An Early Phase 1 interventional study of Placebo TMS Sham and Marinol 10Mg Capsule TMS Sham in Neurosciences, Substance-Related Disorders and Behavior Problem, sponsored by Michael J. Wesley, PhD. Completed at 1 site in United States. Open to participants aged 18 Years to 34 Years. Per ClinicalTrials.gov, last updated 2024-04-05.
Sponsored by Michael J. Wesley, PhD · Early Phase 1, Interventional, and Basic science
Emerging adults are a particularly vulnerable group for experiencing the immediate and potentially lifelong negative impacts of habitual cannabis use, and trends suggest that cannabis use disorder (CUD) will soon escalate in this population. The proposed research will combine clinical pharmacology, non-invasive brain stimulation, and neuroimaging techniques to establish the brain mechanisms of cannabinoid-impaired decision-making processes in emerging adults with CUD. Results from this project will inform CUD prevention/treatment efforts in this high-risk group and address a growing public health concern.
This mentored career development award (K01) will enable Dr. Michael J. Wesley to achieve his long-term goal of becoming an independent investigator with a clinical research program examining cannabis use disorder (CUD) in emerging adults, which is a current NIDA funding priority. Dr. Wesley is a new Assistant Professor at the University of Kentucky (UK) College of Medicine. The activities proposed in this award build on Dr. Wesley's background in neuroimaging and drug abuse research and will allow him to accomplish these specific short-term objectives: Become an expert in (1) clinical pharmacology and (2) non-invasive brain stimulation research, and enhance/develop his (3) knowledge of the responsible conduct of research, (4) skills for scientific communication and grant writing, and (5) ability to manage an independent research program. UK has numerous faculty and projects focused on drug abuse research and is an ideal environment for Dr. Wesley to successfully complete this award. Dr. Wesley has assembled a stellar mentoring team consisting of Dr. Josh Lile (Mentor), who runs a successful NIH-funded clinical pharmacology research program at UK and Drs. Mark George (Co-Mentor) and Colleen A. Hanlon of the Brain Stimulation Laboratory at the Medical University of South Carolina, Together they will guide and oversee Dr. Wesley's training in clinical pharmacology, brain stimulation, and scientific communication and grant writing. Dr. Wesley has proposed to engage in a series of formal classes, lab exchanges, and research seminars/meetings that will assist him in accomplishing the objectives of this award.
The proposed research project is novel, innovative, and rigorous. It will combine the acute administration of Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, with brain stimulation and neuroimaging to examine the role of the dorsal lateral prefrontal cortex (DLPFC) and connected brain areas in drug-impaired decision-making processes. Specifically, transcranial magnetic stimulation (TMS) will be used to raise or lower DLPFC functionality following the administration THC in randomized, double-blind, placebo- and sham-controlled experiments.
Aim 1 will test the hypotheses that excitatory TMS (raising DLPFC functionality) will attenuate the impairing effects of THC on study outcomes.
Aim 2 will test the hypotheses that inhibitory TMS (lowering DLPFC functionality) will enhance the impairing effects of THC on study outcomes.
Results from this project will improve the investigator's understanding of the mechanisms involved in cannabis-impaired decision-making, which will inform CUD management and address a growing public health concern.
2,181 studies on the registry are indexed under Substance-Related Disorders; 399 are open to participants now.
This study's enrollment of 66 is below the median of 108 across 1,770 interventional studies indexed under Substance-Related Disorders.
Browse Substance-Related Disorders studies →Michael J. Wesley, PhD is the lead sponsor of 2 studies on the registry; 1 is open to participants now.
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Exclusion Criteria:
Individuals assigned to this group will receive excitatory (real and sham) TMS in combination with 0, 10, and 30mg THC.
Device: Placebo TMS Sham · Drug: Marinol 10Mg Capsule TMS Sham · Drug: Marinol 30Mg Capsule TMS Sham · Device: Placebo TMS Real · Other: Marinol 10Mg Capsule TMS Real · Other: Marinol 30Mg Capsule TMS Real
Individuals assigned to this group will receive inhibitory (real and sham) TMS in combination with 0, 10, and 30mg THC.
