Determining the Toxic Elements in Cannabinoid and Opioid Drugs and Their Impact on Addicts' Health

doi:10.21203/rs.3.rs-3565706/v1

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Determining the Toxic Elements in Cannabinoid and Opioid Drugs and Their Impact on Addicts' Health

https://doi.org/10.21203/rs.3.rs-3565706/v1

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Drug addiction is associated with significant health risks, including cardiovascular complications, cancer, and mental disorders. Illicit drugs, such as cannabinoids and opioids, including prescription medications, are widely consumed and have profound health consequences. Understanding the health effects of the toxic elements in these substances is critical for overdose prevention and effective recovery strategies. This study aimed to determine the toxic elements, including arsenic (As), cadmium (Cd), mercury (Hg), and nickel (Ni), in cannabinoid and opioid drugs and in biological samples (blood, scalp hair, and serum) from 311 male drug abuse patients aged 15 to 60 years with a history of drug abuse. The participants were categorized into three age groups. The comparative analysis involved 113 reference subjects of the same age groups. The sample preparation employed microwave-assisted acid digestion, and the toxic elements were quantified using atomic absorption spectrophotometry. Accuracy was ensured using certified reference materials for hair, blood, and serum. Drug-addicted subjects had significantly higher concentrations of toxic elements (arsenic, cadmium, mercury, and nickel) in biological samples than referent subjects (p > 0.001). Elevated levels of these toxic elements may increase susceptibility to infections, possibly due to malnutrition, drug-related effects, and additional contaminants. These findings necessitate further studies to explore the long-term health outcomes, potential treatment options, and broader socioeconomic impacts of substance abuse. This study serves as a baseline for future research in this critical public health field.

Arsenic

Cadmium

Mercury

Nickel

Drug Abusers

Male

The global medical landscape has consistently grappled with the challenges posed by the misuse of cannabinoids and opioids. These compounds, historically recognized for their therapeutic potential, have become a double-edged sword in modern medicine. On the one hand, they offer relief from chronic pain, anxiety, and other ailments. However, their misuse has led to a myriad of health complications, some of which are only beginning to be understood (Birnbaum et al. 2011). Recent advancements in analytical chemistry have enabled researchers to delve more deeply into the compositions of these drugs. A concerning revelation from these studies is the contamination of cannabinoids and opioids with toxic elements, notably heavy metals such as lead, cadmium, and mercury (Hasin et al. 2015). The sources of these contaminants are diverse. They can be introduced during the cultivation phase, when plants absorb heavy metals from polluted soils, or during the processing and synthesis stages, particularly in clandestine laboratories with subpar safety and purity standards (Neumark et al. 2002; Winters & Lee 2008). The clinical implications of the ingestion or inhalation of these toxic elements are profound. For instance, chronic exposure to lead has been linked to neurotoxicity, manifesting as cognitive impairments and behavioral anomalies (Griffin & McMahon 2020). Cd, another common contaminant, can lead to renal dysfunction and bone demineralization (Bariola et al. 2011). These health risks are further compounded by the pharmacological effects of the drugs themselves. For addicts, this presents a dual threat: the inherent risks of the drug and the added dangers of contaminants (Williams et al. 2020). However, when negative emotions are not properly balanced, this sensitive and precise mechanism may occasionally become dysfunctional (Grandey & Melloy, 2017). Maladaptive behaviors may result from this imbalance, especially during puberty, when emotional states should be carefully controlled (Flouri & Mavroveli, 2013). Given the widespread prevalence of cannabinoid and opioid consumption for both medical and recreational purposes, understanding the extent and implications of this contamination is paramount. It is not just a matter of drug safety, but also a broader public health concern. With millions of individuals consuming these drugs, even trace amounts of contaminants can translate into significant health burdens at the population level (Tamir & Gutentag 2017). Therefore, this study is positioned at this critical juncture. Utilizing the precision of electrothermal atomic absorption spectrometry (ETAAS), we aimed to provide a comprehensive estimation of toxic elements in various samples of cannabinoids and opioids. Beyond mere quantification, we seek to understand the potential health ramifications of addicts. How do these contaminants interact with the active compounds of drugs? What are the long-term health trajectories of individuals exposed to these contaminants? How can this knowledge inform clinical interventions and public health policies?

