Global Impact of Non-essential Heavy Metal Contaminants in Industrial Cannabis Bioeconomy

The intrinsic signatures of Cannabis species to bioaccumulate non-essential harmful heavy metals (HMs) are substantially determined by their high tolerance, weedy propensities, phenotypic plasticity attributes, and pedoclimatic stress adaptation in an ecological niche. The detection trends of HMs contaminants in cannabis products have reshaped the 2027 forecast and beyond for global cannabis trade valued at $57 billion. Consumer base awareness for the cohort of HMs contaminants viz., lead (Pb), mercury (Hg), arsenic (As), chromium (Cr), cadmium (Cd), and radioactive elements, and the associative dissuading effects signicantly impact cannabis bioeconomy. On the premise that ber hemp (Cannabis sativa L.) could be repurposed to diverse non-consumable products, concerns over HMs contamination would not signicantly decrease ber trade, a trend that could impact globally by 2025. The economic trend will depend on acceptable consumer risk, regulatory instruments, and grower's due diligence to implement agronomic best practices to mitigate HMs contamination in marketable cannabis-related products. In this unstructured meta-analysis study based on published literature, the application of Cannabis species in HMs phytoremediation, new insights into transportation, distribution, homeostasis of HMs, the impact of HMs on medical cannabis, and cannabis bioeconomic are discussed. Furthermore, a blueprint of agronomic strategies to alleviate HMs uptake by plant is proposed. Considering that one-third of the global arable lands are contaminated with HMs, revamping global production of domesticated cannabis requires a rethinking of agronomic best practices and post-harvest technologies to remove HMs contaminants.


Introduction
The 21st century rejuvenated interest in Cannabis sativa Linn, known as industrial hemp (when expressing tetrahydrocannabinol (THC) < 0.3%) or marijuana (THC > 0.3%) is predicted to grow to a $57 billion bioeconomy by 2025 (Reporterlinker 2019) even though growing the plant remains largely illegal worldwide. Exposure to air pollutants, domestic e uents, direct root absorption from the earth's crust, cross-contamination during the drying process, and post-processing adulteration with additives to enhance market value are the main sources of non-essential heavy metals (HMs) in cannabis products (Busse et al. 2008). Decision-making in industrial cannabis production must integrate the following: (1) that one-third of the global arable lands are contaminated (Tripathi et al. 2016) with HMs such as lead (Pb), chromium (Cr), arsenic (As), zinc (Zn), cadmium (Cd), copper (Cu), mercury (Hg), and nickel (Ni), (2) that Cannabis species have a high propensity to bioaccumulate HMs from their growing medium (Galić et al. 2019;Husain et al. 2019;Linger et al. 2005), and (3) that there is no market value for cannabis product contaminated with Hg, Cd, As, and Pb above the permissible threshold. This cohort of elements (As, Pb, Cd, Hg, Cr) are often with unknown biological purposes and toxic at higher concentrations in plants ( Fig. 1; Hajar et al. 2014). While de ciency and excessive uptake of bene cial elements in cannabis is phenotypically expressed, hyperaccumulation of HMs in the roots and above-ground tissues is associated with no detectable morphological changes (Galić et al. 2019;Linger et al. 2005). This suggests that the cultivation of cannabis should be accompanied by HMs monitoring at all growth stages. Interestingly, a comparative gene expression analysis for known HMs transporter in six cannabis genotypes (Fedora 17, Felina 32, Ferimon, Futura 75, Santhica 27, and USO 31 expressing THC < 0.3%) grown on HMs contaminated soil, and two commercial soils (Miracle-Gro Potting Mix ® and PRO-MIX Mycorrhizae High Porosity Grower Mix ® ) did not uncover major signi cant differential expression for HMs transporter genes such as phosphate transporter PHT1:1 and PHT1:4, heavy metal transporter 3 (HMA3) and vacuolar cation-proton exchanger (CAX) genes (Husain et al. 2019). From this study, it is tempting to hypothesize that domesticated cannabis genotypes have an evolved pedoclimatic stress adaptation in their ecological niche that enhanced their propensity to function as HMs accumulators by constitutively expressing HMs transporters. In this light, HMs contamination levels in cannabis products are positively correlated to the degree of plant exposure to the metals in a given ecological niche that could severely affect end-users. In this unstructured meta-analysis study based on published literature, the application of Cannabis species in HMs phytoremediation ( Fig. 1, 2), new insights into the transportation, distribution, and homeostasis of HMs in the cannabis plant (Fig. 3), the impact of HMs on medical cannabis (Fig. 4), and the bioeconomy (Fig. 5) are discussed. We proposed novel blueprint agronomic strategies to mitigate HMs uptake at the farm level. We discuss the direct impact of HMscontamination in a hypothetical scenario by 2025 should cannabis stakeholders fail to address the issue in marketed cannabis products.

