Paul Glue

University of Otago, Taieri, Otago, New Zealand

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Publications (80)299.92 Total impact

  • Christopher Gale · David Menkes · Paul Glue
    BMJ (online) 08/2015; 351. DOI:10.1136/bmj.h4315 · 17.45 Impact Factor
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    ABSTRACT: Use of synthetic cannabinoids is associated with a range of mental health harms. The 2013 Psychoactive Substances Act (PSA) was intended to limit retail availability of synthetic cannabinoids which had acceptable safety profiles. We evaluated numbers and clinical characteristics of patients presenting with mental health harms associated with use of synthetic cannabinoids for three months before and after implementation of the PSA on 18July 2013. Retrospective audit of case notes of patients presenting to an emergency psychiatric service (EPS) in Dunedin. In the three months post-PSA, there was a 42% reduction in EPS contacts and 52% reduction in patient presentations, compared with the three months pre-PSA. Patient demographics (predominantly young males with prior contact with mental health services), presenting symptoms (mood and psychotic symptoms and suicidality), and management and disposition were identical in both periods. The decrease in mental health harms, as measured by frequency of EPS contacts, appeared to be due to reduced retail availability of synthetic cannabinoids rather that reduced toxicity of available products.
    The New Zealand medical journal 06/2015; 128(1414):15-19.
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    ABSTRACT: Evaluation of noribogaine safety, pharmacokinetics and effects on opioid withdrawal in methadone-dependent patients Paul Gluea, Michelle Lockhartb, Fred Lamc, Noelyn Hungc, C Tak Hungc, Donna Tunnicliffed, Gavin Caped, Jane Devanee, Holger Weise, John Howese and Lawrence Friedhofff aUniversity of Otago, Dunedin, New Zealand; bUniversity of Auckland, NZ; cZenith Technology Ltd, Dunedin, NZ; dCommunity Alcohol and Drug Service, Dunedin, NZ; eDemeRx, Inc., Fort Lauderdale, Florida, USA; fPharmaceutical Special Projects Group, LLC Introduction: The iboga alkaloids appear to have striking efficacy for treatment of substance dependence in individual and case series reports, but no blinded, controlled clinical trials have been performed. This study tested single doses of noribogaine hydrochloride (NI), an analog of ibogaine, in opioid-dependent patients. Objectives: To evaluate the safety, tolerability, pharmacokinetics (PK) and changes in withdrawal ratings after single doses of NI or placebo (PLA) administered to opioid-dependent patients. Methods: This was a phase 1B, randomized, double-blind, placebo-controlled, single ascending dose study in 27 patients seeking to discontinue methadone opioid substitution treatment (OST). The study was conducted in 3 cohorts each with 6 active and 3 placebo patients. NI doses were 60mg, 120mg or 180mg. 1 week prior to NI administration, methadone was replaced by oral, controlled-release morphine (6 days) followed by 1 day of oral immediate-release (IR) morphine. On the NI treatment day, a single dose of IR morphine was administered followed 2 hours later by a single blinded oral dose of NI or PLA. Patients resuming OST received morphine within 24h of blinded NI/PLA dosing, and methadone post-24h. PK blood samples were collected for 7 days following NI/PLA. Safety assessments were conducted to Day 21 (±3) following NI/PLA. Safety monitoring included: physical examinations, vital signs, serum chemistry, hematology, urinalysis, 12 lead ECGs, Holter monitoring, telemetry, oximetry, capnography, pupillometry, opioid withdrawal rating scales and mood VAS. Results: NI was well tolerated. In addition to signs and symptoms of opioid withdrawal, the most frequent treatment-emergent adverse events were headache and nausea. Non-euphoric changes in light perception occurred at ~1h post dosing and decreased/disappeared by 2.5-3h post-dose. NI peak concentrations occurred 2-4 hours post-dose, with dose-linear increases for AUC and Cmax. The drug was slowly eliminated with t1/2 estimates of 24-30 hours across dose groups. There was a concentration-dependent increase in QTcI (0.17msec/ng/mL) and dose-dependent peak increases in QTcI of ~16msec, 28msec, and 42msec in the 60mg, 120mg, and 180mg groups, respectively. There were no changes in vital signs or safety laboratory tests. There were no statistical differences between the mean time to OST in the NI cohorts vs PLA. The 120mg cohort had the longest time to OST resumption with trend significance vs PLA. NI showed a trend to decrease total scores in the opioid withdrawal rating scales, most notably at the 120mg dose, but the study was not powered for this endpoint. Conclusions: NI pharmacokinetic parameters in opioid-dependent patients were similar to those from a prior healthy volunteer study. NI was well tolerated. The main safety finding was a concentration-dependent increase in QTcI. QTc increases from NI continued to decline after restarting methadone. The lack of statistically significant dose-related changes in time to OST resumption could be due to the small number of patients, and possible contamination effects from co-localization of patients during the in-patient portion of the study. Future multiple-dose NI studies are planned, using dosing regimens to limit changes in QTc.
