Cannabis Abuse, Cannabis Dependence, Marijuana Dependence, Nicotine Dependence, Nicotine Withdrawal
Conditions
Keywords
Marijuana Abuse, Nicotine Dependence, Nicotine Withdrawal, neurokinin Receptor, NK1 Receptor antagonist, Substance P, Recurrence, Substance Withdrawal Syndrome, Substance-Related Disorders, Disorders of Environmental Origin, Mental Disorders, Disease Attributes, Pathologic Processes, Tetrahydrocannabinol, Therapeutic Uses, Psychotropic Drugs, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Narcotic Antagonists, cannabis
Brief summary
The primary objective of this application is to test the neurobehavioral mechanisms and effects of aprepitant as a new cessation agent for cannabis, tobacco or both.
Detailed description
Stress (emotional, physical, social) facilitates drug seeking behavior through the activation of the HPA axis, autonomic nervous system, and brain DA systems. Furthermore, alterations within several neuropeptide systems (CRF, Substance P, and others) also contribute to the role of stress in addiction. Central to this project is that anxiety and stress responses are modulated by substance P and its preferred target, the NK1 receptor. Therefore the aim of this pilot clinical trial is to determine the safety and efficacy of aprepitant (a neurokinin 1 (NK1) receptor antagonist). We hypothesize that the NK1 receptor antagonist, aprepitant, will be safe, tolerable and efficacious at reducing the withdrawal symptoms, cue craving, and reinforcement value for both cannabis and tobacco resulting from the cessation of either or both drugs. We will assess this hypothesis in the context of a carefully controlled human laboratory study in which subjects (N=72) will be randomized in a 3 x 2 factorial design to one of 3 behavioral conditions; a) withdrawn from both substances, b) withdrawn from tobacco only, or c) withdrawn from cannabis only, and to receive one of 2 medication dose conditions: placebo or aprepitant (160 mg/day). Medication will be administered for 5 days, followed by a cue challenge, choice procedure, and then a consequence (i.e., oral cannabis or a cigarette or money) also on day 5.
Interventions
DRUGActive Aprepitant
Active Aprepitant 160 mg once daily for 5 days
DRUGPlacebo Aprepitant
Placebo Aprepitant 0 mg once daily for 5 days
Sponsors
National Institute on Drug Abuse (NIDA)
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Must meet DSM-IV/ICD-10 criteria for cannabis abuse or dependence * Must be non-treatment seeking individuals * Participant does not meet DSM-IV criteria for any current (i.e., criteria met at any point in the past 30 days) dependence on a substance other than alcohol, nicotine, caffeine, or marijuana or physiological dependence on alcohol requiring medical detoxification. * No subjects who have trouble reading the English language or visual or hearing problems that may interfere with the collection of data * Not currently taking other medications (with the exception of oral contraceptives) that would preclude safe participation in this study * Must test negative for pregnancy prior to inclusion * females using birth control pills must agree to use a condom during intercourse for 1 month after participation in study because the study medication will decrease the effectiveness of the birth control pill rendering it ineffective * Should be in general good health * No evidence of recent use of other illicit drugs on a urine toxicity screen prior to admission
Exclusion criteria
* Major current (within last 90 days) Axis I psychopathology (e.g., major depressive disorder, bipolar disorder, schizophrenia) * Presence of significant medical illness (e.g., diabetes, cardiovascular disease, hypertension, cancer, epilepsy, kidney disease) * Current, repeated illicit drug use (other than marijuana) * Subject is breastfeeding or pregnant * Concurrent therapy with drugs known to inhibit CYP3A4 activity * Request for drug treatment * Current parole or probation * Recent history of significant violent or suicide behavior * Allergic to sesame oil
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| withdrawal symptom severity, measured on a 0 (not at all) to 3 (severe) scale | collected on each study day | Subjective experience of withdrawal symptoms for cannabis, tobacco, and both (eg: Irritability, Sleep difficulty, Chills, Nervousness) |
| craving measured using the Marijuana craving questionaire and the tobacco craving questionaire | collected on each study day | Subjective measures of craving for cannabis, tobacco, and both Questionaires are anchored with strongly disagree to strongly agree (1-7) |
| reinforcing effects, as measured using the Multiple Choice Questionaire | collected each day of study | Reinforcement value of cannabis and tobacco as measured by preference for money over the administration of either drug; questionaire has 70 questions and money value vs. drug ranges from 25 cents to 25 dollars 1-70. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| sleep quality | collected on each study day | A VAS sleep questionnaire will be used each morning to assess daily sleep quality. |
| Neurocognitive Function | collected on days 1-4 of the study | The purpose of examining the neurocognitive function of our participants on days 1-4 is to examine the safety of the co-administration of aprepitant at 160 mg/day with oral THC (dronabinol 10 mg) on brain function. Tasks used are the DSST - The Digit Symbol Substitution Test measures the learning of integrating visual and motor skills, and the SRTT- The Simple reaction Time Task is a well validated computerized test for assessing the effects of psychoactive drugs on performance. |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | each day of study | Blood pressure, pulse, and a Systematic Assessment For Treatment Emergent Events (SAFTEE) are collected daily. Electrocardiograms (EKGs) are collected at baseline and discharge. |
Countries
United States
Outcome results
None listed