Unbiased database search strategy and synthesis
An unstructured review was performed on HMs contamination in cannabis based on available data in published literature (from Medline, Scopus, Google Scholar, and CINAHL) and gray literature in book chapters and unindexed sources, including local and global agencies entries such as the FAO, and WHO in February-May 2021. Keywords for the unstructured search were "cannabis HMs contaminant", "cannabis trace metals", "hemp HMs contaminant", "hemp trace metals", "cannabis phytoremediation of HMs", "hemp phytoremediation of HMs", "cannabis mercury toxicity", "cannabis proteins and chelators" and "hemp proteins and chelators". Key MeSH terms used included "hemp bioaccumulation of metals", "hemp bioaccumulation of HMs", "metals in cannabis smoke", "metals in hemp smoke" and "harmful effects of heavy metals in cannabis and hemp". A re ned search was performed using the aforementioned keywords except that the word "metal" was replaced either by arsenic, cadmium, lead, and mercury, and cannabis (or hemp) was replaced by Cannabis sativa L. After reading the abstract for relevance, the most appropriate articles were fully reviewed and synthesized. The overarching data set of 25 articles (Additional information S1) were consolidated with the objectives of the study as follows: i) the application of cannabis in phytoremediation, ii) fate of HMs in cannabis, iii) medical impact of HMs in cannabis, iv) agronomic strategies to mitigate HMs uptake, and v) impact of HMs in cannabis bioeconomy.

Cannabis mediated phytoremediation of heavy metals contaminants
The average cost of remediating HMs contaminant soil using plants is $37.7/m 3 (Wan et al. 2016), a lucrative and cheaper option to other remediation technologies. This led to the search for plant species having traits for HMs bioaccumulation and tolerance capabilities. We discussed the inherent features of cannabis to remediates radioactive metals, HMs, the mechanism of transport, and the impact of this bioaccumulation trait in the cannabis business.
3.1.1 There is a high likelihood that radioactive cannabis ends up with consumers: Increasing detection of HMs load in Cannabis species on one hand emerged as the ultimate answer to land remediation efforts owing to its unique morphological characteristics such as stem length, fast growth at the vegetative stage, root area and leaf surface, high photosynthetic activity, fewer nutrient requirements for survival, and shorter life cycle (~ 180 days). Cannabis species exhibits a great geo-demographic diversity showing prominence in the wild and cultivated lands (Mura et al. 2004) and on soil pH 5-7 which are excellent attributes for phytoremediation. The use of plants to remove, transfer, stabilize and destroy contaminants in the soil and groundwater ( Fig. 1) is called phytoremediation. Cannabis species are endowed with stress-tolerant genes which ensure in part their phenotypic and chemotypic plasticity as a mechanism for adaptation in an ecological niche. Cannabis species act as a hyper-accumulator of radioactive elements, toxins, pesticides, and polycyclic aromatic hydrocarbons such as chrysene and benzo[a]pyrene through the fundamental processes of phytoaccumulation, phytovolatilization, and phytodegradation in their leaves (Campbell et al. 2002;Greipsson 2011; Morin-Crini et al. 2018). When cannabis was grown in emulated Chernobyl conditions with radiocesium (Cs-137), radioactivity was detected in all plant tissues as well as retting water, ber, seed oil, and biofuel which could potentially end up in the hands of consumers (Vandenhove and Van Hees 2005). Akin to the above study, maximum absorption, and distribution of strontium (Sr-90) was 45%, 45%, and 15% in roots, stem, and leaves, respectively (Hoseini et al. 2012). The extensive rhizosphere of cannabis owing to its long root system (~ 2.4 m below the ground level), naturally resistant to pests, thus, obviating the need for pesticides gives cannabis species an extra edge over other plants used for phytoremediation. With this high propensity to bioaccumulate radioactive material from the soil, it is obvious that cannabis used in phytoremediation (or cannabis that is erroneously grown on radioactively contaminated soil) cannot nd its place as animal feed, human food, supplements nor textile. Thus, impeding the cannabis bioeconomy. Nonetheless, repurposing radioactive cannabis biomass for electricity and ethanol production could be a possibility to salvage grower's investment, even though poor oxidation stability in biodiesel production has been reported (Li et al. 2010).
