Heather G. Fulton

Diffusion tensor imaging and olfactory identification testing in early-stage Parkinson's disease

Evidence from imaging, clinical studies, and pathology suggests that Parkinson’s disease is preceded by a prodromal stage that predates clinical diagnosis by several years but there is no established method for detecting this stage. Olfactory impairment, which is common in Parkinson’s disease and often predates clinical diagnosis, may be a useful biomarker for early Parkinson’s. Evidence is emerging that diffusion imaging parameters might be altered in olfactory tract and substantia nigra in the early stages of clinical Parkinson’s disease, possibly reflecting pathological changes. However, no study has examined olfaction and diffusion imaging in olfactory tract and substantia nigra in the same group of patients. The present study compared newly diagnosed Parkinson’s disease patients with a matched control group using both olfactory testing and diffusion tensor imaging of the substantia nigra and anterior olfactory structures. Fourteen patients with stage 1–2 Hoehn & Yahr Parkinson’s disease were matched to a control group by age and sex. All subjects then completed the University of Pennsylvania Smell Identification Test, as well as a series of MRI scans designed to examine diffusion characteristics of the olfactory tract and the substantia nigra. Olfactory testing revealed significant impairment in the patient group. Diffusion tensor imaging revealed significant group differences in both the substantia nigra and anterior olfactory region, with fractional anisotropy of the olfactory region clearly distinguishing the Parkinson’s subjects from controls. This study suggests that there may be value in combining behavioral (olfaction) and MRI testing to identify early Parkinson’s disease. Since loss of olfaction often precedes the motor symptoms in Parkinson’s disease, the important question raised is “will the combination of olfactory testing and MRI (DTI) testing identify pre-motor Parkinson’s disease?”

Energy drink co-administration is associated with increased reported alcohol ingestion

INTRODUCTION AND AIMS While energy drinks (EDs) and alcohol have been reported to be frequently co-administered, little is known about the effect of this co-administration on alcohol drinking patterns. The purpose of the present research was to characterise patterns of ED and alcohol co-administration. DESIGN AND METHODS Seventy-two ED users were recruited from the Halifax university community. Participants provided information about their lifetime ED and other substance use, in addition to detailing instances of their ED and alcohol use during the previous week using a timeline follow-back interview. RESULTS Seventy-six per cent of participants reported ever deliberately mixing alcohol with EDs and 19% reported doing so during the previous week. Relative to alcohol drinking sessions in which EDs were not used, participants reported drinking significantly more alcohol when it was co-administered with EDs. DISCUSSION AND CONCLUSIONS Alcohol and ED co-administration is relatively common among ED users and seems to be associated with increased alcohol ingestion. It is recommended that this matter receive more clinical and research attention.

Characteristics of quetiapine misuse among clients of a community-based methadone maintenance program.

To the EditorsQuetiapine is an atypical antipsychotic approved for treatment of schizophrenia and bipolar depression. It has become an increasingly popular pharmacotherapy for anxiety and insomnia,1 with demonstrated efficacy in treating these conditions.2–4 Similar to other medications with sedativ

A Demonstration of Intravenous Nicotine Self-Administration in Humans?

