medRxiv
July 19, 2026
Naama Levy‐Cooperman, Edward M. Sellers, Paul Glue et al.
Psilocybin shows therapeutic promise for several psychiatric disorders, but the acute perceptual and cognitive alterations produced by conventional doses (10-25 mg) require in-clinic supervision, which limits scalability. Whether the therapeutically relevant pharmacology of psilocybin can be separated from its hallucinogenic activity remains unresolved. To address this gap, we conducted a Phase...
The International Journal of Neuropsychopharmacology
July 6, 2026
Shabah M. Shadli, Neda Nasrollahi, Calvin K. Young et al.
BACKGROUND: Neurotic disorders - major depressive disorder (MDD), panic disorder, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and specific phobia - have differing pharmaceutical profiles. But all, even when resistant to conventional treatment (TR), respond quickly to low dose (0.5-1.0 mg/kg I.M.) ketamine....
The British Journal of Psychiatry
July 6, 2026
Nick Glozier, Richard W. Morris, Elizabeth Stratton et al.
BACKGROUND: Longer-term outcome and safety data of repeated subcutaneous racemic ketamine for treatment-resistant depression (TRD) is lacking, as is knowledge of the impact of prior ketamine treatment on subsequent response. AIMS: To evaluate the effectiveness and safety of a 4-week course of subcutaneous racemic ketamine over 6 months and investigate whether prior ketamine treatment influences...
J Clin Pharmacol
June 1, 2026
Paul Glue, Ben Beaglehole
Ketamine is a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) glutamate receptor. It was approved by the US Food and Drug Administration for anesthesia in 1970. The only other related US regulatory approval since then has been for esketamine nasal spray for depression in 2019. Over this time ketamine has been repurposed by mainly academic researchers, reporting clinical activity...
Archives of suicide research : official journal of the International Academy for Suicide Research
May 9, 2026
Gregory Carter, Maree Hackett, Stevan Nikolin et al.
Ketamine has disputed effects on suicidal ideation scores in depressed populations. This study assessed effectiveness of ketamine in adults with treatment resistant depression, examining a secondary outcome of suicidal ideation. Phase III, double-blind, randomized, active-controlled, multicenter trial. Participants were randomized to twice-weekly subcutaneous racemic ketamine or midazolam for 4...
Wilderness & environmental medicine
March 18, 2026
Elizabeth E Davidson, Sean L Davidson, Paul Glue
Anomalous perceptual experiences (APEs) have been reported anecdotally in ultra-endurance athletes. These experiences occur in the absence of psychiatric illness and may reflect the effects of extreme physiologic and environmental stressors. However, the literature is fragmented and terminology inconsistent, limiting understanding of the nature, prevalence, and mechanisms of these experiences....
Journal of the Royal Society of New Zealand
February 1, 2026
Neil McNaughton, Shabah M. Shadli, Ben Beaglehole et al.
The neurotic disorders (e.g., depression, dysthymia, generalized anxiety disorder, panic disorder, agoraphobia, social anxiety, post-traumatic stress disorder, and obsessive-compulsive disorder) are costly and difficult to treat. Diagnosis is based on symptoms not biological causes. Here, we summarize New Zealand-based work developing EEG biomarkers and novel treatments. Working at the...
Journal of Affective Disorders
October 15, 2025
Mary Lou Chatterton, Johana Kevin Perez, Thao Thai et al.
2 citations
Ketamine is effective for treatment resistant depression (TRD); but cost-effectiveness evidence remains limited. To evaluate the cost-effectiveness of subcutaneous ketamine for TRD from health sector and societal perspectives. A cost-utility analysis alongside the KADS randomised controlled trial (RCT) involved 174 participants receiving ketamine or midazolam (active control) twice weekly for 4...
BJPsych Open
October 1, 2025
Ben Beaglehole, Paul Glue, Shona Neehoff et al.
5 citations
We provide preliminary support for the efficacy and tolerability of i.m. ketamine in a community sample of individuals with PTSD. Further work is required to establish the optimal dosing regimen and longer-term role of ketamine in treatment of PTSD, but our findings are encouraging given the well-known of treatments in this area.
Journal of psychopharmacology (Oxford, England)
June 5, 2025
Ben Beaglehole, Paul Glue, Shona Neehoff et al.
