Study to Test the Safety and Efficacy of Cannabidiol as a Treatment Intervention for Opioid Relapse

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Yasmin Hurd, Hurd,Yasmin, Ph.D.
ClinicalTrials.gov Identifier:
NCT01311778
First received: March 7, 2011
Last updated: March 20, 2013
Last verified: March 2013
  Purpose

Despite the current available therapies for opioid-dependent patients, most patients relapse. This research project focuses on the development of a novel compound, cannabidiol, to modulate opioid craving in humans based on animal models showing its selective effectiveness to inhibit drug-seeking behavior. The development of a targeted treatment for opioid relapse would be of tremendous medical and public health value.


Condition Intervention Phase
Opiate Addiction
Drug: Cannabidiol
Drug: Fentanyl
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Cannabidiol as Treatment Intervention for Opioid Relapse

Resource links provided by NLM:


Further study details as provided by Hurd,Yasmin, Ph.D.:

Primary Outcome Measures:
  • To determine the safety of cannabidiol oral administration prior to fentanyl IV administration. [ Time Frame: 9 timepoints: -10 min, 30, 60, 90, 120, 180, 240, 360, 480 ] [ Designated as safety issue: Yes ]
    We will assess safety and adverse effects with the Systematic Assessment for Treatment Emergent Events (SAFTEE). Excessive sedation (GCS<10), cardiac dysrhythmia (on telematry monitor), hypotension (blood pressure < 90/60 mmHg), bradycardia (heart rate 50/minute),severe anxiety, or seizures (partial or generalized tonic-clonic) after the administration of either Fentanyl or Cannabidiol would result in discontinuation of the study for the subject and immediate medical attention.


Secondary Outcome Measures:
  • General cannabidiol pharmacokinetics [ Time Frame: 9 timepoints: -10 min, 30, 60, 90, 120, 180, 240, 360, 480 ] [ Designated as safety issue: No ]
    Blood will be taken at specified times to determine cannabidiol peak plasma concentration (Cmax), time to reach peak serum concentration (tmax) and serum elimination half-life (t1/2).

  • Cortisol levels [ Time Frame: -10 min, 30, 60, 90, 120, 180, 240, 360, 480 ] [ Designated as safety issue: No ]
    Variation in plasma levels of cortisol will be measured at various time points.

  • Cannabidiol clearance [ Time Frame: 5 timepoints: -60 min, 45, 120, 240, 480 ] [ Designated as safety issue: No ]
    Urine will be taken at specified times to estimate cannabidiol concentration in order to assess clearance and excretion functions.

  • Vital signs-BP [ Time Frame: -10, 30, 60, 75, 90, 120, 180, 240, 360, 480 min ] [ Designated as safety issue: No ]
    Blood pressure (mmHg) will be monitored and change from baseline will be studied across the multiple time points.

  • Vital signs-HR [ Time Frame: -10, 30, 60, 75, 90, 120, 180, 240, 360, 480 min ] [ Designated as safety issue: No ]
    Heart rate (beats/minute) will be monitored and change from baseline will be studied across the multiple time points.

  • Vital signs - RR [ Time Frame: -10, 30, 60, 75, 90, 120, 180, 240, 360, 480 min ] [ Designated as safety issue: No ]
    respiratory rate (respirations/minute) will be monitored and change from baseline will be studied across the multiple time points.

  • Vital signs - O2 [ Time Frame: -10, 30, 60, 75, 90, 120, 180, 240, 360, 480 min ] [ Designated as safety issue: No ]
    % oxygen saturation will be monitored and change from baseline will be studied across the multiple time points.

  • Vital signs - temp [ Time Frame: -10, 30, 60, 75, 90, 120, 180, 240, 360, 480 min ] [ Designated as safety issue: No ]
    body temperature (degrees Fahrenheit) will be monitored and change from baseline will be studied across the multiple time points.

  • Vital signs - EKG [ Time Frame: -10, 30, 60, 75, 90, 120, 180, 240, 360, 480 min ] [ Designated as safety issue: No ]
    EKG will be monitored and change from baseline will be studied across the multiple time points.

  • Subjective measures-VAS [ Time Frame: -1, 30, 65, 90, 120, 240, 360, 480 min. ] [ Designated as safety issue: No ]
    Questionnaires will be used to measure subjective responses. Anxiety will be assessed using a visual analog scale (VAS).

  • Subjective measures-PANAS [ Time Frame: -1, 30, 65, 90, 120, 240, 360, 480 min. ] [ Designated as safety issue: No ]
    Questionnaires will be used to measure subjective responses. The PANAS (Positive and Negative Affect Schedule) will allow obtaining positive and negative affect measures.

  • Subjective measures-Opiate effect [ Time Frame: -1, 30, 65, 90, 120, 240, 360, 480 min. ] [ Designated as safety issue: No ]
    Questionnaires will be used to measure subjective responses. Global Intoxication and Withdrawal Rating will be administered to assess potential variations in the subjective effects associated to fentanyl.

  • Subjective measures- OVAS [ Time Frame: -1, 30, 65, 90, 120, 240, 360, 480 min. ] [ Designated as safety issue: No ]
    Questionnaires will be used to measure subjective responses. Opiate Visual Analog Scales (OVAS) will be administered to assess potential variations in the subjective effects associated to fentanyl.


Enrollment: 18
Study Start Date: February 2010
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Subjects will receive placebo
Drug: Fentanyl
All subjects will receive 0.5 mcg/kg and 1mcg/kg of Fentanyl (test session 1 and test session 2)
Other Name: Fentanyl Citrate
Experimental: CBD 400 mg
Subjects will receive 400 mg CBD
Drug: Cannabidiol

Subjects in Arm CBD 400 mg will receive 400 mg of Cannabidiol in two test sessions along with 0.5 mcg/kg and 1mcg/kg of fentanyl.

