Cannabis Use Disorder
Conditions
Brief summary
In this trial we will work with a group of participants who are having problems related to marijuana use (they have Cannabis Use Disorder) and who want to reduce the amount of marijuana they use or quit using marijuana completely. We are testing to see if a treatment called repetitive transcranial magnetic stimulation (rTMS) can help them achieve that goal when combined with a brief three-session counseling therapy. Participants will receive rTMS to one of two different parts of the brain (the dorsolateral prefrontal cortex--the DLPFC or the ventromedial prefrontal cortex--the vmPFC) to see if applying rTMS to one brain area is more helpful than the other brain area.
Detailed description
In this preliminary trial, we will test whether applying repetitive transcranial magnetic stimulation (rTMS) to one of two brain areas will help participants with Cannabis Use Disorder reduce the amount of cannabis they use or quit using cannabis completely. To do so, we will recruit participants from the community (or addictions medicine treatment centers) who meet the criteria for Cannabis Use Disorder (heavy use of cannabis causing social, occupational, or health problems) and want to either substantially reduce the amount of cannabis they use or quit using cannabis entirely. Participants will be randomized (in a 1:1 allocation) to receive rTMS to either the left dorsolateral prefrontal cortex (DLPFC) or the ventromedial prefrontal cortex (vmPFC). All participants will also receive evidence-based counseling to help them reduce the amount of cannabis they use. We will deliver study treatment with rTMS to participants over 18-study-visits occurring either two or three times each week and then will see whether the study treatment has helped by meeting with participants four times over six weeks. We will also see how the rTMS effected brain function by having participants undergo two scans using magnetic resonance imaging (MRI).
Interventions
DEVICERepetitive Transcranial Magnetic Stimulation (rTMS)
Patterned pulsed magnetic stimulation delivered using an electromagnet. We will use a MagVenture rTMS device and a Cool-B65 coil.
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Participants must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments. 2. Participants must be between the ages of 18 and 60. 3. Participants must meet DSM-5 criteria for at least moderate Cannabis Use Disorder, with use of at least 20 out of the last 28 days. 4. Participants must express a desire to reduce cannabis use or quit. 5. Participants must have a positive UDS for cannabis during their enrollment visit (confirming they are regular users). 6. The investigative team must believe each participant is a good study-candidate.
Exclusion criteria
1. Participants must not be pregnant or breastfeeding. 2. Participants must not meet moderate or severe use disorder of any other substance with the exception of tobacco/nicotine. 3. Participants must not be on any medications that have central nervous system effects that have changed in the past 4-weeks. 4. Participants must not have a history of/or current psychotic disorder or bipolar disorder. 5. Participants must not have any other Axis I condition requiring current treatment. 6. Participants must not have a history of Dementia or other cognitive impairment. 7. Participants must not have active suicidal ideation, or a suicide attempt within the past 180 days. 8. Participants must not have any contraindications to receiving rTMS or MRI (e.g. metal implanted above the head, history of seizure, any known brain lesion). 9. Participants must not have any unstable general medical conditions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number (%) of Participants Who Started and Completed Treatment | 6 to 9 weeks | — |
| Number (%) of Participants Who Had Successful Generation of Functional Magnetic Resonance Imaging (fMRI) Targets | Day 1 (90 minutes to complete scan) | — |
| Number (%) Weeks of Abstinence From Cannabis | 13 weeks (final 7 weeks of active treatment plus 6-week post-treatment follow-up) | Number (%) of weeks where the participant does not use any cannabis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days of Use Per Week. | 4 weeks prior to baseline assessment and 7 weeks at the end of treatment through 6-week post-treatment follow-up | Number of days per week (0-7) where the participant uses any cannabis. At the time of enrollment participants were asked to recall the number of days of cannabis use per week for the 4 weeks prior to enrollment. Participants were then asked (over a period of 7 weeks) to recall days of use at the last fMRI visit (during prior week) and at the week 2, 4, and 6 follow-up visits. Average values are reported for the 4-week period prior to enrollment and the 7-week period at end of treatment at follow-up. |