Device: Placebo TMS Sham · Drug: Marinol 10Mg Capsule TMS Sham · Drug: Marinol 30Mg Capsule TMS Sham · Device: Placebo TMS Real · Other: Marinol 10Mg Capsule TMS Real · Other: Marinol 30Mg Capsule TMS Real
Individuals will receive placebo dose and sham TMS.
Also known as: Placebo, Sham TMS
Individuals will receive 10mg dose and sham TMS.
Also known as: 10mg THC, Sham TMS
Individuals will receive 30mg dose and sham TMS.
Also known as: 30mg THC, Sham TMS
Individuals will receive placebo and real TMS.
Also known as: Placebo, Real TMS
Individuals will receive10mg THC and real TMS. Intervention type: Other (combination device/drug intervention)
Also known as: 10mg THC, Real TMS
Individuals will receive 30mg THC and real TMS. Intervention type: Other (combination device/drug intervention)
Also known as: 30mg THC, Real TMS
Alpha Learning Rate
In a Probabilistic Reinforcement Learning Choice (PRLC) task, two stimuli are presented and choosing either could result in a monetary reinforcer, but the reinforcement probabilities of the stimuli differ, and change throughout the task. Individuals attempt to optimize choices according to learned probabilities and track changing probabilities over time. PRLC performance allows mathematical modeling of trial-by-trial data under "real-world" uncertainty and yields computational parameters, such as the learning rate. Choice data were analyzed using a Rescorla-Wanger learning model with an alpha learning rate, beta inverse temperature, and perseveration global parameters. Model-derived learning rates are indicative of an individual's ability to learn from previous choice outcomes to update future decision-making. For this task, learning rates range from 0-1 with lower values indicative of more optimal learning.
Time frame: Measure collected at 2 time points: Baseline (0HR) and Post TMS Administration (3HR)
Self-Report Subjective "High"
A Visual Analogue Scale (VAS) was used to measure the acute subjective effects of THC at varying doses (0mg, 10mg, 30mg). Responses are made for VAS items along a 100-unit scale anchored on the extremes by "Not At All" (0) and "Extremely" (100) with a higher score meaning more of the effect. Participants were instructed to select "Not At All" (0) for all baseline (0HR) measures. Post-TMS administration (real or sham), participant self-reported their subjective "high" on the VAS with higher values indicating a more intense sensation of "high".
Time frame: Measured 2 times: Baseline (0HR) and 3 hours (3HR) after capsule administration on each drug condition (0mg, 10mg, 30mg)
Elasticity of Demand
Elasticity of Demand was measured by the Cannabis Purchase Task (CPT) where participants are asked how many "hits" of cannabis they would consume at 16 different price points in ascending order ($0-$140). Higher elasticity values indicate a greater sensitivity to changing price points resulting in a reduced demand for "hits" of THC at increasing price points.
Time frame: Measured 2 times: Baseline (0HR) and Post-TMS (3HR) after THC administration on each drug condition (0mg, 10mg, 30mg).
Working Memory Performance
Working memory (WM), the ability to hold a finite amount of information for a set amount of time, is measured by the N-Back task. Here, participants were presented with a sequence of letters and must indicate when the letter currently being viewed matches the one from N steps earlier in the sequence. The load factor "N" is adjusted between 0, 1, and 2 to adjust the difficulty of the task (0-Back = no WM load, 1-Back = minimal WM load, 2-Back = greater WM load) where a higher score means better memory performance. Outcomes are reported as the Total Accuracy Percentage (Correct Choices/Total Choices) x 100%
Time frame: Measured 2 times: Baseline (0HR) and Post-TMS (3HR) after THC administration on each drug condition (0mg, 10mg, 30mg).
