Ketamine-assisted psychotherapy for methamphetamine use disorder

The intervention consists of four sessions (1:1, face-to-face) of psychotherapy (cognitive behavioural therapy; CBT) over four weeks with adjuvant ketamine in the 24 to 48 hours prior to the second, third and fourth sessions. 1. CBT The routine 4-session manualised Cognitive Behavioural Therapy (CBT) program developed by Baker et al (2003) will be provided by trained therapists to all participants in the trial. The broad content and aims of each session are outlined below, with sessions lasting approximately 1.5 hours each: Session 1 - Motivational interviewing. Key aims of this session: engagement and building motivation for change in relation to methamphetamine (MA) use, preparing to reduce MA use, and introduction to behavioural self-monitoring. Session 2 - Coping with cravings and lapses. Key aims of this session: reinforcing motivation to maintain abstinence/reduced level of use, coping with cravings to use, preparing for a lapse. Session 3 - Controlling thoughts about amphetamine use and pleasurable activities. Key aims of this session: introduction to the concept that thoughts influence behaviour, developing a plan of achievement and pleasurable tasks to carry out through the week, and continuing to cut down/maintain abstinence. Session 4 - Amphetamine refusal skills and preparation for future high-risk situations. Key aims of this session: learning and practicing MA refusal skills, identifying potential high-risk situations that may occur in the future, developing a specific relapse prevention/relapse management plan for anticipated high-risk situation, encouraging use of relapse prevention/relapse management plan to prevent use of MA, learning how to deal with a lapse. Therapists are defined as staff with graduate qualifications in a relevant health discipline (such as counselling, nursing, social work, psychology, psychiatry), including trainees with adequate skills, that have undergone training on the use of the manual. Therapists will be trained by a senior psychologist with expertise in CBT for MAUD. Training will be face-to-face, delivered during a workshop, at least 1 week prior to the first participant enrolment. Session checklists will be completed post-session by the therapist to assess treatment fidelity and discussed during group supervision with a senior psychologist. As per Baker et al (2003), study participants will be encouraged to complete homework tasks in-between sessions. Therapists will also be certified in ICH-GCP. The initial assessment will take place as part of CBT session 1, covering: (1) alcohol and other drug use history, (2) mental health assessment, (3) client’s readiness to change MA use. Information about what will happen during the first ketamine dose session will be provided. One week later, a preparation session will be undertaken immediately prior to ketamine dose 1. Psychological preparation and pre-infusion relaxation exercises will be given, and participants be briefed on what to expect during the ketamine dose along with a discharge information sheet. Within 24-48 hours of ketamine dose 1, CBT session 2 will be undertaken, guided initially by an integration session where experiences of the ketamine session will be briefly explored. This approach will be used for the remaining sessions. Therapists will coordinate the four sessions to occur at least one week apart. Session 1 will occur during week 1; Sessions 2, 3 and 4 will occur during weeks 2,3 and 4 respectively within 24-48 hours of participants receiving study medication. An optional one-hour 'booster’ session with the therapist will be offered at week 6. CBT session attendance will be used to monitor adherence to the intervention. 2. Medication The medication under investigation is the TGA approved ketamine hydrochloride 200mg/ml, commercially available and branded in Australia formulated in liquid solution for intravenous and intramuscular injection as an anaesthetic agent. It has also been administered subcutaneously in the sub-anaesthetic doses used in study trials for TRD (Loo et al., 2016, 2023). A total of three subcutaneous doses, at least 7 days apart, will be administered by a registered nurse, once weekly during Weeks 2, 3 and 4. An increasing dose regimen will be used as follows: - Dose 1: 0.75mg/kg - Dose 2: if dose 1 well tolerated, increase to 0.9mg/kg. If dose 1 moderately tolerated, reduce to 0.75mg mg/kg. If dose 1 poorly tolerated, reduce to 0.6mg/kg. - Dose 3: dose range 0.5mg/kg to 0.9mg/kg depending on tolerability of dose 2. Direct observation will be used to monitor adherence to the intervention.