dehydrated alcohol (Ablysinol)

Effects of direct cannabinoid receptor modulation on alcohol craving and withdrawal: a systematic review.

Archey Drennan Meggan L ML, Hetelekides Eleftherios M EM, Karoly Hollis C HC

Alcohol use disorder (AUD) is a prevalent condition associated with significant morbidity and mortality rates. Existing pharmacological and psychosocial treatments offer limited long-term effectiveness. At present, there is a critical need for novel AUD treatments. The endogenous cannabinoid system (ECS) may offer some therapeutic promise for AUD, given that it appears to play a role in alcohol use motivation, while alcohol alters ECS function. Since craving and withdrawal are key AUD symptoms and represent important treatment targets, the role of the ECS in mediating craving and withdrawal should be fully explored. Exploitation of the ECS may have potential as a treatment target for AUD. This review synthesizes results from preclinical investigations into the impact of cannabinoid (CB) receptor modulation on measures of craving and withdrawal since the discovery of the CB1 receptor. Researchers identified studies published between 1988 and 2026 involving direct CB receptor modulation, measuring outcomes pertaining to craving or withdrawal, and containing a control group were included in qualitative synthesis. Studies focused on alcohol consumption were not analyzed unless craving or withdrawal-related outcomes were reported. Risk of bias was examined using the SYRCLE tool for preclinical studies. Thirty-nine studies met inclusion criteria, all preclinical. Overall, CB1 activation generally increases craving-related behaviors, while antagonism tends to attenuate craving and some withdrawal-related outcomes, although dose-dependent effects were also reported. CB2 may mediate reinforcing effects of alcohol, but direction of effects is inconsistent. Evidence regarding withdrawal is limited and inconsistent. Preclinical evidence suggests that cannabinoid receptor modulation influences alcohol craving and withdrawal-related behaviors. Integration of these behavioral findings with the broader ECS literature suggests that CB1-mediated reward and motivational processes, and CB2-mediated neuroimmune signaling may represent important mechanisms underlying these phenotypes. Greater methodological standardization and clinical investigation are needed to confirm these mechanisms and determine their translational potential for AUD treatment. The protocol was pre-registered through Prospero (registration CRD42022309872) on 5/31/22.

Fetal Alcohol Spectrum Disorder as a Potential Early-Life Risk Factor for Dementia: A Life-Course Perspective.

Park So-Hee SH

Current models of modifiable dementia risk span the life course but begin with formal education, leaving the prenatal period unexamined. Prenatal alcohol exposure (PAE) is the leading preventable cause of neurodevelopmental disability; its clinical expression is fetal alcohol spectrum disorder (FASD), of which fetal alcohol syndrome is the most severe form. FASD affects about 0.8% of children worldwide and considerably more in residential and foster care, yet its late-life trajectory is unstudied: the first diagnosed cohort is only now in its sixth decade. This review examines whether PAE may be an early-life dementia risk factor. In rodent models, developmental alcohol exposure produces hippocampal, cholinergic, and epigenetic changes demonstrable in adult animals; the report of Alzheimer-type markers in middle-aged exposed animals rests on a single unreplicated study. In humans, FASD is associated with low cognitive reserve, social adversity, and a high prevalence of adult alcohol use disorder, each an established dementia risk factor. Two hypotheses are distinguished: a pathology hypothesis, in which PAE promotes neurodegenerative change, and a reserve hypothesis, in which lower premorbid reserve brings forward clinical expression at comparable pathological burden. The expected phenotype is more likely mixed than purely Alzheimer-type. No human evidence yet links PAE to incident dementia; the proposition remains a hypothesis, not an established association. Given the mechanistic plausibility, examination is warranted through midlife biomarker studies and record linkage in cohorts with documented exposure; recording PAE in memory clinic history taking and at entry into residential and foster care would supply the data required.

Preferences for mobile HIV pre-exposure prophylaxis delivery among young men with alcohol use in rural South Africa: A discrete choice experiment.

Castle Alison C AC, Mthembu Nkosinathi I NI, Nzimande Lucky L, Ncube Thenjiwe T et al.

Young men who use alcohol have an elevated risk for HIV in South Africa but have low engagement with pre-exposure prophylaxis (PrEP). We conducted a discrete choice experiment (DCE) to explore preferences for mobile HIV prevention services in rural KwaZulu-Natal. Men aged ≥ 18 years with self-reported alcohol use participating in an HIV-prevention clinical trial completed a DCE. Attributes included clinic location (soccer fields, shebeens [informal bars], taxi ranks), operating hours (weekday, week-evening, weekend), and HIV prevention modality (event-driven oral PrEP, injectable PrEP, condoms only). Preferences were estimated using hierarchical Bayesian multinomial logit models. Relative attribute importance quantified each attribute's contribution to decision-making. Exploratory subgroup analyses examined variation by prior PrEP use, alcohol risk (AUDIT-C > 4), and age. Among 185 participants (mean age 27 years), HIV prevention modality was the most influential attribute (62.8% relative importance), followed by clinic location (26.3%) and clinic timing (10.9%). Services located at soccer fields were strongly preferred, while delivery at shebeens was disfavoured. Clinic timing showed minimal variation in preferences. Event-driven oral PrEP was preferred over condoms-only delivery, while injectable PrEP showed mixed preferences. Men with prior PrEP experience and high-risk alcohol use preferred injectable PrEP, whereas PrEP-naïve men and those with lower-risk drinking patterns preferred event-driven oral PrEP. PrEP programmes for young men should pair prevention choice with acceptable service locations. Event-driven oral PrEP may be an entry point for PrEP-naïve men; injectable PrEP may appeal more to men with prior PrEP experience or higher-risk alcohol use.

Semaglutide and alcohol use disorder: An evidence gap India must fill.

Dixit Tanya T, Panda Udit K UK