Forty young adults (N=40; n=20 per Experiment) aged 18-34 who report habitual cannabis use (20 or more days per month) or meet hazardous cannabis use criteria will complete the study. A 15% dropout rate is assumed. Subjects will be matched on sex, age and education. Enrollment will approximate the demographic proportions of Fayette County, KY. so we anticipate enrolling members mostly from those demographic categories.
| Milestone | Excitatory TMS | Inhibitory TMS |
|---|---|---|
| Started | 58 | 8 |
| Training session | 24 | 5 |
| 0mg marinol sham tms | 13 | 4 |
| 0mg marinol real tms | 14 | 4 |
| 10mg marinol sham tms | 13 | 4 |
| 10mg marinol real tms | 12 | 4 |
| 30mg marinol sham tms | 12 | 5 |
| 30mg marinol real tms | 12 | 4 |
| Completed | 11 | 4 |
| Not completed | 47 | 4 |
| Withdrew: Withdrawal by subject | 22 | 4 |
| Withdrew: Lost to follow-up | 18 | 0 |
| Withdrew: Failed medical screening | 7 | 0 |
In a Probabilistic Reinforcement Learning Choice (PRLC) task, two stimuli are presented and choosing either could result in a monetary reinforcer, but the reinforcement probabilities of the stimuli differ, and change throughout the task. Individuals attempt to optimize choices according to learned probabilities and track changing probabilities over time. PRLC performance allows mathematical modeling of trial-by-trial data under "real-world" uncertainty and yields computational parameters, such as the learning rate. Choice data were analyzed using a Rescorla-Wanger learning model with an alpha learning rate, beta inverse temperature, and perseveration global parameters. Model-derived learning rates are indicative of an individual's ability to learn from previous choice outcomes to update future decision-making. For this task, learning rates range from 0-1 with lower values indicative of more optimal learning.
| Alpha Coefficient | Excitatory TMS | Inhibitory TMS |
|---|---|---|
| Baseline 0mg Sham | .62 ± .28 | .43 ± .37 |
| 3HR 0mg Sham | .55 ± .31 | .21 ± .23 |
| Baseline 0mg Real | .71 ± .27 | .53 ± .41 |
| 3HR 0mg Real | .58 ± .33 | .48 ± .34 |
| Baseline 10mg Sham | .62 ± .32 | .49 ± .15 |
| 3HR 10mg Sham | .62 ± .28 | .52 ± .41 |
| Baseline 10mg Real | .63 ± .27 | .53 ± .38 |
| 3HR 10mg Real | .63 ± .28 | .32 ± .38 |
| Baseline 30mg Sham | .64 ± .29 | .48 ± .37 |
| 3HR 30mg Sham | .60 ± .29 | .41 ± .30 |
| Baseline 30mg Real | .66 ± .32 | .24 ± .16 |
| 3HR 30mg Real | .79 ± .17 | .30 ± .22 |
A Visual Analogue Scale (VAS) was used to measure the acute subjective effects of THC at varying doses (0mg, 10mg, 30mg). Responses are made for VAS items along a 100-unit scale anchored on the extremes by "Not At All" (0) and "Extremely" (100) with a higher score meaning more of the effect. Participants were instructed to select "Not At All" (0) for all baseline (0HR) measures. Post-TMS administration (real or sham), participant self-reported their subjective "high" on the VAS with higher values indicating a more intense sensation of "high".
| score on a 100pt VAS scale | Excitatory TMS | Inhibitory TMS |
|---|---|---|
| "High" 0mg THC Real TMS | 2.9 ± 5.4 | 0 ± 0 |
| "High" 10mg THC Real TMS | 13.8 ± 24.4 | 3.8 ± 7.5 |
| "High" 30mg THC Real TMS | 24.6 ± 27.3 | 5 ± 10 |
| "High" 0mg THC Sham TMS | 1.2 ± 2.2 | 3.8 ± 7.5 |
| "High" 10mg THC Sham TMS | 15 ± 20.3 | 1.3 ± 2.5 |
| "High" 30mg THC Sham TMS | 36.5 ± 32 | 12.5 ± 21.8 |
Elasticity of Demand was measured by the Cannabis Purchase Task (CPT) where participants are asked how many "hits" of cannabis they would consume at 16 different price points in ascending order ($0-$140). Higher elasticity values indicate a greater sensitivity to changing price points resulting in a reduced demand for "hits" of THC at increasing price points.
