Rethinking Informed Consent in Research on Heroin‐Assisted Treatment

Can heroin addicts give consent to research on trials in which heroin is prescribed to them? Analyses of addicts and informed consent have been objects of debate in several articles. Informed consent requires the agent not only to be competent but also to give consent voluntarily. This has been questioned because of alleged features of heroin addiction. Until recently the discussion has focused on heroin addicts' desires for heroin, whether these are irresistible and thus pose a problem for giving consent. Still, in light of empirical evidence, there seems to be a consensus more or less that the problem is not whether the addicts can resist their desire for heroin. A recent article concentrates specifically on heroin addicts' false assumptions of options and voluntariness. We argue that the prevailing framing of the options in this discussion in terms of heroin and access to it is problematic. The way in which the options are typically laid out suggests an assumption that participation in the research is allegedly based on the addicts' views on using the drug. We argue that this way of presenting the options is, first, a mismatch to the studies carried out and, second, symptomatic of potential misconceptions about heroin addiction and addicts. Furthermore, we also suggest that the account of voluntariness needs to be realistic in order for subjects to be able to give consent voluntarily in actual situations, and for medical research to carry out studies on improving outcomes in addiction treatment in an ethical way.     

Addiction,Voluntary Choice,and Informed Consent: A Reply to Uusitalo and Broers

In an earlier article in this journal I argued that the question of whether heroin addicts can give voluntary consent to take part in research which involves giving them a choice of free heroin does not – in contrast with a common assumption in the bioethics literature – depend exclusively on whether or not they possess the capacity to resist their desire for heroin. In some cases, circumstances and beliefs might undermine the voluntariness of the choices a person makes even if they do possess a capacity for self‐control. Based on what I took to be a plausible definition of voluntariness, I argued that the circumstances and beliefs typical of many vulnerable heroin addicts are such that we have good reasons to suspect they cannot give voluntary consent to take part in such research, even assuming their desire for heroin is not irresistible. In a recent article in this journal, Uusitalo and Broers object to this on the grounds that I misdescribe heroin addicts' options set, that the definition of voluntariness on which I rely is unrealistic and too demanding, and, more generally, that my view of heroin addiction is flawed. I think their arguments derive from a misunderstanding of the view I expressed in my article. In what follows I hope therefore to clarify my position.     

ADDICTION AND AUTONOMY: CAN ADDICTED PEOPLE CONSENT TO THE PRESCRIPTION OF THEIR DRUG OF ADDICTION?

It is often claimed that the autonomy of heroin addicts is compromised when they are choosing between taking their drug of addiction and abstaining. This is the basis of claims that they are incompetent to give consent to be prescribed heroin. We reject these claims on a number of empirical and theoretical grounds. First we argue that addicts are likely to be sober, and thus capable of rational thought, when approaching researchers to participate in research. We reject behavioural evidence purported to establish that addicts lack autonomy. We present an argument that extrinsic forces must be irresistible in order to make a choice non-autonomous. We argue that heroin does not present such an irresistible force. We make a case that drug-oriented desires are strong regular appetitive desires, which do not compromise consent. Finally we argue that an addict's apparent desire to engage in a harmful act cannot be construed as evidence of irrational or compulsive thought. On these arguments, a sober heroin addict must be considered competent, autonomous and capable of giving consent. More generally, any argument against legalisation of drugs or supporting infringement of the liberty of those desiring to take drugs of addiction must be based on considerations of harm and paternalism, and not on false claims that addicts lack freedom of the will.     

Addiction,Heroin‐Assisted Treatment and the Idea of Abstinence: A reply to Henden

In our previous article on the question whether heroin addicts are able to give informed consent voluntarily to research on heroin‐assisted treatment, we criticized the ongoing bioethical discussion of a flawed conceptualization of heroin addicts' options. As a participant in this discussion, Edmund Henden defends the conceptualization as sufficient for determining whether heroin addicts are able to give informed consent to the research on heroin‐assisted treatment voluntarily. This discussion on research on heroin‐assisted treatment seems to go astray in several respects. In his reply to our article Henden maintains some of the biases, such as the necessity of abstinence in recovery, that seem to prevail in addiction research on a more general level as well. These biases run the danger of having implausible ethical implications on stakeholders in addiction research and treatment. In our reply to him, we will further clarify and discuss the importance of describing the relevant issues in plausible terms that do justice to the realities of the cases of informed consent in research on heroin‐assisted treatment and also raise a wider issue of the ethics of wording as well as of the narrow scope, or ‘tunnel vision’, in addiction research as currently conducted.     