    The 46th ASAM Annual Conference, Austin, Texas, USA; 04/2015
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    ABSTRACT: Noribogaine is the active metabolite of the naturally occurring psychoactive substance ibogaine, and may help suppress withdrawal symptoms in opioid dependent subjects. The objectives of this Phase I study were to assess the safety, tolerability, pharmacokinetic and pharmacodynamic profile of noribogaine. In this ascending single-dose, placebo-controlled, randomised, double-blind, parallel-group study in 36 healthy drug-free male volunteers, four cohorts (n=9) received oral doses of 3, 10, 30 or 60mg or matching placebo, with intensive safety and pharmacokinetic assessments out to 216h, along with pharmacodynamic assessments sensitive to the effects of mu-opioid agonists. Noribogaine was rapidly absorbed, with peak concentrations occurring 2-3 hours after oral dosing, and showed dose-linear increases of AUC and Cmax between 3-60mg. The drug was slowly eliminated, with mean half-life estimates of 28-49 hours across dose groups. Apparent volume of distribution was high (mean 1417-3086 L across dose groups). No safety or tolerability issues were identified in any cohort. No mu-opioid agonist pharmacodynamic effects were noted in pupillometry or cold-pressor testing. Single oral doses of noribogaine 3-60mg were safe and well tolerated in healthy volunteers.
    The Journal of Clinical Pharmacology 02/2015; 55(2). DOI:10.1002/jcph.404 · 2.48 Impact Factor
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    ABSTRACT: Conversion of ibogaine to its active metabolite noribogaine appears to be mediated primarily by CYP2D6. We compared 168 h pharmacokinetic profiles of both analytes after a single oral 20 mg dose of ibogaine in 21 healthy subjects who had been pretreated for 6 days with placebo or the CYP2D6 inhibitor paroxetine. In placebo-pretreated subjects, ibogaine was rapidly converted to noribogaine. Median peak noribogaine concentrations occurred at 4 h. Compared with placebo-pretreated subjects, paroxetine-pretreated subjects had rapid (Tmax = 1.5 h) and substantial absorption of ibogaine, with detectable levels out to 72 h, and an elimination half-life of 10.2 h. In this group, ibogaine was also rapidly converted to noribogaine with a median Tmax of 3 h. Extent of noribogaine exposure was similar in both groups. CYP2D6 phenotype was robustly correlated with ibogaine AUC0-t (r = 0.82) and Cmax (r = 0.77). Active moiety (ibogaine plus noribogaine) exposure was ∼2-fold higher in paroxetine-pretreated subjects. Single 20 mg ibogaine doses were safe and well tolerated in all subjects. The doubling of exposure to active moiety in subjects with reduced CYP2D6 activity suggests it may be prudent to genotype patients awaiting ibogaine treatment, and to at least halve the intended dose of ibogaine in CYP2D6 poor metabolizers. This article is protected by copyright. All rights reserved
    The Journal of Clinical Pharmacology 02/2015; 55(6). DOI:10.1002/jcph.471 · 2.48 Impact Factor
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    Australian and New Zealand Journal of Psychiatry 01/2015; 49(1):9-12. DOI:10.1177/0004867414563453 · 3.41 Impact Factor
  • JAMA Psychiatry 11/2014; 71(11):1298-9. DOI:10.1001/jamapsychiatry.2014.673 · 12.01 Impact Factor
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    ABSTRACT: Aims: To evaluate the influence of the Otago Medical Programme's rural entry pathway and rural immersion programme on postgraduate medical training and location. Methods: Retrospective cohort study of 2008-2011 medical school graduates. Rural background/training included students gaining preferential entry to medical training based on rural residence or schooling, and/or those who spent a year training in a rural setting. Postgraduate medical training and location were obtained from the NZ Medical Register in December 2013. Results: 112/733 students (15.3%) had rural background/training. Significantly more students with rural background/training were training in rural hospital medicine or general practice after graduation. Multiple logistic regression identified both variables (rural background and rural training) as independently statistically significant (Odds Ratios (95%CI); rural background OR 2.1, 95%CI 1.2-3.6; rural training OR 2.5, 95%CI 1.4-4.5; p=0.002). Almost twice as many students with rural background/training were working in non-Major Urban Centres. Conclusions: These findings are similar to international reports on the influence of medical schools' rural initiatives on postgraduate training choices and practice location. University policies aimed at increasing the proportion of medical graduates practising in rural areas appear to be working as intended.
