Amphetamine and cannabis are frequently abused substances, and experimental evidence shows that cannabis use is associated with negative risks for non-medical amphetamine users²². The purpose of this cross-sectional study is to assess the effects of cannabis and amphetamines on various sociodemographic and biochemical characteristics in individuals who abuse, specifically in the Qassim region of Saudi Arabia, and may not be generalizable to other populations due to cultural, environmental, and genetic differences that can influence substance abuse patterns and health outcomes.

The sociodemographic variables of the 50 amphetamine plus cannabis abusers' participants in this study (Table 1). For age, it is noticed that the majority, about half (52%), were 18–30 years of age, fewer (36%) were 31–40 years of age, and only 12 percent were above the age of 41 years. Most of the abusers (56%) are in secondary school-level education; a few (14%) were in preparatory school, and a few (4%) were in elementary school, whereas 26 percent were college-educated. It may suggest that adolescents often experiment with drugs due to rapid physical and intellectual development, which can be influenced by life events and social group affiliations, leading to an experimental attitude and increased drug use risk^23–25.

A significant difference was observed in the employee ratio, where a considerable number of abusers are unemployed. Our findings are supported by a previous study²⁶ that revealed that people who were jobless and had the lowest degree of education were more likely to be heavy drinkers, smokers, and physically inactive. Other variables of the present study were whether the participants had other health issues, and the majority of the answers were no. Lastly, the number of years of abuse that constituted 50 percent were from 5 to 10 years, slightly less (32%) was less than 5 years, and just 18% were drug abusers for more than 10 years.

Chronic abuse of amphetamine can cause a decrease in RBC count and hemoglobin levels due to drug-induced stress on the body. In contrast, cannabis abuse has been shown to have minimal effects on blood indices. Some studies have reported slight decreases in RBC count and hemoglobin levels, but these changes are usually within the normal range and not clinically significant^4,5,20. Our results are consistent with these studies showing the possible negative consequences of drug misuse on immunity. As shown in Table 2, there were significant changes in different leukocyte blood types, including neutrophils (NE; p value = 0.001), lymphocytes (LYM; p value = 0.001), monocytes (MON; p value = 0.002), eosinophils (EO; p value = 0.001), and basophils (BASO; p value = 0.001). Additional research revealed that the immunosuppressive effects of drug compounds could not be directly attributable to the drugs' effects on immune cells but rather may be explained by the production of endogenous immunomodulatory chemicals such as cytokines, free radicals, etc.^{4–11,11–27}.

In addition, the microscopic view of blood film for patients who abuse the mixing drugs “Amphetamine and Cannabis”, shows segmented neutrophils with toxic change (Fig. 1B,C) have chromatin that is uneven and less condensed in the lobes, as well as a large number of large purple or dark blue cytoplasmic granules (primary granules) brought on by the retention of ribosomal RNA and cytoplasmic vacuolization. As opposed to their abnormal counterparts, normally matured segmented neutrophils in Fig. 1A (control) possess comparatively small nuclei, chromatin that is densely packed, and white cytoplasm with a majority of fine pink secondary granules. The exact cause of neutrophil toxicity is not fully understood, but several theories include direct toxic effects on bone marrow cells, activation of the immune system, and abnormal maturation of neutrophils. These effects can lead to nuclear granulation, which is not exclusive to cannabis and amphetamine abuse but can also occur in other conditions like infections and autoimmune diseases. Cytokines, primarily correlated with C-reactive protein, can cause toxic changes in neutrophils. Furthermore, it may be suggested that it is due to oxidative stress, which is characterized by the release of excess free radicals, reactive oxygen species, and cytokines and can lead to neutrophil cell destruction, causing cytotoxicity^28,29.

Amphetamine abuse has been associated with liver damage, primarily due to the increased release of stress hormones and oxidative stress caused by the drug. Prolonged amphetamine abuse can lead to hepatotoxicity, characterized by elevated liver enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Cannabis abuse, on the other hand, has shown conflicting results in terms of its effects on the liver profile. Some studies suggest a minor increase in liver enzymes, such as ALT and AST, in cannabis users. However, these changes are typically mild and not associated with severe liver damage³⁰. Our results suggest no significant difference was observed in AST-GOT, ALT-GPT, and alkaline phosphatase levels, as depicted in Table 3, further validating the previously reported results³⁰.

Amphetamine abuse has been linked to kidney damage, largely due to its vasoconstrictive effects and increased release of stress hormones. Long-term abuse of amphetamines can lead to renal impairment, characterized by elevated serum creatinine levels and a decreased glomerular filtration rate (GFR). In contrast, cannabis abuse has shown a limited impact on the kidney profile. Studies have been inconclusive, with some reporting a potential association between long-term cannabis use and mild kidney dysfunction, while others have found no significant effects³¹. Further validate our finding that neither creatinine nor blood urea nitrogen (BUN) levels were significantly affected among abusers (Table 3).

It is alarming to see that, in a fungus culture test using sputum samples from amphetamine and cannabis users, the majority of the samples (35 cultures) showed positive growth while just 15 cultures showed negative growth. Additionally, a few of the positive colonies are later stained with “Crystal Violet” and put under a microscope for inspection. A single or group of oval-shaped cells with budding features is seen in Fig. 2d; this is an example of a unicellular fungus that may suggest that due to the suppressed immunity, observed with blood results in opportunistic pathogens like yeast and mold inhabiting the upper respiratory tract of these chronic immunocompromised patients of drug abuse. However, further studies should be performed to identify the specific type. Our finding further validates the concept of "fungal priority pathogens", published by WHO recently (2022) which includes 19 groups of fungal pathogens that cause high-risk morbidity and mortality and aims to direct research to increase public health measures against invasive fungal diseases (IFDs)²¹.

The research aims to improve drug abuse research, diagnostics, treatment, and public health. It highlights that chronic amphetamine abuse has more severe effects on blood indices, liver profile, and kidney profile than cannabis abuse. However, individual variations in drug abuse patterns and susceptibility may influence these effects.