Sofuoglu et al (in press) recently reported a demonstration of self-administration of intravenous (i.v.) nicotine in male and female smokers. Given the recent controversy surrounding the addictive properties of nicotine in the absence of tobacco (eg Dar and Frenk, 2004), we read this article with great interest. In this study, participants completed three experimental sessions where they could chose to receive injections from two syringes beginning 15 min after sampling both. In each experimental session, one randomly assigned syringe contained saline and the other contained a randomly assigned dose of nicotine (0.1, 0.4, 0.7 mg). The authors reported a greater preference for the 0.4 and 0.7 mg doses of nicotine relative to saline and concluded that these findings demonstrate nicotine in the absence of tobacco is reinforcing to smokers. However, we believe that this conclusion may be premature. A substantial body of evidence suggests that individuals’ expectancies regarding a substance can significantly affect how they respond to it (eg Montcrieff et al, 2004). The expectancies and, in turn, responses can be influenced to the degree by which participants are able to distinguish between the active drug and placebo based on stimulus properties (eg Testa et al, 2006; Perkins et al, 2003; Greenberg and Fisher, 1994) as well as by a priori knowledge of what substances they may be receiving (eg de la Fuente-Fernandez et al, 2001; Mitchell et al, 1996). Evidence suggests that smokers are able to correctly distinguish between nicotine and inactive placebo on the basis of their subjective effects (eg Hughes et al, 1985) and that they will show an increased preference for a substance that they believe to be nicotine irrespective of whether or not they are actually receiving it (Hughes et al, 1989). It is therefore critical for participants to be adequately blinded to the potential receipt of nicotine in order to adequately evaluate its reinforcing properties. Unfortunately, the blinding procedures in the Sofuoglu study are not clearly reported. A priori knowledge by participants that they would be selecting between nicotine, a drug they may believe they are addicted to, and an inactive placebo would be expected to confound the results, especially if they were able to distinguish between the substances. This is a particularly important consideration given the robust subjective and physiological responses reported for the self-administered nicotine doses relative to placebo in the Sofuoglu study. Interestingly, in the only previous ‘demonstration’ of i.v. nicotine self-administration in humans, participants were explicitly informed that they would be responding for either nicotine or placebo (Harvey et al, 2004). Furthermore, numerous investigations that failed to observe nicotine self-administration have used protocols that have either attempted to blind participants to the substances they would be receiving (eg Henningfield et al, 1983) or to mask the stimulus properties of the placebo (eg Perkins et al, 1996). We argue that until nicotine self-administration is demonstrated (and replicated) using paradigms that employ adequately blinded conditions, it is premature to conclude that nicotine has reinforcing properties in the absence of tobacco in humans.

The relationship between self-reported substance use and psychiatric symptoms in low-threshold methadone maintenance treatment clients

BackgroundOngoing psychiatric symptoms and substance use are common difficulties experienced by clients enrolled in methadone maintenance treatment (MMT). However, little research to date has evaluated if specific types of current substance use are related to specific types of current psychiatric symptoms. The present study investigated these relationships with a sample of clients enrolled in a low-threshold MMT program (i.e., clients are not expelled if they continue to use substances). Some clients enrolled in low-threshold programs may never achieve complete abstinence from all substances. Thus, understanding the possibly perpetuating relationships between concurrent substance use and psychiatric symptoms is important. Understanding such relationships may aid in developing possible target areas of treatment to reduce substance use and/or related harms in this population.MethodsSeventy-seven individuals were interviewed regarding methadone usage and current and past substance use. Current psychiatric symptoms were assessed using a modified version of the Psychiatric Diagnostic Screening Questionnaire (PDSQ). Relationships between types of substances used in the past 30 days and the types and number of psychiatric symptoms experienced in the same timeframe were examined.ResultsThe majority of participants (87.0%) reported using alcohol, illicit substances, non-prescribed prescription opioids, or non-prescribed benzodiazepines in the past 30 days and 77.9% of participants reported currently experiencing psychiatric symptoms at levels that would likely warrant diagnosis. Current non-prescribed benzodiazepine use was a predictor for increased severity (i.e., symptom count) of almost all anxiety and mood disorders assessed. Conversely, number and presence of generalized anxiety symptoms and presence of social phobia symptoms predicted current non-prescribed benzodiazepine and alcohol use, respectively.ConclusionsIndividuals enrolled in the present low-threshold MMT program experience a wide variety of psychiatric symptoms and continue to use a variety of substances, including opioids. There was a particularly consistent pattern of associations between non-prescribed benzodiazepine use and a variety of psychiatric symptoms (particularly anxiety) suggesting that addressing concurrent illicit benzodiazepine use and anxiety symptoms in MMT clients warrants further clinical attention and research.

Powder and crack cocaine use among opioid users: is all cocaine the same?