3.1.2 Non-essential heavy metal contaminated cannabis ends up with consumers: While selenium (Se) is a bene cial element in plants, excess in human results in nausea, vomiting, nail discoloration, nail brittleness, nail loss, hair loss, fatigue, irritability, and foul breath odor (MacFarquhar et al. 2010). C. sativa sequestrates Se mainly in leaf vasculature and seed embryos, with predominant Se speciation in C − Se − C forms (57 − 75% in leaf and more than 86% in seeds) (Stonehouse et al. 2020). Equally, cannabis seed extracts contain selenomethionine and methyl-selenocysteine which are excellent dietary Se sources, highlighting the implication of cannabis in phytoremediation as well as bioforti cation.
Cannabis species follows a unique genotype-dependent pattern for accumulating non-essential HMs as evident from various studies: For example, when grown in moderate Cd levels of 17 mg/kg soil showed seasonal changes in photosynthetic performance whereas extreme levels above 800 mg/kg caused signi cant loss of vitality and biomass (Girdhar et al. 2014). The cannabis strain, Zenit (THC < 0.3%) had a high iron accumulation property (1859 mg/kg) compared to other varieties (Mihoc et  From these studies, we postulate that cannabis exhibits bioaccumulation preferences for HMs which is genotype-dependent as well as growing medium pH-dependent ( Fig. 3) irrespective of their nutritional requires. This thesis is supported by the apparent constitutive expression of HMs transporters genes viz., PHT1:1, PHT1:4, HMA3, and CAX genes (Husain et al. 2019). It is tempting to suggest that cannabis has evolved the HMs accumulation mechanism which is not dependent on the growing medium but the availability of HMs in the medium, type of heavy metal, plant genotype, and medium pH.
3.1.3 Insights into the molecular mechanism of HMs phytoremediation in cannabis: Differential gene expression has been observed during phytoremediation of HMs in cannabis. Metal cation uptake is routed through four steps in the cannabis plant starting from metal uptake through the root system, loading into the xylem vessels, translocation, chelation, and sequestration during tra cking to the phloem. The in ux of metal cations into the root occurs via symplastic and apoplastic pathways wherein metal tra cking ZRT-YRT-like proteins, yellow stripe-like transporters (YSL), and natural resistance- Thus, we suggest the application of reverse genetics to silence HMs transporters in the developmental process of next-generation domesticated cannabis. This approach has the potential to mitigate the intrinsic phytoremediation propensity, ensure consumer safety, and boost cannabis safety and its bioeconomy.

The fate of non-essential heavy metals in cannabis trichome, seed, and consumers
Cannabis reproductive structures such as seed and ower are arguably highly valued on the market for phytocannabinoids, avonoids, terpenoids, rich protein sources, and omega-6 and omega-3 oil-rich in a desirable range between 1:2 and 1:3 (Callaway 2004). Understanding the fate of HMs homeostasis in these reproductive structures is thus critical for consumer safety as more than 500 different compounds characterized in Cannabis species are used for several medical interventions (Wang and Xiong 2018) an indication that they serve as zinc sequestration and storage-hub in the reproductive tissues of cannabis. While these two seed storage proteins have not been reported in trichomes, one might be tempted to ask whether cannabis seed storage proteins play a role in entrapping and sequestering non-essential Hg, Cr, Cd, As, and Pd akin to Zn? It could be interesting to investigate the interactions of HMs with metallothionein and phytochelatins at the trichome level to gain insights into their potential to form complexes that could be transferred to end-users of cannabis products.

