Behavior Problem, Neurosciences, Substance-Related Disorders
Conditions
Brief summary
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.
Detailed description
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.
Interventions
Individuals will receive placebo dose and sham TMS.
Individuals will receive 10mg dose and sham TMS.
Individuals will receive 30mg dose and sham TMS.
Individuals will receive placebo and real TMS.
Individuals will receive10mg THC and real TMS. Intervention type: Other (combination device/drug intervention)
Individuals will receive 30mg THC and real TMS. Intervention type: Other (combination device/drug intervention)
Sponsors
Study design
Masking description
Functionality will be tested following combinations of THC and TMS will be tested in randomized, double-blind, placebo- and sham-controlled experiments.
Intervention model description
Participants will be assigned to either excitatory or inhibitory TMS treatment arms. All individuals will receive multiple doses of oral THC (0, 10 and 30mg) and TMS (real or sham).
Eligibility
Inclusion criteria
* Habitual cannabis use problems * Body Mass Index ≤30
Exclusion criteria
* Past or current serious physical or mental health * Sesame seed oil allergy * Irregular health issues identified by the Study Physician * Standard magnetic resonance imaging and transcranial magnetic stimulation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alpha Learning Rate | Measure collected at 2 time points: Baseline (0HR) and Post TMS Administration (3HR) | 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. |
| Self-Report Subjective High | Measured 2 times: Baseline (0HR) and 3 hours (3HR) after capsule administration on each drug condition (0mg, 10mg, 30mg) | 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. |
| Elasticity of Demand | Measured 2 times: Baseline (0HR) and Post-TMS (3HR) after THC administration on each drug condition (0mg, 10mg, 30mg). | 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. |
| Working Memory Performance | Measured 2 times: Baseline (0HR) and Post-TMS (3HR) after THC administration on each drug condition (0mg, 10mg, 30mg). | 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% |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Excitatory TMS Combinations of THC and excitatory TMS.
Marinol: Individuals will receive 0, 10, 30mg of Marinol.
Transcranial Magnetic Stimulation: Individuals will receive real and sham TMS | 58 |
| Inhibitory TMS Combinations of THC and inhibitory TMS.
Marinol: Individuals will receive 0, 10, 30mg of Marinol.
Transcranial Magnetic Stimulation: Individuals will receive real and sham TMS | 8 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Failed Medical Screening | 7 | 0 |
| Overall Study | Lost to Follow-up | 18 | 0 |
| Overall Study | Withdrawal by Subject | 22 | 4 |
Baseline characteristics
| Characteristic | Excitatory TMS | Inhibitory TMS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 58 Participants | 8 Participants | 66 Participants |
| Age, Continuous | 22.8 years STANDARD_DEVIATION 4.5 | 27 years STANDARD_DEVIATION 7 | 23.8 years STANDARD_DEVIATION 5.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants | 8 Participants | 65 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 | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 1 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 37 Participants | 7 Participants | 44 Participants |
| Region of Enrollment United States | 58 participants | 8 participants | 66 participants |
| Sex: Female, Male Female | 13 Participants | 3 Participants | 16 Participants |
| Sex: Female, Male Male | 45 Participants | 5 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 17 | 1 / 17 |
| other Total, other adverse events | 1 / 18 | 0 / 17 | 0 / 17 |
| serious Total, serious adverse events | 0 / 18 | 0 / 17 | 0 / 17 |
Outcome results
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)
