The endocannabinoid enzyme, fatty acid amide hydrolase (FAAH), has been proposed as a therapeutic target for alcohol use disorder (AUD) and co-morbid psychiatric illnesses. Investigating this target in the living human brain and its relationship to clinical outcome is a critical step of informed drug development. Our objective was to establish whether brain FAAH levels are low in individuals with AUD and related to drinking behavior. In this pilot study, treatment-seeking patients with AUD completed two PET scans with the FAAH radiotracer [C-11]CURB after 3-7 days (n = 14) and 2-4 weeks (n = 9) of monitored abstinence. Healthy controls (n = 25) completed one scan. FAAH genetic polymorphism (rs324420) and blood concentrations of anandamide and other N-acylethanolamines metabolized by FAAH were determined and AUD symptoms assessed. In AUD, brain FAAH levels were globally lower than controls during early abstinence (F(1,36) = 5.447; p = 0.025)) and FAAH substrates (anandamide, oleoylethanolamide, and N-docosahexaenoylethanolamide) were significantly elevated (30-67%). No significant differences in FAAH or FAAH substrates were noted after 2-4 weeks abstinence. FAAH levels negatively correlated with drinks per week (r = −0.57, p = 0.032) and plasma concentrations of the three FAAH substrates (r > 0.57; p < 0.04)). Our findings suggest that early abstinence from alcohol in AUD is associated with transiently low brain FAAH levels, which are inversely related to heavier alcohol use and elevated plasma levels of FAAH substrates. Whether low FAAH is an adaptive beneficial response to chronic alcohol is unknown. Therapeutic strategies focusing on FAAH inhibition should consider the possibility that low FAAH during early abstinence may be related to drinking.

Anxiogenic drugs, as a class, did not uniformly alter the 50-kHz call rate or subtype profile. Amphetamine-induced effects on 50-kHz call rate and profile do not reflect anxiety.

DESCRIPTIONAn 82-year-old man with previous bioprosthetic aortic valve replacement for aortic stenosis had a routine ECG (figure 1). This was thought to represent an atrial tachycardia with cycle length 280 ms and 3:1 atrioventricular response. A diagnosis of atrial flutter was made based on tachycardia cycle length, p-wave morphology and previous cardiac surgery. He had a mild left-sided tremor in keeping with known Parkinson's disease. The patient was anticoagulated and admitted electively for an electrophysiology (EP) study. In the EP laboratory, the patient had a 12-lead ECG ( figure 2A) showing sinus rhythm with a ventricular rate of 60 bpm. Figure 2B shows the EP electrogram recorded in the coronary sinus confirming sinus rhythm. However, it was noted that the 'flutter waves' in the original ECG were most marked in the left limb leads. In the EP laboratory, ECG labels are placed on the torso, as opposed to the limbs. After moving ECG labels to the forearms, the surface ECG is shown ( figure 3) with re-emergence of 'flutter' waves. A diagnosis of pseudo-atrial flutter was made.Parkinsonian tremor characterised by a 5 Hz upper-limb dyskinesia can result in a pseudo p-wave artefact on ECG at a rate of 300 bpm, mimicking atrial flutter.1 2 However, pseudo p-waves are usually only seen in the limb leads. We Figure 1 Twelve-lead ECG showing apparent atrial tachycardia with atrial rate of 200/min, leftward axis deviation and ventricular rate of 55 bpm.

With chronic exposure, morphine acutely enhances 50-kHz calling and differentially promotes trill calls, mainly at the expense of flat calls. These effects appear consistent with a positive affect interpretation of 50-kHz vocalizations.

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Background Reduced function of fatty acid amide hydrolase, the catabolic enzyme for the endocannabinoid anandamide, can be inherited through a functional genetic polymorphism (FAAH rs324420, C385A, P129T). The minor (A) allele has been associated with reduced FAAH enzyme activity and increased risk for substance use disorders in adults. Whether this inherited difference in endocannabinoid metabolism relates to alcohol use disorder etiology and patterns of alcohol use in youth is unknown. Methods To examine this question, heavy‐drinking youth (n = 302; mean age = 19.74 ± 1.18) were genotyped for FAAH C385A. All subjects completed a comprehensive interview assessing alcohol use patterns including the Timeline Follow‐back Method, Alcohol Use Disorders Identification Test (AUDIT), and Drinking Motives Questionnaire. Analyses of Covariance (ANCOVAs) were conducted to assess differences in drinking patterns and drinking motives between genotype groups, and mediation analyses investigated whether drinking motives accounted for indirect associations of genotype with alcohol use severity. Results Youth with the FAAH minor allele (AC or AA genotype) reported significantly more drinking days (p = 0.045), significantly more frequent heavy episodic drinking (p = 0.003), and significantly higher alcohol‐related problems and consumption patterns (AUDIT score p = 0.045, AUDIT‐C score p = 0.02). Mediation analyses showed that the association of FAAH C385A with drinking outcomes was mediated by coping motives. Conclusions These findings extend previous studies by suggesting that reduced endocannabinoid metabolism may be related to heavier use of alcohol in youth, prior to the onset of chronic drinking problems. Furthermore, differences in negative reinforcement‐related drinking could account in part for this association.

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