performance. Statistical parametric mapping (SPM99) techniques were used to analyze the SPECT data to detect significant regional perfusion abnormalities in the cocaine group relative to normal controls, and resulting abnormal SPECT counts were employed for comparison with the assessment measures to examine the relationship between cocaineinduced perfusion abnormalities and cognitive performance. Results. SPECT data analysis revealed significant regional perfusion abnormalities in the cocaine abuse sample relative to controls and significant differences in neuropsychological functioning on measures of executive functioning, complex attention, memory, and manual dexterity. For chronic cocaine abusers, however, within-group comparisons of the magnitude of abnormal perfusion and neuropsychological performance were largely nonsignificant, with the exception of complex attention and motor speed. Conclusions. Perfusion abnormalities and neuropsychological impairments readily distinguished cocaine abusers from normal controls. However, when the magnitude of cocaine-induced perfusion abnormalities is examined in relation to cognitive performance, motor speed and complex attention appear to be the best behavioral indicants of the severity of perfusion dysfunction within this substance abuse population.

The aims of this study are to assess psychiatrists' comfort using office-based opiate agonist treatment (OBOT) and to identify psychiatrist characteristics associated with OBOT comfort. A random sample of 2,323 AMA Masterfile of Physicians psychiatrists were surveyed through the 2002 APIRE National Survey of Psychiatric Practice (NSSP). Of the 52% responding (N = 1,203), 80.6% (SE = 1.8%) were not comfortable providing OBOT. Males, addiction-certified psychiatrists, and those treating substance abuse patients were more comfortable providing OBOT. These findings highlight significant barriers in providing buprenorphine treatment. Increasing the understanding of specific financing and services delivery barriers that clinicians face is needed to inform the development of effective integrated services models and policies to facilitate OBOT implementation.

The effect of lifetime depression was examined in a randomized clinical trial in 164 opioid- and cocaine-dependent patients who were treated with desipramine in combination with either methadone or buprenorphine. We examined treatment retention, illicit opioid and cocaine use, and depressive symptoms, and found that opioid-free urines at baseline, but not later in treatment, were greater among the depressed than non-depressed patients. Among the depressed patients, depressive symptoms at baseline, but not later in treatment, were greater in patients treated with buprenorphine than methadone. Desipramine did not reduce depressive symptoms more than placebo. Finally, the depressed patients treated with desipramine and buprenorphine showed the least improvement in opioid-free urines, while the non-depressed patients treated with desipramine and methadone had more opioid-free urines than those patients treated with placebo desipramine. Cocaine-free urines showed no association with depression. This poor outcome with desipramine and buprenorphine suggests that this medication combination is not indicated in depressed opioid-dependent patients.

Aims We sought to evaluate the safety and efficacy of the GABAergic agent tiagabine in reducing cocaine use among methadone-treated patients. Design Ten-week randomized double-blind placebo-controlled trial. Setting Opiate Treatment Research Program, Veteran's Affairs Connecticut Healthcare System in West Haven, Connecticut, USA. Participants The participants were 45 cocaine-dependent methadone-treated patients who were predominately Caucasian (75.6%), male (77.8%) and never married (53%) with an average age of 38 years (SD = 6.5). Interventions Comparison groups received tiagabine 12 mg/day (n = 15), tiagabine 24 mg/day (n = 15) or placebo (n = 15). Measures Baseline assessments included the Structured Clinical Interview for DSM-IV, the Addiction Severity Index, a urine drug test, self-reported use and opiate withdrawal scales. Urine drug tests were performed thrice weekly. Findings Treatment retention was over 80% for all treatment groups. The sample mean (± SE) of cocaine-free urines for the first week after study entry and before tiagabine was started was 1.16 (0.19) urines/week. During weeks 9 and 10 cocaine-free urines increased significantly from baseline by 33% with high-dose tiagabine (24 mg/day), by 14% with low-dose tiagabine (12 mg/day) and decreased by 10% with placebo (hierarchical linear model, Z= 2.03; P

Aims During 3 months where contingency management (CM) had an escalating value for each consecutive drug-free urine (escalating CM), cocaine- and heroin-abusing patients significantly increased drug-free urines. The ‘escalating CM’ was eliminated during months 4‐6 to assess any reduction in drug-free urines. Design Patients who completed a 3-month, randomized, double-blind, trial evaluating CM versus non-CM and desipramine (DMI) versus placebo, had an ‘escalating CM’ eliminated during months 4‐6. The CM and non-CM groups were compared using thrice-weekly urine samples. Setting Out-patient buprenorphine maintenance for 6 months. Participants All 75 of the 160 original study patients who completed month 3 of the clinical trial. Intervention The ‘escalating CM’ was eliminated for all 3 months and during months 5 and 6 the response requirement was also increased to two and then three consecutive drug-free urines in order to obtain a voucher. Measurements Urine toxicology for opiates and cocaine. Findings After eliminating the ‘escalating CM’, the CM group showed a decline in combined opioid- and cocaine-free urines. This decline within the CM group was greater in those treated with DMI than placebo. Conclusions Buprenorphine with DMI maintained drug abstinence after eliminating the ‘escalating CM’, but not after increasing the response requirement, suggesting the need for more intensive psychosocial interventions during CM.