Medical implications of regulated heavy metals in cannabis
The current trends at which non-essential HMs is been detected in cannabis products (Saltiola 2020; Wakshlag et al. 2020) had failed to dissuade human interest in the crop bers and therapeutic uses despite concerns of accumulation in the body of end-users. Cannabis, like other crops, richly contains essential heavy metals such as iron, cobalt, copper, manganese, molybdenum, and zinc which are required for biochemical and physiological processes (Briffa et al. 2020) but toxic at higher concentrations (Singh et al. 2011). Evidence-based concerns over Cd, Pb, Hg, As, and Cr contaminations encountered during the cultivation and post-harvest processing (Gauvin et al. 2018) have emerged as a major drawback to the global use of cannabis species in medicine. Also, premeditated adulteration of cannabis products for market pro t as in the case of Leipzig, Germany that resulted in acute poisoning of 150 people (Busse et al. 2008) is an inhibitive factor for medical utilization in several countries. The high amount of HMs contamination in cannabis can cause various health problems because these elements are rarely metabolized, thus, accumulates in speci c areas of the human body (Fig. 4).
The most common mechanism of HMs toxicity in the human body is via the production of reactive oxygen species (ROS) and free radicals which damage either enzymes, proteins, lipids, and nucleic acids resulting in carcinogenesis and neurotoxicity (Engwa et al. 2019). Cannabis consumed in combustive form represents the greatest danger to human health. Using tobacco, it was shown that less than one percent of Hg remains in the ash after combustion ("smoking"), while elemental mercury (Hg°) is carried in the smoke (Andren and Harriss 1971). Furthermore, smoking any form of contaminated cannabis introduces the whole mercury load in the biomass into the lungs where 75-85% of Hg is absorbed and retained within 40 hours (Siegel et al. 1988), a scenario more likely for Cd, Cr, As, and Pb. Interestingly, most smoke from un ltered cannabis products is rich in aluminum, Cr, Cu, Pb, and Hg (Gauvin et al. A recent study showed that NatureDry© lyophilized FINOLA® hemp juice grown on ne-sandy moraine soil in central Finland contained minute concentrations of Cd, Hg, and Pb (Saltiola 2020), but, su cient to trigger a long-term chronic effect. Chronic toxicity effects of HMs often damage and alter the functioning of organs such as the brain, kidney, lungs, liver, and blood, which lead to muscular, physical, and neurological disorders associated with Parkinson disease, Alzheimer disease, multiple sclerosis, muscular dystrophy and cancer ( neurological toxicity in three stages viz., (i) inhibits N-methyl-d-aspartate receptor, (ii) block the neuronal voltage-gated calcium (Ca 2+ ) channels, and (iii) reduce the expression of brain-derived neurotrophic factor (Neal and Guilarte 2013). Hence, consumption of HMs contaminated cannabis above permissible levels might lead to severe medical conditions in the long term (Fig. 4). Thus, this could dissuade new medical and recreational consumers of cannabis products impeding the cannabis bioeconomy worldwide from achieving the predicted $57 billion trade value by 2027.

Blueprint agronomic strategies to mitigate non-essential HMs in cannabis product
Atomic absorption spectrometer and inductively coupled plasma mass spectrometry (ICP-MS) have emerged as the method of choice to detect and quantify HMs in cannabis products in the United States.
With the prevailing evidence that cannabis species have the propensity to uptake HMs from any growing medium, efforts to shield consumers from HMs should occur principally at the farm level through best agronomic practices. This is because one-third of global arable lands are contaminated with nonessential HMs (Tripathi et al. 2016 Cd (0.2 µg/g ICP and 0.5 µg/g OCP), Pb (0.5 µg/g ICP and 0.5 µg/g OCP), Ar (0.2 µg/g ICP and 1.5 µg/g OCP) and Hg (0.1 µg/g ICP and 3.0 µg/g OCP). These values suggest that outdoor growers must perform their due diligence in choosing their outdoor cultivation sites. The following blueprints can be adopted to avoid post-harvest losses caused by HMs: i) Select cultivation sites away from industrialized zones, zones with mining activities), zones with contemporary volcanic activities (Siegel et al., 1988), and consult the soil conservation service for HMs data.
ii) Perform air quality test for HMs emanating from industrially polluted air-To this effect, analyses on invasive weeds growing on the selected site could provide clues for soil quality and HMs content.
iii) Perform irrigation water test, soil test, and soil pH test before and during cannabis Soil pH is very critical for HMs bioaccumulation in cannabis At pH > 7.0 bioaccumulation of HMs from the soil in decreasing order is Cu > Cr > Cd > Mo > Hg > Zn > Ni > Co > As > Pb while at pH < 7.0 the pattern is as follows Zn > Cd > Cr > Ni > Hg > Cu > Mo > As > Co > Pb (Galić et al. 2019). By exploring the data in Galić et al.
