A current overview on adolescent alcohol misuse and its potential negative impacts

■ INTRODUCTION

Adolescence is the transitional phase between childhood and adulthood, often defined as the age range from 10 to 19 years, but more accurately 10 to 24 years to reflect developmental and social realities [1]. Adolescence constitutes a critical developmental life period that involves significant behavioural, cognitive, emotional, physical, and social changes. In this sense, the psychological features of adolescence include enhanced impulsive behaviour, sensation seeking and reward sensiti¬vity, but reduced self-control to inhibit emotional responses [2]. This contributes to high rates of engagement in risky behaviours, including drug use, due to reasons such as curiosity and the desire to experiment [3]. The fact that alcohol is a legal drug and, therefore, socially accepted, in addition to its easy accessibility, makes it one of the most frequently consumed substances by adolescents [4]. This is worrying, since alcohol consumption during this specific life stage is associated with very negative health consequences, such as comorbid mental disorders, dependence, polysubstance use, reduced performance capacity, social problems, and premature death [5-8]. Despite these concerns, alcohol intake usually begins during adolescence [3], thereby affecting the neurological development of young people [9], which in turn results in reduced cognitive functioning due to alterations of certain structures, such as the corpus callosum, as well as the cingulate, prefrontal, and temporal regions [10-12]. The recent proliferation of reckless forms of alcohol consumption among adolescents contributes to a greater risk of acute poisoning and to a range of potential negative consequences, such as higher levels of unprotected sex, aggressive behaviour, suicide, sexual violence, traffic accidents, and death by intoxication [13-15]. This phenomenon seems to be closely related to the influence of online social networks, electronic media, and the internet, where the indiscriminate spread of dangerous practices and challenges has become a worrying trend [16-19].
Social media, in particular, have created an environment where teenagers are constantly exposed to risky behaviours that they can readily imitate, including substance use [20, 21]. In this respect, the ease of access to the internet and the possibility of sharing videos and testimonies in real time have facilitated the popularisation of diverse kind of aberrant activities, influencing adolescents’ behaviour [22].
Given the significant clinical and social implications associated with alcohol misuse, this narrative review first addresses current trends among adolescents, including practices related to binge-drinking and non-oral routes of consumption, and then explores alcohol as a substance, including its pharmacological basis of action, its negative health-related effects, the mechanisms underlying its impact, and the potential social implications stemming from its use.

■ METHOD

Driven by the central aim of merging clinical aspects of alcohol consumption with social phenomena, alongside the heterogeneous scope of themes and study types within the existing research, the methodology adopted in this study is a narrative review [23], selected to provide a comprehensive overview of the topic under investigation, focusing on contemporary risky behaviours among adolescents, with an emphasis on the pathophysiological, pharmacological, and social impacts of alcohol as the underlying basis for such practices. Data collection was conducted between July 25 and December 20, 2024. The databases used were Dialnet, PubMed, ResearchGate, and SciELO. The search strategy employed was exploratory, incorporating several keyword combinations to ensure a broad and inclusive review of the literature. The following keywords were used: “adolescents”, “alcohol”, “alcohol abuse”, “alcohol administration routes”, “alcohol misuse”, “alcohol pathophysiology”, “alcohol pharmaco-logy”, “alcohol use”, “alcohol use disorder”, “binge drinking”, “brain”, “health consequences”, “health effects”, “high-risk alcohol use practices”, “mechanisms”, “mental health”, “non-oral alcohol consumption”, “social consequences”, “stigma”, and “young populations”. The search strategy also included the examination of reference lists belonging to studies on the topic under investigation. Article selection was based on predefined exclusion and inclusion criteria. Discrepancies in article selection were addressed by re-evaluating initial assessments, thereby revisiting and cross-checking the selection criteria to ensure consistency and accuracy. The quality of studies was appraised based on their relevance and contribution to the research objectives. The exclusion criteria were articles (i) inaccessible or unavailable for retrieval, and those (ii) lacking information relevant to the objectives of this study or whose subject matter was not pertinent to the research aims. The inclusion criteria were articles focused on (i) the pathophysiology and pharmacology of alcohol consumption, (ii) binge-drinking and related practices, (iii) non-oral alcohol consumption and its health consequences, (iv) the specific health-related effects of alcohol use. Also included were those (v) analysing the social consequences of drinking alcohol, (vi) of a clinical or social nature with direct or indirect implications in the framework of adolescent alcohol consumption, (vii) considering relevant physiological and health aspects in relation to alcohol misuse. There were no restrictions on publication date, language, or study type. Duplicate studies identified during the search process were removed to avoid redundancy. Retrieved studies were screened based on their titles and abstracts to filter out not pertinent articles. Studies that met preliminary criteria underwent a thorough examination of their full text to assess their appropriateness for inclusion in the review, ensuring alignment with the research objectives and criteria.

