The medical management of adolescent heroin dependence

The use of heroin by American adolescents is at its highest levels since the heroin epidemic of the 1960s. This clinical perspective reviews medical issues associated with adolescent heroin dependence. Older, as well as potential newer, treatments for adolescent heroin dependence are discussed. Multiple obstacles face a heroin-dependent adolescent who seeks treatment, including a lack of evidenced-based research on pharmacotheraputic agents for this population, strict restrictions on medications with demonstrated efficacy in adults, and a general lack of clinical experience in treating this population.     

Sex, ethnicity, age and education effects on the Trail Making Test in a sample of heroin abusers.

Sex, ethnicity, age and education effects on the Trail Making test (TMT), a test often used for screening for cognitive impairment, are examined in a sample of heroin abusers in drug abuse treatment programs. A mixed race sample was drawn from electronic files of data from the Drug Abuse Treatment outcome Study (DATOS). The DATOS was a naturalistic, prospective cohort study that collected data from 1991-1993 in 96 programs in 11 cities in the United States. The number of heroin abusers with TMT scores available for analysis was 1548. Data were analyzed to determine the effects of sex, ethnicity, age and education variables on the two parts of the TMT in this large treatment sample of heroin abusers. The variables of sex, age, ethnicity and education were statistically significant for both parts A and B of the TMT. Nonetheless, R-Square values for overall models were quite weak (A = .08, B = .13) suggesting that sex, ethnicity, age and education effects on the TMT, while clearly present, account for relatively little overall variance in terms of heroin users' TMT performance. These results are consistent with earlier research using a more heterogenous drug abuse treatment sample.     

男女海洛因依赖者成瘾严重程度的比较

目的：了解男女海洛因依赖者成瘾严重程度的差异,为针对不同性别海洛因依赖者制定干预措施提供依据。方法：采用自制个案调查表和成瘾行为严重度指数量表（addiction severity index,ASI）对199例男性和239例女性海洛因依赖者进行评估,比较不同性别海洛因依赖者ASI量表中各维度分值的差异。结果：女性依赖者ASI中因子4（药物使用）评分平均为（0.52±0.28）分和因子7（精神健康状况）平均（0.15±0.24）分显著高于男性的（0.43±0.34）分和（0.08±0.19）分（P〈0.05或P〈0.01）;男性依赖者因子5（法律状况）评分平均（0.07±0.13）分高于女性的（0.03±0.10）分（P〈0.01）。将年龄、首次吸毒年龄及吸毒时间与ASI分量表进行偏相关分析发现,年龄（r=-0.182）、吸毒时间（r=0.158）与因子4（药物使用）分数存在显著相关;进一步相关分析发现,年龄与吸毒时间存在显著相关（r=0.364,P〈0.01）。结论：男女海洛因依赖者在成瘾行为严重程度方面存在差异,临床治疗与康复过程中应针对不同性别特征制定个体化的治疗方案以满足不同性别患者的需求。     

Naltrexone in the treatment of heroin dependence: relationship with depression and risk of overdose

OBJECTIVE: This article examines the use of naltrexone in the treatment of heroin dependence. The relationship between naltrexone and depression as well as risk of overdose is examined. METHOD: The existing literature is reviewed along with recent interim data from clinical trials underway in Victoria. RESULTS: Naltrexone is a recent addition to treatment for heroin dependence in Australia. The relationship between depression and naltrexone has been examined in previous literature. Underlying rates of depression in heroin users are high and treatment may resolve or exacerbate depression. Research to date demonstrates that the addition of naltrexone does not necessarily increase depression in patients. The risk of non-fatal heroin overdose is significantly elevated after naltrexone treatment as a result of reduced tolerance. Data from clinical trials underway in Victoria demonstrate a significantly elevated rate of non-fatal overdose in naltrexone patients compared to those in substitution maintenance treatment. The mortality rate subsequent to naltrexone treatment appears to be equivalent to or greater than that for untreated heroin users. Further research is required. CONCLUSIONS: Clinicians need to carefully monitor depression in patients, and warn patients of the risks of reduced tolerance to opiates following naltrexone treatment. Agonist treatments such as methadone, LAAM and buprenorphine carry much less risk of overdose.     