19 citations
We previously completed a double-blind randomised crossover study assessing intramuscular ketamine for treatment-resistant depression (TR-D), post-traumatic stress disorder (TR-PTSD) and obsessive-compulsive disorder (TR-OCD). Here, we report an extension study to explore the ongoing benefits and tolerability of maintenance oral ketamine. All participants from the original study were eligible...
The British journal of psychiatry : the journal of mental science
January 7, 2025
Natalie T Mills, Stevan Nikolin, Nick Glozier et al.
3 citations
Retracted
Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties. To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD. The Ketamine for Adult Depression Study was a multisite 4-week randomised, double-blind, active...
Journal of psychopharmacology (Oxford, England)
2025
Ben Beaglehole, Paul Glue, Shona Neehoff et al.
12 citations
Obsessive-Compulsive Disorder (OCD) may respond to ketamine treatment. To examine the responsiveness and tolerability of treatment-refractory OCD to intramuscular (IM) ketamine compared to IM fentanyl. This was a randomised double-blind psychoactive-controlled study with single doses of racemic ketamine 0.5 mg/kg, 1.0 mg/kg or fentanyl 50 µg (psychoactive control). Pre-dosing with 4 mg oral...
Psychedelic Medicine
October 15, 2024
Thivya Turner, Paul Glue
1 citation
Background: The underlying mechanism(s) of action of psychedelic-assisted therapy (PAT) to reduce distress, depression, and/or anxiety symptoms in life-threatening illness are poorly understood. It has been postulated that addressing death anxiety, and components of spiritual and existential distress, may be mediating factors. Method: This systematic review describes the current evidence base...
Nature Medicine
July 1, 2024
Paul Glue, Colleen Loo, Johnson Fam et al.
60 citations
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 multicenter clinical trial, male and female adult patients with TRD and Montgomery-Asberg Depression...
Trials
May 21, 2024
Chiranth Bhagavan, Paul Glue, Will Evans et al.
7 citations
Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6 months in this patient group. Drawing upon related therapeutic mechanisms,...
BMJ Open
May 1, 2024
Ben Beaglehole, Richard Porter, Katie Douglas et al.
5 citations
Although short-term benefits follow parenteral ketamine for treatment-resistant major depressive disorder (TR-MDD), there are challenges that prevent routine use of ketamine by clinicians. These include acute dissociative effects of parenteral ketamine, high relapse rates following ketamine dosing and the uncertain role of psychotherapy. This randomised controlled trial (RCT) seeks to establish...
BJPsych Open
October 13, 2023
Ben Beaglehole, Paul Glue, Mike Clarke et al.
9 citations
Background The evidence base for racemic ketamine treatment for treatment-resistant major depressive disorder (TRD) continues to expand, but there are major challenges translating this evidence base into routine clinical care. Aim To prepare guidelines for ketamine treatment of TRD that are suitable for routine use by publicly funded specialist mental health services. Method We consulted with...
British Journal of Psychiatry
July 14, 2023
Colleen Loo, N. Glozier, David Barton et al.
70 citations
Background Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. Aims To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au. Method This phase 3,...
Journal of psychopharmacology (Oxford, England)
February 1, 2021
Dylan Truppman Lattie, Hayley Nehoff, Shona Neehoff et al.
13 citations
Ketamine has rapid anxiolytic effects in treatment-resistant obsessive compulsive, post-traumatic stress, generalised anxiety and social anxiety disorders. This study aimed to assess changes following acute and maintenance ketamine therapy on the Fear Questionnaire (FQ) subscales and the Spielberger State Anxiety Inventory (SSAI). This secondary analysis used data from a mixed open-label and...
Journal of Psychopharmacology
March 1, 2020
Paul Glue, Shona Neehoff, A. Sabadel et al.
97 citations
Background: We previously reported that ketamine has anxiolytic effects in patients with treatment-resistant generalized anxiety and social anxiety disorders. Aims: The purpose of this study was to replicate our earlier report about ketamine‘s anxiolytic activity, using a more robust study design. Methods: This was a double-blind, psychoactive-controlled ascending dose study in 12 patients with...
Journal of clinical pharmacology
February 17, 2020
Paul Glue, Natalie J. Medlicott, Peter Surman et al.
44 citations
Parenteral ketamine has fast‐onset antidepressant and antianxiety effects; however, it causes dissociation, hypertension, and tachycardia shortly after dosing. Ketamine's antidepressant effects may be due to active metabolites rather than to ketamine itself. We hypothesized that oral controlled‐release ketamine tablets would improve safety and tolerability compared with injected ketamine by...
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 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.
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...
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...