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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if recalling positive memories can aid individuals with methamphetamine use disorder (MUD) who are undergoing treatment. Researchers seek to discover whether reflecting on happy times can improve mood and alter brain activity related to decision-making. Participants will be divided into two groups: one recalling positive memories (Positive Autobiographical Memory Recall) and the other recalling neutral ones. This study targets adults with a recent MUD diagnosis who are already in a treatment program. As an unphased trial, it provides a unique opportunity to explore new therapeutic approaches that could enhance the treatment experience.

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 prior data suggests that this method is safe for individuals with methamphetamine use disorder?

Research shows that recalling happy memories is generally safe and well-received. This method involves thinking about positive past experiences to boost mood. No direct evidence indicates safety concerns with this approach. However, studies on similar methods, such as music therapy, have shown positive effects without serious side effects in people with substance use issues. These studies suggest that using happy memories can be safe and might even help reduce cravings. Although detailed safety data for this exact method is lacking, the absence of reported problems in similar techniques suggests it is likely safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the mood modulation technique for methamphetamine abuse because it offers a unique approach compared to existing treatments like behavioral therapies and medication-assisted treatments. This technique uses positive autobiographical memory recall, tapping into happy and emotionally pleasurable memories to potentially alter mood and reduce cravings. Unlike traditional treatments that often focus directly on drug use, this method targets emotional states, offering a fresh angle that could enhance recovery outcomes. Additionally, the non-drug nature of this therapy presents a promising alternative for individuals looking for non-pharmacological options.

What evidence suggests that Positive Autobiographical Memory Recall might be an effective treatment for methamphetamine use disorder?

This trial will compare two approaches for mood modulation in individuals with methamphetamine use disorder (MUD). Participants in the "Positive mood modulation" arm will use happy, positive autobiographical memories that are vivid, emotionally pleasurable, and not drug-related. Research has shown that recalling happy memories can help people with substance use problems feel better and gain self-awareness. This method involves remembering positive past events. Studies have found that focusing on these good memories can reduce negative emotions and may help the brain function more normally. Although specific data for MUD is limited, the general idea is that recalling positive memories can boost mood and improve decision-making, potentially helping people manage cravings and reduce substance use. Meanwhile, the "Neutral mood modulation" arm will involve the use of neutral, procedural autobiographical memories that are vivid, emotionally neutral, and not drug-related. ^{3 6 7 8 9}

Who Is on the Research Team?

Maelle Gueguen, PhD

Principal Investigator

Laureate Institute for Brain Research, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

Citations

1. researchgate.net researchgate.net/publication/230825462_Autobiographical_memory_and_differentiation_of_schematic_models_in_substance-dependent_patients

Autobiographical memory and differentiation of schematic ... Background and objectives: This study aims at investigating reduced autobiographical memory specificity in substance-dependent patients.

2. etiadpajohi.ir etiadpajohi.ir/article-1-1024-en.pdf

Research on Addiction Quarterly Journal of Drug Abuse Objective: The present study was an attempt to examine the effectiveness of therapeutic community in executive functions and autobiographical memory in ...

3. withpower.com withpower.com/trial/phase-methamphetamine-abuse-6-2024-552a2

Mood Modulation for Methamphetamine Abuse Research on autobiographical memory in substance abuse suggests that recalling personal memories can help improve emotional regulation and identity, which are ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8098650/

Methamphetamine Use Disorder: The Next Addiction Crisis Others reported that brief cognitive behavioral therapy (CBT) resulted in significant reductions in frequency of methamphetamine use, MUD severity, and number ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10196796/

Substance abuse and susceptibility to false memory ... The impact of substance abuse on false memory formation is not clear. There seem to be few studies looking into provoked and spontaneous ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4332474/

Effects of Acute Methamphetamine on Emotional Memory ... METH can enhance memory for salient emotional stimuli but only if it is present at the time of study, where it can affect both encoding and consolidation.

7. sciencedirect.com sciencedirect.com/science/article/am/pii/S0149763423001574

The Acute Effects of Psychoactive Drugs on Emotional ... Triazolam at encoding impaired the recall of both negative and positive memories but not neutral memories, though performance for neutral stimuli was at floor, ...

8. mdpi.com mdpi.com/2076-3425/13/2/259

Neuroplastic Changes in Addiction Memory—How Music ... Recent findings indicate that Music Therapy (MT) and Music-Based Interventions (MBIs) may reduce craving symptoms in people with Substance Use Disorders (SUD).

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7162911/

“Chasing the first high”: memory sampling in drug choice - PMC We propose a framework in which drug choices are biased by selective sampling of individual memories during two phases of addiction.