Cannabinoid Receptor Function & Alcoholism - Full Text View

Sponsor:	Yale University
Collaborator:	National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by:	Yale University
ClinicalTrials.gov Identifier:	NCT00624715

Purpose

Background: A family history of alcoholism is a risk factor for the development of alcohol problems. Factors that modulate the positive and negative reward valence of alcohol effects may influence the likelihood of repeated and or problematic use, and are therefore of interest. Alcohol has multiple targets in the brain that independently contribute to its behavioral effects. Studies with various pharmacological probes including alcohol, ketamine and benzodiazepines suggest differences between healthy FHP and FHN individuals. There is growing preclinical evidence suggesting involvement of brain cannabinoid receptor (CB-1R) function in the pharmacological actions of alcohol and in alcohol-drinking behaviors. Cannabinoids and alcohol activate the same reward pathways. CB-1R agonists stimulate while CB-1R antagonists suppress, alcohol self-administration and the motivational properties of alcohol. Comparison to wild type mice, CB-1R knockout mice show 1) significantly lower levels of alcohol preference and consumption, 2) slower rate of acquisition of alcohol drinking behavior, 3) lower alcohol sensitivity, and 4) blunted alcohol-induced dopamine release in the nucleus accumbens. Finally, alcohol-preferring mice have a significantly lower level of CB-1R binding sites and higher affinity for CB-1R agonist than alcohol-avoiding mice. Despite these preclinical data, there is a paucity of clinical research in this area.

Hypotheses: Individuals with a family history of alcoholism (FHP) will exhibit blunted 1) euphoric, 2) perceptual and 3) amnestic effects in response to d-9-tetrahydrocannabinol (d-9-THC) administration compared to individuals without a family history of alcoholism (FHN).

Condition	Intervention	Phase
Alcoholism	Drug: THC Drug: Placebo	Phase I

Study Type:	Interventional
Study Design:	Basic Science, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment
Official Title:	Cannabinoid Receptor Function & Alcoholism: Effects of Δ-9-THC

Resource links provided by NLM:

MedlinePlus related topics: Alcoholism

U.S. FDA Resources

Further study details as provided by Yale University:

Primary Outcome Measures:

Clinician Administered Dissociative Symptoms Scale, Visual Analog Scale ("High" rating), Rey Auditory Verbal Learning Test [ Time Frame: Baseline, +15, +25 (RAVLT only), +70, +240 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

THC serum levels, visual analog scale (other feeling states - "calm/relaxed", and "tired"), Biphasic Alcohol Effects Scale (BAES), similarities to alcohol effects, comparison to # standard alcohol drinks, long-term follow-up of cannabis use [ Time Frame: Baseline (for VAS, BAES, THC levels), +15 (for VAS, BAES), +20 (THC levels), +70 (for VAS, BAES, THC levels), +240(for VAS, BAES, THC levels, similarity to alcohol effects). Long term followup (1,3, 6 months post study completion). ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	36
Study Start Date:	July 2007
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
THC: Active Comparator High dose: 0.036 mg/kg (2.5 mg in a 70 kg individual) IV (in the vein) dissolved in ethanol.Equivalent to smoking a full joint Low dose: 0.018 mg/kg (1.25 mg in a 70kg individual)IV (in the vein) dissolved in ethanol.Equivalent to smoking ½ of a joint Very low dose: 0.0036 mg/kg (0.25 mg in a 70 kg individual)IV (in the vein) dissolved in ethanol.Equivalent to smoking 1/10 of a joint	Drug: THC High dose: 0.036 mg/kg (2.5 mg in a 70 kg individual)IV (in the vein) dissolved in ethanol. Equivalent to smoking a full joint Low dose: 0.018 mg/kg (1.25 mg in a 70kg individual) IV (in the vein) dissolved in ethanol.Equivalent to smoking ½ of a joint Very low dose: 0.0036 mg/kg (0.25 mg in a 70 kg individual)IV (in the vein) dissolved in ethanol. Equivalent to smoking 1/10 of a joint
Placebo: Placebo Comparator Placebo: Small amount of ethanol IV (in the vein), (quarter teaspoon).	Drug: Placebo Placebo: Small amount of ethanol IV (in the vein), (quarter teaspoon).