In conclusion, the objective of this study was not merely academic. It is a pursuit to enhance the safety profiles of commonly used drugs and safeguard the health of millions. By bridging the existing knowledge gaps, we aspire to contribute valuable insights to medical discourse, ultimately driving evidence-based interventions in the realms of drug safety and public health.

2.1. Ethical Considerations and Recruitment

This study was approved by the National Centre of Excellence in Analytical Chemistry (NCEAC) and the University of Sindh (Approval: NCEAC/1476/2018; Registration: DRGS/1265/2018) and adhered to the Declaration of Helsinki. All participants provided written informed consent, and confidentiality was ensured through unique identification codes and secure data storage.

2.2. Apparatus, Reagents and Glassware

The apparatus used in this study was closely based on the methods explained in the work of (Nizamani et al. 2019; Oan Muhammad Sahito & Rahoojo 2022). Specifically, we used a Milestone microwave oven (model Rotar MPR-300/12S) with a pressure tolerance of up to 35 bar and temperature capacity of 300°C. The analytical measurements were carried out using a Hitachi model 180 − 50 (Tokyo) equipped with a graphite furnace GA-3, flame burner, and deuterium lamp background corrector, in strict compliance with the operating parameters recommended by the manufacturer. Data collection was facilitated by a Hitachi recorder, model 056, with a 5-mV range. In particular, the critical instrument parameters, including those relevant to the analysis of As, Cd, Hg, and Ni, are comprehensively cataloged in Supplementary Table S1. Signal acquisition in the flame absorption mode required precise measurement of the absorption peak heights. Sample preparation and digestion were carefully carried out in a Pel household microwave oven (model PMO23) with a heating power of 900 W, and the solutions were carefully stored in acid-washed polytetrafluoroethylene (PTFE) jars/bottles. Concurrent analysis included parallel runs of blank reagents and working standards, with adjustments made as necessary. For a comprehensive presentation of instrumental conditions and methodological subtleties, we provide detailed data in Supplementary Table S1. In addition, for a holistic understanding of the methods used, we discussed (Nizamani et al. 2019; Oan Muhammad Sahito & Rahoojo 2022) in our previous study.

2.3. Study design and pretreatment

Initially, we aimed to collect biological samples from over 500 individuals who visited a psychiatric hospital multiple times per week. Of the 521 samples collected, 210 individuals had used multiple drugs and were thus excluded. Ultimately, the study included 311 drug-addicted individuals aged 15–60 years. The procedures for sample collection followed those previously described (Nizamani et al. 2019; Oan Muhammad Sahito & Rahoojo 2022). Demographic data for referent subjects and drug abuser patients are presented in Supplementary Table S2, whereas Supplementary Table S3 contains pathological and biochemical information for referent subjects and various categories of drug abusers.

2.4. Biological Sample Collection and Processing for Trace Element Analysis in Drug Patients and Controls

In this study, blood samples were carefully collected using aseptic techniques from two different groups: subjects with a documented history of drug use and control participants. To ensure the integrity of the trace elements important for our study, we used special trace-element-specific tubes for blood collection. After a 12-hour overnight fast, 5 ml of venous blood was collected from each participant. At the same time, hair samples (1.00.5 g) were carefully collected from the nape of the neck using sterilized stainless-steel scissors and then stored in metal-free containers. Hair segments measuring 0.5 to 2.0 cm collected near the scalp were subjected to thorough cleaning with double distilled water before being placed in individual plastic bags labeled with subject information. Strict adherence to the established protocols described in our previous publications (Chanihoon et al. 2022a; Chanihoon et al. 2022b; Li et al. 2023; Ning et al. 2023; Nizamani et al. 2019; Oan Muhammad Sahito & Rahoojo 2022), ensured optimal clotting times, and maintained the reliability of our collected data.