■ RESULTS

Current trends in adolescent alcohol misuse

Binge-drinking and related practices
Binge-drinking refers to consumption of alcohol high enough to imply a severe deterioration in cognitive functioning and in motor coordination [24]. Specifically, Esser et al. [25] define this behaviour as the intake of five or more alcoholic beverages consecutively on one or more occasions over the past 30 days. During last decades, binge-drinking among adolescents and young adults has been considered a worldwide emerging problem because the health and social risks derived from this type of consumption at early ages are significantly amplified [24-26]. In this respect, drinking games can encourage binge-drinking behaviours among young people for a variety of reasons, such as having fun, facilitating social interactions, fear of missing out, the idea of competition, and the rapid form of consumption [13, 15, 27-29]. LaBrie et al. [30], analysing 100 drinking games with a sample of 3421 college students from the United States, identified five categories: (i) targeted and skills games (participants use their skill to either avoid drinking or cause others to drink); (ii) communal games (consumption is prompted by external cues, with everyone taking a drink each time the cue appears); (iii) games of chance (random elements that determine drinking actions or rules); (iv) extreme consumption games (one or more standard drinks are consumed as fast as possible); and (v) competitions (individuals or teams compete against each other, and usually the losing side must drink as a “forfeit”).
The beer bong, also known as drink funnel, is one of the most recognised methods at student parties to facilitate the rapid consumption of alcoholic beverages [30]. It consists of a funnel connected to a tube, through which the beverage is poured and subsequently consumed. The primary mechanism relies on gravity, as the funnel is typically elevated above the participant’s mouth, allowing the liquid to flow rapidly [15]. The social acceptance and prevalence of beer bongs at gatherings may perpetuate risky drinking behaviours, as their use is often normalised and even glamorised in popular culture. For instance, beer bongs frequently appear in movies and in television shows, where they are depicted as a hallmark of party culture and excessive drinking. This media portrayal can contribute to the widespread adoption among teenagers and young adults of methods for binge-drinking, reinforcing the notion that rapid alcohol consumption is something desirable [18, 31, 32].
Consumption of alcohol through shots has been considered a high-risk drinking behaviour [33]. Shot games consist of participants consuming a series of small, concentrated doses of alcohol, typically over a short period of time. A recent study [34] conducted in Portugal reported that drinking shots tends to be more frequent among male students with fewer years of academic experience, although college parties appear to significantly influence drinking behaviour, regardless of academic seniority. The variants of shot games present specific rules and formats, such as power hour (consumption of one shot of alcohol every minute for an hour), battle shots (a variation of the classic Battleship board game – when there is a hit, the opponent has to drink the corresponding shot), shot book (a physical booklet where each page contains a unique drinking challenge), or body shot (licking or sucking alcohol from different parts of a person’s body like the navel while the drink is poured into that area) [13, 15]. Nevertheless, despite the differences among shot games, they all share the common feature of encouraging the fast consumption of alcohol. Therefore, shot games are particularly dangerous since participants strive to outdrink for keeping up with the pace set by the game, which can lead to levels of consumption that are far beyond of safe health limits.
Several authors [16, 35-37] highlighted a recent, particularly dangerous social media-based drinking game, usually known as Neknomination or Neknominate, in which participants record themselves while consuming excessive quantities of alcohol and later nominate friends to do the same within 24 hours. A study [28] conducted in United Kingdom reported that male individuals are more likely to engage in this precise game, and that the participation is influenced by specific peer pressure rather than by general drinking game involvement, which suggests that social media-related peer pressure may be a key factor in binge-drinking behaviours. Neknomination became famous few years ago but, as its popularity grew, its practice intensified and participants carried out the challenge in more extreme circumstances (e.g., using higher alcohol content drinks, performing riskier tasks during or after drinking alcohol). Barbieri et al. [13] also refer to a variant of Neknomination based on pouring alcohol into the toilet, followed by the immersion of the participant’s head, which beyond the risk of alcohol poisoning, also carries the threat of infection from microbial pathogens commonly present in human fluids and/or in suspended faecal matter [38, 39] . Neknomination appears to have been responsible of multiple fatalities, including deaths, leading to calls for social networking platforms to implement warnings aimed at deterring the activity in question. However, behavioural change is likely to occur only when participants find alternative activities that fulfil their needs and desires; to effectively support healthier behaviour in teenagers, adults must learn to address the current motivations and pressures influencing young people [35]. Table I (Annex) presents several empirical studies on current alcohol drinking patterns among young populations, including binge-drinking and other related practices.

Non-oral alcohol consumption and related practices
Non-oral alcohol consumption is becoming increasingly common among the young population, probably due to curiosity, fast onset of effects, experiencing a more intense intoxication, preventing vomiting or hangover symptoms, or avoiding both caloric intake or alcohol detection on the breath [3, 50, 51]. In addition, non-oral routes can be alternative forms of consumption for alcohol-dependent individuals who suffer from pathological conditions related to their digestive system. To date, the known routes of non-oral alcohol consumption are anal, vaginal, ocular, and pulmonary [51].
The alcohol enema, also known as butt-chugging, involves the introduction of an alcoholic drink into the rectum via the anus [52]. The most common ways to implement an alcohol enema are the insertion of a tampon soaked in alcohol, or a tube connected to a funnel (similar in mechanics to a beer bong). Although it may seem unusual, it is known that this practice was already carried out by ancient civilisations, who used rudimentary syringes to inject the fluid, commonly accompanying it with other psychoactive substances, thus achieving ecstatic states [53]. While alcohol ingested orally does not cause damage to the gastrointestinal tract, the colonic mucosa can be strongly compromised by this form of consumption, as demonstrated by several reports of serious damage, mainly chemical proctocolitis [54-57]. Besides, rectal administration of alcohol produces much faster and more powerful intoxication, since the substance penetrates directly into the bloodstream without being filtered [57]. This happens because the lower gastrointestinal tract lacks the enzyme alcohol dehydrogenase (ADH) present in the stomach and liver, which breaks down ethanol into acetaldehyde. Furthermore, consuming alcohol rectally does not dispose of the body’s ability to reject the toxin through vomiting. These facts demonstrate that consumption of alcohol through the rectum may constitute an elevated risk for health, including death [58, 59], so its potential harmful effects will depend ultimately on the amount of drink poured into the large intestine, on the reiteration over time of this practice, as well as on the type of drink used, since many of them differ in ethanol content, ingredients, forms of fermentation, and even whether the beverage is carbonated or not.
Vodka tampon, also known in Spain as “tampodka” or “tampax on the rocks”, involves the introduction into the vagina of tampons previously soaked in alcohol, which promotes rapid absorption, but can cause injuries and infections in the mucous membrane of the vagina [60], altering its host immunity and microbiota. This non-oral method of alcohol consumption is similar to that used through rectum. Therefore, the primary difference between them lies in the anatomical and physiological characteristics of both organs. In this respect, both the rectum and vagina have rich blood supplies, but the rectal mucosa has a more permeable and thinner epithelial layer compared to the vaginal mucosa, which can result in more rapid absorption of alcohol into the bloodstream [61]. Additionally, the rectal environment presents a higher pH compared to the vaginal mucosa (approximately 4.5), thus rectal mucosa has a pH closer to neutral, while vaginal mucosa has a more acidic pH [62]. Although pH difference can impact the solubility and absorption rate of various substances, the effect of pH on alcohol absorption specifically is less pronounced. Interestingly, a study found that tampons, when soaked in vodka, absorb only minimal amounts of ethanol, with the maximum absorption recorded at around 31 ml of vodka per tampon [63]. This suggests that, while absorption may occur, it is unlikely to result in severe intoxication if the tampons remain in their applicators, but experimentation with higher amounts could increase risks, particularly when non-applicator tampons are used.
Eyeballing, also known as “vodka eyeballing”, refers to the direct instillation of alcohol into one or both eyes [50]. Although this method has been mainly used to achieve a faster rate of intoxication, the amount of alcohol absorbed by the conjunctiva and the cornea is too small to intoxicate a person quickly [50]. In terms of health consequences, eyeballing include burning, pain, blurred vision, conjunctive injection, corneal ulcers, permanent vision damage, and even blindness [64]. In this sense, the ocular mucosa is sensitive to foreign substances, and alcohol possess dehydrating properties and irritant effects that can compromise the natural defences of the eyes and chemically burn the ocular tissues.
The pulmonary route of alcohol consumption includes inhalation, spraying, or vaporisation, for which there are different specific devices that facilitate these modes of administration [65]. For instance, in a method known as “alcohol without liquid”, a nebuliser is used to mix alcohol with oxygen to create a mist [66]. The use of these devices is restricted or prohibited in various defined jurisdictions within states worldwide; however, they are readily available online [60, 65]. The impact of inhaled alcohol on brain function might be more intense than suggested by blood alcohol content alone; analogous to nicotine, which shows higher arterial levels than venous concentrations, inhaled alcohol could exert particularly strong effects. However, despite potential differences in pharmacodynamics between oral and inhaled alcohol, both routes appear to similarly affect brain regions involved in addiction behaviours [66] . Table II (Annex) presents several empirical studies and case reports on non-oral alcohol consumption.

