Assessment of safety, cardiovascular and subjective effects after intravenous cocaine and lofexidine.

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the three participants at the 0.8mg dose level discontinued, and five of 11 participants at the 0.2mg dose level were withdrawn (or voluntarily discontinued) after hemodynamic AEs.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.

Abuse of flunitrazepam (Rohypnol) and other benzodiazepines in Austin and south Texas.

Flunitrazepam (Rohypnol) is a benzodiazepine sedative-hypnotic that has generated significant media attention in the United States because of its abuse and its association with "date rape." A field investigation was conducted in south Texas to ascertain the nature and consequences of the abuse of flunitrazepam. In semistructured interviews, 66 subjects identified as flunitrazepam users were asked about their use of alcohol and other drugs and their sexual behaviors. Many subjects identified the drugs they had used as "roches" and gave descriptions of tablets of other benzodiazepines that were not consistent with flunitrazepam. Almost all subjects used other drugs, primarily alcohol and marijuana. Adverse consequences included amnesia, discoordination, automobile accidents, sexual assault, and respiratory depression or arrest. A significant proportion of the subjects reported that continued use was unappealing to them. The abuse of sedative-hypnotics in southeast Texas involves several benzodiazepines and is not limited to flunitrazepam.