Population: Of the 58 total participants assigned to the excitatory TMS condition, 15 individuals completed at least one experimental session.~Of the 8 total participants assigned to the inhibitory TMS condition, 6 individuals completed at least one experimental session.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Excitatory TMS | Alpha Learning Rate | Baseline 0mg Sham | .62 Alpha Coefficient | Standard Deviation 0.28 |
| Excitatory TMS | Alpha Learning Rate | 3HR 0mg Sham | .55 Alpha Coefficient | Standard Deviation 0.31 |
| Excitatory TMS | Alpha Learning Rate | Baseline 0mg Real | .71 Alpha Coefficient | Standard Deviation 0.27 |
| Excitatory TMS | Alpha Learning Rate | 3HR 0mg Real | .58 Alpha Coefficient | Standard Deviation 0.33 |
| Excitatory TMS | Alpha Learning Rate | Baseline 10mg Sham | .62 Alpha Coefficient | Standard Deviation 0.32 |
| Excitatory TMS | Alpha Learning Rate | 3HR 10mg Sham | .62 Alpha Coefficient | Standard Deviation 0.28 |
| Excitatory TMS | Alpha Learning Rate | Baseline 10mg Real | .63 Alpha Coefficient | Standard Deviation 0.27 |
| Excitatory TMS | Alpha Learning Rate | 3HR 10mg Real | .63 Alpha Coefficient | Standard Deviation 0.28 |
| Excitatory TMS | Alpha Learning Rate | Baseline 30mg Sham | .64 Alpha Coefficient | Standard Deviation 0.29 |
| Excitatory TMS | Alpha Learning Rate | 3HR 30mg Sham | .60 Alpha Coefficient | Standard Deviation 0.29 |
| Excitatory TMS | Alpha Learning Rate | Baseline 30mg Real | .66 Alpha Coefficient | Standard Deviation 0.32 |
| Excitatory TMS | Alpha Learning Rate | 3HR 30mg Real | .79 Alpha Coefficient | Standard Deviation 0.17 |
| Inhibitory TMS | Alpha Learning Rate | Baseline 30mg Real | .24 Alpha Coefficient | Standard Deviation 0.16 |
| Inhibitory TMS | Alpha Learning Rate | Baseline 0mg Sham | .43 Alpha Coefficient | Standard Deviation 0.37 |
| Inhibitory TMS | Alpha Learning Rate | Baseline 10mg Real | .53 Alpha Coefficient | Standard Deviation 0.38 |
| Inhibitory TMS | Alpha Learning Rate | 3HR 0mg Sham | .21 Alpha Coefficient | Standard Deviation 0.23 |
| Inhibitory TMS | Alpha Learning Rate | 3HR 30mg Sham | .41 Alpha Coefficient | Standard Deviation 0.3 |
| Inhibitory TMS | Alpha Learning Rate | Baseline 0mg Real | .53 Alpha Coefficient | Standard Deviation 0.41 |
| Inhibitory TMS | Alpha Learning Rate | 3HR 10mg Real | .32 Alpha Coefficient | Standard Deviation 0.38 |
| Inhibitory TMS | Alpha Learning Rate | 3HR 0mg Real | .48 Alpha Coefficient | Standard Deviation 0.34 |
| Inhibitory TMS | Alpha Learning Rate | 3HR 30mg Real | .30 Alpha Coefficient | Standard Deviation 0.22 |
| Inhibitory TMS | Alpha Learning Rate | Baseline 10mg Sham | .49 Alpha Coefficient | Standard Deviation 0.15 |
| Inhibitory TMS | Alpha Learning Rate | Baseline 30mg Sham | .48 Alpha Coefficient | Standard Deviation 0.37 |
| Inhibitory TMS | Alpha Learning Rate | 3HR 10mg Sham | .52 Alpha Coefficient | Standard Deviation 0.41 |
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).
Population: Of the 58 participants assigned to the excitatory TMS condition, 13 individuals had usable data from at least one experimental session.~Of the 8 participants assigned to the excitatory TMS condition, 4 individuals had usable data from at least one experimental session.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Excitatory TMS | Elasticity of Demand | Baseline 30mg THC Real TMS | .004 log(hits per dollar) | Standard Deviation 0.002 |
| Excitatory TMS | Elasticity of Demand | 3HR 0mg THC Real TMS | .006 log(hits per dollar) | Standard Deviation 0.009 |
| Excitatory TMS | Elasticity of Demand | Baseline 0mg THC Sham TMS | .005 log(hits per dollar) | Standard Deviation 0.009 |
| Excitatory TMS | Elasticity of Demand | 3HR 0mg THC Sham TMS | .005 log(hits per dollar) | Standard Deviation 0.009 |
| Excitatory TMS | Elasticity of Demand | Baseline 10mg THC Sham TMS | .006 log(hits per dollar) | Standard Deviation 0.009 |
| Excitatory TMS | Elasticity of Demand | Baseline 10mg THC Real TMS | .005 log(hits per dollar) | Standard Deviation 0.008 |
| Excitatory TMS | Elasticity of Demand | 3HR 10mg THC Sham TMS | .005 log(hits per dollar) | Standard Deviation 0.009 |
