To date, many medications, such as antimicrobials, antihypertensives, antidepressants, antipsychotics, antineoplastics, agents in cigarette smoke, and ethanol use, have been associated with chemosensory disturbances [31,32]. The potential olfactory dysfunction mechanisms based on these substances may be due to olfactory epithelium damage or central nervous system damage. Based on clinical experiences, this study initially hypothesised that illicit drug use might be associated with smell and taste function changes. However, we observed no association between participants with smell or taste dysfunction and cannabis or illicit drug use history. Notably, the association did not remain statistically significant after adjustments for confounders, including age, race, gender, or other physical comorbidities in males, females, and participants with different age groups.

Previous studies have investigated the relationship between substance use and smell/taste function. However, most current research only examined the impact of smoking and alcohol on taste or smell functions. Therefore, potential impacts on olfactory function have remained controversial. For instance, a study enrolled 48 drug addicts between the ages of 16 and 48. Although 52.1% of the participants showed disturbances in olfactory performance, 16.7% were diagnosed with ageusia. Additionally, olfactory problems were detected in those who took drugs intravenously and smoked or inhaled drugs [33]. Another study enrolled 21 smokers and 59 non-smokers. Although their results showed smaller olfactory bulb volumes in smokers than in non-smokers, no difference in olfactory function between the two groups was observed [18]. Moreover, though Schriever et al. suggested that smoking negatively affects the olfactory system before it becomes obvious in decreased olfactory function, Vennemann et al. noted that heavy smokers (20 or more cigarettes per day) had an increased risk for impairments in smell and taste senses [19]. Therefore, since the temporal lobe mediates olfactory processing, and a correlation between general olfactory function and olfactory bulb volumes has been proposed, factors that affect the optimal function of this system could result in issues [9].

Our study focused on the relationship between cannabis, illicit drug use, and smell or taste function changes. Some prior studies have also investigated the relevant issue of cannabis. As reported, cannabinoids are involved in the neuromodulatory regulation of the sensory systems [34,35]. The active ingredient of cannabis, delta-9-tetrahydrocannabinol (THC), has also been reported to palliate symptoms in cancer patients [36,37,38]. Furthermore, it stimulates the orosensory reward pathway and enhances food enjoyment. Although cannabinoid type-1 receptors are located in different brain olfactory areas, including the olfactory epithelium and bulb [39,40], cannabinoid receptor agonists increase the hedonic reactions to sweet taste and reduce the aversive responses to quinine [24,35,36,41]. However, participants in that research were cancer patients who were explicitly administered THC. Case reports from students with an experience of marijuana intoxication also reported more vivid taste sensations and a richer sense of smell when intoxicated [42]. Similarly, a recent study showed that cannabidiol (CBD) protects against the psychoactive effects of THC [43]. Moreover, Woelfl et al. conducted a randomised controlled trial, which showed that CBD intake did not affect healthy volunteers, and a single dose of CBD before taking THC administration was insufficient to mitigate the impact of THC [44]. Nevertheless, cannabis contains over 400 chemical entities, with the ratios of each compound in recreational cannabis making it challenging to investigate the effect of drug users in real-world situations [45,46]. Our study did not notice a change in the smell or taste of individuals who ever used cannabis.

Additionally, our study did not find correlations between illicit drug use and dysfunction of taste or smell. Some previous research also investigated relevant issues. For instance, cocaine is usually administered illegally from the nasal route, and abusers often complain of decreased olfaction. Clinical pathology that contributes to reduced olfaction includes immune-mediated diseases and even nasal defects that require surgical reconstruction [47,48]. However, no olfactory or gustatory function tests were conducted on those users. Roebber et al. suggested that cocaine exposure did not change the taste sensitivity of animal models of mice [28]. Another study by Gordon et al. reported from three olfaction tests that most cocaine abusers did not develop permanent olfactory dysfunction [49]. Beidler and Smallman also proposed that nerves innervating the taste buds could regenerate after abrasion, making the taste buds retain function [50]. Therefore, there might be a restoration of chemosensory perception after quitting illicit drug use. Nevertheless, exploring the underlying mechanisms of individuals after using illicit drugs is needed.

Furthermore, Perl et al. noticed that heroin addicts estimated sweet tastes and savoury smells as more pleasant, and bitter, sour or putrid tastes and odours were considered less unpleasant by them than detoxified former addicts and healthy controls [26]. A randomised controlled trial with a small sample size measured sweet and salt taste perceptions of heroin users, recently detoxified subjects, and healthy volunteers. The results showed that heroin users and recently detoxified subjects had significantly greater measures of taste perception, and even this effect could be reversed by opiate antagonists [27]. These results suggest that heroin addicts might have altered taste and odour hedonic brain mechanisms. Findings in previous literature were similar to the trends found in our study. We observed that individuals with and without smell dysfunction included 2.4% and 3.2% of heroin users, respectively. Even though the relationship did not reach statistical significance, heroin users were more sensitive to odours. With amphetamine, a scarce study investigated the association between smell or taste dysfunction and amphetamine use.

This study had some unique strengths. First, it included a large-scale sample size from a population with a history of illicit drug use and relatively accurate examination results on smell and taste function. Second, we used both self-reported questionnaires and examinations (including an 8-item odour identification test and 1-mM quinine whole-mouth taste identification test) to identify the smell and taste dysfunctions, eliminating recall bias from respondents. Finally, this study investigated the relationships between smell/taste dysfunction and illicit drugs, including cannabis or hashish, cocaine, heroin, and methamphetamine. Moreover, based on our extensive literature search, this research is the first to comprehensively study the relationship between different illicit drugs and smell/taste dysfunction. Notwithstanding, several limitations were encountered in this study. First, we could not explore the causal relationships because of the cross-sectional nature of this study. Second, this study did not consider certain medications that may affect smell and taste because the database lacked detailed information.