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Cannabis and synthetic cannabinoids are abused in spite of possible adverse health consequences. The current study investigated the reinforcing effects of an ecologically relevant mode of administration (inhalation) of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, and three synthetic cannabinoids detected in synthetic cannabinoid products (JWH-018, JWH-073, and HU-210) in non-human primates (NHPs). Male and female (N = 4 each) rhesus macaques were trained to inhale warm air via a metal stem to receive a candy reinforcer, an alcohol aerosol vehicle was then paired with the candy. Dose-dependent responding for inhaled aerosols of THC (2.0-16.0 μg/kg/inhalation), JWH-018 (0.2-1.6 μg/kg/inhalation), JWH-073 (2.0-8.0 μg/kg/inhalation), and HU-210 (1.0-8.0 μg/kg/inhalation) was established using a fixed-ratio five schedule of reinforcement and compared to vehicle (alcohol) self-administration. Dose-dependent responding for inhaled heroin (25.0-100.0 μg/kg/inhalation), a known reinforcer in NHPs, was also established. Responding approximated vehicle levels for many drug doses tested, but at least half of the monkeys responded for ≥ one dose of each cannabinoid and heroin above vehicle, with the exception of THC. Drug deliveries calculated as percent vehicle followed a prototypical inverted-U shaped dose-response curve for cannabinoids and heroin except for THC and JWH-018 (in males). Grouped data according to sex demonstrated that peak percent of vehicle reinforcers earned for THC was greater in males than females, whereas peak percent of vehicle reinforcers earned for JWH-018, HU-210, and heroin were greater in females than males. These findings indicate minimal reinforcing effects of CB1 receptor agonists when self-administered by NHPs via aerosol inhalation. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Women with a history of childhood sexual abuse (CSA) are at greater risk to develop alcohol use disorders. Whereas impulsivity has been postulated as a behavioral mechanism linking childhood trauma and alcohol use, few studies have comprehensively examined impulsivity in women with CSA. We compared women with a history of CSA (n = 21) and control women who did not endorse CSA or other major traumas (CON; n = 21) on self-report measures of impulsivity and risk taking. Additionally, performance on behavioral impulsivity and subjective response to alcohol were examined before and after acute alcohol (0.00, 0.50, 0.75 g/kg) administration. Overall, women with CSA responded more impulsively than CON women on the immediate and delayed-memory tasks (measures of response initiation) and the GoStop task (a measure of response inhibition). Whereas alcohol produced dose-related increases in impulsive responding on the immediate memory task in both groups, alcohol-induced increases in response inhibition on the GoStop task were evident only in the CSA group. In contrast, women with CSA exhibited less risk taking than the CON group on the balloon analogue risk task. Alcohol produced dose-related increases on several subjective response measures (e.g., alcohol liking) in both groups; however, these ratings tended to be greater in women with CSA. These preliminary data suggest that women with CSA may be more impulsive. Importantly, impulsivity can lead to hazardous drinking, and alcohol consumption can further increase impulsivity, putting women with CSA at increased risk for sexual revictimization, particularly in the context of alcohol use. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background The hypocretin/orexin system is involved in regulating arousal, and much recent work demonstrates that decreasing hypocretin receptor-1 (HCRTr1) activity using antagonists decreases appetitive behavior, including stimulant drug self-administration and reinstatement. Methods The present study determined the effects of hypocretin-1 and HCRTr1 antagonists on responding reinforced by intravenous (i.v.) cocaine self-administration (0.0125 – 0.05 mg/kg/infusion) in 5 female rhesus monkeys. Responding was examined using 3 schedules of reinforcement: 1) a Fixed interval 1 min, Fixed ratio 10 Chain schedule [FI 1-min (FR10:S)], 2) a Progressive Ratio (PR) schedule, and 3) a cocaine vs. candy. Results Choice schedule: the HCRTr1 antagonist SB-334867 (8–24 mg/kg, i.m.) decreased cocaine taking under the Chain schedule and PR schedule in all 5 monkeys and in 4 of the 5 monkeys under the Choice schedule. d- Amphetamine (0.06 – 0.25 mg/kg, i.m.), tested as a control manipulation, decreased cocaine taking in all 5 monkeys under the Chain schedule. The peptide hypocretin-1 (0.072 mg/kg, i.v.) increased cocaine taking in the monkeys with low rates of cocaine taking under the Chain (3/4) and Choice (4/5) schedules. Reinstatement of extinguished cocaine responding following response-independent delivery of a large dose of cocaine (0.3 mg/kg) was attenuated in 3 of the 5 monkeys by the HCRTr1 antagonist SB-334867. Conclusions These data expand upon work accomplished in predominantly male rodents suggesting that the hypocretin system modulates the response to appetitive stimuli. A better understanding of this system offers promise as a novel approach in medication development for appetitive disorders.

