| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
De La Garza, R. Galloway, G. P. Newton, T. F. Mendelson, J. Haile, C. N. Dib, E. Hawkins, R. Y. Chen, C-Y A. Mahoney, J. J. Mojsiak, J. Lao, G. Anderson, A. Kahn, R. |
| Description |
Author Affiliation: De La Garza R ( Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, Houston, TX, United States. Electronic address: rg12@bcm.edu.); Galloway GP ( California Pacific Medical Center Research Institute, San Francisco, CA, United States.); Newton TF ( Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, Houston, TX, United States.); Mendelson J ( California Pacific Medical Center Research Institute, San Francisco, CA, United States.); Haile CN ( Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, Houston, TX, United States.); Dib E ( California Pacific Medical Center Research Institute, San Francisco, CA, United States.); Hawkins RY ( Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, Houston, TX, United States.); Chen CY ( California Pacific Medical Center Research Institute, San Francisco, CA, United States.); Mahoney JJ ( Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, Houston, TX, United States.); Mojsiak J ( National Institute on Drug Abuse, NIH, Bethesda, MD, United States.); Lao G ( National Institute on Drug Abuse, NIH, Bethesda, MD, United States.); Anderson A ( National Institute on Drug Abuse, NIH, Bethesda, MD, United States.); Kahn R ( National Institute on Drug Abuse, NIH, Bethesda, MD, United States.) |
| Abstract |
The primary objective of this study was to determine the safety of lofexidine, an 2 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. |
| File Format |
HTM / HTML |
| ISSN |
02785846 |
| e-ISSN |
18784216 |
| DOI |
10.1016/j.pnpbp.2013.11.013 |
| Journal |
Progress in Neuro-Psychopharmacology and Biological Psychiatry |
| Volume Number |
50 |
| Language |
English |
| Publisher |
Elsevier |
| Publisher Date |
2014-04-03 |
| Publisher Place |
Great Britain (UK) |
| Access Restriction |
Open |
| Subject Keyword |
Discipline Psychiatry Behavior, Addictive Drug Therapy Blood Pressure Drug Effects Clonidine Analogs & Derivatives Cocaine Administration & Dosage Adverse Effects Heart Rate Adolescent Adrenergic Alpha-2 Receptor Agonists Therapeutic Use Cocaine-related Disorders Dopamine Uptake Inhibitors Double-blind Method Drug Administration Schedule Drug Interactions Drug Users Psychology Infusions, Intravenous Randomized Controlled Trial Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Biological Psychiatry Pharmacology |
