Background It has been well documented that cocaine and methamphetamine use can lead to the onset of psychotic symptoms similar to schizophrenia. However, the research and literature on gender differences and stimulant-induced psychosis have been mixed. Objective The primary aim of this study was to investigate gender differences in the reporting of psychotic symptoms in cocaine-versus methamphetamine-dependent individuals. Methods Participants were recruited from the Los Angeles, California, community via radio and newspaper advertisements. All met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for cocaine or methamphetamine dependence, and all reported either methamphetamine or cocaine as their primary drug of abuse. During a screening interview, participants answered questions from the Psychotic Symptom Assessment Scale, which characterizes various types of psychotic symptoms during drug use (“while high”) or during periods of nonuse (“while abstinent”). Results Participants included 42 cocaine-dependent individuals (27 men, 15 women) and 43 methamphetamine-dependent individuals (25 men, 18 women). Among cocaine users, there were no significant differences between men and women with regard to ethnicity, years of use, route of administration, and amount used in the past week, though they differed significantly with regard to age (P = 0.029). In the “while abstinent” condition, women were significantly more likely than men to report experiencing auditory hallucinations (13% vs 0%, respectively; P = 0.050) and tactile hallucinations (20% vs 0%; P = 0.016), whereas men were more likely to report delusions of grandeur (48% vs 6%; P = 0.006). During the “while high” condition, women were significantly more likely than men to report delusions of grandeur (13% vs 0%, respectively; P = 0.050), tactile hallucinations (33% vs 0%; P = 0.001), and olfactory hallucinations (13% vs 0%; P = 0.050). Among methamphetamine users, there were no significant differences between men and women with regard to age, ethnicity, years of use, route of administration, or amount used in the past week. In the “while abstinent” condition, women were significantly more likely than men to report feeling that something was wrong with the way a part of their body looked (72% vs 32%, respectively; P = 0.009), olfactory hallucinations (39% vs 8%; P = 0.010) and dressing inappropriately (22% vs 0%; P = 0.010). During the “while high” condition, women were more likely than men to report delusions of grandeur (33% vs 16%, respectively; P = 0.030), paranoia (50% vs 16%; P = 0.017), and tactile hallucinations (61% vs 32%; P = 0.050). Conclusions The findings of the present study revealed that cocaine- and methamphetamine-dependent women were more likely than their male counterparts to report experiencing various psychotic symptoms. This information may be useful for clinicians and mental health professionals, who should take these symptoms into account as potential barriers that may impede effective treatment.

Rates of cigarette smoking are 3- to 4-fold greater among those with cocaine-dependence, and compared to non-users, cocaine users are at greater risk of incurring smoking-related negative health effects and death. The current study examined D-cycloserine’s (0 or 50 mg once weekly) 2) effects on 1) extinction of cue-induced craving for cigarettes, 2) cigarette smoking in conjunction with cognitive-behavioral therapy, and 3) safety and tolerability in cocaine-dependent smokers. This was a double-blind, placebo-controlled, between groups, outpatient study. Participants (N=29) were concurrent cocaine- and nicotine-dependent volunteers seeking treatment for their cigarette smoking. Study visits were 3 times per week for 4 consecutive weeks. At each visit, participants received cognitive-behavioral therapy for smoking, were exposed to smoking cues. A subset of participants (N=22) returned for 6-month follow-up visits. While craving decreased, no significant effects of D-cycloserine treatment were observed. Likewise, significant decreases in smoking were observed at study days 6 (p <0.002) and 12 (p <0.0001) relative to baseline, although no participants achieved complete abstinence. However, there was no effect of D-cycloserine on cigarette smoking during treatment or at 6-mos follow-up. The treatment was safe and tolerable, with nearly 90% of treatment sessions attended based on an intent-to-treat analysis. While no effects of D-cycloserine on craving or smoking were observed in the current study, the results do suggest smoking treatment is well accepted and may be effective for cocaine-dependent individuals.

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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 20 mg of cocaine on Day 1, and saline and 40 mg 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 0.2 mg QID (N=11). On Days 6 and 7, subjects received double-blind infusions of saline and 20 mg of cocaine on Day 6, and saline and 40 mg 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 0.8 mg dose level discontinued, and five of 11 participants at the 0.2 mg 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 0.2 mg, 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.