| Excitatory TMS | Elasticity of Demand | Baseline 0mg THC Real TMS | .005 log(hits per dollar) | Standard Deviation 0.008 |
| Excitatory TMS | Elasticity of Demand | Baseline 30mg THC Sham TMS | .004 log(hits per dollar) | Standard Deviation 0.004 |
| Excitatory TMS | Elasticity of Demand | 3HR 10mg THC Real TMS | .006 log(hits per dollar) | Standard Deviation 0.009 |
| Excitatory TMS | Elasticity of Demand | 3HR 30mg THC Sham TMS | .005 log(hits per dollar) | Standard Deviation 0.006 |
| Excitatory TMS | Elasticity of Demand | 3HR 30mg THC Real TMS | .006 log(hits per dollar) | Standard Deviation 0.008 |
| Inhibitory TMS | Elasticity of Demand | 3HR 30mg THC Sham TMS | .007 log(hits per dollar) | Standard Deviation 0.007 |
| Inhibitory TMS | Elasticity of Demand | Baseline 0mg THC Sham TMS | .005 log(hits per dollar) | Standard Deviation 0.006 |
| Inhibitory TMS | Elasticity of Demand | Baseline 0mg THC Real TMS | .004 log(hits per dollar) | Standard Deviation 0.003 |
| Inhibitory TMS | Elasticity of Demand | 3HR 0mg THC Real TMS | .007 log(hits per dollar) | Standard Deviation 0.007 |
| Inhibitory TMS | Elasticity of Demand | Baseline 10mg THC Real TMS | .003 log(hits per dollar) | Standard Deviation 0.002 |
| Inhibitory TMS | Elasticity of Demand | 3HR 10mg THC Real TMS | .002 log(hits per dollar) | Standard Deviation 0.001 |
| Inhibitory TMS | Elasticity of Demand | 3HR 30mg THC Real TMS | .000 log(hits per dollar) | Standard Deviation 0 |
| Inhibitory TMS | Elasticity of Demand | 3HR 0mg THC Sham TMS | .006 log(hits per dollar) | Standard Deviation 0.009 |
| Inhibitory TMS | Elasticity of Demand | Baseline 10mg THC Sham TMS | .004 log(hits per dollar) | Standard Deviation 0.002 |
| Inhibitory TMS | Elasticity of Demand | 3HR 10mg THC Sham TMS | .003 log(hits per dollar) | Standard Deviation 0.002 |
| Inhibitory TMS | Elasticity of Demand | Baseline 30mg THC Sham TMS | .004 log(hits per dollar) | Standard Deviation 0.004 |
| Inhibitory TMS | Elasticity of Demand | Baseline 30mg THC Real TMS | .005 log(hits per dollar) | Standard Deviation 0.003 |
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)
Population: Of the 58 participants assigned to the Excitatory TMS condition, as max of 14 participants had usable data from at least one experimental session.~Of the 8 participants assigned to the Inhibitory TMS condition, as max of 4 participants had usable data from at least one experimental session.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Excitatory TMS | Self-Report Subjective High | High 30mg THC Real TMS | 24.6 score on a 100pt VAS scale | Standard Deviation 27.3 |
| Excitatory TMS | Self-Report Subjective High | High 10mg THC Sham TMS | 15 score on a 100pt VAS scale | Standard Deviation 20.3 |
| Excitatory TMS | Self-Report Subjective High | High 0mg THC Sham TMS | 1.2 score on a 100pt VAS scale | Standard Deviation 2.2 |
| Excitatory TMS | Self-Report Subjective High | High 10mg THC Real TMS | 13.8 score on a 100pt VAS scale | Standard Deviation 24.4 |
| Excitatory TMS | Self-Report Subjective High | High 30mg THC Sham TMS | 36.5 score on a 100pt VAS scale | Standard Deviation 32 |
| Excitatory TMS | Self-Report Subjective High | High 0mg THC Real TMS | 2.9 score on a 100pt VAS scale | Standard Deviation 5.4 |
| Inhibitory TMS | Self-Report Subjective High | High 30mg THC Sham TMS | 12.5 score on a 100pt VAS scale | Standard Deviation 21.8 |
| Inhibitory TMS | Self-Report Subjective High | High 0mg THC Real TMS | 0 score on a 100pt VAS scale | Standard Deviation 0 |
| Inhibitory TMS | Self-Report Subjective High | High 10mg THC Real TMS | 3.8 score on a 100pt VAS scale | Standard Deviation 7.5 |
| Inhibitory TMS | Self-Report Subjective High | High 30mg THC Real TMS | 5 score on a 100pt VAS scale | Standard Deviation 10 |
| Inhibitory TMS | Self-Report Subjective High | High 10mg THC Sham TMS | 1.3 score on a 100pt VAS scale | Standard Deviation 2.5 |
| Inhibitory TMS | Self-Report Subjective High | High 0mg THC Sham TMS | 3.8 score on a 100pt VAS scale | Standard Deviation 7.5 |
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).
