Not Yet RecruitingPhase 2ACTRN12626000603314

Assessing the effect of ketamine on disruption of memory reconsolidation in Post Traumatic Stress Disorder

Evaluating the efficacy of ketamine as a memory reconsolidation blocker to reduce trauma-related memories in treatment-resistant individuals with Post-Traumatic Stress Disorder

Sponsor

University of the Sunshine Coast

Enrollment

44 participants

Start Date

Jun 22, 2026

Study Type

Interventional

Conditions

Mental Health

Summary

This study is pioneering in its investigation of ketamine for the treatment of Post Traumatic Stress Disorder (PTSD). We will do this by reactivating traumatic memory via a short writing task. Ketamine will then be administered following the retrieval of these unpleasant, traumatic memories. When a stored memory is reactivated, it may transition from a consolidated state to a more malleable one, where its content or meaning can be modified. This altered memory is then re-stored through a process called reconsolidation. This mechanism is particularly relevant to PTSD, as theories suggest that the disorder is connected to the processes of fear learning and memory updating. Theoretically, by pharmacologically disrupting this reconsolidation process with ketamine, specific memories can be selectively weakened. This temporary window of memory instability following reactivation provides a novel opportunity to directly alter trauma-related memories and reduce their potential to trigger relapse.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 70 Yearss

Inclusion Criteria7

Men or women, 18-70 years of age.
Participants must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign a written informed consent document.
Meets criteria for DSM-5 diagnosis of PTSD according to CAPS 5 (CAPS-5 score>33).
Treatment resistant PTSD defined as
(a) Minimum 1x trial of an antidepressant (SSRI or SNRI) for minimum of 6 weeks without adequate response OR (b) completed a course of trauma-focused psychotherapy.
Antidepressant medications on stable doses (no dosing adjustments/changes for 4
weeks) prior to beginning of the study.

Exclusion Criteria10

Unwillingness/unable to sign informed consent.
Previous or current participation in trauma-exposed therapy and/or ketamine treatment.
Evidence of mental retardation, pervasive developmental disorder and/or
moderate/severe cognitive impairment (MMSE score allowed: minimum of 27).
Any unstable medical or non-psychiatric CNS condition.
Lifetime history of psychosis-related disorder, bipolar disorder I or II disorder, Complex PTSD and dissociative Identity disorder or any condition other than PTSD judged to be the primary presenting psychiatric diagnosis.
Moderate to severe traumatic brain injury (mental status change or loss of consciousness greater than30 min; Glasgow Coma Scale 24hours; visible lesion on CT/MRI brain scan).
Active alcohol/illicit substance use disorder within 6 months of initial assessment; presence of illicit drugs by positive urine toxicology.
For women: pregnancy (confirmed by lab test), initiation of female hormonal treatments within 3 months of screening, or inability/ unwillingness to use a medically accepted contraceptive method during the study.
Imminent risk of suicidal/homicidal ideation and/or behaviour with intent and/or plan.

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Interventions

Randomised, double-blind, active placebo-controlled, parallel-group study evaluating the efficacy of oral ketamine as a memory reconsolidation blocker in treatment-resistant PTSD. Oral ketamine dose

Randomised, double-blind, active placebo-controlled, parallel-group study evaluating the efficacy of oral ketamine as a memory reconsolidation blocker in treatment-resistant PTSD. Oral ketamine dose will start at 1 mg/kg and titrate up to a maximum of 3 mg/kg as tolerated -frequency of dosing; once per week; -overall duration of dosing, six weeks -Oral dose will be provided as capsules -whether dosing will be supervised, Yes, it will be supervised by a psychiatrist, a Psychiatry registrar, an anesthetist or a nurse with a doctor available on call. -whether the dosing will be accompanied by guided therapy or whether dosing will occur without any therapy or guided imagery exercises: Yes the dosing will be accompanied by guided therapy, memory reconsolidation therapy. -Monitoring of adherence to the intervention : Not applicable Participants will be asked to reactivate a traumatic memory via a short writing task every week for six weeks, with ketamine dosing to occur following this task. The anticipated time needed to complete the task is about 30 minutes.