Cannabis Use Disorder
Conditions
Brief summary
Effective and durable treatments for cannabis use disorder remain elusive. Given the increasing prevalence rates of cannabis use and CUD nationwide, investigation of novel treatments is warranted. Implicit cognitive processing is an emerging, and potentially critical therapeutic target. Cognitive models of addiction posit an override of explicit control-related cognitive processes by implicit reward-driven processes resulting from chronic drug exposure. One form of implicit cognitive processing is approach bias, or, the automatic tendency to approach rather than avoid drug cues, which has been identified for alcohol, nicotine, opioids, and cannabis. Cannabis approach bias predicts increased cannabis use, dependence severity, and cannabis-related problems among heavy cannabis users. Approach bias modification (ABM) is a novel treatment approach that seeks to reduce approach bias by attenuating the incentive-salience of drug cues, and subsequently, drug cue reactivity and drug use. ABM has been shown to reduce relapse rates in alcohol dependent adults by 10-13% at one-year follow-up, and dependence severity in nicotine dependent adults. Our pilot data suggests that ABM may also reduce cannabis craving and that gender may moderate the effect of ABM on cannabis sessions per day in non-treatment seeking adults with CUD. A recent fMRI study with alcohol-dependent adults found decreased mesolimbic activation in participants who received ABM compared to sham-control participants. ABM appears to target implicit reward-driven processes, and could be an effective adjunct to traditional psychosocial and/or future pharmacological interventions that target explicit control-related processes. Building on our promising feasibility data, the proposed K23 research study will examine the effects of ABM on cue-reactivity and cannabis outcomes in a four-session randomized, double-blind, sham-controlled pilot treatment trial. One-hundred and six (106) treatment-seeking adults with moderate to severe CUD will be randomized to receive either MET/CBT plus ABM or Motivational Enhancement Therapy/Cognitive Behavioral Therapy(MET/CBT) plus sham-ABM. An equal number of men and women will be recruited and randomization will be stratified by gender. ABM sessions will occur following each of the three weekly MET/CBT therapy sessions. Primary outcomes will include cannabis cue-reactivity and cannabis use.
Interventions
BEHAVIORALApproach Bias Modification (ABM)
Approach bias modification (ABM) is a novel treatment that involves retraining the implicit action tendency to approach a drug cue by manipulating contingencies in a stimulus-response paradigm.
BEHAVIORALSham ABM
Sham ABM involves similar computerized procedures that mimic the active experimental condition, but do not involve manipulation of response contingencies and thus it does not contain any active intervention.
BEHAVIORALPsychosocial therapy for cannabis use disorder.
All participants will receive psychosocial therapy for cannabis use disorder.
Sponsors
National Institute on Drug Abuse (NIDA)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Be age 18-65 and must be able to provide informed consent. 2. Meet DSM-5 criteria for current moderate to severe CUD (past 60 days). 3. Identify cannabis as their primary substance of choice. 4. Consent to remain abstinent from alcohol and cannabis for 12 hours immediately prior to study visits and other drugs of abuse (except nicotine) for three days prior (see Additional Instrumentation below for methods); by restricting cannabis and other substance use as proposed, participants should not be under the acute effects of cannabis or other substances.
Exclusion criteria
1. Evidence of, or a history of serious medical or neurological disease that may affect cognitive processing. 2. History of, or current psychotic disorder, bipolar disorder, and attention-deficit hyperactivity disorder, or current untreated major depressive disorder as these may interfere with subjective measurements. 3. Current use of psychotropic medications because these may affect subjective measurements (individuals taking antidepressants will be allowed). 4. Current suicidal ideation. Individuals who endorse suicidal ideation will be seen by a psychologist or psychiatrist in the office and will be referred to treatment as necessary. 5. Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control. 6. Moderate to severe DSM-5 substance use disorder within the past 60 days (other than nicotine or cannabis).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cannabis Approach Bias | Baseline, End of Treatment (4 weeks), Follow-Up (8 weeks) | Using a cue-reactivity paradigm, we will evaluate the efficacy of approach bias modification on cannabis approach bias. Participants are presented with cannabis related and neutral images on a computer screen and are asked to push or pull a joystick in response to a non-content related stimulus feature (i.e. image border color - blue or yellow). Joystick movement activates a zooming feature, which has been shown to effectively simulate approach (pull-zoom in) and avoidance (push-zoom out), and reaction times are calculated from image onset to zoom off-screen. Participants are asked to respond as quickly and accurately as possible. Cannabis approach bias is computed by subtracting pull CB cue reaction times (RTs) from push CB cue RTs (CBpushRT - CBpullRT); a positive value thus indicates greater cannabis approach bias. Approach bias assessments occurred at 3 time points: baseline (pre-assessment), end of study (post-assessment), and follow-up (follow-up assessment). During t |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Days Using Cannabis | Baseline, End of Treatment (4 weeks), Follow-Up (8 weeks) | Using self-report we will evaluate the efficacy of ABM on percent days using cannabis, measurements will be summarized at end of study treatment and at the follow up visit. |
| Marijuana Craving Questionnaire Total Score (Craving) | 8 weeks | Cannabis craving was assessed using the Marijuana Craving Questionnaire-Short Form (MCQ-SF) a self-reporting tool with 12 items rated on a 7-point Likert scale from 1 (strongly disagree) to 7 (strongly agree). The 12 items are grouped by certain characteristics and the score of each of resulting groups correlates to the intensity of the four craving dimensions (compulsivity, emotionality, expectancy, and purposefulness). Scores from the four subscales are summed with total possible scores ranging from 12 - 84. Higher scores are indicative of increased craving. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active ABM + CBT/MET Participants in the Active ABM condition will receive approach bias modification (ABM) training sessions aimed at reducing cognitive bias for cannabis cues.
