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

Opiate Addiction Clinical Trial

Official title:

Cannabidiol as Treatment Intervention for Opioid Relapse

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01311778
• Other study ID #: R21DA027781
• Status: Completed
• Phase: Phase 1
• First received: March 7, 2011
• Last updated: March 20, 2013
• Start date: February 2010
• Est. completion date: October 2011

Study information

• Verified date: March 2013
• Source: Hurd,Yasmin, Ph.D.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Opiate Addiction

Intervention

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.
• Fentanyl
All subjects will receive 0.5 mcg/kg and 1mcg/kg of Fentanyl (test session 1 and test session 2)

Locations

Country	Name	City	State
United States	Mount Sinai Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hurd,Yasmin, Ph.D.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the safety of cannabidiol oral administration prior to fentanyl IV administration.	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.	9 timepoints: -10 min, 30, 60, 90, 120, 180, 240, 360, 480	Yes
Secondary	General cannabidiol pharmacokinetics	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).	9 timepoints: -10 min, 30, 60, 90, 120, 180, 240, 360, 480	No
Secondary	Cortisol levels	Variation in plasma levels of cortisol will be measured at various time points.	-10 min, 30, 60, 90, 120, 180, 240, 360, 480	No
Secondary	Cannabidiol clearance	Urine will be taken at specified times to estimate cannabidiol concentration in order to assess clearance and excretion functions.	5 timepoints: -60 min, 45, 120, 240, 480	No
Secondary	Vital signs-BP	Blood pressure (mmHg) will be monitored and change from baseline will be studied across the multiple time points.	-10, 30, 60, 75, 90, 120, 180, 240, 360, 480 min	No
Secondary	Vital signs-HR	Heart rate (beats/minute) will be monitored and change from baseline will be studied across the multiple time points.	-10, 30, 60, 75, 90, 120, 180, 240, 360, 480 min	No
Secondary	Vital signs - RR	respiratory rate (respirations/minute) will be monitored and change from baseline will be studied across the multiple time points.	-10, 30, 60, 75, 90, 120, 180, 240, 360, 480 min	No
Secondary	Vital signs - O2	% oxygen saturation will be monitored and change from baseline will be studied across the multiple time points.	-10, 30, 60, 75, 90, 120, 180, 240, 360, 480 min	No
Secondary	Vital signs - temp	body temperature (degrees Fahrenheit) will be monitored and change from baseline will be studied across the multiple time points.	-10, 30, 60, 75, 90, 120, 180, 240, 360, 480 min	No
Secondary	Vital signs - EKG	EKG will be monitored and change from baseline will be studied across the multiple time points.	-10, 30, 60, 75, 90, 120, 180, 240, 360, 480 min	No
Secondary	Subjective measures-VAS	Questionnaires will be used to measure subjective responses. Anxiety will be assessed using a visual analog scale (VAS).	-1, 30, 65, 90, 120, 240, 360, 480 min.	No
Secondary	Subjective measures-PANAS	Questionnaires will be used to measure subjective responses. The PANAS (Positive and Negative Affect Schedule) will allow obtaining positive and negative affect measures.	-1, 30, 65, 90, 120, 240, 360, 480 min.	No
Secondary	Subjective measures-Opiate effect	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.	-1, 30, 65, 90, 120, 240, 360, 480 min.	No
Secondary	Subjective measures- OVAS	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.	-1, 30, 65, 90, 120, 240, 360, 480 min.	No