The pharmacological basis of alcohol action

Mechanisms of action in the brain
Alcohol alters neurotransmission in the brain, resulting in an imbalance between excitatory and inhibitory synaptic inputs and in a modification of the function of several neurotransmitters and modulators [69]. In addition, evidence points to the roles of the endogenous opioid and endocannabinoid systems as well as nicotinic cholinergic transmission in the mediation and modulation of alcohol reward and addiction [70, 71]. Alcohol constitutes a non-specific pharmacological agent, but several molecular pharmacology studies have demonstrated that it primarily targets only a few key receptors: N-methyl D-aspartate (NMDA), gamma-aminobutyric acid A (GABAA), glycine, 5-hydroxytryptamine-3 (5-HT₃) and neuronal nicotinic acetylcholine (nACh) receptors as well as L-type Ca²⁺ channels and G protein-activated inwardly rectifying K⁺ channels [72-74]. The initial impact of alcohol on specific brain targets results in disinhibition, psychotropic effects and sedation. Alcohol induces disinhibition primarily through the antagonistic effect on NMDA receptors, inhibiting NMDA-activated currents in a concentration-dependent manner. In addition, alcohol enhances GABAA receptor function by acting as an agonist, particularly on receptors containing δ subunits. The sedative and psychotropic effects of alcohol are primarily due to its agonistic effect on GABA_A receptors and antagonistic effect on NMDA receptors. Moreover, alcohol potentiates the function of glycine, 5-HT₃, and nACh receptors, contributing to sedation and altered neurotransmitter release. Beyond these direct actions, alcohol also induces indirect effects on multiple neurotransmitter and neuropeptide systems in the second phase. These include modulation of monoamines, opioids, and endocannabinoids, which further enhance the overall psychotropic effects of alcohol [75].
Like other drugs of abuse, ethanol triggers the release of dopamine (DA) in the nucleus accumbens (NAC) shell, which is thought to play a role in alcohol reinforcement. While various neurotransmitter and neuropeptide systems contribute to this neurochemical response, a significant mechanism involves the disinhibition of GABAergic neurons. Acute alcohol intake elevates extracellular DA in the NAC by altering GABAergic feedback to the ventral tegmental area (VTA) [73]. In addition, the dorsal raphe nucleus 5-HT system modulates DAergic activity in both the VTA and the NAC, primarily through the 5-HT₃ receptor. The direct action of ethanol on the 5-HT₃ receptor, together with its capacity to promote serotonin release, enhances DA release within the NAC. Thus, blocking 5-HT₃ receptors specifically inhibits this ethanol- induced DA release within the NAC [76].
Neuronal nACh receptors are key targets of ethanol influencing DA release. Systemic administration of the nACh receptor antagonist mecamylamine blocks ethanol’s DA-releasing effects. Besides, inhibiting nACh receptors within the VTA suppresses the activation of DA neurons by conditioned ethanol cues. This indicates that nACh receptor-mediated acetylcholine/DA interaction plays a pivotal role in conditioned alcohol reinforcement [77]. Furthermore, glycine receptors, another primary target of ethanol, influence the properties of dopaminergic neurons in the VTA, particularly A10 neurons [78], which are also involved in the reward system of the brain. In essence, systemic alcohol use affects a range of neurochemical pathways involving the NAC, the VTA, and their afferents, which provide various points of access to DAergic A10 neurons. Many of these access points then constitute primary targets of alcohol, with alcohol modulating several neurotransmitter and neuropeptide systems such as DA, GABA, and serotonin, which underlie the effects on reward, pleasure, euphoria, memory impairment, and relaxation. Additionally, the acti¬vity of these dopaminergic neurons is influenced by endocannabinoids and endogenous opioid systems, which further contribute to the reinforcing properties of alcohol [79]. />
Ethanol metabolism
A large fraction of ingested alcohol in the stomach (92-95%) is absorbed directly into the bloodstream and degraded by the enzymes ADH and aldehyde dehydrogenase (ALDH), expressed at higher levels in the liver but at lower levels in other tissues such as the stomach, brain, and intestines, leading to the production of acetaldehyde and acetate [80, 81]. The breakdown of alcohol to acetaldehyde by ADH involves the reduction of nicotinamide adenine dinucleotide (NAD⁺) to NADH, which decreases the NAD⁺/NADH ratio, thereby reducing the availability of mitochondrial glutathione (mGSH) and the cellular antioxidant reserve. Acetaldehyde can react with proteins and cell membranes, forming acetaldehyde-protein adducts that contribute to tissue injury [82]. The conversion of acetaldehyde to acetate by ALDH2, which is a specific isoenzyme of ALDH located in the mitochondria [81], further decreases the cellular NAD⁺/NADH ratio [83]. Furthermore, alcohol can also be metabolised by cytochrome P450, leading to the production of reactive oxygen species (ROS). In this respect, CYP2E1, primarily located in the liver, but also present in other tissues such as the stomach, lungs, and brain, metabolises ethanol to generate ROS, such as superoxide (O₂^–) and hydrogen peroxide (H₂O₂), contributing to oxidative stress and cellular damage, as well as to the formation of highly reactive hydroxyl radicals and carcinogenic DNA adducts [82, 84-86]. Similar to the liver, the brain expresses metabolic pathways involved in the elimination of xenobiotics, including ROS, free radical products, and electrophilic agents [85]. Therefore, alcohol, along with the generation of ROS and its metabolite acetaldehyde, collectively contribute to cell and tissue injury [87]. Chronic ethanol ingestion also increases CP450 expression in liver and in the mucosa of the oesophagus and colon. In all these tissues, the increased activity of CP450 enzymes correlates significantly with the levels of carcinogenic etheno-DNA adducts [82]. Figure 1 illustrates the process of alcohol metabolism.

