title: Assessment of safety, cardiovascular and subjective effects after intravenous cocaine and lofexidine.
abstract: The primary objective of this study was to determine the safety of lofexidine, an α2 receptor agonist, alone and concurrent with cocaine in non-treatment seeking cocaine-dependent or cocaine-abusing participants. After screening, eligible participants received double-blind, randomized infusions of saline and 20mg of cocaine on Day 1, and saline and 40mg of cocaine on Day 2. Subjects were randomized and started receiving daily administration of placebo (N=4) or lofexidine on Day 3 and continued on this schedule until Day 7. Two dosing regimens for lofexedine were investigated: 0.8 QID (N=3) and 0.2mg QID (N=11). On Days 6 and 7, subjects received double-blind infusions of saline and 20mg of cocaine on Day 6, and saline and 40mg of cocaine on Day 7. The data reveal a notable incidence of hemodynamic-related AEs over the course of the study. Two of the three participants at the 0.8mg dose level discontinued, and five of 11 participants at the 0.2mg dose level were withdrawn (or voluntarily discontinued) after hemodynamic AEs. Subjective effects and cardiovascular data were derived from all participants who were eligible to receive infusions (i.e., did not meet stopping criteria) on Days 6 and 7 (6 received lofexidine 0.2mg, QID and 4 received placebo, QID). As expected, cocaine significantly increased heart rate and blood pressure, as well as several positive subjective effects. There was a trend for lofexidine to decrease cocaine-induced cardiovascular changes and cocaine-induced ratings for "any drug effect", "good effects", and "desire cocaine", but sample size issues limit the conclusions that can be drawn. Despite the trends to reduce cocaine-induced subjective effects, cardiovascular AEs may limit future utility of lofexidine as a treatment for this population.
authors: Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, Houston, TX, United States. Electronic address: rg12@bcm.edu.
authors: R
authors: R
authors: De La Garza
authors: California Pacific Medical Center Research Institute, San Francisco, CA, United States.
authors: G P
authors: GP
authors: Galloway
authors: Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, Houston, TX, United States.
authors: T F
authors: TF
authors: Newton
authors: California Pacific Medical Center Research Institute, San Francisco, CA, United States.
authors: J
authors: J
authors: Mendelson
authors: Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, Houston, TX, United States.
authors: C N
authors: CN
authors: Haile
authors: California Pacific Medical Center Research Institute, San Francisco, CA, United States.
authors: E
authors: E
authors: Dib
authors: Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, Houston, TX, United States.
authors: R Y
authors: RY
authors: Hawkins
authors: California Pacific Medical Center Research Institute, San Francisco, CA, United States.
authors: C-Y A
authors: CY
authors: Chen
authors: Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, Houston, TX, United States.
authors: J J
authors: JJ
authors: Mahoney
authors: National Institute on Drug Abuse, NIH, Bethesda, MD, United States.
authors: J
authors: J
authors: Mojsiak
authors: National Institute on Drug Abuse, NIH, Bethesda, MD, United States.
authors: G
authors: G
authors: Lao
authors: National Institute on Drug Abuse, NIH, Bethesda, MD, United States.
authors: A
authors: A
authors: Anderson
authors: National Institute on Drug Abuse, NIH, Bethesda, MD, United States.
authors: R
authors: R
authors: Kahn
mesh_terms: D000293:Adolescent; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D016739:Behavior, Addictive / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003042:Cocaine / Q000008:administration & dosage* / Q000009:adverse effects*; D019970:Cocaine-Related Disorders / Q000188:drug therapy; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004347:Drug Interactions; D055030:Drug Users / Q000523:psychology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D003000:Clonidine; C025655:lofexidine
keywords: Addiction; Cocaine; Lofexidine; Norepinepherine; Treatment