2.5. Microwave-assisted Acid Digestion Method

Duplicate samples were prepared along with six replicates of standard blood and serum references. Each flask contained 200 mg of scalp hair and certified reference material, along with 0.2 ml of blood and serum. These flasks were treated with HNO₃–H₂O₂ solution to facilitate digestion. After cooling, the contents were diluted to a final volume of 10.0 mL. The same procedure was followed for the blank solution. Subsequently, an electrothermal atomic absorption spectrophotometer (ETAAS) was employed to determine the concentrations of As, Cd, Hg, and Ni in all samples. The detailed procedure for the digestion of biological samples has been described in our previous study (Nizamani et al. 2019; Oan Muhammad Sahito & Rahoojo 2022).

2.6. Statistical Analysis and Analytical Figures of Merit

Statistical analysis was carried out using Excel XL Stat and Minitab 13.2. Elemental concentrations were evaluated using two-way ANOVA. We discussed the analytical parameters, calibration curves for As, Cd, Hg, and Ni, and detection limits (LOD and LOQ) in our previous publication (Nizamani et al. 2019; Oan Muhammad Sahito & Rahoojo 2022). The validation of our method for analyzing biological samples, which included the use of certified reference samples (Supplementary Table S4), revealed no significant differences between the certified and test values (p > 0.05).

3.1. Toxic Elements in Drug Abusers

The concentrations of the four toxic elements in different types of cannabinoid (Marijuana and Hashish) and opioid (Opium and Heroin) samples are shown in Table 1. The highest level of mercury contamination was observed in the Opioid (Opium and Heroin) samples with a 95% confidence interval (C.I.) (18.4–19.7 µg/g), and (17.8–19.9 µg/g) the lowest level was in Cannabinoid (Marijuana and Hashish) samples (95% C.I. 15.3–17.8, 16.3–18.4) µg/g}. The Cd concentration in opioid (Opium and Heroin) samples was observed at 95% C.I.. (0.56–0.72 µg/g), and (0.52–0.64 µg/g)}, while in cannabinoid (Marijuana and Hashish) samples, Cd contents were found to be (95% C.I. 15.3–17.8, 16.3–18.4) µg/g}.

Table 1

Concentrations of Toxic Elements in Different Types of Abused Drugs
Drugs	Types of Drugs	Mercury	Cadmium	Nickel	Arsenic
Cannabinoid	Marijuana	16.5 ± 2.50 14.5–18.3	0.65 ± 0.17 0.58–0.70	10.5 ± 1.52 9.72–11.3	2.75 ± 0.35 2.58–2.95
Cannabinoid	Hashish	17.3 ± 1.96 15.8–19.3	0.57 ± 0.13 0.51–0.64	9.66 ± 0.96 9.10–10.2	3.09 ± 0.29 2.95–3.34
Opioid	Opium	19.5 ± 1.15 19.0–20.3	0.62 ± 0.15 0.55–0.68	9.97 ± 0.79 9.42–10.4	3.39 ± 0.51 3.12–3.67
Opioid	Heroin	18.9 ± 2.03 17.8–20.0	0.79 ± 0.20 0.67–0.88	10.3 ± 0.85 9.87–10.8	3.25 ± 0.45 3.02–3.49

The Cd concentration in opioid (Opium and Heroin) samples was observed at 95% C.I.. (0.56–0.72 µg/g), and (0.52–0.64 µg/g)}, while in cannabinoid (Marijuana and Hashish) samples, Cd contents were found to be (95% C.I. 15.3–17.8, 16.3–18.4) µg/g}. The Ni contents in the opioid (Opium and Heroin) samples were observed at 95% C.I.. (9.82–11.3 µg/g), and (9.12–10.2 µg/g)}, while in cannabinoid (Marijuana and Hashish) samples, Ni contents were found to be (95% C.I. 9.55–10.4, 9.8–10.8) µg/g}. The As contents in opioid (opium and heroin) samples were observed at 95% C.I.. (2.57–2.95 µg/g), and (2.80–3.24 µg/g)}, while in cannabinoid (marijuana and hashish) samples, the contents were found to be (95% C.I. 3.15–3.65, 3.06 ± 3.52) µg/g}.