| Number of Participants Who Had a Period of 4-consecutive Weeks of Abstinence During the Follow-up Period | Follow-up period (final week of active treatment plus 6-week post-treatment follow-up) | Based on patient self-report of any 4-week period of abstinence |
| Average Number of Use Sessions Per Week. | 4 weeks prior to baseline assessment and 7 weeks at the end of treatment through 6-week post-treatment follow-up | Number of use sessions per week where the participant uses any cannabis. At the time of enrollment participants were asked to recall the number of cannabis use sessions per week for the 4 weeks prior to enrollment. Participants were then asked (over a period of 7 weeks) to recall the number of cannabis use sessions at the last fMRI visit (during prior week) and at the week 2, 4, and 6 follow-up visits. Average values are reported for the 4-week period prior to enrollment and the 7-week period at end of treatment at follow-up. |
| Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) Scale Score | Baseline and end of the follow-up period (12 to 15 weeks post-baseline) | The Q-LES-Q-SF overall score range is from 14 to 70, with higher scores indicating greater satisfaction and enjoyment. The total score is expressed as a percentage of the maximum possible score (1-100). |
Countries
United States
Participant flow
Recruitment details
Participants receive 6 to 9 weeks of active treatment, then enter a 7 week follow-up period, from the last treatment (up to 1 week) plus 6 weeks post-treatment.
Pre-assignment details
22 participants signed informed consent, and 20 were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Dorsolateral Prefrontal Cortex (DLPFC) 36 sessions of high frequency (10Hz) rTMS. | 10 |
| Ventromedial Prefrontal Cortex (vmPFC) 36 sessions of low frequency (1Hz) rTMS. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Dorsolateral Prefrontal Cortex (DLPFC) | Total | Ventromedial Prefrontal Cortex (vmPFC) |
|---|---|---|---|
| Age, Continuous | 28.9 years STANDARD_DEVIATION 6.5 | 33.3 years STANDARD_DEVIATION 9.8 | 37.7 years STANDARD_DEVIATION 10.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 6 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 14 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 8 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 3 Participants | 3 Participants |
| Region of Enrollment United States | 10 Participants | 20 Participants | 10 Participants |
| Sex: Female, Male Female | 5 Participants | 10 Participants | 5 Participants |
| Sex: Female, Male Male | 5 Participants | 10 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 3 / 10 | 4 / 10 | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Number (%) of Participants Who Had Successful Generation of Functional Magnetic Resonance Imaging (fMRI) Targets
Time frame: Day 1 (90 minutes to complete scan)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dorsolateral Prefrontal Cortex (DLPFC) | Number (%) of Participants Who Had Successful Generation of Functional Magnetic Resonance Imaging (fMRI) Targets | 10 Participants |
| Ventromedial Prefrontal Cortex (vmPFC) | Number (%) of Participants Who Had Successful Generation of Functional Magnetic Resonance Imaging (fMRI) Targets | 9 Participants |
Primary
Number (%) of Participants Who Started and Completed Treatment
Time frame: 6 to 9 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dorsolateral Prefrontal Cortex (DLPFC) | Number (%) of Participants Who Started and Completed Treatment | 8 Participants |
| Ventromedial Prefrontal Cortex (vmPFC) | Number (%) of Participants Who Started and Completed Treatment | 8 Participants |
Primary
Number (%) Weeks of Abstinence From Cannabis
Number (%) of weeks where the participant does not use any cannabis.
Time frame: 13 weeks (final 7 weeks of active treatment plus 6-week post-treatment follow-up)
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Dorsolateral Prefrontal Cortex (DLPFC) | Number (%) Weeks of Abstinence From Cannabis | 0 patient weeks |
| Ventromedial Prefrontal Cortex (vmPFC) | Number (%) Weeks of Abstinence From Cannabis | 56 patient weeks |
Secondary
Average Number of Use Sessions Per Week.