Giving addicts their drug of choice: the problem of consent

Researchers working on drug addiction may, for a variety of reasons, want to carry out research which involves giving addicts their drug of choice. In carrying out this research consent needs to be obtained from those addicts recruited to participate in it. Concerns have been raised about whether or not such addicts are able to give this consent. Despite their differences, however, both sides in this debate appear to be agreed that the way to resolve this issue is to determine whether or not addicts have irresistible cravings for drugs – if they do, then they cannot consent to this type of research; if they do not, then they can. This I will argue is a mistake. Determining whether or not addicts can say 'No' to offers of drugs will not help us to make much progress here. Instead we need to look at the various ways in which different types of research may undermine an addict's competence to give consent. What we will find is that the details of the research make a big difference here and that, as such, we need to steer a course between, on the one hand, painting all addicts as being unable to consent to research which involves providing them with drugs, and, on the other, maintaining that there are no problems in obtaining consent from addicts to take part in such research.     

网络成瘾的生物学机制研究与展望

网络成瘾是指由于过度使用网络而导致社会及心理损害的现象,危害极大,故受到广泛关注。网络成瘾主要受生物学机制的调控。在脑神经机制方面,通过对成瘾者的自发脑电、事件相关电位以及成瘾者静息态BOLD-f MRI的分析,发现成瘾者脑功能区出现异常。同时,网络成瘾也受到自主神经功能的影响。另外,脑内奖赏系统和成瘾记忆模型也可能成为引发网络成瘾的脑神经机制。体内化学物质的失衡也能引发网络成瘾。鉴于此,一些治疗方法如药物干预、行为干预、认知干预以及综合干预疗法使得根治网络成瘾成为可能。本文拟从网络成瘾的概念、表现特点、不良影响及其发生的生物学机制等方面的研究进展进行阐述,以期为相关研究提供一些有价值的参考依据。     

Imbalanced Decision Hierarchy in Addicts Emerging from Drug-Hijacked Dopamine Spiraling Circuit

Despite explicitly wanting to quit, long-term addicts find themselves powerless to resist drugs, despite knowing that drug-taking may be a harmful course of action. Such inconsistency between the explicit knowledge of negative consequences and the compulsive behavioral patterns represents a cognitive/behavioral conflict that is a central characteristic of addiction. Neurobiologically, differential cue-induced activity in distinct striatal subregions, as well as the dopamine connectivity spiraling from ventral striatal regions to the dorsal regions, play critical roles in compulsive drug seeking. However, the functional mechanism that integrates these neuropharmacological observations with the above-mentioned cognitive/behavioral conflict is unknown. Here we provide a formal computational explanation for the drug-induced cognitive inconsistency that is apparent in the addicts'' “self-described mistake”. We show that addictive drugs gradually produce a motivational bias toward drug-seeking at low-level habitual decision processes, despite the low abstract cognitive valuation of this behavior. This pathology emerges within the hierarchical reinforcement learning framework when chronic exposure to the drug pharmacologically produces pathologicaly persistent phasic dopamine signals. Thereby the drug hijacks the dopaminergic spirals that cascade the reinforcement signals down the ventro-dorsal cortico-striatal hierarchy. Neurobiologically, our theory accounts for rapid development of drug cue-elicited dopamine efflux in the ventral striatum and a delayed response in the dorsal striatum. Our theory also shows how this response pattern depends critically on the dopamine spiraling circuitry. Behaviorally, our framework explains gradual insensitivity of drug-seeking to drug-associated punishments, the blocking phenomenon for drug outcomes, and the persistent preference for drugs over natural rewards by addicts. The model suggests testable predictions and beyond that, sets the stage for a view of addiction as a pathology of hierarchical decision-making processes. This view is complementary to the traditional interpretation of addiction as interaction between habitual and goal-directed decision systems.     

Failure of the gamma-aminobutyric acid (GABA) derivative, baclofen, to stimulate growth hormone secretion in heroin addicts.

