The effects of FAAH inhibition on the neural basis of anxiety-related processing in healthy male subjects: a randomized clinical trial

Regulation of cocaine-related behaviours by estrogen and progesterone

Cannabis use among US adults with anxiety from 2008 to 2017: The role of state-level cannabis legalization.

Interoception and alcohol: Mechanisms, networks, and implications.

Cannabidiol (CBD) is a non-psychotropic phytocannabinoid of the plant Cannabis sativa L. CBD is increasingly being explored as an alternative to conventional therapies to treat health disorders in dogs and cats. Mechanisms of action of CBD have been investigated mostly in rodents and in vitro and include modulation of CB1, CB2, 5-HT, GPR, and opioid receptors. In companion animals, CBD appears to have good bioavailability and safety profile with few side effects at physiological doses. Some dog studies have found CBD to improve clinical signs associated with osteoarthritis, pruritus, and epilepsy. However, further studies are needed to conclude a therapeutic action of CBD for each of these conditions, as well as for decreasing anxiety and aggression in dogs and cats. Herein, we summarize the available scientific evidence associated with the mechanisms of action of CBD, including pharmacokinetics, safety, regulation, and efficacy in ameliorating various health conditions in dogs and cats.

Scientific Validation of Cannabidiol for Management of Dog and Cat Diseases.

INTRODUCTION Alcohol may influence the nicotine metabolite ratio (NMR), an index of the rate of nicotine metabolism that is associated smoking level and lapses. We examined if NMR changes during alcohol use disorder (AUD) treatment and how changes in NMR relate to reductions in drinking. METHODS Using an observational design, 22 daily smokers [63.64% male, Mage = 46.77 (11.37)] receiving AUD treatment completed baseline and follow-up appointments 3 weeks apart. At each appointment, daily alcohol and cigarette use, salivary and urinary NMR, nicotine exposure via urinary total nicotine equivalents, and carbon monoxide were assessed. Multilevel models examined the change over time in NMR and its within-person relations with changes in drinks per week. Sex differences were evaluated. RESULTS There were significant reductions in both salivary and urinary NMR over time for men (p = .02; p = .01, respectively) but not for women (p = .54; p = .90, respectively). There were no changes over time in total nicotine equivalents (p = .09), carbon monoxide (p = .44), or cigarette use (p = .44) in either sex. Drinks per week were significantly reduced for men (29.12 drink reduction, p < .001) but not for women (2.28 drink reduction, p = .80); however, within-person changes in drinking were not associated with changes in salivary or urinary NMR (p = .99; p = .19). CONCLUSIONS The reduction in alcohol use and NMR in men provides indirect support for alcohol increasing NMR. In contrast, the low baseline drinking and lack of alcohol reduction likely underlie the lack of change in NMR in females. Reasons for NMR reductions during AUD treatment and its effects on smoking require further study. IMPLICATIONS Three weeks of alcohol use disorder treatment among daily smokers coincided with a significant reduction in both alcohol use and NMR for men; however, neither drinking level nor NMR changed for women. The findings indirectly support that heavy drinking increases NMR, which is reversed with reduced drinking. Additional research is needed to establish if these changes in NMR correlate with smoking and cessation outcomes.

Changes in Nicotine Metabolite Ratio Among Daily Smokers Receiving Treatment for Alcohol Use Disorder.

The current study investigated whether the stimulus effects of morphine can function as a positive and negative feature in a Pavlovian occasion setting drug discrimination preparation in male and female rats. Sprague-Dawley rats were assigned to a feature positive (FP) or feature negative (FN) training group and all received intermixed morphine (3.2 mg/kg, IP) or saline injections 15 min before 20-min daily training sessions. For FP rats, on morphine sessions, each of eight 15-s white noise (WN) presentations was followed by 4-s access to sucrose (0.01 ml, 26% w/v); on saline sessions, sucrose was withheld. FN rats learned the reverse contingency. FP discrimination was acquired somewhat sooner than FN discrimination, and females, but not males, became sensitized to the locomotor effects of morphine, which did not influence conditioned responding. Rats then entered dose generalization testing. There was no sex difference in dose generalization for FN groups (ED50 1.26 for males and 1.57 for females). Yet for FP rats, the dose response curve for females was shifted to the right compared to males (ED50 0.54 for males and 1.94 for females). FP females exhibited enhanced responding at a dose higher than that of their original training. These findings reveal the need to reassess our notions of drug stimuli that guide appropriate associative behaviours from the perspective of sex differences.

Sex differences in the discriminative stimulus characteristics of a morphine occasion setter in rats.

Over the past decade, adolescent cigarette smoking has been declining. However, adolescent nicotine consumption via electronic cigarettes is rapidly gaining popularity. Earlier onset nicotine use is associated with increased risk of dependence. A bidirectional relationship between nicotine and stress exists; perceived stress is a predictor for nicotine use, and stress reduction is a commonly reported reason for using nicotine. We assessed the prolonged impact of adolescent high-dose nicotine and/or footshock exposure on adult nicotine self-administration, anxiety-like behaviour, and hormonal responsivity. During adolescence (postnatal day [P]28-56) male Sprague-Dawley rats were assigned to one of five groups: saline (SALPRE: 1 ml/kg, SC, every day), nicotine (NICPRE: 1 mg/kg, SC, alternating daily with saline; 14 total nicotine injections), footshock (SHOCKPRE: 8 of 0.5 s, 0.8 mA alternating sessions; saline every day), or combination nicotine and footshock (NIC+SHOCK: concurrent and alternating daily with saline, or NIC–SHOCK: alternating with saline on shock sessions). On P70, one cohort underwent spontaneous intravenous nicotine self-administration (0.03 mg/kg/infusion); another cohort was assessed for open-field behaviour (P71), then corticosterone (CORT) response to nicotine or footshock in adulthood (P72-73). Intermittent adolescent nicotine or footshock alone (NICPRE and SHOCKPRE) did not potentiate adult spontaneous nicotine intake compared to SALPRE. However, both combination groups (NIC+SHOCK, NIC–SHOCK) showed increased adult nicotine consumption without associated differences in baseline anxiety-like behaviour or CORT response. Adolescent nicotine and footshock stressors have a synergistic effect on adult nicotine consumption, enhancing nicotine intake. Avenues toward reducing stress in adolescent nicotine users may provide opportunities to reduce vulnerability to adult nicotine consumption.

Adolescent nicotine and footshock exposure augments adult nicotine self-administration and drug-seeking without affecting baseline anxiety-like behaviour or stress responsivity in male rats

Sex Differences in the Discriminative Stimulus Characteristics and Conditioned Enhancing Effects of a Morphine Occasion Setter in Rats

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