Neural Mechanisms of Cannabinoid-impaired Decision-Making in Emerging Adults

NCT03944954 | Completed Early Phase 1 Results DMC FDA Drug FDA Device

• 1 other identifier: K01DA043652
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Neurosciences; Substance-Related Disorders; Behavior Problem

Outcome Measures

Primary Outcomes (4)

• 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.

  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".

  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.

  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%

  Measured 2 times: Baseline (0HR) and Post-TMS (3HR) after THC administration on each drug condition (0mg, 10mg, 30mg).

Study Arms (2)

Excitatory TMS

EXPERIMENTAL

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

Inhibitory TMS

EXPERIMENTAL

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

Interventions

Placebo TMS Sham DEVICE

Individuals will receive placebo dose and sham TMS.

Also known as: Placebo, Sham TMS

Excitatory TMS; Inhibitory TMS

Marinol 10Mg Capsule TMS Sham DRUG

Individuals will receive 10mg dose and sham TMS.

Also known as: 10mg THC, Sham TMS

Excitatory TMS; Inhibitory TMS

Marinol 30Mg Capsule TMS Sham DRUG

Individuals will receive 30mg dose and sham TMS.

Also known as: 30mg THC, Sham TMS

Excitatory TMS; Inhibitory TMS

Placebo TMS Real DEVICE

Individuals will receive placebo and real TMS.

Also known as: Placebo, Real TMS

Excitatory TMS; Inhibitory TMS

Marinol 10Mg Capsule TMS Real OTHER

Individuals will receive10mg THC and real TMS. Intervention type: Other (combination device/drug intervention)

Also known as: 10mg THC, Real TMS

Excitatory TMS; Inhibitory TMS

Marinol 30Mg Capsule TMS Real OTHER

Individuals will receive 30mg THC and real TMS. Intervention type: Other (combination device/drug intervention)

Also known as: 30mg THC, Real TMS

Excitatory TMS; Inhibitory TMS

Eligibility Criteria

• Age: 18 Years - 34 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Habitual cannabis use problems
• Body Mass Index ≤30

You may not qualify if:

• Past or current serious physical or mental health
• Sesame seed oil allergy
• Irregular health issues identified by the Study Physician
• Lack of affective form of birth control (females)
• Pregnancy (females)

Sponsors & Collaborators

• Michael J. Wesley, PhD: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Neurobehavioral Systems Lab of the University of Kentucky College of Medicine

Lexington, Kentucky, 40507, United States

Location

MeSH Terms

Conditions

Substance-Related Disorders; Mental Disorders

Interventions

Dronabinol

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr. Michael J Wesley
• Organization: University of Kentucky

michael.wesley@uky.edu

8593230579

Study Officials

• Michael J Wesley, PhD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Functionality will be tested following combinations of THC and TMS will be tested in randomized, double-blind, placebo- and sham-controlled experiments.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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).

Study Record Dates

• First Submitted: May 6, 2019
• First Posted: May 10, 2019
• Study Start: July 15, 2017
• Primary Completion: December 13, 2023
• Study Completion: December 13, 2023
• Last Updated: April 5, 2024
• Results First Posted: April 5, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)