Health consequences of alcohol consumption

Effects of alcohol on the digestive system
Alcohol plays a significant role in the development of gastroesophageal reflux disease by lowering the pressure of the lower oesophageal sphincter and impairing oesophageal motility [88]. Additionally, specific alcoholic beverages and their components, such as succinic and maleic acids, have been shown to elevate gastrin levels and stimulate acid secretion. While alcohol contributes to the progression of superficial and chronic atrophic gastritis, it has not been conclusively linked to the formation of peptic ulcers.
The consumption of alcohol has been associated with the development of various cancers, including those of the oropharynx, oesophagus, stomach, and colon. It also disrupts nutrient absorption in the small intestine and increases the translocation of toxins across the intestinal barrier, potentially exacerbating alcohol-induced damage to multiple internal organs [89]. Although ethanol itself lacks genotoxic, mutagenic, and carcinogenic properties, research suggests multiple carcinogenic pathways. These mechanisms include localised exposure to acetaldehyde, alcohol-induced inflammatory responses, induction of CYP2E1 enzymes, alterations in DNA methylation, impaired immune function, and nutritional deficiencies [90].
Hatta et al. [91] highlighted that the combination of alcohol consumption and tobacco smoking amplifies acetaldehyde production, particularly in individuals with inadequate oral hygiene. Furthermore, the chronic intake of alcohol stimulates CYP2E1 activity, which metabolises ethanol into acetaldehyde and may activate carcinogenic compounds derived from tobacco like nitrosamines. These synergistic effects of alcohol and tobacco smoking are strongly implicated in the pathogenesis of gastric cancer.
As alcohol metabolism primarily occurs in the liver, hepatocytes are the first vulnerable cells to alcohol-induced injuries, inducing steatosis that occasionally progress to alcoholic steatohepatitis, cirrhosis, or hepatocellular carcinoma, which depends on genetic, metabolic, and environmental risk factors [92]. In addition, oxidative stress affects diverse biological processes and synergises with the immunopathological effects of alcohol on the gut, decreasing mucosal barrier integrity and promoting bacterial dysbiosis [93, 94].
Effects of alcohol on the brain Acetaldehyde plays a key role in the effect of alcohol on the brain, since excessive alcohol consumption could generate enough acetaldehyde for different types of alkaloids to condense in the brain. Regarding the actions of alcohol on synaptic transmission, GABAA and NMDA receptors are the main receptors affected by this substance. Traditionally, moderate alcohol consumption has been considered harmless and even beneficial due to its potentially favourable effects on cardiovascular health. However, there is a negative correlation between alcohol use and brain structural health, as alcohol use can produce widespread reductions in grey and white matter volume, as well as cortical thickness [9, 95]. That is why alcohol intake, which usually begins during adolescence, affects the neurological development trajectories of young people, causing losses in brain density, as well as neuronal apoptosis. For this reason, some adolescents who abuse alcohol present a decrease in brain volume, deterioration in cognitive performance, and alterations in various brain regions [10, 11].
The alcohol-related brain damage encompasses structural and functional brain impairments resulting from chronic alcohol use, excluding better-defined neurological conditions associated with alcoholism. These conditions include hepatic encephalopathy, Wernicke encephalopathy (WE), Korsakoff syndrome (KS), Marchiafava-Bignami disease, and central pontine myelinolysis [96].
WE manifests in fewer than 30% of patients with symptoms such as ocular motor abnormalities (e.g., nystagmus or ophthalmoplegia) and cerebellar dysfunction. The latter may include loss of balance, gait incoordination, trunk ataxia, dysdiadochokinesia, and occasionally limb ataxia or dysarthria. In contrast, approximately 80% of individuals with WE present with mental state fluctuations, including lethargy, apathy, confusion, agitation, hallucinations, mimicking psychosis, or even coma [96]. KS constitutes a long-term sequela of WE that is predominantly characterised by severe global amnesia. In more advanced cases, cognitive and behavioural impairments may also arise [97].
Chronic and excessive ethanol consumption has been strongly associated with oxidative damage to neurons, ultimately leading to cell death. Ethanol contributes to oxidative stress through several mechanisms, such as (i) increased production of ROS, including hydroxyethyl radicals, (ii) upregulation of cytochrome P450 enzymes (e.g., CYP2E1), (iii) disruptions in cytokine signalling pathways, and (iv) elevated production of prostanoids [98]. Considering that many neurodegenerative diseases are linked to oxidative and inflammatory processes in the brain [99], it is plausible that prolonged ethanol exposure may accelerate the progression of these conditions.
Effects of alcohol on adipose tissue and the skeletal muscle Alcohol consumption also induces an inflammatory effect in adipose tissue, as well as alterations in adipocyte function, adipose redistribution, adipokine release, and dyslipidaemia [100]. The dysfunctions in adipocytes provoked by alcohol indicate a potential link between the intake and the risk of metabolic syndrome.
Another consequence of alcohol consumption is muscle fibre atrophy called skeletal-muscle myopathy [101]. Several studies have reported that both acute alcohol intoxication and prolonged alcohol consumption may cause (i) decreased basal muscle protein synthesis, (ii) attenuated or inhibited increase in muscle protein synthesis induced by hormones, nutrients and muscle contraction, and (iii) amplified decrease in muscle protein synthesis caused by catabolic stimuli [102].