Population: Of the 58 participants assigned to the excitatory TMS condition, 14 individuals had usable data from at least one experimental session.~Of the 8 participants assigned to the excitatory TMS condition, 4 individuals had usable data from at least one experimental session.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Excitatory TMS | Working Memory Performance | Baseline 2back 30mg THC Sham TMS | 86.9 percentage of correct choices | Standard Deviation 6.9 |
| Excitatory TMS | Working Memory Performance | Baseline 1back 0mg THC Real TMS | 93.0 percentage of correct choices | Standard Deviation 4.2 |
| Excitatory TMS | Working Memory Performance | 3HR 0back 0mg THC Real TMS | 97.5 percentage of correct choices | Standard Deviation 3.4 |
| Excitatory TMS | Working Memory Performance | Baseline 0back 0mg THC Sham TMS | 98.1 percentage of correct choices | Standard Deviation 2.2 |
| Excitatory TMS | Working Memory Performance | 3HR 1back 0mg THC Real TMS | 91.4 percentage of correct choices | Standard Deviation 3.1 |
| Excitatory TMS | Working Memory Performance | Baseline 2back 10mg THC Real TMS | 90.2 percentage of correct choices | Standard Deviation 4.9 |
| Excitatory TMS | Working Memory Performance | 3HR 2back 0mg THC Real TMS | 87.3 percentage of correct choices | Standard Deviation 5.8 |
| Excitatory TMS | Working Memory Performance | Baseline 1back 0mgTHC Sham TMS | 92.1 percentage of correct choices | Standard Deviation 4.8 |
| Excitatory TMS | Working Memory Performance | 3HR 0back 10mg THC Real TMS | 96.7 percentage of correct choices | Standard Deviation 3.1 |
| Excitatory TMS | Working Memory Performance | Baseline 0back 0mg THC Real TMS | 98.0 percentage of correct choices | Standard Deviation 1.7 |
| Excitatory TMS | Working Memory Performance | 3HR 1back 10mg THC Real TMS | 92.5 percentage of correct choices | Standard Deviation 4.9 |
| Excitatory TMS | Working Memory Performance | Baseline 2back 0mg THC Sham TMS | 88.3 percentage of correct choices | Standard Deviation 4.3 |
| Excitatory TMS | Working Memory Performance | 3HR 2back 10mg THC Real TMS | 87.3 percentage of correct choices | Standard Deviation 7.5 |
| Excitatory TMS | Working Memory Performance | Baseline 1back 10mg THC Real TMS | 93.3 percentage of correct choices | Standard Deviation 4.3 |
| Excitatory TMS | Working Memory Performance | 3HR 0back 30mg THC Real TMS | 96.7 percentage of correct choices | Standard Deviation 3.6 |
| Excitatory TMS | Working Memory Performance | Baseline 0back 10mg THC Sham TMS | 96.4 percentage of correct choices | Standard Deviation 3.8 |
| Excitatory TMS | Working Memory Performance | 3HR 2back 30mg THC Real TMS | 86.9 percentage of correct choices | Standard Deviation 5.9 |
| Excitatory TMS | Working Memory Performance | Baseline 2back 0mg THC Real TMS | 90.1 percentage of correct choices | Standard Deviation 4.7 |
| Excitatory TMS | Working Memory Performance | 3HR 0back 0mg THC Sham TMS | 96.7 percentage of correct choices | Standard Deviation 4.1 |
| Excitatory TMS | Working Memory Performance | Baseline 1back 10mg THC Sham TMS | 92.1 percentage of correct choices | Standard Deviation 4.9 |
| Excitatory TMS | Working Memory Performance | 3HR 1back 0mg THC Sham TMS | 91.7 percentage of correct choices | Standard Deviation 5.6 |
| Excitatory TMS | Working Memory Performance | Baseline 0back 30mg THC Real TMS | 97.7 percentage of correct choices | Standard Deviation 2.2 |
