Effects of Sativex(Registered Trademark) and Oral THC on Attention, Affect, Working Memory, Reversal Learning, Physiology and Brain Activation

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01037608
First received: December 19, 2009
Last updated: December 31, 2011
Last verified: December 2011
  Purpose

Background:

  • The therapeutic modalities of cannabis have received more research attention recently with the discovery of its ability to stimulate appetite and to provide pain and nausea relief in patients with AIDS, cancer, and multiple sclerosis, among other diseases. Sativex(Registered Trademark), an experimental drug derived from the marijuana plant, contains tetrahydrocannabinol (THC) and cannabidiol (CBD), both of which affect brain activity. Sativex(Registered Trademark) is being tested to determine how and to what extent it affects brain activity.
  • Functional magnetic resonance imaging (fMRI) uses magnetic waves to study brain activity. Researchers are interested in using fMRI to study how Sativex(Registered Trademark) affects regional brain activity, including thinking abilities and behavior.

Objectives:

  • To study changes in regional brain activity produced by Sativex(Registered Trademark) compared with THC and placebo.
  • To determine how Sativex(Registered Trademark) is processed by the body.

Eligibility:

- Individuals between 18 and 45 years of age who are either current users of cannabis (less than daily) or healthy volunteers who do not use cannabis.

Design:

  • The study will involve one training session and five testing sessions on separate days.
  • At every session, subjects will receive either THC or placebo capsules and either Sativex(Registered Trademark) or placebo spray.
  • Participants will complete a training session in a mock fMRI scanner to adapt to the fMRI scanning environment. In the training session, participants will practice the tests that will track thinking ability, attention, working memory, and other cognitive tasks.
  • Participants will have five fMRI scanning sessions with the tests they have practiced previously, and will provide blood, urine, and saliva samples as required by the researchers. Participants will be discharged approximately 12 hours after they arrive for the study sessions....

Condition Intervention Phase
Cannabis
Dependence
Cannabis Abuse
Pharmacokinetics
fMRI
Drug: Sativex(Registered Trademark)
Drug: THC
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Official Title: Effects of Sativex(Registered Trademark) and Oral THC on Attention, Affect, Working Memory, Reversal Learning, Physiology and Brain Activation

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Pharmacokinetics/Pharmacodynamics

Estimated Enrollment: 108
Study Start Date: May 2007
Study Completion Date: December 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Sativex(Registered Trademark)
    N/A
    Drug: THC
    N/A
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • Eligibility Criteria for Cannabis Users

INCLUSION CRITERIA:

  1. 18 to 45 years of age;
  2. Cannabis use with a minimum frequency of once in the last 90 days and maximum frequency of less than daily during the three months prior to study entry;
  3. Blood pressure (BP) and heart rate (HR) at or below the following values while sitting after five min rest: Systolic BP (SBP) 140 mm Hg, diastolic BP (DBP) 90 mm Hg, heart rate (HR) 100 bpm;
  4. 12-lead standard ECG and three-minute rhythm strip without clinically relevant abnormalities;
  5. Peripheral veins suitable for repeated venipuncture and placement and maintenance of an IV catheter;
  6. Ability to swallow capsules;
  7. Ability to communicate well with the investigators and to comply with study requirements;
  8. If female with reproductive potential, must be using a reliable method of birth control or abstaining from vaginal sexual intercourse;
  9. Estimated IQ greater than or equal to 85 determined by the Wechsler Abbreviated Scale of Intelligence;
  10. Right-handed.

EXCLUSION CRITERIA:

  1. History or presence of any clinically significant illness, as detected by history, physical examination, and/or laboratory tests, that might put the subject at increased risk of adverse events or that might interfere with the absorption, distribution, metabolism, or excretion of study drugs. Clinically significant is defined as being likely to affect the safety of the subject during his/her participation in this trial, or preclude achievement of the protocol objectives.
  2. Current tolerance to any substance other than nicotine or caffeine;
  3. Positive serological tests for syphilis or HIV infection;
  4. Positive purified protein derivative (PPD) test in the absence of a negative chest X-ray;
  5. History of a clinically significant adverse event associated with cannabis intoxication or withdrawal;
  6. History of epileptic seizures or head trauma with loss of consciousness greater than three min;
  7. History of psychosis or any current DSM-IV axis I disorder (other than caffeine or nicotine dependence, or simple phobia);
  8. Family history of psychosis (except that related to acute drug intoxication) in a first-degree relative;
  9. Donation of more than 500 mL of blood within 30 days of study drug administration;
  10. Regular use of alcohol (greater than or equal to five standard drinks per day) four or more times per week in the month prior to study entry;
  11. If female, pregnant or nursing;
  12. ADHD Screening Rating Scale score greater than or equal to 24 on either the A or B subscale;
  13. Allergy to sesame seed oil (ingredient in dronabinol capsules), propylene glycol, ethanol, or peppermint oil (ingredients in Sativex(Registered Trademark));
  14. Currently interested in or participating in drug abuse treatment, or participated in drug abuse treatment within 60 days preceding study enrollment.
  15. Claustrophobia that precludes being able to tolerate an fMRI session.
  16. Magnetizable metal on or within the body that cannot be removed.

Eligibility Criteria for Controls

The goal of the eligibility criteria for control subjects is to obtain a group approximately comparable to the cannabis users in terms of age, sex, ethnicity, tobacco use, and intelligence.

INCLUSION CRITERIA:

  1. 18 to 45 years of age;
  2. BP and HR at or below the following values while sitting after five min rest: SBP 140 mm Hg, DBP 90 mm Hg, HR 100 bpm;
  3. Ability to communicate well with the investigator and to comply with study requirements;
  4. If female with reproductive potential, must be using a reliable method of birth control or abstaining from vaginal sexual intercourse;
  5. Estimated IQ greater than or equal to 85 determined by the Wechsler Abbreviated Scale of Intelligence;
  6. Right-handed.

EXCLUSION CRITERIA:

  1. History or presence of any clinically significant illness, as detected by history, physical examination, and/or laboratory tests that might put the subject at increased risk of adverse events. Clinically significant is defined as being likely to affect the safety of the subject during his/her participation in this trial, or preclude achievement of the protocol objectives.
  2. A positive urine test for any illicit drug at any time during screening or study participation;
  3. Current physical dependence on any substance other than nicotine or caffeine; Self-reported lifetime use of any illicit drug other than cannabis; Self-reported lifetime use of cannabis greater than ten times, or use within the last year;
  4. Positive serological tests for syphilis or HIV infection;
  5. History of epileptic seizures or head trauma with loss of consciousness greater than three min;
  6. History of psychosis or any current DSM-IV axis I disorder (other than caffeine or nicotine dependence, or simple phobia);
  7. Regular use of alcohol (greater than or equal to five standard drinks per day) four or more times per week in the month prior to study entry;
  8. If female, pregnant or nursing;
  9. ADHD Screening Rating Scale score greater than or equal to 24 on either the A or B subscale;
  10. Claustrophobia that precludes being able to tolerate an fMRI session;
  11. Magnetizable metal on or within the body that cannot be removed.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01037608

Locations
United States, Maryland
National Institute on Drug Abuse, Biomedical Research Center (BRC)
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT01037608     History of Changes
Other Study ID Numbers: 999907423, 07-DA-N423
Study First Received: December 19, 2009
Last Updated: December 31, 2011
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Sativex
fMRI
Alternative Matrices
Brain Imaging
THC

Additional relevant MeSH terms:
Marijuana Abuse
Substance-Related Disorders
Mental Disorders
Tetrahydrocannabinol
Hallucinogens
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on July 23, 2014