Brain Exercise and Addiction Trial

NCT ID: NCT04902092

Last Updated: 2023-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-23
• Study Completion Date: 2022-11-21

Brief Summary

Heavy cannabis use is associated with substantive learning and memory impairments and elevated risk of psychopathology. It has been repeatedly demonstrated that the hippocampus, centrally implicated in these processes, is particularly vulnerable to the deleterious effects of prolonged exposure to cannabis. This deterioration of hippocampal structure, function, and biochemistry can be reversed, but this requires two or more years of abstinence from cannabis. However, most heavy cannabis users find it extremely difficult to maintain abstinence over extended periods and current treatments for cannabis use disorders are inadequate. There is a pressing clinical need for an intervention that rapidly accelerates hippocampal recovery, ameliorates the associated cognitive impairments and mental health symptoms, and leads to improved treatment outcomes. One promising candidate is physical exercise. In addition to the well-known physical health benefits, regular exercise also has a potent positive effect on brain health. The current study will investitive the capacity of two different neuroscientifically-informed 12-week exercise programs can restore brain health for heavy long term cannabis users.

Detailed Description

Heavy cannabis use is associated with substantive learning and memory impairments and elevated risk of psychopathology. It has been repeatedly demonstrated that the hippocampus, centrally implicated in these processes, is particularly vulnerable to the deleterious effects of prolonged exposure to cannabis. This deterioration of hippocampal structure, function, and biochemistry can be reversed, but this requires two or more years of abstinence from cannabis. However, most heavy cannabis users find it extremely difficult to maintain abstinence over extended periods and current treatments for cannabis use disorders are inadequate. There is a pressing clinical need for an intervention that rapidly accelerates hippocampal recovery, ameliorates the associated cognitive impairments and mental health symptoms, and leads to improved treatment outcomes. One promising candidate is physical exercise. In addition to the well-known physical health benefits, regular exercise also has a potent positive effect on brain health and can increase the size of the hippocampus. It's not yet known how much or what kind of exercise produces the best results. This study has been designed to compare the effects of two different exercise programs.

1. 12 weeks of regular HIIT exercise

2. 12 weeks of regular strength training

The research team are investigating whether the programs have a positive impact on brain health and, if they do, whether one is more effective than the other. The research team will also measure whether engaging in either program leads to a reduction in cannabis consumption, and improvements in thinking skills, mental health, and general wellbeing.

Conditions

Cannabis Use Disorder, Moderate; Cannabis Use Disorder, Severe

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

High Intensity Physical Training

12-week, 36 session, cardiorespiratory-focussed physical exercise program delivered by an accredited exercise physiologist

Group Type: ACTIVE_COMPARATOR

High Intensity Interval Training

Intervention Type: BEHAVIORAL

Exercise sessions will commence with an initial 3-week accustomization period whereby training load will increase incrementally from 2 x 45min sessions with effort peaking at 60% VO2 max (week 1) increasing to 3 x 45minute with effort peaking at 80% VO2max (week 3). Participants will transition to the full HIIT protocol for the remaining weeks. The HIIT component will comprise a work-rest ratio of ≥1:1minutes, with alternating exertion epochs at \>80% VO2max and \<60% VO2max. As VO2max is likely to increase as fitness improves toward the end of the 3-month program, adjustments to HIIT will be made by the exercise physiologist based on real-time heart rate monitoring, ensuring greater accuracy in participants achieving their heart rate targets.

Low Intensity Physical Training

12- week, 36 session, strength-focussed physical exercise program delivered by an accredited exercise physiologist

Group Type: ACTIVE_COMPARATOR

Strength and Resistance Training

Intervention Type: BEHAVIORAL

Exercise sessions will comprise a combination of strength, coordination and mobility exercises. The strength component will consist of 2-3 sets of resistance exercises at ≤70% of a predicted 1 repetition maximum, targeting all body segments. Heart rate tracking will occur to ensure participants do not exceed 70% v02 (or exceed Lactate Threshold).

Interventions

High Intensity Interval Training

Exercise sessions will commence with an initial 3-week accustomization period whereby training load will increase incrementally from 2 x 45min sessions with effort peaking at 60% VO2 max (week 1) increasing to 3 x 45minute with effort peaking at 80% VO2max (week 3). Participants will transition to the full HIIT protocol for the remaining weeks. The HIIT component will comprise a work-rest ratio of ≥1:1minutes, with alternating exertion epochs at \>80% VO2max and \<60% VO2max. As VO2max is likely to increase as fitness improves toward the end of the 3-month program, adjustments to HIIT will be made by the exercise physiologist based on real-time heart rate monitoring, ensuring greater accuracy in participants achieving their heart rate targets.

Intervention Type: BEHAVIORAL

Strength and Resistance Training

Exercise sessions will comprise a combination of strength, coordination and mobility exercises. The strength component will consist of 2-3 sets of resistance exercises at ≤70% of a predicted 1 repetition maximum, targeting all body segments. Heart rate tracking will occur to ensure participants do not exceed 70% v02 (or exceed Lactate Threshold).

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

1. Aged 20-55 years

2. Voluntary and able to provide informed consent

3. Fluent in English

4. Current moderate - severe cannabis use disorder

5. Major history of cannabis use (i.e. ≥3 days per week on average for ≥4 of the past 6 years)

6. Capacity to tolerate physical exercise according to 'Fitness to Exercise'

Exclusion Criteria

1. Have a history of cardiovascular disease, high blood pressure, musculoskeletal injury or other condition that would preclude safe engagement in VO2 max fitness testing and/or regular physical exercise

2. Severe claustrophobia, non-MR compatible metallic implant, or other contraindication to MRI scanning

3. Lifetime history of significant neurological illness, or moderate - severe brain injury,

4. Current major unstable medical illness or chronic pain condition

5. Lifetime history of schizophrenia, schizoaffective disorder, OCD, PTSD, bipolar disorder

6. Current significant depression or anxiety that precludes ability to reliably engage in the exercise program

7. Current moderate - severe substance use disorder for substances other than cannabis (excluding nicotine)

8. Currently pregnant or lactating

9. Shift work employment schedule within the prior 6-months

10. Have engaged in ≥5 sessions of HITT or resistance training within the past 12-months

11. History of treatment with antipsychotic medications

12. Current participation in psychosocial treatment for substance use disorder

13. Other psychoactive medications or psychosocial treatments will be considered on a case-by-case basis. Where a current psychoactive medication is deemed acceptable, both dose and type must have been stable for a minimum of four weeks prior to baseline assessment, and remain stable throughout the 12-week exercise phase of the study.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Turning Point

OTHER

Sponsor Role: collaborator

Monash University

OTHER

Sponsor Role: lead

Responsible Party

Rebecca Segrave

Senior Research Fellow

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Murat Yucel

Role: PRINCIPAL_INVESTIGATOR

Monash University

Locations

Monash University, BrainPark

Melbourne, Victoria, Australia

Countries

Australia

References

Richardson KE, Suo C, Albertella L, Maleki S, Coxon J, Hendrikse J, Hughes S, Pitt J, Kayayan E, Brown C, Nguyen L, Solowij N, Lubman DI, Segrave R, Yucel M. High-Intensity Exercise and Hippocampal Integrity in Adults With Cannabis Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2025 Sep 10:e252319. doi: 10.1001/jamapsychiatry.2025.2319. Online ahead of print.

Reference Type: DERIVED

PMID: 40928796 (View on PubMed)

Other Identifiers

12563

Identifier Type: -

Identifier Source: org_study_id