Similarly, the former continental-scale meta-analysis of fossil pollen and archeological evidence indicates that the IP was among the last European areas – along with the British Isles and the Scandinavian region – where Cannabis was cultivated, and this occurred during the Roman Empire and the Early Middle Ages . However, these continental-wide analyses include only a few IP sites in their compilations. For example, Clarke and Merlin mentioned a single, yet representative, site where Cannabis was submitted to intensive cultivation and retting and used it to propose the arrival of Cannabis to the IP by 600 CE. McPartland et al. retrieved their Iberian sites from the European Pollen Database and other internet facilities and considered 10 IP sites, including two from the Balearic Islands . In this way, although the incoming of Cannabis to the IP may be placed within a rather general European context, the precise timing and pathways of arrival, as well as the internal and external dispersal trends, remain largely unknown. Due to the peculiar climatic, biogeographic and cultural features of the IP mentioned above, a thorough survey focused on this specific region to reconstruct Cannabis history is worth attempting. The potential of the IP for providing useful information in this sense is high, as demonstrated by some studies that have recorded relevant historical developments in the drying rack cannabis industry based on pollen analyses of lake sediments. Among them, the most significant examples were found in lakes Estanya and Montcort`es , where hemp was exploited since the Early Middle Ages.
The advantage of these sites is that the amount of Cannabis pollen deposited in the sediments is consistent with local cultivation and/or retting rather than with dispersal from regional and long-distance sources. Indeed, some aerobiological studies have demonstrated that relevant amounts of northAfrican Cannabis pollen can be transported to the southern IP in a few days . Similarly, a recent study of modern sedimentation in Lake Montcort`es recorded significant percentages of Cannabis pollen, but the parent plant was absent from the region . This long-distance dispersal ability implies that only the presence of this pollen is not sufficient to infer the local occurrence of Cannabis populations. However, this is not the case for Estanya and Montocort`es, as we discuss at following. In the sediments of Lake Estanya, the first appearance of Cannabaceae pollen was recorded ca. 600 CE during the Early Middle Ages . From then, the record was continuous until the 1990s. Hemp pollen was accompanied by other cultivated plants, such as Olea , Secale and other undifferentiated cereal pollen. Hemp percentages remained relatively stable until the 14th century, when they underwent a significant increase of up to 25% around the middle of the 18th century . This increase was interpreted in terms of hemp retting in the lake, coinciding with a local increase in the cultivation of this plant . This was supported by the study of proxies for water quality and non-pollen palynomorphs. This phase coincided with the maximum hemp production in Spain due to the high demand from the Spanish navy . After these dates, hemp pollen decreased abruptly to values below 10% during the 20th century.
The authors attributed this hemp crisis to a general decrease in cultivation due to the depopulation of the area during the first half of the 20th century. The first pollen records of Cannabis pollen in Lake Montcort`es sediments also occurred at approximately 600 CE and coincided with the disappearance of cereals , which indicates a shift in local cultivation practices from cereals to hemp . Further increases in wild grasses and weeds such as Artemisia and Plantago are consistent with the expansion of pastures. Hemp pollen experienced three main phases of abundance, separated by two phases of scarcity. The first two phases were interpreted in terms of low-intensity cultivation/retting to cover local needs for fiber. The third phase, however, was characterized by significantly high abundances and was difficult to explain in terms of only local consumption . As in Lake Estanya, this phase was coeval with the maximum development of the Spanish navy and, as a consequence, of hemp cultivation across the entire country. The same abrupt decrease in hemp pollen was recorded at the end of the 19th century, which has been related to the dismantling of the royal navy, the onset of hemp importation from other countries, the substitution of hemp fiber by other materials such as cotton and synthetic fibers, and the decrease in human pressure . The further increase in hemp pollen in the late 20th century may have been due to the renewed interest in hemp, likely favored by EU subsides.The combination of the meta-analysis discussed above and the case studies of Estanya and Montcort`es may suggest that wild Cannabis reached the IP during the postglacial period and that cultivated Cannabis entered much later, by 600 CE. Notably, both entries would have proceeded from the north-eastern sector.
However, in the present state of knowledge, it is still premature to confirm these assessments. The lag of sufficient localities also hinders knowing what happened on the IP with Cannabis during the large gap between post-glacial times and the Middle Ages. The development of a thorough database for the IP, as a basis for further meta-analyses, is essential to understand when and how wild and cultivated Cannabis reached the IP, as well as what happened since those times. In addition to the information available from the above reviews and meta-analyses, other sources of information should be accessed. For example, many other sites are available in the compilation by Carri´ on that have not been included in the former studies. This compilation gathered almost all pollen records available for the IP by the time of publication and is now being updated with new studies developed during the last decade.A number of these studies are not easy to locate, as they are available only in dissertations and local journals. Finally, some studies do not include Cannabis/Humulus pollen in the diagrams due to its scarcity, but the authors have data in their counting sheets and they can be recovered. Therefore, personal contact with palynologists working on the IP is also needed. All these information sources, along with others that may be located further, should be included in a thorough IP-wide study. Epilepsy is a common neurological disorder affecting 0.5–1% of children.
