Mood Modulation for Methamphetamine Abuse

(MDM-MUD Trial)

Overseen By Maëlle CM Gueguen, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Laureate Institute for Brain Research, Inc.

Disqualifiers: Psychotic disorders, Bipolar I, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

80 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot participate if you test positive for drugs other than cannabis or prescribed benzodiazepines.

What data supports the effectiveness of the treatment Positive Autobiographical Memory Recall for methamphetamine abuse?

Research on autobiographical memory in substance abuse suggests that recalling personal memories can help improve emotional regulation and identity, which are often disrupted in addiction. This implies that Positive Autobiographical Memory Recall might aid in addressing these issues in methamphetamine abuse. ^{1 2 3 4 5}

How is Positive Autobiographical Memory Recall treatment different from other treatments for methamphetamine abuse?

Positive Autobiographical Memory Recall is unique because it focuses on recalling positive personal memories to improve mood and emotional regulation, which is different from other treatments that may focus on cognitive or behavioral interventions. This approach leverages the power of positive memories to counteract the emotional dysregulation often seen in methamphetamine abuse. ^{1 2 6 7 8}

What is the purpose of this trial?

In this project, the investigators examine behavior and associated brain activity during explore-exploit decision-making tasks performed pre- and post-modulation of affective state using autobiographical memory recall. The investigators hypothesize that a positive memory recall will reduce negative affective state, reduce explore-exploit biases and normalize the associated brain activity. The investigators propose a randomized double-blind, sham-controlled trial of positive autobiographical memory recall with 80 adults (n=40 per arm) with methamphetamine use disorder (MUD) currently involved in abstinence only treatment centers.

Research Team

Maelle Gueguen, PhD

Principal Investigator

Laureate Institute for Brain Research, Inc.

Eligibility Criteria

This trial is for adults with Methamphetamine Use Disorder (MUD) who are currently in abstinence-only treatment centers. The study aims to include 80 participants, split into two groups.

Inclusion Criteria

English proficiency as evaluated by language ability during screening

Actively enrolled in treatment for substance use disorder

Past-year diagnosis of DSM-5 methamphetamine use disorder (MUD) confirmed by the MINI

Exclusion Criteria

I have been diagnosed with a psychotic disorder, bipolar I, or major depression with psychosis.

Any medical condition interfering with the participation in the study as determined by medical screening

fMRI contraindications as listed on the MR environment screening form

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Mood Modulation

Participants undergo mood modulation using autobiographical memory recall to assess its impact on explore-exploit decision-making tasks

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in affective state and decision-making post-intervention

1 day

1 visit (in-person)

Treatment Details

Interventions

• Positive Autobiographical Memory Recall

Trial Overview The study tests if recalling positive personal memories can affect mood and decision-making. Participants will be randomly assigned to either the memory recall intervention or a sham (fake) procedure, without knowing which one they receive.

Participant Groups

Group I: Positive mood modulation Active Control 1 Intervention

Use of happy/positive autobiographical memories which are vivid, emotionally pleasurable and not drug-related, as assessed by individual interview and ratings

Group II: Neutral mood modulation Placebo Group 1 Intervention

Use of neutral/procedural autobiographical memories which are vivid, emotionally neutral and not drug-related, as assessed by individual interview and ratings

Who Is Running the Clinical Trial?

Laureate Institute for Brain Research, Inc.

Lead Sponsor

Trials

53

Recruited

5,400+

National Institute of General Medical Sciences (NIGMS)

Collaborator

Trials

315

Recruited

251,000+

Findings from Research

The study is testing a modified intervention called Goal Management Training+ (GMT+) to improve executive functions in individuals with Methamphetamine Use Disorder (MUD) during residential rehabilitation, involving 48 participants and a cluster randomized crossover design.

The primary focus is to assess the acceptability and feasibility of GMT+, as well as its impact on executive functioning and clinical outcomes, with evaluations occurring at multiple time points to gather comprehensive data for future larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol for a cluster randomised crossover pilot trial of Goal Management Training+ (GMT+) for methamphetamine use disorder. Anderson, AC., Robinson, AH., Lubman, DI., et al.[2022]

Disrupted sleep is a significant factor in the cognitive and emotional challenges faced by individuals abusing methamphetamine, affecting memory and emotional regulation.