Effects of alcohol on the cardiovascular system
The relationship between alcohol consumption and cardiovascular (CV) diseases, including hypertension, coronary artery disease, stroke, peripheral arterial disease, and cardiomyopathy, has been extensively studied. Nevertheless, this association is also influenced by a range of behavioural, genetic, and biological factors [103]. Evidence suggests that low-to-moderate alcohol intake may reduce the risk of certain CV diseases by modulating haemostatic mechanisms and mitigating the atherosclerotic and inflammatory processes underlying these conditions [104].
However, the potential benefits of moderate alcohol use must be balanced against its significant physiological and pathological impacts. These include mitochondrial dysfunction, alterations in circulation, inflammatory responses, oxidative stress, programmed cell death, and structural damage to the CV system, particularly the heart [103]. Chronic ethanol consumption exceeding 90-100 g/day, which is approximately 5 to 12 drinks/day if assumed that each standard drink contains between 8 and 20 g of ethanol [105], has been shown to cause direct cardiac damage, substantially increasing the risk of sudden cardiac death and cardiac arrhythmias [106].

Effects of alcohol on endocrine and immune system
Excessive alcohol consumption disrupts the communication between the nervous, endocrine, and immune systems, leading to physiological disturbances that affect multiple body mechanisms. Alcohol-induced hormonal dysregulation has been linked to a variety of disorders, including abnormalities in stress response, reproductive deficits, growth impairments, thyroid dysfunction, immune suppression, cancer development, bone diseases, and psychological or behavioural disorders [107].
The neuroendocrine and immune systems are closely interconnected, primarily through the hypothalamic-pituitary-adrenal (HPA) axis. This connection is evident in the immunosuppressive effects of glucocorticoids, particularly cortisol. Upon binding to its glucocorticoid receptor, cortisol can inhibit the activity of key transcription factors such as NF-κB and AP-1, thereby suppressing the transcription of numerous inflammatory molecules. Chronic alcohol abuse is frequently associated with elevated systemic inflammation, heightened levels of circulating pro-inflammatory cytokines, and persistently high cortisol levels [108].
Building on the aforementioned, acute alcohol consumption directly and indirectly activates the HPA axis, leading to elevated levels of glucocorticoids, with cortisol being the most prominent. The development of alcohol dependence involves periodic increases in blood cortisol levels (i.e., hypercortisolism), which occur as a consequence of repeated episodes of alcohol intoxication and withdrawal-related stress. This transition is associated with an allostatic shift in HPA axis regulation, resulting in diminished cortisol responsiveness [109]. Thus, in the context of alcohol dependence, the allostatic load (i.e., a hypothetical measure of cumulative stress) increases, driving the organism to excessive exposure to stress hormones, peptides, and pro-inflammatory cytokines [110].
Preclinical studies have demonstrated that developmental-stage ethanol exposure induces neurotoxic effects, leading to long-term impairments in both the stress regulatory axis and immune function [111]. In addition, pubertal alcohol consumption may also lead to lower testicular weight and to the development of smaller sexual organs [112]. This may be because alcohol consumption at an early age alters neuroendocrine functions, suppressing serum levels of growth hormone, luteinising hormone, testosterone and oestradiol. In this sense, it is known that alcohol acts within the hypothalamus, modifying genetic expression and corrupting the function of excitatory and inhibitory neurohormones, which are essential for the production of adequate levels of gonadoliberin [113].