In order to establish possible alterations in the gamma aminobutyric acid (GABA)ergic control of growth hormone (GH) secretion in heroin addicts, ten patients (age, 25.8 +/- 1.07 yr (mean +/- SE); duration of heroin addiction, range 3-8 yr; weight, 67.3 +/- 0.87 kg body weight), and ten age (29.1 +/- 0.84 yr)- and weight (69.7 +/- 0.87 kg)-matched normal controls were tested with the GABAergic B-receptor agonist baclofen (10 mg p.o. at 09.00 h) (experimental test) or a placebo (control test). Blood samples for GH assay were taken every 15 min for the next 150 min. Normal controls underwent one control and one experimental test. Heroin addicts were submitted to both baclofen and placebo test twice, once around the time of their admission to a recovery community for drug abusers, when they were still assuming heroin, and again after two months of permanence in the community. From the time of their admission to the community, the patients were forbidden to use heroin. For two weeks after admission they were treated with clonidine and acetylsalicilic acid to attenuate withdrawal symptoms. Thereafter, the patients underwent a period of wash-out of pharmacological treatments for at least 6 weeks before being retested. Basal GH levels were similar in normal controls and heroin addicts in all tests and remained unmodified during control tests in all subjects. The administration of baclofen increased four times the serum GH levels within 120 minutes in the normal controls, whereas it did not modify serum GH concentrations in heroin addicts either during the period of drug abuse or after two months of abstinence. These data show that the control of GH secretion mediated by GABAergic B-receptors is impaired in heroin addicts. It is hypothesized that this neuroendocrine alteration might represent a trait marker of heroin addiction, or more likely, that it was a consequence of a long addiction to heroin persisting after two months of abstinence.     

Serum Proteomic Analysis Reveals High Frequency of Haptoglobin Deficiency and Elevated Thyroxine Level in Heroin Addicts

Heroin addiction is a chronic, complex disease, often accompanied by other concomitant disorders, which may encumber effective prevention and treatment. To explore the differences in expression profiles of serum proteins in control and heroin addicts, we used two-dimensional electrophoresis coupled to MALDI-TOF/TOF, and identified 4 proteins of interest. Following validation of the increase in serum transthyretin, we assessed serum levels of thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4), and observed a robust increase in T4 in heroin addicts compared to controls. In addition, we performed haptoglobin (Hp) phenotyping, and showed that the frequency of Hp0 (serum devoid of haptoglobin) was significantly higher in heroin addicts. Altogether, these findings indicated that: (1) thyroid hormone imbalance is present in heroin addicts; (2) anhaptoglobinemia (Hp0) might a risk factor or a deleterious effect of heroin abuse.     

The personality traits and social characteristics of Croatian heroin addicts and cannabis users

The purpose of this study was to investigate differences in social characteristics (level of education, working and family status, and criminal record) between heroin addicts, cannabis users and a control group. Additional goal was to explore the possibility of discerning subjects of different addiction status (of both gender) based on their scores on Eysenck Personality Questionnaire (EPQ). In comparison to the control group, heroin addicts and cannabis users had lower level of education, were more frequently unemployed and with criminal record, and more often came from dysfunctional families. In cannabis users the frequency of these characteristics was generally lower than in heroin addicts. Proportion of correct classification of subjects in groups of different addiction status based on the EPQ scores was 23.3% for males (higher than by chance alone), and 30% for females.     

Abnormal brain default-mode network functional connectivity in drug addicts

Background

The default mode network (DMN) is a set of brain regions that exhibit synchronized low frequency oscillations at resting-state, and is believed to be relevant to attention and self-monitoring. As the anterior cingulate cortex and hippocampus are impaired in drug addiction and meanwhile are parts of the DMN, the present study examined addiction-related alteration of functional connectivity of the DMN.

Methodology

Resting-state functional magnetic resonance imaging data of chronic heroin users (14 males, age: 30.1±5.3 years, range from 22 to 39 years) and non-addicted controls (13 males, age: 29.8±7.2 years, range from 20 to 39 years) were investigated with independent component analysis to address their functional connectivity of the DMN.

Principal Findings

Compared with controls, heroin users showed increased functional connectivity in right hippocampus and decreased functional connectivity in right dorsal anterior cingulate cortex and left caudate in the DMN.

Conclusions

These findings suggest drug addicts'' abnormal functional organization of the DMN, and are discussed as addiction-related abnormally increased memory processing but diminished cognitive control related to attention and self-monitoring, which may underlie the hypersensitivity toward drug related cues but weakened strength of cognitive control in the state of addiction.     

