Therapeutic Advances in Psychopharmacology
2020
Paul Glue, Natalie J. Medlicott, Shona Neehoff et al.
43 citations
Background: Ketamine’s defining side effects are dissociation and increased blood pressure/heart rate. An oral formulation with delayed absorption could minimize these effects. We recently reported safety and tolerability data for an extended release ketamine tablet in healthy volunteers. Methods: To assess safety, tolerability, efficacy, and pharmacokinetics of an extended release oral...
Journal of Psychopharmacology
October 2018
Martin Le Nedelec, Paul Glue, Helen Winter et al.
Ketamine has been shown to produce a rapid and potent antidepressant response in patients with treatment-resistant depression. Currently ketamine is most commonly administered as a 40-minute intravenous infusion, though it is unknown whether this is the optimal route of administration. To determine the plasma concentration time course of the R- and S-enantiomers of ketamine and norketamine...
The International Journal of Neuropsychopharmacology
August 1, 2018
Shabah Mohammad Shadli, Tame Kawe, Daniel Martin et al.
Ketamine is swiftly effective in a range of neurotic disorders that are resistant to conventional antidepressant and anxiolytic drugs. The neural basis for its therapeutic action is unknown. Here we report the effects of ketamine on the EEG of patients with treatment-resistant generalized anxiety and social anxiety disorders. Twelve patients with refractory DSM-IV generalized anxiety disorder...
Journal of Psychopharmacology
June 2018
Paul Glue, Shona Neehoff, Natalie J. Medlicott et al.
In this maintenance treatment study, we sought to evaluate the effect on anxiety ratings, safety and tolerability of 3 months of weekly ketamine in 20 patients with treatment-refractory DSM IV generalised anxiety disorder (GAD) and/or social anxiety disorder (SAD), and subsequent assessment of remission post-treatment. This was an uncontrolled open-label study in 20 patients who had been...
Drug delivery and translational research
June 2018
Martin Le Nedelec, Paul Glue, Helen Winter et al.
Peripheral BDNF changes after ketamine administration have been proposed as a biomarker for brain BDNF changes. However, published data are conflicting and come from studies in paired animal groups. This study determined the time course of plasma BDNF concentrations following the administration of a single 10 mg/kg dose of ketamine by different routes of administration in rats. Brain BDNF...
Journal of Psychopharmacology
April 2018
Verònica Gálvez, Adrienne Li, Christina Huggins et al.
Ketamine research in depression has mostly used intravenous, weight-based approaches, which are difficult to translate clinically. Intranasal (IN) ketamine is a promising alternative but no controlled data has been published on the feasibility, safety and potential efficacy of repeated IN ketamine treatments. This randomised, double-blind, placebo-controlled pilot study compared a 4-week course...
Journal of Affective Disorders
December 1, 2017
Shona Neehoff, Paul Glue
8 citations
• A number of reasons might explain the different findings between two evaluations of CADSS performance.
American Journal of Geriatric Psychiatry
November 2017
Duncan George, Verònica Gálvez, Donel Martin et al.
To assess the efficacy and safety of subcutaneous ketamine for geriatric treatment-resistant depression. Secondary aims were to examine if repeated treatments were safe and more effective in inducing or prolonging remission than a single treatment. In this double-blind, controlled, multiple-crossover study with a 6-month follow-up (randomized controlled trial [RCT] phase), 16 participants (≥60...
Journal of Psychopharmacology
October 1, 2017
Cameron Castle, Andrew Gray, Shona Neehoff et al.
20 citations
Patients receiving ketamine for refractory depression and anxiety report dissociative symptoms in the first 60 min post-dose. The most commonly used instrument to assess this is the Clinician-Administered Dissociative States Scale (CADSS), developed based on the assessment of patients with dissociative symptoms. Its psychometric properties for ketamine-induced dissociation have not been...
Journal of Psychopharmacology
October 2017
Paul Glue, Natalie J. Medlicott, Sarah Harland et al.
The N-methyl-D-aspartate receptor antagonist ketamine has rapid onset activity in treatment-resistant depression, post-traumatic stress disorder and obsessive compulsive disorder. Due to similarities in brain network activity in depression and anxiety disorders, we hypothesized that ketamine might also be active in other refractory anxiety disorders. We evaluated the efficacy and safety of...
Clinical Pharmacology in Drug Development
November 1, 2016
Paul Glue, Gavin Cape, Donna Tunnicliff et al.
66 citations
Ibogaine is a psychoactive substance that may reduce opioid withdrawal symptoms. This was the first clinical trial of noribogaine, ibogaine's active metabolite, in patients established on methadone opioid substitution therapy (OST). In this randomized, double-blind, placebo-controlled single ascending-dose study, we evaluated the safety, tolerability, and pharmacokinetics of noribogaine in 27...
Journal of Ethnopharmacology
August 2, 2016
Bridget Forsyth, Liana Machado, Tim Jowett et al.
35 citations
Root bark from Tabernanthe iboga has been used traditionally in West Africa as a psychoactive substance in religious rituals. In smaller doses it is reported anecdotally to have stimulant properties. To evaluate the influence of a single 20mg ibogaine dose on psychological variables reflecting subjective mood state and a range of cognitive functions. 21 healthy male volunteers received single...
Acta Psychiatrica Scandinavica
July 1, 2016
C. Loo, Verònica Gálvez, E. O'Keefe et al.
This pilot study assessed the feasibility, efficacy and safety of an individual dose‐titration approach, and of the intravenous (IV), intramuscular (IM) and subcutaneous (SC) routes for treating depression with ketamine.
The Journal of Clinical Pharmacology
June 1, 2015
Paul Glue, Helen Winter, Kira Garbe et al.
39 citations
Conversion of ibogaine to its active metabolite noribogaine appears to be mediated primarily by CYP2D6. We compared 168 hours 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....
The Journal of Clinical Pharmacology
February 1, 2015
Paul Glue, Michelle Lockhart, Fred Lam et al.
61 citations
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 profiles of noribogaine. In this ascending single-dose, placebo-controlled, randomized, double-blind,...
The World Journal of Biological Psychiatry
September 1, 2014
R. Lai, Natalie Katalinic, Paul Glue et al.
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...
Paul Glue, Colleen Loo, Johnson Fam et al.
preprint
Abstract Ketamine has rapid-onset antidepressant activity in patients with treatment-resistant major depression (TRD). The safety and tolerability of racemic ketamine may be improved if given orally, as an extended release tablet (R-107), compared with other routes of administration. In this phase 2 multicentre clinical trial, adult patients with TRD and Montgomery-Asberg Depression Rating...