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BACKGROUND: Women with serious mental illnesses like bipolar disorder and schizophrenia are more likely to be tobacco smokers as compared to women without mental illness. Antipsychotic medications may impact craving and nicotine’s rewarding effects via dopaminergic neurotransmitter activity. Differences in pharmacologic profiles and receptor affinity among antipsychotic agents may lead to variability in impact on craving and/or substance use. Aripiprazole, a partial dopamine agonist antipsychotic, may impact tobacco craving. To our knowledge, no one has specifically examined tobacco craving/usage patterns in women with psychotic disorders treated with adjunctive aripiprazole. METHODS: We report baseline and endpoint tobacco use/craving data for cigarette smokers completing a 16-week randomized double-blind placebo-controlled trial of adjunct aripiprazole vs placebo. Participants recruited were all women with high prolactin levels and not reporting any desire to change smoking behaviors, which provides the opportunity to look at a naturalistic population. Assessments included the Fagerstrom Test for Nicotine Dependence (FTND) Scale, the Tobacco Craving Questionnaire-Short Form (TCQ-SF), the Drug and Alcohol Use Summary, expired carbon monoxide (CO), and all answered questions about smoking habits at baseline, 8 weeks, and 16 weeks (endpoint). Between-group changes from baseline to endpoint were measured by Effect size (Cohen’s D) due to the underpowered pilot nature of the data. RESULTS: Of the 16 women smokers included, 9 were assigned to aripiprazole and 7 to placebo. The average age of participants was 38.5 years (SD=9.9) and mean age at onset of illness was 20.9 (SD=8). The average number of cigarettes smoked daily was 10.6 (SD=7.6) and the average years of smoking was 20.9 (SD=10.4). Of the 16 participants, 2 (12.5%) were diagnosed with bipolar disorder, 4 (25%) had schizoaffective disorder, and 10 (62.5%) had schizophrenia. There were no baseline differences in demographic or smoking measures between groups. During the 16-week study the FTND scores were moderately decreased with aripiprazole relative to placebo with an effect size (ES) of -0.49. The ES for expired CO favoring aripiprazole was -0.86, however there wasn’t a decrease in the aripiprazole group, only an increase noted in the study with placebo. Aripiprazole, compared to placebo, did not appear to affect the number of cigarettes smoked daily (ES= -0.22) or the TCQ-SF scores (ES= 0.20). DISCUSSION: This pilot study is the first to evaluate the effect of adjunct aripiprazole on measures of tobacco and use and craving in women smokers with psychotic disorders. In this small sample there were moderate effect size favoring adjunct aripiprazole on a decrease in dependency scores but not in craving and cigarette smoking. Future research should investigate the impact of aripiprazole on tobacco craving in a larger sample. Additionally, both men and women should be included for a representative sample and to examine potential sex differences. This study was funded by NIMH R01 (MH090071-04) (Kelly PI) and NIDA K23 (DA034034-01A1) (Wehring PI). Aripiprazole and matching placebo were supplied by Bristol-Myers Squibb/Otsuka.

Background: The current pilot study examined whether variables such as stress/trauma and medications modulate levels of serum kynurenine and kynurenic acid (KYNA). Methods: Ten people (5 males and 5 females) with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder (SCZ) and 10 healthy controls (HCs; 5 males and 5 females) were included in the current study. All participants had a study visit that included a blood draw for serum KYNA and kynurenine levels, physiological measurements, demographic data, assessments of current anxiety and perceived stress measured by the State Trait Anxiety Inventory/Visual Analog Scale (STAI_VAS) and the Perceived Stress Scale (PSS), childhood trauma history measured by the Childhood Trauma Questionnaire (CTQ), and medication use. Results: In this pilot study, differences in KYNA and kynurenine between SCZ and HCs were not statistically significant (P > .05). Within SCZ, kynurenine levels were correlated with the total CTQ score (r = .63, P = .049) as well as the physical abuse domain (r = .74, P = .016). KYNA also tended to correlate with the total CTQ (r = .60, P = .069), emotional abuse (r = .42, P = .045), and physical abuse domains (r = .62, P = .058. There were not significant correlations noted between KYNA or kynurenine and CTQ scores in the HC groups. Kynurenine levels were positively correlated with the STAI tense domain also in SCZ subjects (r = .81, P = .004). With regard to differences in medication use, serum KYNA and kynurenine levels were significantly lower in people with schizophrenia taking medications for constipation (P < .05) and anticholinergic medications compared to patients not taking these medications. Conclusion: In this small sample, greater childhood trauma and/or perceived stress symptoms were found to be related to higher levels of serum KYNA and kynurenine in patients with schizophrenia. Further research is needed in a larger sample to assess whether childhood trauma and subsequent stress and/or anxiety symptoms relate to KYNA and kynurenine levels in patients with schizophrenia. Our data suggest that future investigations should also examine the effect of concomitant medications (particularly those with anticholinergic activity) on KYNA and kynurenine levels in schizophrenia. This information will help future investigations identifying psychopathological pathways, leading to studying specific schizophrenia phenotypes and deconstructing the illness.

Background: The prevalence of tobacco use is 2–3 times greater in people with schizophrenia than the general population. Tobacco craving is an important reason why people relapse; cessation efforts in this population have been modest. Understanding the triggers that lead to tobacco craving and potential relapse will help to target the testing of new interventions. Virtual reality (VR) platforms can expose smokers to multisensory tobacco cues/triggers by immersion into an environment where they can see and smell tobacco-related cues and interact in virtual social environments. It is hypothesized that smokers who heavily identify environmental triggers to smoking urges may be more likely to respond to these types of stimuli.

Oral cannabinoids are taken for medicinal or recreational purposes, yet little is known about tolerance to their effects after high-dose extended exposure. The development of tolerance to effects of around-the-clock oral synthetic Δ9-tetrahydrocannabinol (THC) (20 mg every 3.5-6 h) was evaluated in 13 healthy male daily cannabis smokers residing on a secure research unit: 40 mg on Day 1; 100 mg on Days 2-4; 120 mg on Days 5-6. Systolic and diastolic blood pressure (BP), heart rate, and symptoms of subjective intoxication (100 mm visual-analogue scales, VAS) were assessed the morning of Day 1 (before any oral THC), and on Days 2, 4 and 6, every 30 min for 3 h after the first morning THC dose. Morning subjective intoxication ratings increased from Days 1 to 2, and then declined on Days 4 and 6. The morning THC dose increased intoxication ratings on Day 2, but had less effect on Days 4 and 6, a pattern consistent with tolerance. THC lowered BP and increased heart rate over the six days. Plasma THC and 11-OH-THC concentrations increased significantly over the first five days of dosing. Six days of around-the-clock, oral THC produced tolerance to subjective intoxication, but not to cardiovascular effects.