Clinical trial NCT01204723: Medications Development for the Treatment of Cannabis Related Disorders
Official title: Medications Development for the Treatment of Cannabis Related Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Nicotine Withdrawal
Marijuana Dependence
Cannabis Dependence
Nicotine Dependence
Cannabis Abuse
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
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2010-09-17
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: withdrawal symptom severity, measured on a 0 (not at all) to 3 (severe) scale
timeFrame: collected on each study day
measure: "craving" measured using the Marijuana craving questionaire and the tobacco craving questionaire
timeFrame: collected on each study day
measure: reinforcing effects, as measured using the Multiple Choice Questionaire
timeFrame: collected each day of study
Secondary outcomes:
measure: sleep quality
timeFrame: collected on each study day
measure: Neurocognitive Function
timeFrame: collected on days 1-4 of the study
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: each day of study
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: Clinical Pharmacological Research Unit (CPRU), University of Virginia School of Medicine
state: Virginia
city: Charlottesville
country: United States
facility: University of Virginia Center for Addiction Education and Treatment (UVA CARE)
state: Virginia
Study officials:
affiliation: University of Virginia School of Medicine, Dept. Psychiatry and Neurobehavioral Sciences
name: Heather M Haughey, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gunderson EW, Haughey HM, Ait-Daoud N, Joshi AS, Hart CL. A survey of synthetic cannabinoid consumption by current cannabis users. Subst Abus. 2014;35(2):184-9. doi: 10.1080/08897077.2013.846288.