Stroke associated with addiction to heroin.

During a five year period at the Harlem Hospital Center nine heroin addicts were seen with strokes. Four occurred after loss of consciousness following intravenous heroin. Two occurred in patients using heroin at the time, but were not related to overdose or to a particular recent injection. The youth of these patients and lack of other predisposing factors suggests that heroin played a role in their strokes. In the other three patients, the relationships of stroke to heroin is less persuasive. There are several possible mechanisms by which heroin abuse could lead to stroke.     

Mortality in heroin addiction: impact of methadone treatment

The mortality within a cohort of 115 street heroin addicts was studied for 5-8 years using the Kaplan-Meier survival estimate technique. This differed markedly from the relatively low mortality of 166 comparable heroin addicts given methadone maintenance treatment (MT). The street addicts' mortality rate was 63 times that expected, compared with official statistics for a group of this age and sex distribution. When 53 patients in MT were involuntarily expelled from treatment, due to violation of programme rules, they returned to the high mortality of street addicts (55 times that expected). A group of 34 rehabilitated patients who left MT with medical consent retained the low mortality of MT patients (their mortality rate was 4 times that expected). Despite this great improvement in survival, even patients in MT showed a moderately elevated mortality (8 times that expected), mainly due to diseases acquired before entering the treatment programme. It is concluded that MT exerts a major improvement in the survival of heroin addicts.     

Diffusivity of the uncinate fasciculus in heroin users relates to their levels of anxiety

Heroin use is closely associated with emotional dysregulation, which may explain its high comorbidity with disorders such as anxiety and depression. However, the understanding of the neurobiological etiology of the association between heroin use and emotional dysregulation is limited. Previous studies have suggested an impact of heroin on diffusivity in white matter involving the emotional regulatory system, but the specificity of this finding remains to be determined. Therefore, this study investigated the association between heroin use and diffusivity of white matter tracts in heroin users and examined whether the tracts were associated with their elevated anxiety and depression levels. A sample of 26 right-handed male abstinent heroin users (25 to 42 years of age) and 32 matched healthy controls (19 to 55 years of age) was recruited for this study. Diffusion tensor imaging data were collected, and their levels of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Our findings indicated that heroin users exhibited higher levels of anxiety and depression, but the heroin use-associated left uncinate fasciculus was only related to their anxiety level, suggesting that association between heroin and anxiety has an incremental organic basis but that for depression could be a threshold issue. This finding improves our understanding of heroin addiction and its comorbid affective disorder and facilitates future therapeutic development.     

Chronic cannabis use does not affect the normalization of hypothalamic-pituitary-adrenal (HPA) axis induced by methadone in heroin addicts

The hypothalamic-pituitary-adrenal (HPA) axis activity is usually altered by heroin use. In the present study we evaluated in one hundred twenty-one heroin addicts the effects of marijuana smoking on the normalization of HPA axis upon methadone treatment. The study showed that in heroin addicts who are chronic cannabis smokers a treatment with methadone lasting 12 months was able to normalize both plasma corticotropin (ACTH) and cortisol levels, as well as to control both heroin withdrawal symptoms and opioid craving. As expected in the same group of patients marijuana smoking and its craving were not reduced by methadone treatment. Our data confirm that methadone treatment outcomes are not modified by cannabis use and they add in the literature the evidence that chronic cannabis use is not able to affect the normalization of HPA axis upon methadone treatment in heroin addicts.     

