Buprenorphine's Dose Response Curve

Johns Hopkins University12 enrolled

Overview

This is a residential study that looks at the effects of buprenorphine in persons who abuse but are not dependent on opioids. Animal studies show that very high doses of buprenorphine produce less effects than mid-range doses. This suggests that buprenorphine can be a very safe medication. However, no studies in humans have tested higher doses in a similar way. The goal of this study is to show the effects of single doses of buprenorphine, across a range of doses, in persons who are not physically dependent on opioids (but do abuse opioids).

Preclinical studies have demonstrated for a variety of measures that buprenorphine has a bell-shaped dose response curve. However, human studies with buprenorphine have not shown such an effect, although controlled studies have generally not tested higher acute doses of buprenorphine. Current clinical recommendations generally place an upper limit of daily buprenorphine dosing at 32 mg of sublingual tablets, although considerably higher acute doses have been administered to humans (primarily in clinical studies of less than daily dosing). Determining the relationship between higher doses of buprenorphine in humans and effects produced would be valuable; it would be scientifically interesting to demonstrate a bell-shaped curve in humans, and it would help guide clinical practice (for example, with respect to dosing, safety, and side effect considerations. The purpose of this study is to characterize the dose response curve for buprenorphine in humans, utilizing acute single doses of parenteral buprenorphine.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Opioid-related Disorders

Interventions

BuprenorphineDRUG

Intramuscular, doses (8, 16, 32, 48, 60 mg) are blind; administered up to 1-2 times per week.

MorphineDRUG

Intramuscular; up to 1-2 times per week; doses (15, 30 mg) double blind

PlaceboDRUG

Intramuscular; double blind; once per week

Eligibility

Sex: ALLMin age: 21 YearsMax age: 55 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1\. current opioid abuse but not physically dependent on opioids Exclusion Criteria: 1. evidence of significant medical (e.g., insulin dependent diabetes) or psychiatric (e.g., schizophrenia) illness 2. anemia defined as a hematocrit less than 30% 3. females are required to provide a negative pregnancy test prior to study participation 4. baseline electrocardiogram (ECG) showing prolongation of the corrected QT interval (QTc) 5. current significant alcohol or sedative/hypnotic drug use 6. Forced expiratory volume at one second (FEV1) of less than 50% at the time of screening 7. applicants seeking treatment for their substance abuse will not be admitted to the study, and should be provided information about treatment services available

Locations (1)

Johns Hopkins University (BPRU) Bayview Campus

Baltimore, Maryland, United States

Outcomes

Primary Outcomes

Peak Change From Baseline in Drug Effect Assessed by Visual Analog Scale (VAS)

Opioid agonist effects measured by peak change from baseline drug effect visual analog scale. Scores range from 0 (not all all) to 100 (extremely); higher scores indicate a stronger drug effect.