Effects of alcohol on mental health
It is undeniable that alcohol consumption stands out for inhibiting certain states of consciousness, improving mood, calming stress, and reducing neurotic sensations and internal conflict. Precisely, the theory of tension reduction [114] proposes that alcohol is consumed as an alternative for dealing with stress. Stress can be defined as the internal sensation that arises when evaluating an event as threatening or potentially harmful. In relation to this, it could be postulated that alcohol prevents the initial perception of stressful information by inhibiting the activation of memories and anxiety-inducing concepts associated with it. This statement highlights the negative reinforcement so closely linked to the use of this substance. From a social learning perspective, drinking offers a way to cope with the demands of life that can become a bad habit if used in excess. The influence of alcohol on decision making is highly sensitive to social cues; its consumption is reinforced differently depending on the existing circumstances, so it seems to be governed by the same principles that regulate non-alcoholic behaviour: modelling, learning, reinforcement, expectations, and self-efficacy. Regarding the relationship between alcohol intake and stress reduction, research on individual differences aims to identify those subjects for whom alcohol is most likely to reduce stress, while research on situational factors focuses on determining the circumstances under which alcohol consumption is most effective in mitigating stress [115].
Despite the aforementioned, a significant body of evidence underscore the strong association between alcohol use and common mental disorders [116], particularly within the context of binge-drinking patterns [117]. The primary mental health conditions linked to alcohol consumption are anxiety and depression [118, 119]. Research has shown that college students with co-occurring anxiety and depressive symptoms exhibit higher weekly alcohol consumption, greater hazardous use, and more adverse alcohol-related consequences compared to peers without such symptoms [120]. Furthermore, binge-drinking has been associated with adverse mental health outcomes such as reduced life satisfaction and heightened psychological distress [121]. Recent findings by van Beuningen et al. [122] indicate gender-specific differences in the relationship between mental health and alcohol use. Among female students, a linear association was observed for anxiety, life satisfaction, and self-rated mental health, while depression, stress, and happiness followed a curvilinear model. Conversely, no such models were supported for male students.
Alcohol withdrawal syndrome (AWS) is a common health issue among individuals with alcohol use disorder (AUD). It is characterised by hyperactivity of the central and autonomic nervous systems [123]. The syndrome arises from multiple mechanisms and presents with diverse symptoms, including irritability, dysphoria, headaches, seizures, and tremors [124]. Anxiety and hostility have been identified as core psychiatric symptoms in AWS, serving as potential focal points for interventions to disrupt the self-perpetuating cycle of AUD. Impulsiveness is particularly prominent during withdrawal, and anxiety frequently co- occurs with other psychiatric symptoms.
Alcohol-related sleep disturbances are another prevalent concern. Alcohol interferes with sleep by altering electrophysiological sleep architecture, inducing insomnia, and disrupting circadian rhythms, often leading to shorter sleep durations. Moreover, it exacerbates breathing-related sleep disorders, such as snoring and oxygen desaturation, particularly in individuals with pre-existing conditions [125].
Existing research on alcohol use among adolescents has primarily focused on the negative personal and social outcomes that result from the ingestion of this substance. Excessive alcohol consumption can lead to a range of effects, including inhibition, agitation, depression, and impaired judgment. These effects can result in serious consequences such as acute health deterioration, unintentional injuries, vandalism, sexual violence, car accidents, physical assaults, and suicides [126-129].
Based on these outcomes, it is possible to affirm that excessive alcohol consumption constitutes, without a doubt, a widespread problem that endangers the mental health of users and the well-being of society. In addition to these serious consequences, alcohol is also a substance that has a high potential to create addiction, even though it is socially accepted and universally underestimated as a drug of abuse. As with other narcotic substances, the initial reward and pleasure in consumption are supplanted by negative states as the addiction progresses. In this way, the dynamics linked to alcoholism are characterised by calming abstinence and satisfying the desire to drink. According to this, cortisol levels in alcohol-dependent people are negatively correlated with cravings, so relapses may be due, in part, to the capacity of this substance to induce an increase in cortisol. This elevation could disrupt the balance of neuroendocrine stress regulation systems, which are crucial in managing addiction [130]. If this is the case, the aforementioned hormone may play an important role in the motivation to drink, leading to relapse through possible negative reinforcement.

Mechanisms underlying the impact of alcohol

The most frequently reported pathophysiological mechanisms regarding why alcohol causes injuries in organs and tissues are inflammation, increased oxidative stress, mitochondrial injury, epigenetic modifications, irregular post-translational protein modifications, disrupted anabolic signalling, increased catabolic activity, imbalances in lipid metabolism, and altered signal transduction pathways [131, 132].
As previously mentioned, alcohol induces metabolic imbalances in carbohydrates, lipids and proteins, either directly or through its metabolites, affecting the liver, adipose tissue, and skeletal muscle, or indirectly via immune dysregulation. Furthermore, alcohol consumption significantly reduces gluconeogenesis by impairing the hepatic use of alanine, glycerol, and lactic acid as gluconeogenic substrates [133], and also by decreasing the activity of glycolytic and gluconeogenic hepatic enzymes [134]. Table III (Annex) summarises several health parameters linked to alcohol consumption and its related pathophysiological mechanisms and key effects [83, 133, 135, 136].
Based on the physiological alterations outlined, alcohol use may lead to significant clinical consequences across various mechanisms. These include changes in body composition, such as increased insulin resistance, decreased leptin and glucagon like peptide-1, and alteration in sex steroid hormones, which contribute to obesity and loss of lean mass, as well as to increased lipolysis and fatty acid flux.
Alcohol also disrupts glycaemic control by inhibiting liver glycogenolysis and gluconeogenesis, impairing pancreatic function and increasing the risk of type 2 diabetes. Additionally, alcohol alters lipid metabolism, enhancing HDL cholesterol levels while disrupting the balance between lipogenesis and lipolysis, potentially leading to conditions like steatohepatitis. Furthermore, alcohol increases vasoconstriction, raising the risk of hypertension due to alterations in vasoconstrictor levels, including angiotensin II and norepinephrine.