Approximately one-third of people with epilepsy will experience treatment-resistance which is defined as failure of adequate trials of two tolerated, appropriately chosen antiepileptic drugs to achieve seizure-freedom. Children unresponsive to conventional treatments face an increased risk of cognitive, behavioral, and psychosocial dysfunction that can have a negative impact on their health and development. This prognosis has led to strong consumer interest in and uptake of alternative treatments such as artisanal ‘cannabidiol -rich’ products as a way to manage seizures in children with epilepsy. However, such products are typically of unknown quality, composition, and safety, and their use may conceivably pose unpredictable health risks to these children. Despite increasing access to legal pharmaceutical-grade cannabis products globally, many consumers continue to use artisanal cannabis preparations. This may be done for various reasons including lower cost relative to the prescribed product, lack of awareness or knowledge of the patient access pathways, bias against pharmaceutical products, or perceived superior effectiveness and/or tolerability of artisanal products relative to the prescribed products. Artisanal cannabis oils and tinctures are often concentrated to increase the concentrations of active ingredients such as CBD. This, in turn, may result in unusually high levels of residual contaminants in the final product, risking possible toxicity with oral ingestion. The lack of quality control poses potential health risks to individuals via exposure to cannabis contaminated with pesticides, heavy metals, and residual solvents. This would be of particular concern when consumed by children, or immunocompromised or seriously ill adults, and occurs on a long-term basis. With many individuals continuing to self-medicate with artisanal cannabis preparations in Australia and the US, commercial greenhouse supplies contaminants may be unknowingly ingested by many vulnerable individuals suffering chronic illness, including children and adolescents with epilepsy. In a previous study, we collected individual samples of cannabis extracts from families in Australia who were using them to treat their child’s epilepsy, and conducted an analysis of cannabinoid and terpenoid content.
Contrary to family’s expectations, most cannabis products given to children as a way to treat their seizures contained low concentrations of CBD , while delta-9- tetrahydrocannabinol was present in nearly every sample. To extend on this previous analysis, we further analyzed the samples for the presence of residual solvents, heavy metals, and pesticides, and compared the results to known toxicological standards. In the Australian context, pharmaceutical-grade cannabis products are strictly regulated, federally approved, quality-assured products that are only available on prescription via a medical doctor. All other cannabis products are illegal and unregulated– here referred to as ‘artisanal products’ – which are generally of unknown composition and are typically sourced via the illegal gray or black market.Samples were collected between May 2016 and November 2017 across New South Wales and Queensland, Australia, from participants in the Paediatric Epilepsy Lambert Initiative Cannabinoid ANalysis study. A total of 78 cannabis samples were collected from 41 families who were either currently using cannabis products to treat their child’s epilepsy or who had previously used such products and now stopped . Of these, 37 families provided multiple samples. These included 68 liquid-based samples , six solidbased samples , three plant matter samples, and one crystal/powder-based sample. Aside from two families who had obtained a legal prescription, all other families were accessing unregulated artisanal cannabis preparations of unknown strength, composition, and quality either via local/homemade sources or international online suppliers. The two samples obtained on prescription were included in the contaminant analysis as they were representative of the types of products accessed by families at the time of the study. Samples were stored in a 80 C freezer and had previously undergone two freeze–thaw cycles for: phytocannabinoid analysis, and terpenoid analysis, as part of the original study protocol. Further information regarding collection methods and the cannabinoid and terpenoid content of samples can be found in our prior publication. All participants provided written informed consent for the original study protocol while consent for the subsequent contaminants sub-analysis was obtained using an opt-out approach. Ethical approval for the secondary protocol and opt-out consent process was obtained from the University of Sydney Human Research Ethics Committee and the Children’s Health Queensland HREC . Due to the sensitive nature of the information collected in the original study, all cannabis samples were deidentified for confidentiality and recoded to prevent any risk of participant identification. Therefore, information relating to specific cannabis samples and the child could not be linked to the contaminant analysis.
The analysis, including detection, identification, and quantification, of four types of heavy metals, 19 types of residual solvents, and 76 types of pesticides was performed by a National Association of Testing Authorities -accredited analytical chemistry facility . All samples were analyzed using quality-control standards using a 10% replicate approach except those with a small sample volume which were completed in duplicate as a minimum. To account for the variation in sample volumes remaining from prior analyses in the original protocol, a representative sampling approach was chosen. The maximum number of analyses possible on each sample was determined based on volume available, ensuring at least 30 samples per contaminant group. Samples containing >3 g were analyzed for all three categories of possible contaminants; 2.5–3 g for residual solvents and pesticides only; 2.0–2.5 g for pesticides only; 0.7–1.9 g for residual solvents and heavy metals only; 0.6 g for heavy metals only; and <0.5 g for residual solvents only. Using this approach, 51/78 samples were analyzed for heavy metals, 58/78 for residual solvents, and 31/78 for pesticides. Contaminant analysis methods are described in brief in the Supplemental Files.The list of heavy metals and their associated toxicological limits were obtained from the Australian Government Therapeutic Goods Order No. 93 Standard for Medicinal Cannabis for heavy metals.