Brain Exercise and Addiction Trial

NCT04902092 | Completed

• 1 other identifier: 12563
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

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.

Conditions

Cannabis Use Disorder, Moderate; Cannabis Use Disorder, Severe

Outcome Measures

Primary Outcomes (1)

• Change in hippocampal integrity

  Composite score derived from three hippocampal health indices: volume (structural MRI), connectivity (DTI), neuronal health (MRS NAA) calculated as described in Yucel et al (2016), doi:10.1038/tp.2015.201.

  Baseline (0 months), post (3 months)

Secondary Outcomes (14)

• Change in cannabis use

  Baseline (0 months), post (3 months), follow up (6 months)

• Change in cannabis dependence

  Baseline (0 months), post (3 months), follow up (6 months)

• Change in cannabis craving

  Baseline (0 months), post (3 months), follow up (6 months)

• Change in depression symptoms

  Baseline (0 months), post (3 months), follow up (6 months)

• Change in anxiety symptoms

  Baseline (0 months), post (3 months), follow up (6 months)

Study Arms (2)

High Intensity Physical Training

ACTIVE COMPARATOR

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

Behavioral: High Intensity Interval Training

Low Intensity Physical Training

ACTIVE COMPARATOR

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

Behavioral: Strength and Resistance Training

Interventions

High Intensity Interval Training 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.

High Intensity Physical Training

Strength and Resistance Training 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).

Low Intensity Physical Training

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 20-55 years
• Voluntary and able to provide informed consent
• Fluent in English
• Current moderate - severe cannabis use disorder
• Major history of cannabis use (i.e. ≥3 days per week on average for ≥4 of the past 6 years)
• Capacity to tolerate physical exercise according to 'Fitness to Exercise'

You may not qualify if:

• 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
• Severe claustrophobia, non-MR compatible metallic implant, or other contraindication to MRI scanning
• Lifetime history of significant neurological illness, or moderate - severe brain injury,
• Current major unstable medical illness or chronic pain condition
• Lifetime history of schizophrenia, schizoaffective disorder, OCD, PTSD, bipolar disorder
• Current significant depression or anxiety that precludes ability to reliably engage in the exercise program
• Current moderate - severe substance use disorder for substances other than cannabis (excluding nicotine)
• Currently pregnant or lactating
• Shift work employment schedule within the prior 6-months
• Have engaged in ≥5 sessions of HITT or resistance training within the past 12-months
• History of treatment with antipsychotic medications
• Current participation in psychosocial treatment for substance use disorder
• 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.

Sponsors & Collaborators

• Monash University: lead
• Turning Point: collaborator

Study Sites (1)

Monash University, BrainPark

Melbourne, Victoria, 3800, Australia

Location

Related Publications (1)

• 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 Dec 1;82(12):1240-1245. doi: 10.1001/jamapsychiatry.2025.2319.

  PMID: 40928796 DERIVED

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

High-Intensity Interval Training; Resistance Training

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities

Study Officials

• Murat Yucel

  Monash University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Research Fellow

Study Record Dates

• First Submitted: May 13, 2021
• First Posted: May 26, 2021
• Study Start: January 23, 2019
• Primary Completion: June 10, 2022
• Study Completion: November 21, 2022
• Last Updated: October 23, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)