Social implications of alcohol consumption

Alcohol consumption has had a significant impact on varying social cultures for thousands of years [137]. In cultures with infrequent but intense drinking, alcohol use is strongly linked to severe social consequences, while in those with regular but moderate drinking these social consequences are less pronounced [138]. Excessive alcohol consumption has been closely associated with several social issues, including divorce, domestic violence, road traffic accidents, personal relationship changes, and criminal conduct [139]. Notably, in the adolescent context, uncontrolled alcohol intake can also lead to aggressive and sexual behaviours, potentially resulting in sexual assault and/or unprotected sex [13, 14], which increases the risk of sexually transmitted infections [140], as well as the potential for unintended pregnancies, physical trauma, and emotional distress or other adverse psychological repercussions.
AUD are among one the most stigmatised medical conditions existing, and the social stigma associated with AUD reveals a clear lower probability for seeking both professional and informal support [141]. Additionally, the perception of dehumanisation, both by others and oneself, is linked to stigma in individuals with AUD, with stigma awareness increasing dehumanisation and environmental satisfaction reducing it [142]. Stigma is defined as a socially discredited characteristic linked to a specific condition, often associated with lower social status [143]. Substance use disorders (SUD) like AUD are complex conditions based on a drug or polydrug dependence that significantly influence brain function and behaviour, resulting in potential harmful consequences not only to those affected but also to the overall community [144]. The stigma associated with individuals experiencing SUD is a widespread issue that has negatively impacted treatment outcomes, healthcare professionals, therapeutic approaches, research initiatives, policies, and society [145]. Building on this understanding, the derogatory language used to characterise substance use behaviours and individuals with SUD can hinder progress in crucial areas such as employment, insurance policies, and legal frameworks for those striving to recover and contribute meaningfully to society [146, 147]. The relationship between stigma and SUD is complex, as stigma acts as a significant stressor that can lead to psychological responses such as depression and anxiety, which may drive individuals toward substance use as a coping mechanism [148]. In this respect, substance use can further perpetuate stigma, suggesting a reciprocal influence where stigma and SUD are closely linked and negatively influence each other. Yang et al. [144] highlighted four categories related to the stereotypes of individuals with SUD, including dangerousness and unpredictability, incapacity for autonomous decision-making, distrust in treatment effectiveness, and immorality. Furthermore, healthcare professionals commonly exhibit negative attitudes toward patients with SUD, perceiving them as violent, manipulative, and poorly motivated, which obstruct effective healthcare delivery and diminishes patients’ feelings of empowerment, compounded by inadequate education and support for working with this group, ultimately resulting in a more task-oriented approach that reduces personal engagement and empathy in care [149]. Moreover, a significant portion of health insurance costs has been attributed to AUD, which not only reflects the financial burden on healthcare systems, but also underscores societal consequences, including the direct strain on public resources and the indirect effects on communities [139].
Individuals who start drinking at an early age are exposed to a higher risk of developing AUD compared to those who start using this substance at later ages [3]. The consumption pattern in the nighttime economy is characterised by substance abuse by young people, with alcohol being the most consumed drug [4]. The fact that this trend is socially accepted and normalised blurs the potentially serious risks associated with alcohol intoxication, as the culture of drunkenness trivialises the consumption of alcohol, turning it into an inclusive, commendable, and even disciplined practice. These cultural patterns are increasingly global, which is why early age groups from all over the world indulge in consumption that, socially imposed, is consolidated as a habit and an almost ritual lifestyle [34]. Weekend outings to bars, pubs, and discos are presented as the main leisure activity linked to alcohol use among young population. In this respect, seasonality plays a relevant role in certain social contexts, since it determines the flow of people, the type of sociocultural events, as well as mobility. Summer parties, highly popular in hot countries like Spain, offer numerous opportunities for excess in different ways, sometimes resulting in fatal outcomes [150, 151], which suggests that recent trends among adolescents related to alcohol consumption can easily exceed reasonable limits.
Advancements in strengthening current policies and measures aimed at preventing alcohol use have been questioned, especially concerning their effectiveness and implementation [152, 153]. Alcohol marketing normalises consumption among youth and significantly influences drinking behaviours. Regulatory effectiveness is unclear due to measurement challenges, and industry self-regulation often fails. In Spain, despite legal restrictions, advertising strategies frequently evade enforcement, while relaxed regulations regarding controlling physical access to alcohol through licensing have increased its availability, leading to higher binge-drinking [153]. Community-based alcohol reduction programmes and public health interventions are both essential for addressing AUD in young people. Community efforts, supported by federal and private agencies, demonstrate various effective strategies for local action, while public health policies focus on increasing the identification and treatment of alcohol problems through rapid screening and brief interventions in healthcare settings. Integrating these approaches can enhance overall effectiveness in reducing alcohol-related issues [154]. Despite the expansion of treatment options, including both professional and mutual aid programmes, there is a need for improved accessibility, systematic screening, and better integration within healthcare services [153].

