Several lines of evidence link cannabinoid (CB) type 1 (CB1) receptor-mediated endogenous CB (eCB) signaling to the etiology of alcohol dependence (AD). However, to date, only peripheral measures of eCB function have been collected in living humans with AD and no human in vivo data on the potentially critical role of the brain CB1 receptor in AD have been published. This is an important gap in the literature, because recent therapeutic developments suggest that these receptors could be targeted for the treatment for AD.
Medication-free participants were scanned during early abstinence 4 weeks after their last drink. Using positron emission tomography (PET) with a high-resolution research tomograph and the CB1 receptor selective radiotracer [11C]OMAR, we determined [11C]OMAR volume of distribution (VT) values, a measure of CB1 receptor density, in a priori selected brain regions in men with AD (n = 8, age 37.4 ± 7.9 years; 5 smokers) and healthy control (HC) men (n = 8, age 32.5 ± 6.9 years; all nonsmokers). PET images reconstructed using the MOLAR algorithm with hardware motion correction were rigidly aligned to the subject-specific magnetic resonance (MR) image, which in turn was warped to an MR template. Time–activity curves (TACs) were extracted from the dynamic PET data using a priori selected regions of interest delineated in the MR template space.
In AD relative to HC, [11C]OMAR VT values were elevated by approximately 20% (p = 0.023) in a circuit, including the amygdala, hippocampus, putamen, insula, anterior and posterior cingulate cortices, and orbitofrontal cortex. Age, body mass index, or smoking status did not influence the outcome.
These findings agree with preclinical evidence and provide the first, albeit still preliminary in vivo evidence suggesting a role for brain CB1 receptors in AD. The current study design does not answer the important question of whether elevated CB1 receptors are a preexisting vulnerability factor for AD or whether elevations develop as a consequence of AD.
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