Dataset Information

CNR1 and FAAH variation and affective states induced by marijuana smoking.

ABSTRACT: Background: Polymorphisms in cannabinoid receptor type 1 (encoded by CNR1) and fatty acid amide hydrolase (encoded by FAAH) have been associated with cannabis dependence, but it remains unknown whether variation within these genes influences cannabis' acute effects on affect. Objective: Conduct a secondary data analysis study to determine whether previously observed acute effects of tetrahydrocannabinol (THC) on mood was dependent upon variation in CNR1 and FAAH. Methods: A balanced placebo design was used crossing marijuana administration (i.e., 0% THC vs. 2.8% THC) with stimulus expectancy. Participants (N = 118; 64% male) provided DNA and completed the Profile of Mood States questionnaire prior to and after smoking. Haplotypes were constructed from genotyped single nucleotide polymorphisms for CNR1 (rs1049353 and rs806368) and FAAH (rs4141964, rs324420, and rs11576941); rs2023239 (CNR1) and rs6703669 (FAAH) were not part of a phased haplotype block. Analyses tested both main and interaction effects for genotype across CNR1 and FAAH, and drug, and expectancy effects. Results: THC increased levels of POMS Tension-Anxiety and Confusion-Bewilderment over and above the effects of variation in CNR1 and FAAH. Significant drug X genotype/haplotype and expectancy X genotype/haplotype interaction effects were observed for some but not all mood states [e.g., 'C' allele carriers of rs2023239 who received THC had higher levels of Anger-Hostility (?= 0.29 (0.12), p= .02) compared to those who received placebo]. Conclusion: These preliminary findings suggest individual differences in mood states after using marijuana depend on genetic variation. Such information might be useful in understanding either motivation for use of marijuana and/or risk for associated behaviors.

SUBMITTER: Palmer RHC

PROVIDER: S-EPMC6931041 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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CNR1 and FAAH variation and affective states induced by marijuana smoking.

Palmer Rohan H C RHC McGeary John E JE Knopik Valerie S VS Bidwell L Cinnamon LC Metrik Jane M JM

The American journal of drug and alcohol abuse 20190611 5

Background: Polymorphisms in cannabinoid receptor type 1 (encoded by CNR1) and fatty acid amide hydrolase (encoded by FAAH) have been associated with cannabis dependence, but it remains unknown whether variation within these genes influences cannabis' acute effects on affect. Objective: Conduct a secondary data analysis study to determine whether previously observed acute effects of tetrahydrocannabinol (THC) on mood was dependent upon variation in CNR1 and ...[more]

PMID: 31184938

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Project description:IntroductionSmoking to reduce negative affect has been identified as a key motivational feature of tobacco use. Our recent work suggests that smoking very low nicotine content (VLNC) cigarettes reduces the relationship between negative affect and smoking behavior over a 6-week period. Here, we sought to extend our findings by evaluating whether a gradual or immediate approach to switching to VLNC cigarettes led to a differential reduction in the relationship between affect and smoking behavior over a longer (20-week) period.Aims and methodsParticipants (n = 1250) were adult smokers from 10 US sites randomized to one of three groups: gradual nicotine reduction (15.5, 11.7, 5.2, 2.4, and 0.4 mg of nicotine per gram of tobacco [mg/g]), immediate nicotine reduction (0.4 mg/g), or standard nicotine content cigarettes (15.5 mg/g; control), for 20 weeks. We examined whether the relationship between affect-both negative and positive-and cigarettes per day differed as a function of reduction group.ResultsWe found that both negative and positive affect were associated with cigarette consumption in the control group, but not in the gradual or immediate reduction groups across the 20 weeks of exposure.ConclusionsOur results extend previous findings that switching to VLNC cigarettes disrupts the relationship between affect and cigarette consumption by showing that either gradually or immediately reducing cigarette nicotine content achieves this disruption. These findings provide further evidence that switching to VLNC cigarettes reduces nicotine-related reinforcement of cigarette smoking.ImplicationsThese findings support the notion that switching to very low nicotine content cigarettes reduces the association between affect and smoking behavior, and that either a gradual or immediate nicotine reduction approach achieves this reduction. This provides further evidence that switching to very low nicotine content cigarettes weakens reinforcement mechanisms associated with nicotine dependence.

Project description:When an individual attends to certain types of information more than others, the behavior is termed an attention bias. The occurrence of attention biases in humans and animals can depend on their affective states. Based on evidence from the human literature and prior studies in sheep, we hypothesized that an attention bias test could discriminate between pharmacologically-induced positive and negative affective states in sheep. The test measured allocation of attention between a threat and a positive stimulus using key measures of looking time and vigilance. Eighty 7-year-old Merino ewes were allocated to one of four treatment groups; Anxious (m-chlorophenylpiperazine), Calm (diazepam), Happy (morphine) and Control (saline). Drugs were administered 30 min prior to attention bias testing. The test was conducted in a 4 × 4.2 m arena with high opaque walls. An approximately life-size photograph of a sheep was positioned on one wall of the arena (positive stimulus). A small window with a retractable opaque cover was positioned on the opposite wall, behind which a dog was standing quietly (threat). The dog was visible for 3 s after a single sheep entered the arena, then the window was covered and the dog was removed. Sheep then remained in the arena for 3 min while behaviors were recorded. Key behaviors included time looking toward the dog wall or photo wall, duration of vigilance behavior and latency to become non-vigilant. In contrast with our hypothesis, no significant differences were found between treatment groups for duration of vigilance or looking behaviors, although Anxious sheep tended to be more vigilant than Control animals (P < 0.1) and had a longer latency to become non-vigilant (P < 0.001). A total of 24 of 80 animals were vigilant for the entire test duration. This censoring of data may explain why no differences were detected between groups for vigilance duration. Overall, a lack of difference between groups may suggest the test cannot discriminate positive and negative states in sheep. We suggest that the censoring of vigilance duration data, the use of insufficient drug doses, the potential influence of background noise and the age of the sheep may explain a lack of difference between groups. Due to these potential effects, it remains unclear whether the attention bias test can detect positive states in sheep.

Dataset Information

CNR1 and FAAH variation and affective states induced by marijuana smoking.

Publications

<i>CNR1</i> and <i>FAAH</i> variation and affective states induced by marijuana smoking.

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