Number of use sessions per week where the participant uses any cannabis. At the time of enrollment participants were asked to recall the number of cannabis use sessions per week for the 4 weeks prior to enrollment. Participants were then asked (over a period of 7 weeks) to recall the number of cannabis use sessions at the last fMRI visit (during prior week) and at the week 2, 4, and 6 follow-up visits. Average values are reported for the 4-week period prior to enrollment and the 7-week period at end of treatment at follow-up.
Time frame: 4 weeks prior to baseline assessment and 7 weeks at the end of treatment through 6-week post-treatment follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dorsolateral Prefrontal Cortex (DLPFC) | Average Number of Use Sessions Per Week. | Baseline assessment | 50.33 use sessions per week | Standard Deviation 27.28 |
| Dorsolateral Prefrontal Cortex (DLPFC) | Average Number of Use Sessions Per Week. | End of treatment / Follow-up | 29.68 use sessions per week | Standard Deviation 27.26 |
| Ventromedial Prefrontal Cortex (vmPFC) | Average Number of Use Sessions Per Week. | Baseline assessment | 32.55 use sessions per week | Standard Deviation 18.52 |
| Ventromedial Prefrontal Cortex (vmPFC) | Average Number of Use Sessions Per Week. | End of treatment / Follow-up | 11.69 use sessions per week | Standard Deviation 18.71 |
Secondary
Number of Days of Use Per Week.
Number of days per week (0-7) where the participant uses any cannabis. At the time of enrollment participants were asked to recall the number of days of cannabis use per week for the 4 weeks prior to enrollment. Participants were then asked (over a period of 7 weeks) to recall days of use at the last fMRI visit (during prior week) and at the week 2, 4, and 6 follow-up visits. Average values are reported for the 4-week period prior to enrollment and the 7-week period at end of treatment at follow-up.
Time frame: 4 weeks prior to baseline assessment and 7 weeks at the end of treatment through 6-week post-treatment follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dorsolateral Prefrontal Cortex (DLPFC) | Number of Days of Use Per Week. | Baseline assessment | 6.82 days per week | Standard Deviation 0.38 |
| Dorsolateral Prefrontal Cortex (DLPFC) | Number of Days of Use Per Week. | End of treatment / Follow-up | 5.27 days per week | Standard Deviation 1.95 |
| Ventromedial Prefrontal Cortex (vmPFC) | Number of Days of Use Per Week. | Baseline assessment | 6.68 days per week | Standard Deviation 0.69 |
| Ventromedial Prefrontal Cortex (vmPFC) | Number of Days of Use Per Week. | End of treatment / Follow-up | 2.82 days per week | Standard Deviation 3.25 |
Secondary
Number of Participants Who Had a Period of 4-consecutive Weeks of Abstinence During the Follow-up Period
Based on patient self-report of any 4-week period of abstinence
Time frame: Follow-up period (final week of active treatment plus 6-week post-treatment follow-up)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dorsolateral Prefrontal Cortex (DLPFC) | Number of Participants Who Had a Period of 4-consecutive Weeks of Abstinence During the Follow-up Period | 0 Participants |
| Ventromedial Prefrontal Cortex (vmPFC) | Number of Participants Who Had a Period of 4-consecutive Weeks of Abstinence During the Follow-up Period | 4 Participants |
Secondary
Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) Scale Score
The Q-LES-Q-SF overall score range is from 14 to 70, with higher scores indicating greater satisfaction and enjoyment. The total score is expressed as a percentage of the maximum possible score (1-100).
Time frame: Baseline and end of the follow-up period (12 to 15 weeks post-baseline)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dorsolateral Prefrontal Cortex (DLPFC) | Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) Scale Score | Baseline assessment | 56.25 score on a scale | Standard Deviation 13.61 |
| Dorsolateral Prefrontal Cortex (DLPFC) | Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) Scale Score | End 6-week follow-up | 62.50 score on a scale | Standard Deviation 11.01 |
| Ventromedial Prefrontal Cortex (vmPFC) | Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) Scale Score | Baseline assessment | 54.82 score on a scale | Standard Deviation 11.97 |
| Ventromedial Prefrontal Cortex (vmPFC) | Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) Scale Score | End 6-week follow-up | 67.63 score on a scale | Standard Deviation 11.15 |