3.2. Comparative Clinical and Biochemical Profiles of Diverse Drug Abusers

When examining the clinical and biochemical parameters of drug-addicted patients in comparison to healthy subjects across different age groups, no significant disparities were identified ( Supplementary Table S3). However, many drug-addicted patients had reduced WBCs, platelet, RBCs, and Hb% counts. Conversely, levels of Hct, fasting plasma glucose, malondialdehyde (MDA), whole blood HbA1c, serum LDL cholesterol, serum HDL cholesterol, immunoglobulin G, immunoglobulin M, and immunoglobulin A were elevated in comparison to the reference subjects across the age groups.

3.3. Toxic Elemental Analysis in Biological Samples of Individuals with Different Types of Drug Abuse

As discussed in Table 2, we thoroughly examined the concentrations of toxic elements: arsenic (As), cadmium (Cd), mercury (Hg), and nickel (Ni). These concentrations were assessed in serum, blood, and scalp hair samples obtained from male individuals with drug addiction. These individuals were categorized into three age groups:15–30, 31–45, and 46–60 years. The outcomes underscored notable elevations in toxic element concentrations among those with drug addiction compared to reference subjects (Supplementary File 1). To delve into specifics, the arsenic concentrations in blood, serum, and scalp hair samples of the reference subjects within the age groups demonstrated values falling within the ranges of [Confidence Interval (CI): (0.48–0.53), (0.69–0.77), (0.88–0.95)] µg/g, [(0.69–0.83), (0.83–1.04), (1.04–1.24)] µg/l, and [(0.21–0.23), (0.25–0.29), (0.29–0.34)] µg/l, respectively. Importantly, these concentrations were significantly elevated in individuals with drug addiction, a finding visually depicted in Fig. 1.