Differential regional effects of methadone maintenance compared to heroin dependence on mu-opioid receptor desensitization in rat brain

Methadone maintenance therapy has been the mainstay of treatment for heroin addiction since the 1970s. Recent studies indicate that methadone is of greater relative intrinsic efficacy than the active metabolites of heroin at mu-opioid receptors and that the extent of mu-opioid receptor desensitization is dependent upon agonist efficacy. Regional differences have been found for mu-opioid receptor desensitization with chronic heroin self-administration, and a similar paradigm was employed to compare regional differences between the effects of heroin and methadone. Rats were trained to self-administer heroin i.v., and the dose available was increased incrementally to a terminal value of 6 mg/kg for each infusion. Half of these rats were allowed to continue to self-administer heroin, while dependence was maintained in the others by hourly infusions of 3 mg/kg of methadone. A separate group of animals was kept on a low dose of heroin. Activation of G-proteins by the high efficacy agonist DAMGO was decreased to a greater extent in animals treated chronically with methadone compared with those allowed to self-administer heroin in amygdala, periaqueductal gray, and subicular nucleus. Activation of G-proteins by the partial agonist endomorphin was decreased in striatum, thalamus, and amygdala in rats from all drug treatment groups, but to a greater extent in the striatum in methadone treated rats compared with the heroin groups. Elucidating the mechanisms by which methadone induces differential desensitization of mu-opioid receptors across brain regions compared with heroin could provide insights to improve the pharmacotherapy of heroin addiction.     

Late- and Typical-Onset Heroin Use Among Older Adults Seeking Treatment for Opioid Use Disorder

ObjectiveAnalyze 10-year trends in opioid use disorder with heroin (OUD-H) among older persons and to compare those with typical-onset (age <30 years) to those with late (age 30+) onset.DesignNaturalistic observation using the most recent (2008–2017) Treatment Episode Data Set-Admissions (TEDS-A).SettingAdmission records in TEDS-A come from all public and private U.S. programs for substance use disorder treatment receiving public funding.ParticipantsU.S. adults aged 55 years and older entering treatment for the first time between 2008 and 2017 to treat OUD-H.MeasurementsAdmission trends, demographics, substance use history.ResultsThe number of older adults who entered treatment for OUD-H nearly tripled between 2007 and 2017. Compared to those with typical-onset (before age 30), those with late-onset heroin use were more likely to be white, female, more highly educated, and rural. Older adults with late-onset were more likely to be referred to treatment by an employer and less likely to be referred by the criminal justice system. Those with late-onset were more likely to use heroin more frequently but less likely to inject heroin than those with typical-onset. Those with typical onset were more likely to receive medication for addiction treatment than those with late-onset.ConclusionLate-onset heroin use is increasing among older U.S. adults. Research is needed to understand the unique needs of this population better. As this population grows, geriatric psychiatrists may be increasingly called upon to provide specialized care to people with late-onset OUD-H.     

参与美沙酮维持治疗的海洛因成瘾者自我报告的抑郁症状严重程度：一项横断面调查

背景：美沙酮维持治疗(methadone maintenance treatment, MMT)是一种公认的有效降低毒瘾的措施。美沙酮维持治疗可以减少海洛因成瘾戒断症状,并因此可以提供心理和社会支持,对吸毒者的康复至关重要。
　　目标：比较目前正在接受MMT的海洛因成瘾者和没有接受MMT的海洛因成瘾者之间的抑郁症状严重程度。
　　方法：本研究运用了Beck-13(13-item version of the Beck Depression Inventory, BDI-13)抑郁自评量表和人口学历史资料调查表,对中国三个城市9个美沙酮治疗中心的929例正在接受MMT的海洛因成瘾患者（平均已接受9个月MMT治疗）和已经在中心注册参加MMT治疗但尚未开始的238例海洛因成瘾患者进行评估。
　　结果：与正在接受MMT的成瘾者中有68%(628/929)报告抑郁症状相比,79%(188/238)的未治疗成瘾者报告有抑郁症状(X2=11.69,p<0.001)。未经治疗组的BDI评分中位数（四分位区间）是10.4(7.9-11.4),而MMT 组BDI评分中位数是8.0(5.7-11.6),两者有显著差异(Z=2.75, p=0.006)。在MMT组内,自我报告的抑郁症状严重程度与参加MMT时间呈负相关(rs=-0.24,Z=2.88, p=0.004)。多元线性回归分析发现,在控制所有人口学变量后,治疗组的抑郁症状严重程度仍然轻于非治疗组。在控制MMT疗效后,自我报告家庭关系较差(β=0.118,t=6.56, p<0.001)以及离异(β=0.120,t=3.73, p<0.001)的海洛因成瘾患者抑郁症状较严重。
　　结论：中度至重度抑郁症状常见于海洛因成瘾患者。MMT治疗与海洛因成瘾患者抑郁症状较轻相关,但需要采用前瞻性随机对照试验来确定MMT是否确实改善了海洛因成瘾患者的抑郁症状。与家庭成员的关系较差也与海洛因成瘾患者的抑郁症状有关,这表明对海洛因成瘾患者的治疗需要纳入一些方法来帮助海洛因成瘾患者修复由于他们成瘾造成的社会关系割裂。     