■ DISCUSSION

Alcohol misuse is a widespread social and health phenomenon that affects millions of people around the world. It is well known that excessive and/or persistent alcohol consumption can have significant negative consequences, not only for consumers, but also for their families and communities. In certain contexts, inadequate alcohol intake patterns generate high costs for healthcare systems, for public safety, and also for academic and work productivity. However, alcohol and other naturally derived substances seem to be inherent to all living beings and they do not have to be necessarily harmful if used appropriately. In fact, some epidemiological and clinical evidence seems to underline the protective role on health of the consumption of moderate amounts of alcohol and particularly wine. Wine is considered a drink with unique properties that combines a rich composition in terms of polyphenols and antioxidants. Certain studies suggest that low and moderate consumption of wine is beneficial against cardiovascular diseases, type 2 diabetes, certain neurological disorders, and bacterial pathogens like Helicobacter pylori [155]. Bioactive ingredients are not the only reason for the beneficial effects associated with wine consumption; social factors also have their relevance. The Mediterranean diet is a widely recognised healthy eating model and one of its characteristics is the consumption of wine during meals [156]. When consumed with meals, wine is typically drunk more slowly than other alcoholic beverages, potentially providing metabolic benefits. Besides, the concomitant presence of food in the stomach slows down the absorption of ethanol, which helps metabolism and hepatic clearance, reducing the maximum concentration of alcohol in the blood. Likewise, the combination of wine and food can reduce the amount of alcohol available to the oral microbiota, which has the capacity to metabolise ethanol to acetaldehyde, associated with the tumour effects of ethanol in the upper gastrointestinal tract [157]. In close relation to this issue, it is worth highlighting the implication that the gut microbiota could have in the processes related to AUD, especially the role that different types of treatment might play, such as those based on diet [158], psychobiotics [159], or on faecal microbiota transplantation (FMT) [160]. In this respect, vegetarian dietary patterns have been associated with lower alcohol consumption compared to non-vegetarians [161], while psychobiotics and FMT have been proposed as novel therapeutic tools for addressing AUD and acute liver injury, respectively [162, 163]. Nevertheless, addressing alcohol misuse among adolescents requires a more comprehensive approach that encompasses not only biological and medical intervention but also broader psychosocial measures. These should include educational programmes that focus on resilience and decision-making skills, community-based interventions that promote healthy social norms, and family support strategies aimed at reducing risk factors associated with alcohol use [164-167].
In the present review, a total of 139 scientific articles were examined. Regarding those addressing current trends in adolescent alcohol misuse, several prominent themes merit attention: (i) the role of social factors and peer influence in shaping alcohol consumption patterns, with celebrations, social media trends, and group dynamics as key predictors of higher alcohol consumption [16, 28, 40]; (ii) the gender differences observed in alcohol consumption patterns, with males tending to engage in riskier drinking practices [41, 42], which underscores the importance of considering gender-specific interventions when addressing alcohol misuse, as the factors influencing drinking behaviours may differ between males and females; (iii) the early exposure to alcohol through various media, particularly movies, seems to exert a significant influence on adolescent drinking behaviours [31, 32], suggesting that media portrayals can act as a powerful socialising agent, normalising alcohol use for young viewers; (iv) the detrimental effects of binge-drinking on academic performance, including missed classes, impaired cognitive function, and administrative issues within educational settings [43, 49]; (v) how individual and environmental factors influence the association between alcohol consumption and risk-taking behaviours, including interpersonal social dynamics [47], lack of awareness [44], and external stressors [46]; and (vi) the emergence of unconventional alcohol consumption methods, such as rectal enemas [52, 54, 57, 58], vaginal tampon use [60, 68], eyeballing [16, 50], and inhalation [65, 66, 68], which seem to be infrequent [51, 68] but present a range of significant health risks [57, 58, 64, 67].
Additionally, this review has also explored alcohol as a substance, addressing its pharmacological basis, health-related effects, underlying mechanisms, and social implications. In this respect, several key points emerge from this analysis: (i) alcohol exerts its sedative and psychotropic effects through a combination of both direct and indirect modulation of neurotransmitter and neuropeptide systems [72-75]; (ii) alcohol also modulates reward pathways that contribute to its reinforcing effects [76-79]; (iii) the metabolic products of alcohol produce oxidative stress, tissue damage, and carcinogenic DNA adduct formation [80-87]; (iv) alcohol consumption can potentially lead to multiple health consequences, including cancers [89], liver damage [90], brain impairments [96], inflammation in adipose tissue and skeletal muscle myopathy [100-102], cardiovascular issues [103, 106], and hormonal and immune system dysregulation [107, 108]; (v) alcohol use is linked to adverse mental conditions such as anxiety, depression, disrupted sleep, and impaired behaviour, with binge-drinking exacerbating symptoms and gender differences influencing this relationship [116-125]; (vi) alcohol consumption affects various physiological processes, including body composition, glycaemic control, lipid metabolism, and blood pressure, leading to clinical outcomes such as obesity, insulin resistance, dyslipidaemia, hypertension, and endothelial dysfunction [133-136]; (vii) early initiation of alcohol consumption is associated with a higher risk of developing AUD [3], a highly stigmatised condition that hinders individuals from seeking professional or informal support [141]; and (viii) while there are ongoing debates about the effectiveness and implementation of current alcohol use prevention policies and measures, the normalisation of alcohol consumption through marketing, the weak regulatory enforcement, and the failure of industry oversight continue to undermine these strategies, particularly among youth, highlighting the need for stricter controls, broader access to treatment, better integration of public health interventions, and stronger community-based programmes to address AUD more efficiently [152-154].
Despite providing an exhaustive examination of the effects of alcohol and its connection to adolescent misuse, this narrative review can present some potential limitations: (i) as a narrative review, the findings stem from a range of studies of varying types, including different designs and contexts, which may restrict their broader generalisability; (ii) most of the studies reviewed focus on specific populations, which may affect the applicability of the findings to other populations or cultures; (iii) the literature on alcohol-related mechanisms, effects, patterns, and implications is extensive and complex, which may have led to the potential oversimplification of certain aspects; (iv) while a significant number of articles were reviewed, the inclusion of additional studies employing different methodological approaches or theoretical perspectives could further enrich the analysis performed and provide a more comprehensive overview on the topic; and (v) given the descriptive nature of the review, it does not provide a critical evaluation of the quality of the studies cited, potential biases, or areas where the evidence is weak or controversial.

■ CONCLUSIONS

Alcohol is a highly toxic substance often socially overlooked, yet its risky intake, particularly among adolescents engaging in practices such as binge-drinking or non-oral consumption methods, poses significant concerns. The pathophysiological and pharmacological impacts of alcohol misuse underscore the critical need for heightened awareness and intervention. To effectively prevent these adverse outcomes, public policies should be developed from a public health perspective and grounded in scientific evidence, with a particular focus on young populations. Stricter control of media content, such as alcohol advertising on television, the internet, and at public events, is essential to mitigate the risks of adolescents imitating reckless behaviours. Furthermore, educating families and schools about the potential dangers of alcohol consumption is pivotal in the prevention of these harmful practices, while applying recent regulatory measures on other legal drugs like tobacco to alcohol could strengthen these efforts. Additionally, exploring and implementing psychological and microbial treatment strategies may significantly improve outcomes for adolescents with AUD. Public health campaigns and social intervention programmes aimed at raising awareness and providing support can also play a significant role in reducing alcohol-related risks among young people. It is worth emphasising that, while it is important for adolescents to have fun and socialise, they must do so responsibly to protect their future well-being and also the integrity and functionality of the community.

Conflict of interest/Konflikt interesów

None declared./Nie występuje.

Financial support/Finansowanie

None declared./Nie zadeklarowano.

Ethics/Etyka

The work described in this article has been carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki) on medical research involving human subjects, Uniform Requirements for manuscripts submitted to biomedical journals and the ethical principles defined in the Farmington Consensus of 1997.
Treści przedstawione w pracy są zgodne z zasadami Deklaracji Helsińskiej odnoszącymi się do badań z udziałem ludzi, ujednoliconymi wymaganiami dla czasopism biomedycznych oraz z zasadami etycznymi określonymi w Porozumieniu z Farmington w 1997 roku.

References/Piśmiennictwo