Objectives: Problematic cocaine use is highly prevalent and is a significant public health concern. However, few investigations have distinguished between the 2 formulations of cocaine (ie, powder and crack cocaine) when examining the characteristics of cocaine use. Moreover, research has yet to assess the patterns of powder and crack cocaine use among opioid users, a clinical population in which problematic cocaine use is increasingly common. Using a within-subjects design, this study examined whether opioid users reported different patterns and features of powder and crack cocaine use, along with distinct trajectories and consequences of use. Methods: Seventy-three clients enrolled in a low-threshold methadone maintenance treatment were interviewed regarding their lifetime use of powder and crack cocaine. Results: Compared with crack cocaine, initiation and peak use of powder cocaine occurred at a significantly younger age. In relation to recent cocaine use, participants were significantly more likely to report using crack cocaine than using powder cocaine. Differences in routes of administration, polysubstance use, and criminal activity associated with cocaine use were also found between the 2 forms of cocaine. Conclusions: Results suggest that it may not be appropriate to consider powder and crack cocaine as diagnostically and clinically equivalent. As such, researchers may wish to distinguish explicitly between powder and crack cocaine when assessing the characteristics and patterns of cocaine use among substance users and treat these 2 forms of cocaine separately in analyses.

Prescription opioid misuse: characteristics of earliest and most recent memory of hydromorphone use.

Objectives:Prescription opioid use is highly prevalent and a major physician concern. However, little is known about how individuals initiate into use of these medications or how they use them later in life. Hydromorphone is a medication of particular interest given its subjective similarities to heroin and tendency to be misused by illicit opioid users. The purpose of this study was to evaluate the characteristics of initial, and more recent, hydromorphone use occasions as remembered by a population of individuals in treatment for their opioid use. Methods:Seventy-eight clients enrolled in low-threshold methadone maintenance treatment were interviewed regarding their earliest and most recent uses of hydromorphone. Results:Hydromorphone was first used after trying many different substances (eg, tobacco, alcohol, hallucinogens, powder cocaine). Two-thirds of the sample reported initially using hydromorphone without a prescription. Participants who initially used hydromorphone without a prescription reported using for different reasons (ie, to get high, curiosity vs manage pain), via different routes of administration (ie, injection vs orally), and were more likely to co-use other substances, than those whose earliest hydromorphone use was prescribed. However, these 2 subgroups did not differ greatly during their most recent use occasion (ie, the majority reported using to avoid withdrawal, via injection; almost 50% reported co-use with other substances). Conclusions:There was considerable variability in characteristics of hydromorphone use initiation among individuals enrolled in low-threshold methadone maintenance treatment. However, later use of hydromorphone was remarkably consistent across individuals and shares many characteristics previously documented for heroin use. Additional investigations into hydromorphone are warranted, particularly given previous findings regarding the prevalence of nonmedical use of this drug and its similarities to heroin.

Substance use patterns associated with injection drug use initiation in a low-threshold methadone-maintained sample

Abstract Substance use patterns associated with the initiation of injection drug use were examined in a sample of low-threshold methadone-maintained injection drug users. Injection initiation tended to coincide with concurrent heavy alcohol and cannabis use, increasing use of stimulants such as cocaine, and the onset of prescription opioid and sedative misuse. Nearly half of the sample reported simultaneously using at least one other drug (excluding tobacco) during the first-ever injection drug use session, with alcohol being the most commonly co-administered substance. Findings suggest that specific patterns of multiple substance use may be appropriate targets for prevention of injection drug use.

357 – Characteristics of earliest and most recent injection drug use in a canadian low-threshold methadone maintenance treatment sample

Introduction Despite evidence that the majority of injection drug users (IDU) are polysubstance users and tend to have extensive substance use histories at time of first injection, little is known about the patterns of substance use associated with injection initiation. Aims/objectives To determine how injection drug use was associated with specific patterns of multiple substance use. Both concurrent (any use during a defined time period) and simultaneous (same session) polysubstance use patterns were assessed. Methods IDU receiving treatment at a low-threshold methadone maintenance clinic in Halifax, Nova Scotia, Canada completed structured interviews regarding their substance use histories. Results Injection coincided with: concurrent heavy alcohol use; increasing use of stimulants such as cocaine; and the introduction of misused prescription medications. During their most recent injection session, participants were significantly less likely to inject a stimulant, and were significantly more likely to identify an opioid as their primary drug of injection, when compared to injection initiation. Moreover, alcohol was more likely to be co-administered at time of first-ever injection, whereas prescription sedatives and crack cocaine were more likely to be co-administered during the most recent injection. Conclusions Initiation into injection tended to occur after an extensive and relatively consistent sequence of substance use. First ever and most recent injection drug use often occurred within a polysubstance context; however, the specific patterns of substance use changed with time. Findings suggest that specific patterns of multiple substance use may be appropriate targets for treatment and prevention of injection drug use.