RESPECTING AUTONOMY WITHOUT DISCLOSING INFORMATION

There is widespread agreement that it would be both morally and legally wrong to treat a competent patient, or to carry out research with a competent participant, without the voluntary consent of that patient or research participant. Furthermore, in medical ethics it is generally taken that that consent must be informed. The most widely given reason for this has been that informed consent is needed to respect the patient's or research participant's autonomy. In this article I set out to challenge this claim by considering in detail each of the three most prominent ways in which ‘autonomy’ has been conceptualized in the medical ethics literature. I will argue that whilst these accounts support the claim that consent is needed if the treatment of competent patients, or research on competent individuals, is to respect their autonomy, they do not support the claim that informed consent is needed for this purpose.     

Impaired glucose metabolism in heroin and methadone users

Plasma glucose and insulin responses to both oral and intravenous glucose stimulation were evaluated in heroin and methadone addicts, compared to healthy control subjects. Both groups of addicts had an altered response to oral and intravenous glucose load. These phenomena were linked to a reduced insulin response. Moreover, increased fasting insulin levels in both groups of addicts were observed. These data show that both heroin and methadone addiction may alter glucose metabolism, and, furthermore, stress the findings of similarities between opiate addicts and non-insulin dependent diabetics.     

282例海洛因依赖者复吸原因调查分析

目的探讨海洛因依赖者复吸原因,并分析社会因素、心理因素和戒毒后稽延症状对复吸的影响。方法采用在北京大学中国药物依赖研究所编制的16项复吸原因问卷,调查282例海洛因依赖者吸毒、脱毒后复吸情况以及影响复吸的三方面因素。结果出现稽延性戒断症状（81．9％）、失眠（75．5％）是产生复吸的主要身体因素;消除心情烦恼（39．0％）、打发无聊时间（34．4％）以及再享受最后一次（32．6％）是产生复吸的主要心理因素;毒友影响（43．3％）、旧的吸毒环境又引发毒瘾（33．7％）是产生复吸的主要社会因素。讨论吸毒者的心理康复是预防复吸最重要工作的之一;加强对戒毒后回归社会人员的管理,建立家庭社区综合康复机制,是预防复吸的重要手段;加大在广大青少年人群中禁毒的宣传力度。     

The point of no return: Up to what point should we be allowed to withdraw consent to the storage and use of embryos and gametes?

This article discusses when it is ethically acceptable to withdraw consent for the storage and use of embryos and gametes. Currently, the law in the UK states that consent to use of a gamete or embryo can be withdrawn up to the point of the embryo's transfer to the recipient's uterus or when the gamete is used in providing treatment services; that is, the ‘point of no return’. In this article, we will consider other points of no return and argue that having a single point of no return, a one size fits all form of consent can, in some cases, lead to restrictions on individuals’ autonomy and cause particular types of harm. Therefore, having different points of no return that fit different circumstances could extend autonomy and allow people to enter into agreements that are tailored more to their own particular needs and circumstances.     

Adipocyte-derived hormones in heroin addicts: the influence of methadone maintenance treatment

Heroin addiction markedly affects the nutritional and metabolic status and frequently leads to malnutrition. The aim of our study was to compare circulating concentration of adipose tissue-derived hormones leptin, adiponectin and resistin in 12 patients with heroin addiction before and after one-year methadone maintenance treatment with the group of 20 age- and body mass index-matched healthy subjects. Basal serum leptin and adiponectin levels in heroin addicts were significantly decreased (3.4+/-0.4 vs. 4.5+/-0.6 ng/ml and 18.9+/-3.3 vs. 33.9+/-3.1 ng/microl, respectively; p 0.05) while serum resistin concentrations were increased compared to healthy subjects (10.1+/-1.2 vs. 4.6+/-0.3 ng/ml; p 0.05). Moreover, positive correlation of serum leptin levels with body mass index was lost in the addicts in contrast to control group. One year of methadone maintenance treatment normalized serum leptin, but not serum adiponectin and resistin concentrations. In conclusion, circulating concentrations of leptin, adiponectin and resistin are markedly altered in patients with chronic heroin addiction. These alterations appear to be relatively independent of nutritional status and insulin sensitivity.     