Subjects in Arm CBD 800 mg will receive 800 mg of Cannabidiol in two test sessions along with 0.5 mcg/kg and 1mcg/kg of fentanyl.

Drug: Fentanyl
All subjects will receive 0.5 mcg/kg and 1mcg/kg of Fentanyl (test session 1 and test session 2)
Other Name: Fentanyl Citrate
Experimental: CBD 800mg
Subjects will receive 800 mg CBD
Drug: Cannabidiol

Subjects in Arm CBD 400 mg will receive 400 mg of Cannabidiol in two test sessions along with 0.5 mcg/kg and 1mcg/kg of fentanyl.

Subjects in Arm CBD 800 mg will receive 800 mg of Cannabidiol in two test sessions along with 0.5 mcg/kg and 1mcg/kg of fentanyl.

Drug: Fentanyl
All subjects will receive 0.5 mcg/kg and 1mcg/kg of Fentanyl (test session 1 and test session 2)
Other Name: Fentanyl Citrate

Detailed Description:

Opioid abuse is a significant global public health problem. Of the over million opiate-dependent subjects today, only less than a quarter of such individuals receive treatment. Pharmacotherapeutic approaches traditionally have targeted 5 opioid receptors since heroin and its metabolites bind with highest affinity to this receptor subtype. Although such treatment strategies have improved substance abuse outcomes, they do not effectively block opiate craving and thus are still associated with high rates of relapse. Using a strategy of indirectly regulating neural systems to modulate opioid-related behavior, our preclinical rodent studies consistently demonstrated that cannabidiol (CBD), a nonpsychoactive component of cannabis, specifically inhibited cue- induced heroin-seeking behavior. CBD's selective effect on drug-seeking behavior was pronounced after 24 hrs and endured even two weeks after the last drug administration following short-term CBD exposure. The fact that drug craving is generally triggered by exposure to conditioned cues suggests that CBD might be an effective treatment for heroin craving, specially given its protracted impact on behavior. CBD has already been shown in various clinical studies to be well tolerated with a wide safety margin in human subjects. CBD thus represents a strong candidate for the development as a potential therapeutic agent in humans for opioid craving and relapse prevention. It is the goal of this exploratory phase of the project to (1) determine the safety and basic pharmacokinetic characteristics of CBD when administered concomitantly with opiate in humans and (2) characterize the acute (24 hr) and short-term (3 days) effects of CBD administration on cue-induced craving in drug-abstinent heroin-dependent subjects using a random double blind design. This exploratory investigation together with ongoing complementary preclinical rodent studies has the potential to significantly impact the development of a novel agent for drug relapse prevention that is critical for ending the continued cycle of substance abuse. PUBLIC HEALTH RELEVANCE: Despite the current available therapies for opioid-dependent patients, most patients relapse. This research project focuses on the development of a novel compound, cannabidiol, to modulate opioid craving in humans based on animal models showing its selective effectiveness to inhibit drug-seeking behavior. The development of a targeted treatment for opioid relapse would be of tremendous medical and public health value.

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • being aged between 21 and 65 years old.
  • having exposure at least once to an opioid (i.e. codeine, morphine, Fentanyl) in the past

Exclusion Criteria:

  • using any psychoactive drug or medication at any time during the study, or 24 hours before the test session
  • having a past or current diagnosis of drug abuse or dependence (except for nicotine), based on the SCID-IV interview (Structured Clinical Interview for DSM-IV)
  • being maintained on methadone or buprenorphine, or taking opioid antagonist such as naltrexone
  • having taken any opioid in the last 14 days
  • having medical conditions, including Axis I psychiatric conditions under DSM-IV (examined with the MINI International Neuropsychiatric Interview-MINI), history of cardiac disease, arrhythmias, head trauma, and seizures
  • having a history of hypersensitivity to any opioid or cannabinoid
  • being pregnant or breastfeeding
  • not using an appropriate method of contraception such as hormonal contraception (oral hormonal contraceptives, Depo-Provera, Nuva-Ring), intrauterine device (IUD), sterilization, or double barrier method (combination of any two barrier methods used simultaneously, i.e. spermicide, diaphragm)
  • arriving to the study site visibly intoxicated as determined by a clinical evaluation for signs and symptoms of intoxication and as verified by a drug screen for cocaine, cannabis, opiates, benzodiazepines, barbiturates, phencyclidine and amphetamines
  • being actively treated and currently involved in an addiction treatment program
  • being an anesthesiologist or a pharmacist
  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: NCT01311778

Locations
United States, New York
Mount Sinai Medical Center
New York, New York, United States, 10029
Sponsors and Collaborators
Hurd,Yasmin, Ph.D.
Investigators
Principal Investigator: Yasmin Hurd, PhD Mount Sinai School of Medicine
  More Information

No publications provided

Responsible Party: Yasmin Hurd, Principal Investigator, Hurd,Yasmin, Ph.D.
ClinicalTrials.gov Identifier: NCT01311778     History of Changes
Other Study ID Numbers: R21 DA027781
Study First Received: March 7, 2011
Last Updated: March 20, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Behavior, Addictive
Opioid-Related Disorders
Compulsive Behavior
Impulsive Behavior
Substance-Related Disorders
Mental Disorders
Fentanyl
Analgesics, Opioid
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anesthetics, Intravenous
Anesthetics, General
Anesthetics

ClinicalTrials.gov processed this record on July 26, 2014