University of Otago Pioneers Ketamine's Role in Mental Health Treatment
Radio New Zealand's recent science feature on Our Changing World, aired on April 14, 2026, has spotlighted groundbreaking work at the University of Otago exploring ketamine's therapeutic potential beyond its traditional use as an anaesthetic. Professor Paul Glue, a psychiatrist at Otago's Department of Psychological Medicine, has been at the forefront of this research, transforming a once-maligned party drug into a promising option for treatment-resistant depression and other mental health conditions.
Ketamine, chemically known as (RS)-2-(2-chlorophenyl)-2-(methylamino)cyclohexan-1-one, was first synthesized in 1962 and approved for medical use in the 1970s primarily for anaesthesia due to its dissociative properties that induce a trance-like state while maintaining breathing and airway reflexes. In New Zealand, universities like Otago have shifted focus to its off-label applications in psychiatry, driven by the urgent need for rapid-acting treatments for conditions where standard antidepressants fail after two or more trials.
From Anaesthetic to Antidepressant: The Scientific Evolution
The journey began with a landmark 2000 study from Yale University, where low-dose ketamine infusions led to rapid symptom relief in patients with major depressive disorder. This sparked global interest, including in New Zealand, where Otago researchers confirmed similar effects in local populations. Unlike selective serotonin reuptake inhibitors (SSRIs), which can take weeks to work via gradual neurotransmitter adjustments, ketamine acts within hours by modulating the glutamate system—the brain's primary excitatory neurotransmitter—promoting synaptogenesis or new neural connections.
Otago's early trials in Dunedin and Christchurch targeted end-stage cancer patients with depression, showing one patient with 15 years of symptoms experiencing relief within an hour after infusion, sustained with weekly dosing. Response rates hovered around 60-70% for treatment-resistant cases, a stark contrast to traditional therapies' 30% efficacy ceiling.
Professor Paul Glue's Leadership at Otago University
Returning to New Zealand in 2008 after stints in the UK pharmaceutical industry, Professor Glue established ketamine protocols at Otago. His team expanded to obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and anxiety, with consistent short-term benefits. A pivotal 2016 University of Maryland study revealed that ketamine's metabolites, produced in the liver, drive the antidepressant effects, paving the way for oral formulations that avoid intravenous hassles.
Glue's collaboration with Douglas Pharmaceuticals birthed R-107, an extended-release oral tablet. Initial safety trials in healthy volunteers and small patient cohorts were promising, leading to FDA-backed phase 2/3 trials by Tasman Therapeutics, a US spin-out. This positions Otago as a hub for psychopharmacology innovation, attracting Health Research Council funding and training PhD students in clinical trial design.
Landmark Phase 2 Trial: Nature Medicine Publication
Published in Nature Medicine, a multicenter phase 2 randomized placebo-controlled trial involving 20 sites across New Zealand, Australia, Singapore, and Taiwan tested R-107. Led by Glue, it enrolled treatment-resistant depression (TRD) patients post-open-label enrichment (120mg daily for 5 days). The double-blind phase compared placebo to 30mg, 60mg, 120mg, and 180mg doses twice weekly for 12 weeks.
The 180mg dose significantly reduced Montgomery-Åsberg Depression Rating Scale (MADRS) scores by -6.1 points versus placebo (P=0.019), with 42.9% relapse rate versus 70.6%. Higher doses extended relapse-free time, with excellent tolerability—no blood pressure spikes, minimal dissociation. NZ sites like North Shore Hospital (Auckland) and Christchurch contributed key data, underscoring university-clinic partnerships.Read the full study here.
Ongoing Trials at Otago Christchurch: Oral Ketamine and Behavioural Activation
Currently recruiting, the Behavioural Activation Therapy (BAT) plus oral ketamine trial at Otago's Christchurch campus targets adults 18-65 with TRD. Participants receive twice-weekly oral ketamine for eight weeks, half paired with eight weeks of BAT—a structured therapy increasing rewarding activities. Mood tracking extends 12 weeks post-treatment to assess sustained benefits. This builds on prior Otago studies showing oral ketamine's tolerability over injections.
Exclusion criteria ensure safety: no severe suicidality or comorbidities. Contact via psychmednurse@otago.ac.nz. These trials train Otago medical students and postgrads in ethics, neuroimaging, and pharmacodynamics.
New Zealand Guidelines for Ketamine in TRD
In 2023, a multidisciplinary team including Otago experts developed guidelines for ketamine use in public specialist mental health services. Tailored for NZ's context, they emphasize patient selection, dosing (typically 0.5mg/kg IV over 40 minutes, 2-3 times weekly), monitoring for dissociation/hypertension, and cystitis risks. Updated Royal Australian and New Zealand College of Psychiatrists guidelines (2025) reinforce best practices.
Otago's role in guideline authorship highlights its influence on national policy, fostering research-integrated care.
Challenges and Recreational Use Concerns
While therapeutic promise grows, ketamine's rise as a party drug alarms NZ universities. The 2026 Drug Trends Survey notes surging use among youth, risking 'ketamine bladder' from chronic high doses. Otago researchers advocate education, with Glue stressing supervised low-dose regimens mitigate harms. Trials monitor long-term safety, vital for student mental health amid rising demand.
University Collaborations Driving Innovation
Otago partners with Douglas Pharmaceuticals for R-107 manufacturing and Tasman Therapeutics for US trials, potentially approving in 2.5 years. International ties include Yale and Maryland. Auckland's Centre for Brain Research contributes neuroimaging, enriching NZ's research ecosystem. These alliances offer students interdisciplinary experience in pharma trials.Explore Otago's latest updates.
Photo by Joshua Bayliss on Unsplash
Future Outlook: Transforming NZ Mental Health Research
If approved, R-107 could treat 100,000 Kiwis with TRD, reducing clinic burdens via home dosing. Otago eyes expansions to bipolar depression, chronic pain. As NZ universities like Otago lead, they train next-gen researchers, bolstering psychopharmacology programs amid global shortages.
Career Opportunities in NZ University Mental Health Research
Otago's ketamine program inspires careers in clinical trials, needing postdocs, research assistants. With HRC funding, opportunities abound in glutamate neuroscience, trial design. NZ's collaborative model suits early-career scientists, linking academia, pharma, policy.