The authors propose that measuring sleep parameters could help explain the variability in cognitive and affective symptoms among methamphetamine users, suggesting that improving sleep may be a key target for treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The implications of sleep disruption for cognitive and affective processing in methamphetamine abuse. Lipinska, G., Timol, R., Thomas, KG.[2016]

Opiate addicts demonstrated a significant decrease in episodic autobiographical memory compared to healthy controls, while showing an increase in semantic affective memory, indicating that drug use may impair personal event recollection but not general knowledge about oneself.

The study found that improvements in depressive symptoms occurred in opiate addicts after two months without the use of psychotropic drugs, suggesting that non-pharmacological treatments may effectively address transient depression in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Heroin abuse, autobiographical memory and depression]. Eiber, R., Puel, M., Schmitt, L.[2015]

Adults in remission from methamphetamine addiction (MA-REM) show significant impairments in executive functioning and impulsivity compared to non-addicted controls, based on assessments from 30 MA-REM participants and 24 controls.

The findings indicate that individuals in MA-REM are not only aware of their cognitive deficits but also that these impairments significantly affect their daily lives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Everyday problems with executive dysfunction and impulsivity in adults recovering from methamphetamine addiction. Ellis, C., Hoffman, W., Jaehnert, S., et al.[2020]

Patients with opioid-use disorder (OUD) showed lower specificity and integration in their self-defining memories (SDM) compared to non-dependent individuals, indicating difficulties in recalling personal memories that shape their identity.

Despite similar emotional responses during memory retrieval, OUD patients tended to recall more neutral memories, suggesting a potential emotional disconnection that could contribute to challenges in addressing past experiences and may increase the risk of relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compromises of integration, specificity and emotional content of self-defining memories in patients with opioid-use disorder. Gandolphe, MC., Duprez, C., Enault, F., et al.[2020]

In a study of 19 non-treatment seeking, Meth-dependent individuals, acute low-dose Meth administration improved attention and working memory in those who initially performed poorly on cognitive tests, suggesting a potential temporary benefit for cognitive function.

However, individuals with higher baseline cognitive performance showed no improvement or even decreased performance after Meth exposure, indicating that the effects of Meth can vary significantly based on individual cognitive status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute, low-dose methamphetamine administration improves attention/information processing speed and working memory in methamphetamine-dependent individuals displaying poorer cognitive performance at baseline. Mahoney, JJ., Jackson, BJ., Kalechstein, AD., et al.[2021]

In a study involving 24 participants (12 methamphetamine-dependent and 12 healthy controls), those dependent on methamphetamine showed abnormal brain activity patterns, particularly in areas related to social cognition and emotional regulation, which may contribute to socially maladaptive behaviors.

While both groups activated the amygdala in response to social cues, the methamphetamine-dependent participants exhibited hyperactivity in the dorsal anterior cingulate cortex, indicating a heightened sensitivity to social threats, alongside reduced activation in the ventrolateral prefrontal cortex, suggesting difficulties in processing and regulating emotional responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in cortical activity between methamphetamine-dependent and healthy individuals performing a facial affect matching task. Payer, DE., Lieberman, MD., Monterosso, JR., et al.[2021]

Chronic methamphetamine use leads to significant cognitive impairments, particularly affecting the prefrontal cortex, which is crucial for attention and memory.

The review suggests that using cognitive enhancers during abstinence could help reverse the brain changes caused by prolonged meth use, potentially supporting recovery and reducing relapse rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic methamphetamine self-administration disrupts cortical control of cognition. Bernheim, A., See, RE., Reichel, CM.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Protocol for a cluster randomised crossover pilot trial of Goal Management Training+ (GMT+) for methamphetamine use disorder. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

The implications of sleep disruption for cognitive and affective processing in methamphetamine abuse. [2016]

3. France pubmed.ncbi.nlm.nih.gov

[Heroin abuse, autobiographical memory and depression]. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Everyday problems with executive dysfunction and impulsivity in adults recovering from methamphetamine addiction. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Compromises of integration, specificity and emotional content of self-defining memories in patients with opioid-use disorder. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Acute, low-dose methamphetamine administration improves attention/information processing speed and working memory in methamphetamine-dependent individuals displaying poorer cognitive performance at baseline. [2021]

7. Ireland pubmed.ncbi.nlm.nih.gov

Differences in cortical activity between methamphetamine-dependent and healthy individuals performing a facial affect matching task. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Chronic methamphetamine self-administration disrupts cortical control of cognition. [2022]