| log(hits per dollar) | Excitatory TMS | Inhibitory TMS |
|---|---|---|
| Baseline 0mg THC Real TMS | .005 ± .008 | .004 ± .003 |
| 3HR 0mg THC Real TMS | .006 ± .009 | .007 ± .007 |
| Baseline 10mg THC Real TMS | .005 ± .008 | .003 ± .002 |
| 3HR 10mg THC Real TMS | .006 ± .009 | .002 ± .001 |
| Baseline 30mg THC Real TMS | .004 ± .002 | .005 ± .003 |
| 3HR 30mg THC Real TMS | .006 ± .008 | .000 ± .000 |
| Baseline 0mg THC Sham TMS | .005 ± .009 | .005 ± .006 |
| 3HR 0mg THC Sham TMS | .005 ± .009 | .006 ± .009 |
| Baseline 10mg THC Sham TMS | .006 ± .009 | .004 ± .002 |
| 3HR 10mg THC Sham TMS | .005 ± .009 | .003 ± .002 |
| Baseline 30mg THC Sham TMS | .004 ± .004 | .004 ± .004 |
| 3HR 30mg THC Sham TMS | .005 ± .006 | .007 ± .007 |
Working memory (WM), the ability to hold a finite amount of information for a set amount of time, is measured by the N-Back task. Here, participants were presented with a sequence of letters and must indicate when the letter currently being viewed matches the one from N steps earlier in the sequence. The load factor "N" is adjusted between 0, 1, and 2 to adjust the difficulty of the task (0-Back = no WM load, 1-Back = minimal WM load, 2-Back = greater WM load) where a higher score means better memory performance. Outcomes are reported as the Total Accuracy Percentage (Correct Choices/Total Choices) x 100%
| percentage of correct choices | Excitatory TMS | Inhibitory TMS |
|---|---|---|
| Baseline 0back 0mg THC Real TMS | 98.0 ± 1.7 | 96.3 ± 4.3 |
| Baseline 1back 0mg THC Real TMS | 93.0 ± 4.2 | 90 ± 12.4 |
| Baseline 2back 0mg THC Real TMS | 90.1 ± 4.7 | 86.3 ± 21.4 |
| Baseline 0back 10mg THC Real TMS | 97.1 ± 3.4 | 98.3 ± 1.4 |
| Baseline 2back 10mg THC Real TMS | 90.2 ± 4.9 | 93.3 ± 7.6 |
| Baseline 1back 10mg THC Real TMS | 93.3 ± 4.3 | 93.3 ± 3.8 |
| Baseline 0back 30mg THC Real TMS | 97.7 ± 2.2 | 98.1 ± 1.3 |
| Baseline 1back 30mg THC Real TMS | 92.5 ± 3.68 | 85 ± 21.7 |
| Baseline 2back 30mg THC Real TMS | 89.2 ± 5.5 | 87.5 ± 14.3 |
| Baseline 0back 0mg THC Sham TMS | 98.1 ± 2.2 | 96.9 ± 3.2 |
| Baseline 1back 0mgTHC Sham TMS | 92.1 ± 4.8 | 89.4 ± 11.3 |
| Baseline 2back 0mg THC Sham TMS | 88.3 ± 4.3 | 85.0 ± 21.4 |
| Baseline 0back 10mg THC Sham TMS | 96.4 ± 3.8 | 93.1 ± 12.1 |
| Baseline 1back 10mg THC Sham TMS | 92.1 ± 4.9 | 92.5 ± 10.2 |
| Baseline 2back 10mg THC Sham TMS | 87.9 ± 6.4 | 83.8 ± 19.7 |
| Baseline 0back 30mg THC Sham TMS | 96.5 ± 3.5 | 96.3 ± 2.5 |
| Baseline 1back 30mg THC Sham TMS | 95 ± 2.8 | 90.6 ± 5.5 |
| Baseline 2back 30mg THC Sham TMS | 86.9 ± 6.9 | 87.5 ± 12.6 |
| 3HR 0back 0mg THC Real TMS | 97.5 ± 3.4 | 96.7 ± 3.2 |
| 3HR 1back 0mg THC Real TMS | 91.4 ± 3.1 | 92.5 ± 3.5 |
| 3HR 2back 0mg THC Real TMS | 87.3 ± 5.8 | 89.4 ± 13.6 |
| 3HR 0back 10mg THC Real TMS | 96.7 ± 3.1 | 98.3 ± 1.4 |
| 3HR 1back 10mg THC Real TMS | 92.5 ± 4.9 | 97.5 ± 4.3 |
| 3HR 2back 10mg THC Real TMS | 87.3 ± 7.5 | 95 ± 6.6 |
| 3HR 0back 30mg THC Real TMS | 96.7 ± 3.6 | 98.1 ± 2.4 |