Many patients with bulimia nervosa (BN) also meet criteria for a lifetime alcohol use disorder (AUD). In order to understand possible mechanisms contributing to the co-occurrence and perpetuation of these disorders, this study investigated the importance of impulsivity and test meal intake among patients with BN by comparing women with BN only (n = 18), BN and current/past AUDs (n = 13), and healthy controls (n = 12). All participants completed assessments of eating disorder symptoms, frequency of alcohol use, binge eating, and purging via questionnaires and semi-structured interviews over two sessions. Measures of impulsivity consisted of computerized and self-report measures, and laboratory test meals. Significant differences between individuals with BN with/without comorbid AUDs were not found for test meal intake, impulsivity measures, or self-reported psychological symptoms. As hypothesized, compared to healthy controls, individuals with BN had significantly higher scores on two subscales and the total score of the Barratt Impulsiveness Scale, a trait measure of impulsivity, and consumed significantly more calories in the binge instruction meal. Total Barratt Impulsiveness Scale scores were also significantly related to kcal consumed during the laboratory test meal when individuals were instructed to binge eat (BN groups). Data from this study add to the existing literature implicating impulsivity in the psychopathology of disorders of binge eating, including BN, and also support the use of laboratory meals as a symptom-specific measure of this trait in eating disorder populations.

This study examined how response effort (pressing a keyboard button) for cocaine and the value of an alternative reinforcer (opportunity to play a game of chance for money) combined with ‘free’ cocaine (with no response effort) affected cocaine choice when participants were maintained on modafinil or placebo. Nontreatment-seeking current cocaine smokers were enrolled in a placebo-controlled, double-blind, within-subject study comprising both inpatient and outpatient phases. Participants were maintained on placebo capsules (0 mg/day) during one inpatient phase and modafinil (300 mg/day) capsules during another inpatient phase in counter-balanced order. A minimum of 8 medication-free days separated the two 15-day inpatient phases to allow for medication clearance. Under each medication condition participants had the opportunity to self-administer smoked cocaine (25 mg) when the response effort for cocaine was low (500 responses/dose) and had a low value alternative (2 game plays for money) or when the response effort for cocaine was large (2500 responses/dose) and had a more valuable alternative (4 game plays for money). Under both conditions, participants received one free dose of cocaine (0, 12, 25 or 50 mg) prior to making their first choice of the session. Fifteen individuals began the study and 7 completed it. Participants chose fewer cocaine doses when the response effort for cocaine and the alternative value was high (4.4 ± 0.19) compared to when the response effort for cocaine and the alternative value was low (5.3 ± 0.14). Providing individuals a free “priming” dose of cocaine prior to making their cocaine choice did not alter cocaine taking. Modafinil decreased cocaine choice only when the response effort for cocaine and the alternative value was high. These results suggest that modafinil may be most effective when combined with therapy emphasizing the large personal costs of using cocaine.

Previous studies have demonstrated that sex differences in pain responsivity can be detected using various models of experimentally induced pain. The present study employed the mechanical pressure test in order to examine potential differences in pain report among men, normally menstruating women (NMW), and women taking monophasic oral contraceptives (OCW). Testing occurred during 5 phases of the menstrual cycle (menstrual, follicular, ovulatory, luteal, and late luteal) and all participants completed 10 sessions (2 sessions per phase). Menstrual-cycle phase was estimated for OCW based on their first day of menses. Men were tested at time points that roughly corresponded to the intervals during which the different phases occurred in NMW. During the mechanical pressure test, 4 different weights were placed on the fingers, one at a time, and ratings of pain were recorded for 30 seconds. The statistical decision-making model and a forced-choice procedure were used to analyze the response data. Two variables, based on signal detection theory, were thus generated: P(A), a measure of sensory pain, and B, a measure of response bias. P(A) is believed to be a measure of pain sensitivity while B measures stoicism. NMW tended to report lower P(A) values, indicating reduced ability to discriminate among different stimulus intensities, during the menstrual and late luteal phases compared to the luteal phase. OCW reported lower B values, indicating less stoicism, during the menstrual compared to the follicular and ovulatory phases. Men tended to have significantly lower B values than OCW, but not NMW. These results demonstrate subtle menstrual-cycle effects in NMW and OCW. Sex differences were few, with more group differences and trends emerging between OCW and men, as opposed to men and NMW. Perspective The lack of consistent differences between men and NMW underscores the subtle impact of sex and hormonal changes in pain report. In addition, the data obtained in NMW support the notion that changes in hormone levels during the menstrual cycle can lead to changes in pain responsivity as NMW had trends for better discrimination in menstrual phases when estradiol levels were highest.

Studies using rodents have shown that behavioral responses to a stimulant are enhanced when the stimulant is given within the same context as previous stimulant administrations; this increase in effect related to context is often referred to as sensitization. We examined the role of environmental stimuli in modulating the subjective and cardiovascular effects of cocaine in humans (1) within a daily “binge” and (2) after cocaine abstinence. Ten non-treatment seeking users of smoked cocaine were admitted to the hospital for 17 consecutive days. Participants smoked cocaine (25 mg/dose) under two counterbalanced conditions: paired stimuli (same stimuli presented each session) and unpaired stimuli (varied stimuli presented each session). Under each stimulus condition, participants had cocaine test sessions for three consecutive days, no sessions for the next 3 days, then another cocaine test session on the following day, for a total of eight test days. Stimulus condition had no effect on cardiovascular or subjective effects so data were analyzed as a function of repeated cocaine administration over 2 weeks. Maximal ratings on “good drug” and “drug rating” subjective effects clusters decreased over days of repeated cocaine exposure. In contrast, baseline and peak heart rate and systolic pressure increased over days of repeated cocaine administration. Thus, repeated administration of smoked cocaine to experienced cocaine users resulted in increases in baseline blood pressure and heart rate and modest decreases in positive subjective effects. These data indicate modest tolerance rather than sensitization to the positive subjective effects of cocaine with repeated exposure.