Leucoencephalopathy after heroin inhalation. A case with partial regression of MRI lesions

We report the case of a 41 year old patient who developed a severe cerebellar ataxia. MRI findings were suggestive of myelin damage with symmetrical involvement of the cerebellar hemispheres and, to a lesser extent, the decussation of the superior cerebellar peduncles, the corticospinal tracts and the centrum semiovale. He had been inhaling heroin for the last 5 years. Two years after stopping heroin, he showed clinical improvement with partial regression of the MRI lesions. MRI findings of leucoencephalopathy after heroin inhalation are well described in the literature, however longitudinal studies are rare. It is the purpose of this report to show that clinical and MRI features can be characteristic of this leucoencephalopathy and that regression of white matter lesions can be seen after heroin withdrawal.     

海洛因依赖者伪装和制造疾病临床研究(附221例分析)

目的：了解海洛因依赖者在脱毒过程中伪装和制造疾病的原因和临床表现。方法：对符合中国精神疾病分类方案与诊断标准第2版修订本有关诈病诊断标准的海洛因依赖者进行回顾性研究。结果：发现22l例诈病，发生率4．6％，以青年男性、未婚、初中以下文化、无业占多数，吸毒时间长、多药滥用、涉嫌违法犯罪问题者较多。其动机依次是企图逃避法律惩罚、企图提前解除强戒．骗取成瘾药物、受人唆使胁迫等。方式有说谎、伪装、造伤等。结论：海洛因依赖诈病者较多，应引起注意。     

Buprenorphine responders: a diagnostic subgroup of heroin addicts?

1. A 26-32 month follow-up of 16 heroin-dependent subjects who entered a pilot trial of treatment with buprenorphine (a mixed agonist/antagonist) suggests that positive response to treatment may identify a subgroup of untreated addicts whose levels of psychosocial functioning are intermediate between those for whom methadone (a pure agonist) or naltrexone (a pure antagonist) would be indicated. 2. Buprenorphine's pharmacologic profile provides a missing link in available modalities for opiate dependence treatment, making it acceptable for many addicts who will not accept methadone maintenance treatment, join a residential therapeutic community, or be successful on naltrexone treatment. 3. Eight of the 16 ss were abstinent from heroin while receiving 0.6-3.9 mg/day buprenorphine and counseling. Responders (mean age 34 yrs) had been heroin dependent for a mean of 9.5 years (range 6-17 yrs), all were self-supporting, 4 lived with a non-addicted spouse, 5 had no prior treatment for addiction and 3 had prior naltrexone treatment, but had discontinued it and relapsed. Non-responders (mean age 30 yrs) had been heroin dependent for a mean of 7.4 yrs (range 2-19 yrs), 7 had no regular employment, all were single and 7 had no prior treatment for addiction. 4. Levels of psychosocial functioning (work, home, leisure) and global assessments of functioning were significantly higher for buprenorphine responders than non-responders (p less than .001 and p less than .01 respectively). 5. A new formulation of buprenorphine needs to be developed for addiction treatment, ideally consisting of 0.5 mg and 2.0 mg sublingual tablets.     