    The New Zealand medical journal 10/2014; 127(1403):12-16.
  • Biological psychiatry 08/2014; 76(3):e1-2. DOI:10.1016/j.biopsych.2013.12.010 · 10.26 Impact Factor
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    ABSTRACT: Introduction Anxiety disorders are among the most common mental illness in the western world with a major impact on disability. But their diagnosis has lacked objective biomarkers. We previously developed [1,2] a human EEG anxiety biomarker, goal-conflict-specific-rhythmicity (GCSR) in the stop signal task (SST). GCSR is extracted from human scalp EEG by subtracting the average power in approach and avoidance from that in conflict. Our previous SST was identical to that of Aron et al [3] and had an imbalance in the numbers of short (avoid), medium (conflict) and long (approach) trials as these were simply sorted into 3 groups, with no clear division between them. Here we tested an SST with non-overlapping short and long SSDs set as a proportion of the average Go reaction time [4] with medium SSDs tracking 50% correct stopping as usual. We report: an increased GCSR; an extended frequency band; positive relations to measures of neuroticism and trait anxiety; validation with three different classes of anxiolytic drugs; and confirmation of right frontal source localisation. Methods Personality was assessed with 14 participants (8 female, 6 male); drugs with 34 (18 female, 16 male); and localization with 8 (4 female, 4 male)-age range was 18-30 years. They filled out the EPQ-R, BIS/BAS and STAI-Y questionnaires. EEG recorded at F8, with a 1s Hanning window centred on the 500ms after the stop signal was analysed on stop trials, paired with a matching time for the previous go trial. Fig. 1 shows a schematic of the SST. Thirty simple choice reaction time trials were followed by 3 blocks of 128 trials with 1 stop trial in each set of 4 trials. If Go reaction time during stop testing exceeded 1.5 times simple choice reaction time, a warning message was delivered. One short (20% of mean GoRT in last 16 trials), long (80% of mean GoRT) and medium (tracking 50% correct stopping [3]) SSD occurred, balanced, within each set of 3 stop trials. A pure repeated measures analysis of trial type (go/stop), SSD (short, medium, long), and frequency (4-12Hz in 1 Hz steps) tested the variation in frequency of the interaction of type with the quadratic component of SSD (i.e. the difference in power between the medium and the average of the short and long SSDs). The drug experiment had four groups: placebo, buspirone (10mg), triazolam (0.25mg) and pregabalin (25mg), which were balanced on entry (1:1:1:1) with a block size of four. Over-encapsulation allowed double blind administration. Source localization of high density (128 channels) EEG was performed using standardized low-resolution electromagnetic tomography (sLORETA) over 128 channels using SnPM. Conclusion GCSR, in our new SST should be suitable as a biomarker for an anxiolytic-sensitive disorder in testing of groups, screening of novel anxiolytic drugs, and development of measures suitable for individual diagnosis.