Table 2

Concentrations of Toxic Elements in Biological Samples of Control Subjects and Cannabinoid Abusers
Age Groups	Referent		Cannabinoid Abusers		Opioid Abusers
Age Groups	Referent		Marijuana Abusers	Hashish	Heroine Abusers	Opium Abusers
Scalp Hair
Mercury (ug/g)
15–30		0.75 ± 0.08	2.09 ± 0.36	1.99 ± 0.18	2.35 ± 0.30	2.25 ± 0.29
p- value			0.001		0.001
31–45		1.05 ± 0.05	2.26 ± 0.29	2.19 ± 0.20	2.54 ± 0.22	2.49 ± 0.36
p- value			0.001		0.001
46–60		1.24 ± 0.07	2.53 ± 0.23	2.37 ± 0.32	2.72 ± 0.35	2.62 ± 0.24
p- value			0.001		0.001
Cadmium (ug/g)
15–30		1.17 ± 0.15	4.05 ± 0.27	3.90 ± 0.17	4.47 ± 0.20	5.29 ± 0.32
p- value			0.001		0.001
31–45		1.35 ± 0.19	4.68 ± 0.30	4.52 ± 0.30	4.35 ± 0.27	5.62 ± 0.40
p- value			0.001		0.001
46–60		1.57 ± 0.21	4.97 ± 0.24	5.27 ± 0.34	5.12 ± 0.45	5.87 ± 0.51
p- value			0.001		0.001
Nickel (ug/g)
15–30		1.69 ± 0.18	3.29 ± 0.40	3.53 ± 0.31	3.78 ± 0.61	3.68 ± 0.39
p- value			0.001		0.001
31–45		2.32 ± 0.29	5.17 ± 0.35	5.39 ± 0.20	5.62 ± 0.56	5.76 ± 0.70
p- value			0.001		0.001
46–60		3.59 ± 0.44	6.82 ± 0.54	6.90 ± 0.57	7.30 ± 0.75	7.59 ± 0.60
p- value			0.001		0.001
Arsenic (ug/g)
15–30		0.51 ± 0.05	1.25 ± 0.09	1.12 ± 0.19	1.59 ± 0.24	1.41 ± 0.19
p- value			0.001		0.001
31–45		0.73 ± 0.07	1.59 ± 0.11	1.47 ± 0.12	2.09 ± 0.31	1.75 ± 0.22
p- value			0.001		0.001
46–60		0.92 ± 0.06	1.72 ± 0.13	1.78 ± 0.15	2.51 ± 0.45	2.18 ± 0.28
p- value			0.001		0.001
Serum
Mercury (ug/L)
15–30		1.12 ± 0.17	2.35 ± 0.20	2.48 ± 0.25	2.89 ± 0.36	3.07 ± 0.25
p- value			0.001		0.001
31–45		1.25 ± 0.14	2.59 ± 0.14	2.73 ± 0.34	3.10 ± 0.29	3.29 ± 0.33
p- value			0.001		0.001
46–60		1.32 ± 0.12	2.85 ± 0.12	2.98 ± 0.39	3.45 ± 0.45	3.65 ± 0.45
p- value			0.001		0.001
Cadmium (ug/L)
15–30		1.25 ± 0.31	2.60 ± 0.38	2.79 ± 0.35	2.96 ± 0.45	3.34 ± 0.51
p- value			0.001		0.001
31–45		1.39 ± 0.23	2.93 ± 0.26	3.07 ± 0.23	3.34 ± 0.30	3.56 ± 0.47
p- value			0.001		0.001
46–60		1.47 ± 0.15	3.16 ± 0.35	3.27 ± 0.35	3.64 ± 0.48	3.74 ± 0.62
p- value			0.001		0.001
Nickel (ug/L)
15–30		1.19 ± 0.23	1.95 ± 0.20	2.14 ± 0.32	2.30 ± 0.19	2.53 ± 0.30
p- value			0.001		0.001
31–45		1.26 ± 0.42	2.29 ± 0.23	2.43 ± 0.40	2.58 ± 0.28	2.85 ± 0.44
p- value			0.001		0.001
46–60		1.43 ± 0.35	2.42 ± 0.35	2.55 ± 0.28	2.72 ± 0.45	3.18 ± 0.29
p- value			0.001		0.001
Arsenic (ug/L)
15–30		0.22 ± 0.02	0.53 ± 0.05	0.68 ± 0.09	0.92 ± 0.15	1.27 ± 0.19
p- value			0.001		0.001
31–45		0.27 ± 0.03	0.70 ± 0.07	0.85 ± 0.12	1.25 ± 0.25	1.55 ± 0.31
p- value			0.001		0.001
46–60		0.31 ± 0.03	0.89 ± 0.12	1.23 ± 0.19	1.47 ± 0.30	1.83 ± 0.45
p- value			0.001		0.001
Blood
Mercury (ug/L)
15–30		0.69 ± 0.05	1.35 ± 0.17	1.42 ± 0.14	1.69 ± 0.20	1.55 ± 0.33
p- value			0.001		0.001
31–45		0.82 ± 0.07	1.99 ± 0.29	2.05 ± 0.19	2.15 ± 0.34	2.12 ± 0.29
p- value			0.001		0.001
46–60		0.95 ± 0.08	2.43 ± 0.25	2.53 ± 0.33	2.95 ± 0.39	2.73 ± 0.27
p- value			0.001		0.001
Cadmium (ug/L)
15–30		4.15 ± 0.29	12.3 ± 2.50	11.8 ± 1.55	10.5 ± 2.98	12.7 ± 3.52
p- value			0.001		0.001
31–45		4.49 ± 0.30	13.6 ± 2.95	13.6 ± 2.25	12.9 ± 1.85	14.7 ± 2.75
p- value			0.001		0.001
46–60		4.78 ± 0.45	14.9 ± 3.45	15.2 ± 3.62	15.5 ± 3.06	16.5 ± 3.95
p- value			0.001		0.001
Nickel (ug/L)
15–30		2.36 ± 0.42	5.95 ± 0.50	5.82 ± 0.63	6.75 ± 0.80	6.52 ± 0.60
p- value			0.001		0.001
31–45		2.79 ± 0.51	6.72 ± 0.85	6.58 ± 0.72	7.49 ± 0.94	7.13 ± 0.72
p- value			0.001		0.001
46–60		3.19 ± 0.37	7.35 ± 0.60	7.24 ± 0.55	7.97 ± 0.75	7.69 ± 0.47
p- value			0.001		0.001
Arsenic (ug/L)
15–30		0.76 ± 0.13	2.54 ± 0.35	2.79 ± 0.45	3.95 ± 0.61	3.28 ± 0.57
p- value			0.001		0.001
31–45		0.92 ± 0.20	3.85 ± 0.37	4.13 ± 0.60	5.27 ± 0.39	4.85 ± 0.45
p- value			0.001		0.001
46–60		1.13 ± 0.19	4.69 ± 0.69	4.82 ± 0.51	6.45 ± 0.48	5.91 ± 0.72
p- value			0.001		0.001