(2019) we found that mercury accumulates more in the leaf (~ 0.015 ppm) and roots (0.038 ppm) of cannabis in acid soil more than in basic soil (Fig. 2).
iv) Monitor the crop at all development stages, notably at the vegetative phase as cannabis draws a large number of minerals to maintain its fast growth rate.
v) Use only fertilizers, grow selected variety with certi ed seeds, and use only pesticides with a certi cate of analysis stating HMs-free.
3.4.2 Advanced agronomic practice-based on-site management: Laboratory research must be integrated with agronomic practices to deliver instruments that can mitigate uptake of HMs. We proposed the following blueprints: ii) Avoid the use of Achromobacter: Another trigger for increased HMs uptake in cannabis is associated with Achromobacter sp. strain AO22 that had been shown to concomitantly enhanced plant growth accumulation of Cd and Zn in ber crop plant; sunn hemp (Crotolaria juncea) (Stanbrough et al. 2013).
iii) Field monitoring: Farmers must perform a robust soil test after heavy torrential rainfall and This is applicable for farming sites located in areas where snowfall and snow melting activities are common.
iv) pH modi cation of chemigation, and irrigation water: Cannabis is acidophilic (~ 5.56-7.and the uptake of Pb and Hg in plants occurred at pH below 6.Thus, ensuring pH stays above 6.5 in all chemigation practices can mitigate Pb and Hg absorption from the soil (Azevedo and Rodriguez, 2012). This approach heavily depends on the soil test results for HMs. Unlike Pb and Hg, the highest absorption of Cd in perennial ryegrass (Lolium perenne L), Cocksfoot (Dactylis glomerata L), lettuce (Lactuca sativa L), and watercress (Rorippa nasturstium-aquaticum L) was observed at pH 5.0-7.0 (Hatch et al. 1988).
Thus, while pH modi cation might confer HMs mitigation control, the uniqueness of cannabis biology requires similar experiments to be performed.
v) Coupling ozone water treatment with water softener system: Ozone water treatment could help oxidized HMs in irrigation water and coupling ozonized system with a water softener system, could help remove oxidized forms of the HMs before they are delivered to the cannabis crops.
3.5 Impact of heavy metals contamination on cannabis bioeconomic by 2025 Relaxation on regulatory laws governing industrial cannabis production had generated fortunes to many industrialized nations, notably the United States. For instance, the industrial hemp-cannabidiol (CBD) market contributed $4 billion to the United States economy in 2020, forecasted and valued at $16 billion by 2025 (Kristen 2019) while at the same period the entire hemp industry is expected to generate $26.6 billion (Reporterlinker 2019).
Since 21st -century consumers generally exhibit high demand for quality and health bene ts for products they buy (Sajdakowska et al. 2018), we took the case of the United States of America to illustrate how increasing consumer awareness of HMs contamination in hemp could affect total estimated retail revenue and found divergent pattern as follows. From Hemp Industrial Daily (HID) data (Fig. 5a), we used the yearly prediction upper and lower limits of estimated retail sales to generate average estimated revenue and differential growth (ΔG) as follows: Where ΔG -is differential growth over 5 years based on HMs dissuading impact on consumers U -upper estimate retail sales L -lower estimate retail sales and N -number of years covered by the prediction Based on the average estimated retails (Fig. 5b) assuming that consumers are less aware and concern about HMs contaminated CBD-related products, an exponential economic return valued at about $10.3 billion by 2024 is expected, a margin decreased of $1.5 billion than predicted by Hemp Industrial Daily. This economic boom is only possible should the hemp industry retain the current consumer base, leverage consumer enthusiasm and raise awareness for new bene cial CBD-related products, and prioritized consumer health within 2021 to 2025. By considering the differential growth (ΔG) in a scenario where the consumer-base become aware of HMs contaminants, develops resentment and fewer new consumer are attracted, the CBD total retail sales will slump to about $9.7 billion (Fig. 5b). This represents a margin decrease of $2.1 billion less than predicted by Hemp Industrial Daily at $11.8 billion.
Although the cannabis CBD market had developed faster than the ber market, consumer awareness for HMs contamination could trigger a dramatic repurposing of HMs contaminated crop for bers-related products at the farm level, causing a paradigm-shift in ber production.