| Excitatory TMS | Working Memory Performance | 3HR 2back 0mg THC Sham TMS | 89.0 percentage of correct choices | Standard Deviation 6 |
| Excitatory TMS | Working Memory Performance | Baseline 2back 10mg THC Sham TMS | 87.9 percentage of correct choices | Standard Deviation 6.4 |
| Excitatory TMS | Working Memory Performance | 3HR 0back 10mg THC Sham TMS | 96.2 percentage of correct choices | Standard Deviation 3 |
| Excitatory TMS | Working Memory Performance | 3HR 1back 30mg THC Real TMS | 88.3 percentage of correct choices | Standard Deviation 7.4 |
| Excitatory TMS | Working Memory Performance | 3HR 1back 10mg THC Sham TMS | 92.3 percentage of correct choices | Standard Deviation 5.5 |
| Excitatory TMS | Working Memory Performance | Baseline 0back 30mg THC Sham TMS | 96.5 percentage of correct choices | Standard Deviation 3.5 |
| Excitatory TMS | Working Memory Performance | 3HR 2back 10mg THC Sham TMS | 88.5 percentage of correct choices | Standard Deviation 7 |
| Excitatory TMS | Working Memory Performance | Baseline 0back 10mg THC Real TMS | 97.1 percentage of correct choices | Standard Deviation 3.4 |
| Excitatory TMS | Working Memory Performance | 3HR 0back 30mg THC Sham TMS | 96.7 percentage of correct choices | Standard Deviation 3.7 |
| Excitatory TMS | Working Memory Performance | Baseline 1back 30mg THC Sham TMS | 95 percentage of correct choices | Standard Deviation 2.8 |
| Excitatory TMS | Working Memory Performance | 3HR 1back 30mg THC Sham TMS | 92.9 percentage of correct choices | Standard Deviation 3.2 |
| Excitatory TMS | Working Memory Performance | Baseline 2back 30mg THC Real TMS | 89.2 percentage of correct choices | Standard Deviation 5.5 |
| Excitatory TMS | Working Memory Performance | 3HR 2back 30mg THC Sham TMS | 87.3 percentage of correct choices | Standard Deviation 8.5 |
| Excitatory TMS | Working Memory Performance | Baseline 1back 30mg THC Real TMS | 92.5 percentage of correct choices | Standard Deviation 3.68 |
| Inhibitory TMS | Working Memory Performance | 3HR 2back 30mg THC Sham TMS | 87.5 percentage of correct choices | Standard Deviation 14.9 |
| Inhibitory TMS | Working Memory Performance | 3HR 1back 30mg THC Real TMS | 90.6 percentage of correct choices | Standard Deviation 5.2 |
| Inhibitory TMS | Working Memory Performance | Baseline 0back 0mg THC Real TMS | 96.3 percentage of correct choices | Standard Deviation 4.3 |
| Inhibitory TMS | Working Memory Performance | Baseline 1back 0mg THC Real TMS | 90 percentage of correct choices | Standard Deviation 12.4 |
| Inhibitory TMS | Working Memory Performance | Baseline 2back 0mg THC Real TMS | 86.3 percentage of correct choices | Standard Deviation 21.4 |
| Inhibitory TMS | Working Memory Performance | Baseline 0back 10mg THC Real TMS | 98.3 percentage of correct choices | Standard Deviation 1.4 |
| Inhibitory TMS | Working Memory Performance | Baseline 2back 10mg THC Real TMS | 93.3 percentage of correct choices | Standard Deviation 7.6 |
| Inhibitory TMS | Working Memory Performance | Baseline 1back 10mg THC Real TMS | 93.3 percentage of correct choices | Standard Deviation 3.8 |
| Inhibitory TMS | Working Memory Performance | Baseline 0back 30mg THC Real TMS | 98.1 percentage of correct choices | Standard Deviation 1.3 |
| Inhibitory TMS | Working Memory Performance | Baseline 1back 30mg THC Real TMS | 85 percentage of correct choices | Standard Deviation 21.7 |
| Inhibitory TMS | Working Memory Performance | Baseline 2back 30mg THC Real TMS | 87.5 percentage of correct choices | Standard Deviation 14.3 |