Genetic association analyses of PDYN polymorphisms with heroin and cocaine addiction

Genetic factors are believed to account for 30-50% of the risk for cocaine and heroin addiction. Dynorphin peptides, derived from the prodynorphin (PDYN) precursor, bind to opioid receptors, preferentially the kappa-opioid receptor, and may mediate the aversive effects of drugs of abuse. Dynorphin peptides produce place aversion in animals and produce dysphoria in humans. Cocaine and heroin have both been shown to increase expression of PDYN in brain regions relevant for drug reward and use. Polymorphisms in PDYN are therefore hypothesized to increase risk for addiction to drugs of abuse. In this study, 3 polymorphisms in PDYN (rs1022563, rs910080 and rs1997794) were genotyped in opioid-addicted [248 African Americans (AAs) and 1040 European Americans (EAs)], cocaine-addicted (1248 AAs and 336 EAs) and control individuals (674 AAs and 656 EAs). Sex-specific analyses were also performed as a previous study identified PDYN polymorphisms to be more significantly associated with female opioid addicts. We found rs1022563 to be significantly associated with opioid addiction in EAs [P = 0.03, odds ratio (OR) = 1.31; false discovery rate (FDR) corrected q-value]; however, when we performed female-specific association analyses, the OR increased from 1.31 to 1.51. Increased ORs were observed for rs910080 and rs199774 in female opioid addicts also in EAs. No statistically significant associations were observed with cocaine or opioid addiction in AAs. These data show that polymorphisms in PDYN are associated with opioid addiction in EAs and provide further evidence that these risk variants may be more relevant in females.     

The Use of Propoxyphene Napsylate in the Treatment of Heroin and Methadone Addiction

The use of methadone in the treatment of heroin addiction continues to be controversial. Propoxyphene napsylate (Darvon N®) is a possible alternative and a pilot study was conducted to test its acceptability, safety and clinical efficacy in treating long term, “multi-relapse” heroin addicts.Findings indicate that propoxyphene napsylate suppresses many of the symptoms associated with opioid withdrawal phenomena. It should be viewed as a very promising therapeutic tool to be used in conjunction with psychological counseling and socio-vocational rehabilitation in detoxification and maintenance therapy for heroin or methadone addiction.     

Idling in Mao’s Shadow: Heroin Addiction and the Contested Therapeutic Value of Socialist Traditions of Laboring

The Chinese government has come under attack by international critics for forcing drug users to labor in the name of treatment. While joining these activists in criticizing conditions in compulsory labor centers, former detainees who congregated at a drop-in center in southern Yunnan also defended the therapeutic potential of socialist legacies of laboring. Shuttling between laboring in state compulsory centers and idling in a market economy, long-term heroin users saw their difficulties in recovering from addiction as inextricably linked to their inability to find suitable work opportunities. Certain drop-in center attendees maintained that earlier Communist laboring projects had helped wayward citizens, including drug addicts, “merge into” society as productive workers. This group evoked the stable long-term jobs and benefits once provided by local state-owned enterprises and the radical revolutionary power of “remolding through labor” they imagined to have existed in the first years of the People’s Republic as powerful alternatives to their recent crisis of idling. The nuanced ways that drop-in center regulars revisited the potential healing power of earlier traditions of socialist laboring as remedies to their contemporary struggles complicates long-standing debates about coercion in treatment and the responsibility of the postsocialist state towards marginalized workers.     

Informed consent and nudging

In order to avoid patient abuse, under normal situations before performing a medical intervention on a patient, a physician must obtain informed consent from that patient, where to give genuine informed consent a patient must be competent, understand her condition, her options and their expected risks and benefits, and must expressly consent to one of those options. However, many patients refrain from the option that their physician believes to be best, and many physicians worry that their patients make irrational healthcare decisions, hindering their ability to provide efficient healthcare for their patients. Some philosophers have proposed a solution to this problem: they advocate that physicians nudge their patients to steer them towards their physician's preferred option. A nudge is any influence designed to predictably alter a person's behavior without limiting their options or giving them reasons to act. Proponents of nudging contend that nudges are consistent with obtaining informed consent. Here I argue that nudging is incompatible with genuine informed consent, as it violates a physician's obligation to tell their patients the truth, the whole truth, and nothing but the truth during adequate disclosure.