    International Conference on Cognitive Neuroscience, Brisbane, Australia; 07/2014
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    ABSTRACT: Objectives. Research studies have reported impressive antidepressant effects with ketamine but significant knowledge gaps remain over the best method of administering ketamine, and the relationships between dose, antidepressant response and adverse effects. Methods. In this pilot dose-finding study, the efficacy and tolerability of ketamine given by rapid intravenous (i.v.) infusion were assessed in a double-blind, placebo-controlled, crossover design, in four subjects with treatment- resistant depression. Each subject received up to four i.v. doses of ketamine (0.1, 0.2, 0.3, 0.4 mg/kg), given over 2–5 min, 1 week apart, and one randomly inserted placebo treatment. Results. Three of four subjects achieved antidepressant response (≥ 50% decrease in Montgomery–Asberg Depression Rating Scale scores), two at the minimum 0.1 mg/kg dose, though all relapsed within a week. For two subjects, the greatest improvement occurred at the highest dose received. Rapid infusion over 2 min led to significant adverse psychotomimetic effects which also increased proportionately with ketamine dosage. Conclusions. This is the first trial to present dose–response data of ketamine efficacy and psychomimetic effects in depressed subjects. Antidepressant efficacy may be dose-related. Psychotomimetic effects were dose-related. Rapid infusion over 2 min may not be a feasible clinical approach to treatment, given poor tolerability.
    The World Journal of Biological Psychiatry 06/2014; 15:579-584. DOI:10.3109/15622975.2014.922697 · 4.18 Impact Factor
  • The World Journal of Biological Psychiatry 06/2014; · 4.18 Impact Factor
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    ABSTRACT: Objectives: To examine situations in which compulsory treatment was not approved by the second opinion required under New Zealand's Mental Health Act. Methods: Qualitative and quantitative analysis of 11 index cases where full approval of treatment was not given and of 33 matched controls. Results: The reasons for non-approval of treatment were diverse. Following non-approval, intensive consultation occurred, reflecting significant disagreement between clinicians. The process of resolution included discharge from the Act, patients consenting to treatment and alternative treatment plans. Compared with controls, index cases had significantly lower rates of being mentally well in the community over the subsequent year. Conclusions: Non-approval marks a group of patients with very poor clinical outcome. Explicit processes are needed to manage non-approval of compulsory treatment plans.
    Australasian Psychiatry 06/2014; 22(4). DOI:10.1177/1039856214537879 · 0.47 Impact Factor
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    ABSTRACT: Older adults (≥60 years) perform worse than young adults (18-30 years) when recognizing facial expressions of emotion. The hypothesized cause of these changes might be declines in neurotransmitters that could affect information processing within the brain. In the present study, we examined the neuropeptide oxytocin that functions to increase neurotransmission. Research suggests that oxytocin benefits the emotion recognition of less socially able individuals. Men tend to have lower levels of oxytocin and older men tend to have worse emotion recognition than older women; therefore, there is reason to think that older men will be particularly likely to benefit from oxytocin. We examined this idea using a double-blind design, testing 68 older and 68 young adults randomly allocated to receive oxytocin nasal spray (20 international units) or placebo. Forty-five minutes afterward they completed an emotion recognition task assessing labeling accuracy for angry, disgusted, fearful, happy, neutral, and sad faces. Older males receiving oxytocin showed improved emotion recognition relative to those taking placebo. No differences were found for older females or young adults. We hypothesize that oxytocin facilitates emotion recognition by improving neurotransmission in the group with the worst emotion recognition.
    Neurobiology of Aging 04/2014; 35(10). DOI:10.1016/j.neurobiolaging.2014.04.021 · 5.01 Impact Factor
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    ABSTRACT: Aims and method We compared findings of an audit of New Zealand's version of the second opinion appointed doctor (SOAD) scheme with published information on the equivalent scheme for England and Wales, to consider what might be learnt from the different jurisdictions' experience. Results Strong similarities exist between the two schemes in the demographic profile of individuals subject to the SOAD process and rates of approval of compulsory treatment. The clearer legal framework for the English scheme and its supervision by an independent national agency may offer significant advantages in terms of consistency and transparency, compared with the informal, decentralised structure of New Zealand's scheme. Clinical implications Clinicians may not always favour greater formality or elaborate national structures for administering the Mental Health Act, but there are advantages in promoting clarity and consistency in a mandatory statutory process designed to protect compulsory patients' rights.