Glucose-insulin metabolism in herion addicts.

The insulinemic and glycemic response to a glucose load (100 g per os) was studied in 21 heroin addicts, 16 males and 5 females, age 16-28 years, history of addiction lasting from 6 months to 4 years with heroin alone (from 0.5 to 1.5 g/day i.v.). Nine normal sujects, from the hospital staff, 4 females and 5 males matched for age were use as control. The insulinemic and glycemic response to a glucose load was examined immediately after hospitalization, while the patients were still on heroin, 48 h later off drugs, and in 10 of the 21 cases 5 days later still off drugs. From the results obtained, it appears that in heroin addicts the glycemic response to the glucose load shows a delayed peak time. The insulin curves show increased insulin peaks, delayed peak time and prolonged hyperinsulinemia. The pathomechanism of heroin in inducing the above-metioned impairments is discussed, taking also in cosideration the possible influence of the drug on the neurotransmitter regulation of insulin.     

纳曲酮用于海洛因依赖者抗复吸治疗的结果分析

目的了解纳曲酮抗复吸治疗效果。方法采用回顾性临床资料分析方法，分析145例阿片类药物依赖后自愿戒断使用纳曲酮脱瘾及抗复吸治疗的临床资料。结果纳曲酮对于有固定职业、戒毒愿望强烈、家庭关注较多和个人支持系统相对较好抗复吸疗效好，能明显延长探亲时间，减少吸毒冲动，觅药行为，无明显副作用。结论纳曲酮在抗复吸中有很好的运用前景。     

Assessing the Role of Corticothalamic and Thalamo-Accumbens Projections in the Augmentation of Heroin Seeking in Chronically Food-Restricted Rats

Drug addiction is a chronic disorder characterized by compulsive drug seeking, and involves repetitive cycles of compulsive drug use, abstinence, and relapse. In both human and animal models of addiction, chronic food restriction increases rates of relapse. Our laboratory has reported a robust increase in drug seeking following a period of withdrawal in chronically food-restricted rats compared with sated controls. Recently, we reported that activation of the paraventricular nucleus of the thalamus (PVT) abolished heroin seeking in chronically food-restricted rats. However, the precise inputs and outputs of the PVT that mediate this effect remain elusive. The goal of the current study was to determine the role of corticothalamic and thalamo-accumbens projections in the augmentation of heroin seeking induced by chronic food restriction. Male Long–Evans rats were trained to self-administer heroin for 10 d. Next, rats were removed from the self-administration chambers and were subjected to a 14 d withdrawal period while sated (unlimited access to food) or mildly food-restricted (FDR). On day 14, rats were returned to the self-administration context for a 3 h heroin-seeking test under extinction conditions during which corticothalamic and thalamo-accumbens neural activity was altered using chemogenetics. Surprisingly, chemogenetic activation or inhibition of corticothalamic projections did not alter heroin-seeking behavior. Chemogenetic activation of thalamo-accumbens shell, but not core, projectors attenuated heroin seeking in FDR rats. The results indicate an important role for the PVT to nucleus accumbens shell projections in the augmentation of heroin seeking induced by chronic food restriction.SIGNIFICANCE STATEMENT Relapse to heroin use is one of the major obstacles in the treatment of opiate addiction. Triggers for relapse are modulated by environmental challenges such as caloric restriction. Elucidating the brain mechanisms that underlie relapse is critical for evidence-based treatment development. Here we demonstrate a critical role for the input from the paraventricular thalamus (PVT), a hub for cortical, sensory, and limbic information, to the nucleus accumbens shell (an area known to be important for reward and motivation) in the augmentation of heroin seeking in food-restricted rats. Our findings highlight a previously unknown role for the PVT in heroin seeking following a period of abstinence.