Nine cocaine abusers with cerebral blood flow (CBF) deficits (hypo-perfused areas) on HMPAO SPECT scans were compared to six without these deficits after six doses of isradipine (5 mg TID). When comparing the scan before isradipine to that after using SPM analysis, the ratio of hypo- to hyper-fusion showed a 16% increase in the maximum Z scores and 30% fewer areas of hypo-perfusion among those cocaine abusers with deficits. These deficits may represent segmental cerebral vasospasm that was reversed by this vasodilating agent in cocaine abusers with areas of hypo-perfusion (deficits) as baseline.

Injection drug users are frequently infected with human immunodeficiency virus (HIV) and receive opioid dependence pharmacotherapies and zidovudine (ZDV), the latter as a component of highly active antiretroviral therapy. We previously reported that methadone substantially increases ZDV concentrations. We now report on oral ZDV pharmacokinetics in 52 subjects receiving the opioid dependence pharmacotherapies l- &#102 -acetylmethadol LAAM, buprenorphine, or naltrexone, and 17 non-opioid-treated controls. Relative to the area under the time-concentration curve (AUC) of ZDV in control subjects, no statistically significant differences in ZDV AUC were observed in participants treated with LAAM (p =. 75), buprenorphine (p =. 37), or naltrexone (p =. 34). While methadone maintenance may result in ZDV toxicity and possibly require dose adjustments, other opioid pharmacotherapies should not produce ZDV toxicity. (Am J Addict 2001;10:296- 307)

The authors conducted a 16-week study with nine opioid-dependent individuals (six male; four white/two African American/three Hispanic; age 36.8±2.2 years). Participants were assigned to either a low-dose (165 mg/week; n = 5) or high-dose (330 mg/week; n = 4) Levo-alpha-acetylmethadol (LAAM) condition according to a randomized, double-blind, within-subjects crossover design, such that they were inducted onto one maintenance dose for 4 weeks and then were crossed over to receive the converse for 4 weeks. Subsequently, individuals underwent detoxification from LAAM. Eight of nine participants completed the study protocol. The proportion of urine samples positive for opiates was 0.22 ± 0.08 and 0.53 ± 0.12, under the high- and low-dose conditions, respectively (F = 11.8; P = 0.01). These results show that LAAM dose regimen affects the degree of abstinence from opioids.

This review of anticonvulsants for relapse prevention in substance abusers focuses on a series of clinical trials among cocaine abusers. Based on a preclinical rationale linking kindling with drug craving, several studies by Halikas et al. found reductions in cocaine use and craving among “compliant” subjects with blood levels above 4 u/ml. Three independent randomized trials found no difference from placebo in cocaine use, although treatment retention may be higher during the first 6 weeks, and alcohol use might be less at follow-up after medication discontinuation.

New pharmacotherapies have been developed for acute withdrawal and maintenance treatments of alcohol and opioid dependence but not for cocaine dependence. Highdose, long-acting benzodiazepines, beta-blockers, and two antiseizure agents-carbamuxepine and valproate-are being used for alcohol withdrawal. For maintenance treatment, opioid antagonists and various serotonergic agents, such as fluoxetine and ondansetron, show promise. For opioid dependence, clonidine-na ltrexone detomyication appears quite cost-effective, and buprenoqhine and LAAM (Ievo-alpha-acetylmethadol)s how promise for both detoxification and maintenance. More work is needed, however, to discover an effective agent for target populations of cocaine abusers.

The authors evaluated the effect of an acute reduction in catecholamine synthesis, produced by alpha methyl para tyrosine (AMPT), on cue-induced craving for cocaine in cocaine-dependent patients. AMPT and diphenhydramine were administered under double-blind conditions in a randomized, crossover design. Two cue exposure sessions were conducted 1 week apart. Self-reported assessments of cocaine craving were administered before and after cue exposure. AMPT, but not diphenhydramine, significantly decreased plasma levels of the dopamine metabolite, ho-movanillic acid and the norepinephrine metabolite, 3-methoxy-4-hydroxyphenylethylene glycol. However, AMPT's effects on cue-induced craving interacted with the test-day order in a complex manner.