| Inhibitory TMS | Working Memory Performance | Baseline 0back 0mg THC Sham TMS | 96.9 percentage of correct choices | Standard Deviation 3.2 |
| Inhibitory TMS | Working Memory Performance | Baseline 1back 0mgTHC Sham TMS | 89.4 percentage of correct choices | Standard Deviation 11.3 |
| Inhibitory TMS | Working Memory Performance | Baseline 2back 0mg THC Sham TMS | 85.0 percentage of correct choices | Standard Deviation 21.4 |
| Inhibitory TMS | Working Memory Performance | Baseline 0back 10mg THC Sham TMS | 93.1 percentage of correct choices | Standard Deviation 12.1 |
| Inhibitory TMS | Working Memory Performance | Baseline 1back 10mg THC Sham TMS | 92.5 percentage of correct choices | Standard Deviation 10.2 |
| Inhibitory TMS | Working Memory Performance | Baseline 2back 10mg THC Sham TMS | 83.8 percentage of correct choices | Standard Deviation 19.7 |
| Inhibitory TMS | Working Memory Performance | Baseline 0back 30mg THC Sham TMS | 96.3 percentage of correct choices | Standard Deviation 2.5 |
| Inhibitory TMS | Working Memory Performance | Baseline 1back 30mg THC Sham TMS | 90.6 percentage of correct choices | Standard Deviation 5.5 |
| Inhibitory TMS | Working Memory Performance | Baseline 2back 30mg THC Sham TMS | 87.5 percentage of correct choices | Standard Deviation 12.6 |
| Inhibitory TMS | Working Memory Performance | 3HR 0back 0mg THC Real TMS | 96.7 percentage of correct choices | Standard Deviation 3.2 |
| Inhibitory TMS | Working Memory Performance | 3HR 1back 0mg THC Real TMS | 92.5 percentage of correct choices | Standard Deviation 3.5 |
| Inhibitory TMS | Working Memory Performance | 3HR 2back 0mg THC Real TMS | 89.4 percentage of correct choices | Standard Deviation 13.6 |
| Inhibitory TMS | Working Memory Performance | 3HR 0back 10mg THC Real TMS | 98.3 percentage of correct choices | Standard Deviation 1.4 |
| Inhibitory TMS | Working Memory Performance | 3HR 1back 10mg THC Real TMS | 97.5 percentage of correct choices | Standard Deviation 4.3 |
| Inhibitory TMS | Working Memory Performance | 3HR 2back 10mg THC Real TMS | 95 percentage of correct choices | Standard Deviation 6.6 |
| Inhibitory TMS | Working Memory Performance | 3HR 0back 30mg THC Real TMS | 98.1 percentage of correct choices | Standard Deviation 2.4 |
| Inhibitory TMS | Working Memory Performance | 3HR 2back 30mg THC Real TMS | 90.6 percentage of correct choices | Standard Deviation 8.8 |
| Inhibitory TMS | Working Memory Performance | 3HR 0back 0mg THC Sham TMS | 97.5 percentage of correct choices | Standard Deviation 2 |
| Inhibitory TMS | Working Memory Performance | 3HR 1back 0mg THC Sham TMS | 93.8 percentage of correct choices | Standard Deviation 7.8 |
| Inhibitory TMS | Working Memory Performance | 3HR 2back 0mg THC Sham TMS | 87.5 percentage of correct choices | Standard Deviation 10.6 |
| Inhibitory TMS | Working Memory Performance | 3HR 0back 10mg THC Sham TMS | 90 percentage of correct choices | Standard Deviation 18.4 |
| Inhibitory TMS | Working Memory Performance | 3HR 1back 10mg THC Sham TMS | 85.6 percentage of correct choices | Standard Deviation 19.1 |
| Inhibitory TMS | Working Memory Performance | 3HR 2back 10mg THC Sham TMS | 82.5 percentage of correct choices | Standard Deviation 23.8 |
| Inhibitory TMS | Working Memory Performance | 3HR 0back 30mg THC Sham TMS | 94.4 percentage of correct choices | Standard Deviation 3.8 |
| Inhibitory TMS | Working Memory Performance | 3HR 1back 30mg THC Sham TMS | 91.3 percentage of correct choices | Standard Deviation 7.5 |