All participants will receive MET/CBT therapy.
Approach Bias Modification (ABM): Approach bias modification (ABM) is a novel treatment that involves retraining the implicit action tendency to approach a drug cue by manipulating contingencies in a stimulus-response paradigm.
Psychosocial therapy for cannabis use disorder.: All participants will receive psychosocial therapy for cannabis use disorder. | 53 |
| Sham ABM + CBT/MET Participants in the Sham ABM condition will undergo similar computerized tasks without the manipulation of response contingencies that target modification of approach bias.
All participants will receive MET/CBT therapy.
Sham ABM: Sham ABM involves similar computerized procedures that mimic the active experimental condition, but do not involve manipulation of response contingencies and thus it does not contain any active intervention.
Psychosocial therapy for cannabis use disorder.: All participants will receive psychosocial therapy for cannabis use disorder. | 51 |
| Total | 104 |
Baseline characteristics
| Characteristic | Active ABM + CBT/MET | Sham ABM + CBT/MET | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 52 Participants | 50 Participants | 102 Participants |
| Age, Continuous | 33.6 years STANDARD_DEVIATION 11.7 | 31.1 years STANDARD_DEVIATION 10 | 32.4 years STANDARD_DEVIATION 10.9 |
| Marijuana Craving Questionnaire Total Score (MCQ) | 42.5 units on a scale STANDARD_DEVIATION 16 | 41.9 units on a scale STANDARD_DEVIATION 14.5 | 42.2 units on a scale STANDARD_DEVIATION 15.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 15 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 37 Participants | 33 Participants | 70 Participants |
| Region of Enrollment United States | 53 participants | 51 participants | 104 participants |
| Sex: Female, Male Female | 24 Participants | 23 Participants | 47 Participants |
| Sex: Female, Male Male | 29 Participants | 28 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 51 |
| other Total, other adverse events | 0 / 53 | 0 / 51 |
| serious Total, serious adverse events | 0 / 53 | 0 / 51 |
Outcome results
Primary
Cannabis Approach Bias
Using a cue-reactivity paradigm, we will evaluate the efficacy of approach bias modification on cannabis approach bias. Participants are presented with cannabis related and neutral images on a computer screen and are asked to push or pull a joystick in response to a non-content related stimulus feature (i.e. image border color - blue or yellow). Joystick movement activates a zooming feature, which has been shown to effectively simulate approach (pull-zoom in) and avoidance (push-zoom out), and reaction times are calculated from image onset to zoom off-screen. Participants are asked to respond as quickly and accurately as possible. Cannabis approach bias is computed by subtracting pull CB cue reaction times (RTs) from push CB cue RTs (CBpushRT - CBpullRT); a positive value thus indicates greater cannabis approach bias. Approach bias assessments occurred at 3 time points: baseline (pre-assessment), end of study (post-assessment), and follow-up (follow-up assessment). During t
Time frame: Baseline, End of Treatment (4 weeks), Follow-Up (8 weeks)
Population: All randomized participants with at least one post randomization visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active ABM + CBT/MET | Cannabis Approach Bias | Baseline: neutral | -8.43 seconds | Standard Deviation 57.1 |
| Active ABM + CBT/MET | Cannabis Approach Bias | Baseline: cannabis | 5.43 seconds | Standard Deviation 56.2 |
| Active ABM + CBT/MET | Cannabis Approach Bias | End of Treatment (4 weeks): neutral | 1.8 seconds | Standard Deviation 43.6 |
| Active ABM + CBT/MET | Cannabis Approach Bias | End of Treatment (4 weeks): cannabis | -16.1 seconds | Standard Deviation 41.9 |
| Active ABM + CBT/MET | Cannabis Approach Bias | Follow Up (8 weeks): Neutral | 2.82 seconds | Standard Deviation 47.8 |
| Active ABM + CBT/MET | Cannabis Approach Bias | Follow Up (8 weeks): Cannabis | -6.76 seconds | Standard Deviation 29.4 |
| Sham ABM + CBT/MET | Cannabis Approach Bias | Follow Up (8 weeks): Neutral | -6.34 seconds | Standard Deviation 33.7 |
| Sham ABM + CBT/MET | Cannabis Approach Bias | Baseline: neutral | 4.05 seconds | Standard Deviation 46.1 |
| Sham ABM + CBT/MET | Cannabis Approach Bias | End of Treatment (4 weeks): cannabis | -1.74 seconds | Standard Deviation 47.8 |
| Sham ABM + CBT/MET | Cannabis Approach Bias | Baseline: cannabis | -1.36 seconds | Standard Deviation 41.9 |
| Sham ABM + CBT/MET | Cannabis Approach Bias | Follow Up (8 weeks): Cannabis | 1.66 seconds | Standard Deviation 24.3 |
| Sham ABM + CBT/MET | Cannabis Approach Bias | End of Treatment (4 weeks): neutral | -0.22 seconds | Standard Deviation 49.3 |
Secondary
Marijuana Craving Questionnaire Total Score (Craving)
Cannabis craving was assessed using the Marijuana Craving Questionnaire-Short Form (MCQ-SF) a self-reporting tool with 12 items rated on a 7-point Likert scale from 1 (strongly disagree) to 7 (strongly agree). The 12 items are grouped by certain characteristics and the score of each of resulting groups correlates to the intensity of the four craving dimensions (compulsivity, emotionality, expectancy, and purposefulness). Scores from the four subscales are summed with total possible scores ranging from 12 - 84. Higher scores are indicative of increased craving.
