Substance abuse, particularly the use of cannabis and alcohol, poses significant health risks, yet its biochemical and hematological effects remain largely unexamined in Ghana. Alterations in hemoglobin levels, lipid metabolism, and liver enzyme activity can indicate serious health complications, making it crucial to understand the physiological consequences of substance use. This study sought to address this gap by examining the impact of cannabis and alcohol consumption on these biochemical markers among patients at Accra Psychiatric Hospital. The findings of this study demonstrate that alcohol and cannabis use, whether in isolation or combination, can influence several biochemical parameters relevant to hematological status, lipid metabolism, and liver function.

The predominance of males among all substance usage categories, particularly in the cannabis‐only and dual‐use groups, reflects patterns reported in both local and international studies. Previous epidemiological research in sub‐Saharan Africa, including Ghana, has consistently documented higher rates of alcohol and cannabis consumption among men compared to women, which is often attributed to socio‐cultural norms, gendered differences in risk‐taking behavior, and greater social tolerance of substance use among males [10, 11]. Age distribution indicated that cannabis use was particularly prevalent among younger adults (18–35 years), whereas alcohol‐only use was more common among older adults (36–59 years). This aligns with studies suggesting that cannabis initiation typically occurs during adolescence or early adulthood, possibly due to peer influence, perceived social acceptance, and the experimental phase of youth [12]. Interestingly, the majority of substance users did not perceive their consumption as detrimental to health. This is consistent with findings from behavioral health studies indicating that individuals often underestimate or discount the health risks of substances they consume, particularly when immediate adverse effects are not evident [13].

With regards to the duration and frequency, majority of cannabis‐only users reported use for less than 1 year, which may indicate recent initiation, potentially associated with increased availability or changing societal perceptions of cannabis and consistent with the findings of Chiu et al. [14]. In contrast, alcohol users, particularly in the older age bracket, demonstrated longer use durations, consistent with studies showing that alcohol consumption often develops into a chronic pattern over years [15, 16]. The predominance of occasional use among cannabis users compared to more evenly distributed usage patterns among alcohol users could reflect differences in the social context of consumption, psychoactive effects, and physiological tolerance development.

Our findings revealed significant increase in hemoglobin levels among dual users compared to non‐users and alcohol‐only users, which may be reflection of the combined effect of both substances, possibly mediated by cannabis‐induced erythropoietic stimulation alongside the absence of severe alcohol‐induced bone marrow suppression in this population, which is consistent with findings of Guzel et al. [17].

This study observed distinct alterations in lipid profile parameters among substance users compared to non‐users, with the patterns varying according to the type of substance used. TC levels were generally higher in alcohol‐consuming groups, particularly in dual users, compared to non‐users. LDL‐C followed a similar trend, with higher levels in alcohol users and particularly in dual users. Alcohol may impair LDL receptor function and increase apolipoprotein B‐containing lipoproteins, thereby elevating LDL‐C levels. This mechanism aligns with the observations of Yu et al. [18], who described increased LDL‐C in chronic alcohol consumers, and whose findings are consistent with this study. HDL‐C levels showed a different pattern. Alcohol‐only users demonstrated elevated HDL‐C compared to non‐users.

TG concentrations were higher in alcohol users, with the most marked elevations seen in dual users. Alcohol is known to promote hepatic TG synthesis while inhibiting their oxidation, leading to hypertriglyceridemia [19]. This occurs partly due to increased acetyl‐CoA availability from ethanol metabolism and partly due to reduced activity of lipoprotein lipase (LPL), the enzyme responsible for hydrolyzing TG‐rich lipoproteins. Chronic alcohol intake can therefore lead to an accumulation of VLDL in circulation, as has been reported elsewhere [20]. The elevated TGs in dual users suggest that cannabis may not counteract, and could potentially exacerbate, alcohol‐induced hypertriglyceridemia. This is supported by findings from Leishman et al. [21], which showed that combined substance use could lead to greater lipid perturbations than either substance alone. Cannabis‐only users in this study did not display significant TG elevations, which may indicate a relatively neutral effect on hepatic TG metabolism in the absence of alcohol.

AST levels were consistently higher in all substance user categories, with the most pronounced elevations observed in dual users. Similar to this study, Acierno et al. [22] and Teschke [23] have reported marked increase in AST associated with alcohol use. The increase observed among alcohol‐containing groups is biologically plausible, as chronic alcohol metabolism via alcohol dehydrogenase (ADH) and the microsomal ethanol oxidizing system (MEOS) generates acetaldehyde and reactive oxygen species (ROS), both of which promote oxidative stress, lipid peroxidation, and mitochondrial injury in hepatocytes [22]. This oxidative damage can increase mitochondrial membrane permeability, leading to the release of AST into the bloodstream. ALT levels did not show significant variation between groups and remained within reference ranges in most participants. ALT is generally considered more specific to hepatocellular injury than AST due to its higher cytosolic concentration in hepatocytes [24]. The relative stability of ALT despite increased AST in alcohol‐only users is consistent with the biochemical signature of early alcoholic liver injury, where mitochondrial damage predominates, producing an AST:ALT ratio greater than 2, as described in several studies [22, 25, 26]. GGT was significantly elevated among all substance users, with the highest mean levels in dual users of alcohol and cannabis. Elevated GGT in the absence of proportional increases in ALT and AST may occur in early or subclinical stages of alcoholic liver disease, which has been well documented in previous reports [26, 27] and is consistent with the findings of this study. Changes in bilirubin fractions were also observed, with both direct (conjugated) and indirect (unconjugated) bilirubin elevated in substance users compared to non‐users. Increases in indirect bilirubin may indicate either enhanced heme breakdown or impaired hepatic uptake and conjugation, whereas elevations in direct bilirubin suggest reduced excretion into bile, possibly due to early cholestatic changes or canalicular transport dysfunction. The findings of this study gain empirical support from the study of Nair et al. [28] and Yang [29] and also support the theory that alcohol can impair bilirubin conjugation by damaging the smooth endoplasmic reticulum. While cannabis smoke exposure has been associated with inflammatory changes in the biliary system in some experimental models. The particularly high values in dual users may indicate greater heme catabolism or impaired hepatic clearance, which could reflect combined hepatocellular and cholestatic effects of concurrent alcohol and cannabis use, which is in line with the findings of López‐Malo et al. [30].

This study has several limitations. First, the cross‐sectional design precludes causal inferences between substance use and observed biochemical changes. The sample was drawn exclusively from a single psychiatric hospital, which may limit generalizability to the wider Ghanaian population. Substance use history was based on self‐report, raising the possibility of recall bias or underreporting due to stigma. Although individuals with major metabolic disorders were excluded, other potential confounders such as diet, smoking, concurrent medications, and psychiatric comorbidities were not fully controlled. Finally, biochemical parameters were measured at a single time point, limiting the ability to capture longitudinal changes. These limitations suggest the need for larger, longitudinal studies incorporating detailed substance use assessments and additional biomarkers to better clarify the mechanisms underlying these associations.