Mercury concentrations in the reference subjects were observed to be [CI: (0.71–0.78), (1.02–1.07), (1.21–127)] µg/g, [(0.66–0.72), (0.79–0.85), (0.91–0.99)] µg/l, and [(1.05–1.20), (1.17–1.25), (1.26–1.39)] µg/l across the age groups. Figure 2 further illustrates the increased concentration of Hg in drug addicts.

For cadmium, the concentrations in referent subjects were found to be [CI: (1.07–1.26), (1.26–1.45), (1.45–1.68)] µg/g, [(3.99–4.32), [4.25–4.63), [4.56–4.89)] µg/l, and [(1.09–1.36), (1.28–150), (1.40–1.54)] µg/l. Figure 3 distinctly highlights the elevated cadmium levels in drug addicts.

Nickel concentrations in the referent subjects were measured as [CI: (1.59–1.70), (2.17–2.48), (3.36–3.79)] µg/g, [(2.15–2.57), (2.53–3.05), (3.01–3.38)] µg/l, and [(1.07–1.29), (1.05–1.47), (1.25–1.62)] µg/l. Figure 4 shows the increased Ni concentrations in drug addicts.

To ensure the robustness of our findings, we employed the unpaired Student’s t-test, comparing the reference subjects and drug addicts aged 15–60 years. The derived 't' critical value, assessed at a 95% confidence interval, unequivocally indicated significant disparities in the mean concentrations of the elements between the groups (p < 0.01).

This study comprehensively assessed four toxic elements: arsenic (As), cadmium (Cd), mercury (Hg), and nickel (Ni). We meticulously quantified their concentrations in various cannabinoid and opioid drugs and further evaluated their presence in biological matrices, specifically scalp hair and blood, of male drug abusers aged 15–60 years. The ramifications of drug abuse extend beyond individual health, casting shadows on the socioeconomic landscapes of nations. In Pakistan, the widespread availability of opioids, cannabis derivatives, and other illicit substances underscores a pressing public health concern. Chronic drug consumption is not a benign habit; it erodes the physiological and psychological well-being of individuals. Over time, the body, already grappling with the direct toxic effects of the drugs, further deteriorates due to malnutrition, which is often a consequence of socioeconomic neglect experienced by addicts (Sebastiani et al. 2018). The FAO/WHO has delineated specific provisional tolerable weekly intake (PTWI) benchmarks for these toxic elements. When extrapolated to a daily context, these benchmarks translate to 2.1 µg As/kg, 2.5 µg Cd/kg, 2.8 µg Ni/kg, and 1.6 µg Hg/kg body weight (Kim et al. 2012). Our empirical data, as presented in Table 3, accentuate the perilous elemental concentrations in drugs, especially when considering a hypothetical daily drug consumption of 3 g. A detailed exposition of the daily intake of these elements through drug consumption is presented in Table 3. Neurotoxicity, a grave concern associated with elements such as arsenic, cadmium, nickel, and mercury, has been extensively documented in the scientific literature (Das et al. 2008; Gupta et al. 2018; Jones & Miller 2008). Both Pb and Cd, which are omnipresent environmental contaminants, present formidable health challenges (Barton 2011; Jones et al. 2010). Their insidious effects on the nervous system encompass a spectrum of disruptions ranging from energy metabolism anomalies and oxidative stress to synaptic transmission irregularities and outright neurodegeneration (Chibowska et al. 2016; Jones & Miller 2008; Liu et al. 2009). It was observed that the levels of As in scalp hair, serum, and blood samples of cannabinoid and opioid abusers were 86.9–145 and 137–211%, 140–297 and 318–490% and 234–349 and 332–473% higher than those of referent subjects, respectively, in all age groups. More recently, it has been shown that acute arsenic exposure can disrupt the central nervous system (CNS) (Engwa et al. 2019). As penetrates the brain through a mechanism that is still being studied. As appears to accumulate in the choroid plexus, perhaps as a defense mechanism against As absorption into the brain (Briffa et al. 2020). Arsenite and arsenate can be transported via anion exchange proteins (bands 1–3) in human erythrocytes (Zhang et al. 2000). Although mammalian cells exposed to arsenic over an extended period of time have developed a strategy for greater efflux and decreased storage of arsenic, it is likely that such a mechanism exists (Romach et al. 2000). It was observed that the levels of Hg in scalp hair, serum, and blood samples of cannabinoid and opioid-user subjects were 91.0%–178 and 111–213%, 107%–125 and 148–176%, and 95.6%–166 and 125–210% higher than those of referent subjects, respectively, in all age groups.