| 3HR 1back 30mg THC Real TMS | 88.3 ± 7.4 | 90.6 ± 5.2 |
| 3HR 2back 30mg THC Real TMS | 86.9 ± 5.9 | 90.6 ± 8.8 |
| 3HR 0back 0mg THC Sham TMS | 96.7 ± 4.1 | 97.5 ± 2.0 |
| 3HR 1back 0mg THC Sham TMS | 91.7 ± 5.6 | 93.8 ± 7.8 |
| 3HR 2back 0mg THC Sham TMS | 89.0 ± 6.0 | 87.5 ± 10.6 |
| 3HR 0back 10mg THC Sham TMS | 96.2 ± 3.0 | 90 ± 18.4 |
| 3HR 1back 10mg THC Sham TMS | 92.3 ± 5.5 | 85.6 ± 19.1 |
| 3HR 2back 10mg THC Sham TMS | 88.5 ± 7.0 | 82.5 ± 23.8 |
| 3HR 0back 30mg THC Sham TMS | 96.7 ± 3.7 | 94.4 ± 3.8 |
| 3HR 1back 30mg THC Sham TMS | 92.9 ± 3.2 | 91.3 ± 7.5 |
| 3HR 2back 30mg THC Sham TMS | 87.3 ± 8.5 | 87.5 ± 14.9 |
Collected over 1 day. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 0mg Marinol | 0/18 (0%) | 0/18 (0%) | 1/18 (5.6%) |
| 10mg Marinol | 0/17 (0%) | 0/17 (0%) | 0/17 (0%) |
| 30mg Marinol | 1/17 (5.9%) | 0/17 (0%) | 0/17 (0%) |
| Event | 0mg Marinol | 10mg Marinol | 30mg Marinol |
|---|---|---|---|
| HeadachesInjury, poisoning and procedural complications | 1/18 | 0/17 | 0/17 |
| Age, Categorical(Participants) | Excitatory TMS | Inhibitory TMS | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 58 | 8 | 66 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | Excitatory TMS | Inhibitory TMS | Total |
|---|---|---|---|
| Mean | 22.8 ± 4.5 | 27 ± 7.0 | 23.8 ± 5.3 |
| Sex: Female, Male(Participants) | Excitatory TMS | Inhibitory TMS | Total |
|---|---|---|---|
| Female | 13 | 3 | 16 |
| Male | 45 | 5 | 50 |
| Ethnicity (NIH/OMB)(Participants) | Excitatory TMS | Inhibitory TMS | Total |
|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 1 |
| Not Hispanic or Latino | 57 | 8 | 65 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Excitatory TMS | Inhibitory TMS | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 3 | 0 | 3 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 15 | 1 | 16 |
| White | 37 | 7 | 44 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 3 | 0 | 3 |
| Region of Enrollment(participants) | Excitatory TMS | Inhibitory TMS | Total |
|---|---|---|---|
| United States | 58 | 8 | 66 |
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Plan to share: No
Ran from Jul 2017 to primary completion in Dec 2023, 76 months.
Results were first posted in Apr 2024, 3 months after primary completion.
Of 34 non-industry phase 1 interventional studies under Substance-Related Disorders, half reached primary completion within 31 months of starting (the median), counting those still running; a quarter within 14 and three quarters within 46. This study's 76 months is above that.
Counting every sponsor, half of 57 studies reached it within 12 months; a quarter within 4 and three quarters within 33.
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This study is completed, as verified in Mar 2024. You cannot join it, but the record below documents what was studied.
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Michael J. Wesley, PhD