Arms

Assigned Interventions

THC: Active Comparator

High dose: 0.036 mg/kg (2.5 mg in a 70 kg individual) IV (in the vein) dissolved in ethanol.Equivalent to smoking a full joint
Low dose: 0.018 mg/kg (1.25 mg in a 70kg individual)IV (in the vein) dissolved in ethanol.Equivalent to smoking ½ of a joint
Very low dose: 0.0036 mg/kg (0.25 mg in a 70 kg individual)IV (in the vein) dissolved in ethanol.Equivalent to smoking 1/10 of a joint

Drug: THC

High dose: 0.036 mg/kg (2.5 mg in a 70 kg individual)IV (in the vein) dissolved in ethanol. Equivalent to smoking a full joint
Low dose: 0.018 mg/kg (1.25 mg in a 70kg individual) IV (in the vein) dissolved in ethanol.Equivalent to smoking ½ of a joint
Very low dose: 0.0036 mg/kg (0.25 mg in a 70 kg individual)IV (in the vein) dissolved in ethanol. Equivalent to smoking 1/10 of a joint

Placebo: Placebo Comparator

Placebo: Small amount of ethanol IV (in the vein), (quarter teaspoon).

Drug: Placebo

Placebo: Small amount of ethanol IV (in the vein), (quarter teaspoon).

Detailed Description:

This study attempts to characterize the effects of tetrahydrocannabinol (THC). Tetrahydrocannabinol is the active ingredient of marijuana, cannabis, "ganja", or "pot". This study will involve healthy volunteers who 1) have no history of alcoholism in their family or 2) have a family history of alcoholism. This study looks at individuals with or without a family history of alcoholism to determine if there is a difference between the two groups in the response to THC (euphoric effects, perception, memory changes). The study involves a screening day to determine eligibility and three test days over a period of roughly three weeks. On each of the study days, participants will have one of four doses of THC administered intravenously. During each of the three test days, subjects will receive in random order either:

High dose: 0.036 mg/kg (2.5 mg in a 70 kg individual) dissolved in ethanol. Equivalent to smoking a full joint
Low dose: 0.018 mg/kg (1.25 mg in a 70kg individual) dissolved in ethanol. Equivalent to smoking ½ of a joint
Very low dose: 0.0036 mg/kg (0.25 mg in a 70 kg individual) dissolved in ethanol. Equivalent to smoking 1/10 of a joint
Placebo: Small amount of ethanol, (quarter teaspoon).

THC will be infused over about 20 minutes. Throughout the day subjects will be asked questions about their thinking and mood, and asked to perform some memory tests and puzzles. In addition, heart rate, blood pressure and temperature will be checked by a research nurse and blood samples will be collected several times throughout the day. These evaluations will continue periodically throughout the test day. There will also be three follow up questionnaires at 1, 3, and 6 months after completion of the test days.

Eligibility

Ages Eligible for Study:	18 Years to 30 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Male and female
Greater than 18 years
Exposure to cannabis at least once
Absence of any evidence of substance abuse (with the exception of alcohol abuse)or intoxication on the basis of history
Drug and ethanol-free at the time of testing based on urine toxicology and breath alcohol levels at screening and on each test day
Medically and neurologically healthy on the basis screening

Exclusion Criteria:

DSM-IV Axis I or II disorder other than alcohol abuse
Cannabis naïve: to exclude the theoretical possibility that exposure to THC in the laboratory facilitates future cannabis use/abuse
Cannabis use in the past 3 weeks: to minimize residual effects
We will exclude subjects who have had a serious negative reaction to cannabis (i.e. acute panic or paranoid reaction).
Current treatment with medications that may confound the effects of THC
IQ less than 85
Less than a high school diploma or its educational equivalent
Pregnancy or lactation
Unwillingness to refrain from alcohol use for three days prior to each test day
Major current or recent (<6 weeks) psychosocial stressors. We find that some subjects who have experienced a recent stressor may while intoxicated become unnecessarily distressed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00624715

Contacts

Contact: Michelle K. Carbuto

203-932-5711 ext 4650

michelle.carbuto@yale.edu

Locations

United States, Connecticut
VA Connecticut Healthcare System	Recruiting
West Haven, Connecticut, United States, 06516

Sponsors and Collaborators

Yale University

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

Principal Investigator:

Deepak D'Souza, M.D.

Yale University

More Information

No publications provided

Responsible Party:	Yale University School of Medicine, Dept of Psychiatry ( Deepak Cyril D'Souza, M.D. )
Study ID Numbers:	0707002888, R21 AA 16311
Study First Received:	February 18, 2008
Last Updated:	June 25, 2009
ClinicalTrials.gov Identifier:	NCT00624715 History of Changes
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Mental Disorders
Alcoholism
Substance-Related Disorders
Disorders of Environmental Origin
Alcohol-Related Disorders

ClinicalTrials.gov processed this record on November 09, 2009