Time frame: 8 weeks
Population: All randomized participants that have at least 1 time point of MCQ measured.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active ABM + CBT/MET | Marijuana Craving Questionnaire Total Score (Craving) | Baseline: Non MJ | 39.5 units on a scale | Standard Deviation 16.1 |
| Active ABM + CBT/MET | Marijuana Craving Questionnaire Total Score (Craving) | Baseline: MJ | 43.1 units on a scale | Standard Deviation 17.8 |
| Active ABM + CBT/MET | Marijuana Craving Questionnaire Total Score (Craving) | End of Treatment (4 weeks): Non MJ | 31 units on a scale | Standard Deviation 15.9 |
| Active ABM + CBT/MET | Marijuana Craving Questionnaire Total Score (Craving) | End of Treatment (4 weeks): MJ | 31.4 units on a scale | Standard Deviation 13.9 |
| Active ABM + CBT/MET | Marijuana Craving Questionnaire Total Score (Craving) | Follow up (8 weeks): Non MJ | 28.3 units on a scale | Standard Deviation 16.9 |
| Active ABM + CBT/MET | Marijuana Craving Questionnaire Total Score (Craving) | Follow Up (8 weeks): MJ | 30 units on a scale | Standard Deviation 18.5 |
| Sham ABM + CBT/MET | Marijuana Craving Questionnaire Total Score (Craving) | Follow up (8 weeks): Non MJ | 25.2 units on a scale | Standard Deviation 14.5 |
| Sham ABM + CBT/MET | Marijuana Craving Questionnaire Total Score (Craving) | Baseline: Non MJ | 38.6 units on a scale | Standard Deviation 16.2 |
| Sham ABM + CBT/MET | Marijuana Craving Questionnaire Total Score (Craving) | End of Treatment (4 weeks): MJ | 32.1 units on a scale | Standard Deviation 17.2 |
| Sham ABM + CBT/MET | Marijuana Craving Questionnaire Total Score (Craving) | Baseline: MJ | 40.3 units on a scale | Standard Deviation 17.6 |
| Sham ABM + CBT/MET | Marijuana Craving Questionnaire Total Score (Craving) | Follow Up (8 weeks): MJ | 26.5 units on a scale | Standard Deviation 15.1 |
| Sham ABM + CBT/MET | Marijuana Craving Questionnaire Total Score (Craving) | End of Treatment (4 weeks): Non MJ | 31.1 units on a scale | Standard Deviation 15.8 |
Secondary
Percent Days Using Cannabis
Using self-report we will evaluate the efficacy of ABM on percent days using cannabis, measurements will be summarized at end of study treatment and at the follow up visit.
Time frame: Baseline, End of Treatment (4 weeks), Follow-Up (8 weeks)
Population: all randomized participants that returned post randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active ABM + CBT/MET | Percent Days Using Cannabis | Baseline | 86.6 Percentage of day reported using can | Standard Deviation 20.2 |
| Active ABM + CBT/MET | Percent Days Using Cannabis | End of Treatment (4 weeks) | 74.1 Percentage of day reported using can | Standard Deviation 29.1 |
| Active ABM + CBT/MET | Percent Days Using Cannabis | Follow Up (8 weeks) | 69.1 Percentage of day reported using can | Standard Deviation 35.3 |
| Sham ABM + CBT/MET | Percent Days Using Cannabis | Baseline | 87.7 Percentage of day reported using can | Standard Deviation 18.9 |
| Sham ABM + CBT/MET | Percent Days Using Cannabis | End of Treatment (4 weeks) | 72.0 Percentage of day reported using can | Standard Deviation 28.4 |
| Sham ABM + CBT/MET | Percent Days Using Cannabis | Follow Up (8 weeks) | 71.7 Percentage of day reported using can | Standard Deviation 34.8 |