Table 3

Daily Intake of Heavy Elements through Drug Consumption
Drugs	Age groups	Types of Drugs	Mercury	Cadmium	Nickel	Arsenic
Cannabinoid	15–30	Marijuana	0.900 0.791–0.998	0.0354 0.0316–0.0382	0.573 0.530–0.616	0.15 0.141–0.161
Cannabinoid		Hashish	0.944 0.862–1.08	0.0311 0.0278–0.0349	0.527 0.496–0.556	0.168 0.161–0.182
Opioid		Opium	1.064 1.036 − 1.107	0.0338 0.030- 0.0371	0.544 0.514–0.567	0.185 0.170–0.200
Opioid		Heroin	1.031 0.971 − 1.091	0.0431 0.0365–0.048	0.562 0.538–0.589	0.177 0.164–0.190
Cannabinoid	31–45	Marijuana	0.798 0.702–0.885	0.0314 0.028–0.034	0.508 (0.470–0.547	0.133 0125- 0.143
Cannabinoid		Hashish	0.837 0.765–0.958	0.0276 (0.025–0.031	0.467 (0.440–0.494	0.149 0.143–0.162
Opioid		Opium	0.944 0.919–0.982	0.030 0.027–0.033	0.482 0.456–0.503	0.164 0.151–0.178
Opioid		Heroin	0.915 0.861–0.968	0.0382 0.032–0.043	0.498 0.478–0.523	0.157 0.146–0.169
Cannabinoid	46–60	Marijuana	0.762 0.669–0.845	0.030 0.027–0.032	0.485 0.490–0.522	0.127 0.119–0.136
Cannabinoid		Hashish	0.798 0.729–0.914	0.0263 0.0240–0.030	0.446 0.420–0.471	0.143 0.136–0.154
Opioid		Opium	0.900 0.877–0.937	0.0286 0.0250–0.0310	0.460 0.435–0.480	0.156 0.144–0.169
Opioid		Heroin	0.872 0.822–0.923	0.036 0.0310–0.0410	0.475 0.456–0.498	0.150 0.139–0.161