    04/2014; 39(2):69-73. DOI:10.1192/pb.bp.113.046540
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    ABSTRACT: Auckland and Otago medical programmes have different methods for selecting students. This study compared postgraduate retention in New Zealand (NZ) of medical graduates from the two medical programmes, to assess whether different selection methods influenced retention. Other variables assessed included entrance category and age at graduation. Anonymised databases were created of all graduates from the Otago Faculty of Medicine (1999-2011) and the Auckland medical programme (2000-2012). Demographic and entry category data were recorded. Retention was defined as presence on the NZ Medical Register in December 2012. Risk differences (RD) were calculated to compare retention between the two medical programmes using the Mantel-Haenszel method. The influence of medical programme entrance category on retention was also tested. The influence of covariates on retaining graduates on the register was evaluated using a multiple logistic regression model. The postgraduate retention of graduates of the two medical programmes over 13 years was identical (Auckland 74.9%, Otago 73.6%, P=0.48). Retention of graduate and non-graduate entry students from both medical programmes was similar by 6 years after graduation. Age during medical school did not affect retention. University of attendance had no effect on postgraduation retention of students on the NZ Medical Register, suggesting that retention is not influenced by the different student selection methods at each programme. The data presented shows that New Zealand graduates regardless of programme completed show a similar profile in terms of retention.
    The New Zealand medical journal 01/2014; 127(1388):47-54.
  • Open Journal of Psychiatry 01/2014; 04(02):99-103. DOI:10.4236/ojpsych.2014.42014
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    ABSTRACT: Objectives: There are wide global variations in electroconvulsive therapy (ECT) use patterns. This audit reviewed patient-level ECT use patterns over 10 years at a single New Zealand clinic, including factors associated with clinical response and patterns of repeated administration. Methods: Retrospective audit of all 2003-2012 ECT and clinical file data. Results: A total of 199 patients received ECT, which was used to treat mostly affective disorders in a predominantly female, older population, generally with a single course of treatment. There were different demographics and patterns of ECT use between patients being treated for affective and psychotic disorders. Overall treatment response was high, with over 90% of patients having a full or partial response. Treatment response was not associated with diagnosis, gender, or medication use, but showed a trend in significance for greater response in elderly patients. Conclusions: ECT use patterns in Otago New Zealand are similar to those reported in Australia, USA, and UK, although yearly use rate in Otago is lower. Because of their different demographic and ECT treatment patterns, future studies should report data for patients with affective and psychotic disorders separately.
    Australian and New Zealand Journal of Psychiatry 11/2013; 48(6). DOI:10.1177/0004867413514119 · 3.41 Impact Factor
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    ABSTRACT: Voriconazole is more effective for aspergillosis infections with central nervous system involvement than other antifungal agents. The clinical efficacy of voriconazole for central nervous system infections has been attributed to its ability to cross the blood-brain barrier. However, pharmacokinetic studies are limited to plasma and cerebrospinal fluid, so it remains unclear how much of the drug enters the brain. Fluorinated compounds such as voriconazole can be quantified in the brain using fluorine-19 magnetic resonance spectroscopy (MRS). Twelve healthy adult males participated in a pharmacokinetic analysis of voriconazole levels in the brain and plasma. Open-label voriconazole was dosed per clinical protocol with a loading dose of 400 mg every 12 h on day 1, followed by 200 mg every 12 h administered orally over a 3-day period. MRS was performed before and after dosing on the third day. Voriconazole levels in the brain exceeded the MIC for Aspergillus. The brain/plasma ratios were 3.0 at steady state on day 3 (predose) and 1.9 postdose. We found that voriconazole is able to penetrate the brain tissue, which can be quantified using a noninvasive MRS technique. (This study has been registered at under registration no. NCT00300677.)
    Antimicrobial Agents and Chemotherapy 08/2013; 57(11). DOI:10.1128/AAC.00394-13 · 4.48 Impact Factor
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    JAMA Psychiatry 08/2013; 70(8):880-1. DOI:10.1001/jamapsychiatry.2013.1320 · 12.01 Impact Factor

Publication Stats

772 Citations
299.92 Total Impact Points


  • 2009–2015
    • University of Otago
      • • Department of Psychological Medicine (Dunedin)
      • • Department of Medicine (Dunedin)
      Taieri, Otago, New Zealand
  • 2003–2010
    • Pfizer Inc.
      • Pfizer Pharmaceuticals Group
      New York City, New York, United States
  • 2007
    • University of Toronto
      • Department of Medicine
      Toronto, Ontario, Canada