Interestingly, it has been shown that HMs pollution in industrial hemp does not have any signi cant in uence on ber properties such as neness and tensile strength of single ber bundles (Linger et al. 2005). Based on mean values for HMs in bers (Pb = 2.8 ppm and Cd = 0.8 ppm) and in seeds (Pb = 0.8 ppm and Pb = 1.8 ppm) from Linger et al. (2005), and mindful of the Öko-Tex-Initiative-2000 for textile contamination set for Pb (0.2-1.0 ppm), Ni (1.0-4.0 ppm) and Cd (0.1 ppm) will disqualify the use of most industrial hemp bers produced in the USA to be used in the European Union textile industry. This economic upheaval can be avoided by applying the proposed agronomic blueprints and developing agronomic technologies such as breeding for heavy metal sensitive cannabis genotypes.
Based on these factors: (1) consumer-base awareness for HMs contaminated cannabis, and (2) development of hempcrete and textile derivatives market, we forecast that ber retail trade will soar over the cannabis oil market by 2023, and signi cantly contribute towards the total estimated retail sales (Fig. 5C). This scenario will force consumable CBD-related products to enter a stationary phase in economic return while the global cannabis bioeconomy will continuously grow as multiple governments slowly relax production laws on cannabis species.
For the hemp industry to experience a global boom, information gaps between cannabis research, production, and the consumer-base must be bridged by implementing some of these blueprints: i. New hemp consumers should be attracted via reliable, transparent, and regulated marketing.
ii. Efforts towards building consumer con dence should be intensi ed by testing, certifying, labeling, and branding cannabis products as "heavy metal-free" specifying the actual concentration of HMs such as As, Pb, Hg, Cr, and Cd against their permissible levels. Importantly, studies have shown that consumers often rely on label displayed ingredients, expiration date, health information, and environmental attributes in the purchasing-process (Prentice et al. 2019).
iii. Hemp education should be intensi ed at all levels spear-headed by top-tier universities.
iv. Heavy metal monitoring at the eld level and appropriate repurposing of hemp crop should be promoted over the 0.3% THC threshold values which de ne whether a cannabis plant should be classi ed as hemp or marijuana.
v. New farmland in developing countries having low-level environmental pollution could be used for cannabis-essential oil production or invest in hydroponics cropping system.
vi. The cannabis industry must invest in research that seeks to understand consumer perception of a quality product.
vii. Promote hemp research on heavy metal metabolism and breed for the following cannabis strains: a) heavy metal sensitive, b) heavy metal tolerant, and c) heavy metal resistant varieties and enable knowledge transfer to growers.

Conclusion Of The Matter And Future Directions
The intrinsic signatures of Cannabis species to bioaccumulate heavy metals (HMs) from the earth's crust are substantially determined by their high tolerance, weedy propensities, phenotypic plasticity, and adaptation in an ecological niche. Although HMs accumulation in cannabis seems to be useful for phytoremediation, it does pose a threat from the consumer-base. Application of agronomic best practices such as the choice of cannabis seed varieties, abiding by the industry standards, and choice farmland can critically mitigate HMs contamination. The choice for farmland should include soil pH, nutrient levels, pesticides, microbial communities especially A. mycorrhizae, and heavy metal content. It would be in the interest of growers to avoid re outbreaks near their farms since their crops could absorb chemicals from the re. At the retail level, growers must disclose information on the soil type based on data from soil conservation services and such transparency should be made available to consumers when requested.
Cannabis plants grown for land remediation should not be repurposed for human and animal consumption which might dissuade consumers in the long-term and trigger a slump in the global cannabis trade. Figure 1 Bioaccumulation and distribution of heavy metals (Cd, As, Hg, Cr, and Pb) in the cannabis plant. The constitutive uptake of HMs is associated with no phenotypic alterations at the moderate levels. Excessive accumulation and stabilized contamination in the plant triggers an advent of oxidative outburst manifested by severe leaf and stem disorder.  Example of cannabis gland visualized with a stereoscope at 1000X showing glands bearing resin of cannabinoids in a Sour-diesel strain of marijuana (THC > 0.3%). The homeostasis of heavy metals at the level of cannabis trichome is still unknown.

Figure 4
Typical effects of non-essential heavy metals above the permissible level on the human body.
Hypothetically, the accumulation of HMs below the permissive levels represents a long-term risk factor for several chronic medical conditions.