For instance, elemental mercury vapor inhaled through the lungs and mucosal membranes is easily absorbed and swiftly oxidized, but not quickly enough to avoid the accumulation of significant amounts in the brain (Bridges & Zalups 2010). Although methylmercury is rapidly absorbed by the gut and is deposited in most tissues, it does not penetrate the blood-brain barrier as effectively as elemental mercury. However, it gradually demethylates into elemental mercury before entering the brain (Clarkson et al. 2007). The type of mercury, dose, and rate of exposure all affect how dangerous it is to humans. The brain is the primary target organ of inhaled mercury vapor (Clarkson et al. 2007). As methyl mercury, mercury is widely disseminated throughout the body and particularly harms the lining of the colon and kidneys (Reda et al. 2022). More modest symptoms and clinical findings are caused by low levels of prolonged exposure to elemental or other forms of mercury (Chibowska et al. 2016). Strong SH group binding by oxidized mercury can harm tissues, inactivate enzymes, and disrupt a number of metabolic processes (Roulet et al. 2000). The methylmercury that has been consumed is almost entirely absorbed and circulated in the blood (Awata et al. 2017). Methylmercury is removed along with glutathione, and mostly enters cells by combining with l-cysteine and homocysteine (Awata et al. 2017).

It was observed that the levels of Cd in scalp hair, serum, and blood samples of cannabinoid and opioid-user subjects were (216–247 and 222–352%), (110–123 and 136–167%) and (184–217 and 153–245%) higher than those of referent subjects, respectively, in all age groups. Pb and Cd are two toxic metals that are pervasive in the environment and pose a substantial risk to human health (Jones et al. 2010). These substances have neurotoxic consequences, including abnormalities in energy metabolism, irregular initiation and progression of inflammatory processes, oxidative stress, abnormalities in synaptic transmission, abnormalities in synaptic plasticity, and neurodegeneration (Chibowska et al. 2016; Gupta et al. 2018; Jones & Miller 2008; Liu et al. 2009). It was observed that the levels of Ni in scalp hair, serum, and blood samples of cannabinoid and opioid-user subjects were 89.9–132 and 103–148%, 63.9–92.8 and 90.2–126% and 127–152 and 141–186% higher than those of referent subjects, respectively, in all age groups (Das et al. 2008). The brain is frequently regarded as one of the primary target organs for neurotoxicity. According to He et al. (2013) (He et al. 2013), inhaled Ni accumulates mostly in the cerebral cortex (He et al. 2013) and throughout the brain, leading to a variety of neurological symptoms such as headaches, giddiness, fatigue, lethargy, and ataxia (Das et al. 2008; Slotkin & Seidler 2009; Xu et al. 2010).

Our results demonstrate that various cannabinoid and opioid drugs contain toxic substances, such As, Hg, Cd, and Ni. The presence of these toxic elements in drug samples poses a significant health risk to the users. In addition, bacterial infections in drug users may be related to these pollutants. The bacterial contamination observed with various drugs can be attributed to the presence of these toxic elements in human biological samples and the drugs themselves. While our study provides crucial insights, further investigation with a larger sample and broader range of drugs is essential for more accurate data interpretation.

Author Contributions: All authors contributed equally.

Institutional Review Board Statement: The study was conducted in accordance with the Declaration of Helsinki and approved by the National Centre of Excellence in Analytical Chemistry (NCEAC) and the University of Sindh (Approval: NCEAC/1476/2018; Registration: DRGS/1265/2018).

Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.

Acknowledgments: N/A

Conflicts of Interest: The authors declare no conflict of interest.

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Determining the Toxic Elements in Cannabinoid and Opioid Drugs and Their Impact on Addicts' Health

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Abstract

Figures

1. Introduction

2. Material and Methods

2.1. Ethical Considerations and Recruitment

2.2. Apparatus, Reagents and Glassware

2.3. Study design and pretreatment

2.4. Biological Sample Collection and Processing for Trace Element Analysis in Drug Patients and Controls

2.5. Microwave-assisted Acid Digestion Method

2.6. Statistical Analysis and Analytical Figures of Merit

3. Results

3.1. Toxic Elements in Drug Abusers

3.2. Comparative Clinical and Biochemical Profiles of Diverse Drug Abusers

3.3. Toxic Elemental Analysis in Biological Samples of Individuals with Different Types of Drug Abuse

4. Discussion

Conclusion

Declarations

References

Supplementary Files

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