The list of residual solvents and their associated toxicological limits were obtained from the International Council for Harmonisation guidelines for residual solvents. Ethanol concentration was converted into alcohol by volume to provide an estimate of ethanol content using the density of ethanol and average density of the cannabis oil samples . The average volume consumed by the child per day was calculated from original study data, with the typical serving administered either in mL or drops . The list of pesticides and their associated toxicological limits were obtained from the European Pharmacopeia 10th Edition as per Australian government requirements. The Globally Harmonised System was used to categorize pesticides based on their toxicity ranging from ‘extremely hazardous’ to ‘unlikely to present acute hazard’. Limit of reporting was defined as the lower limit of quantification , adjusted for volume for each individual sample. In cases where LLOQ exceeded the toxicity limit for a specific analyte, the data were deemed as inconclusive . In cases where LLOQ was less than the toxicity limit but not quantifiable, the specific analyte was deemed as ‘below safety limit’ . Samples where a specific contaminant was quantifiable and above the toxicity limit were deemed ‘above safety limit’. All plots were generated using GraphPad Prism 9 Software.Of the 51 cannabis samples tested for the heavy metals, concentrations of arsenic, cadmium, lead, and mercury were below the toxicity limit in 48/51 samples. Results were inconclusive for 2/51 samples for arsenic, and one sample for cadmium and mercury each . Of the 58 cannabis samples tested for residual solvents, 17/58 samples were above the limits specified for ethanol . All were liquid-based preparations. Estimated alcohol by volume percentage for these samples was 6.68 8.6% on average .

One ‘paste’-like extract tested 1.2 times above the limit for isopropanol with an estimated ABV of 0.63% v/v . Results were inconclusive in 3/58 samples for 1,2-Dichloroethane, 6/58 samples for benzene, 1/58 for hexane, and one sample for methanol. One of the 31 samples tested for pesticides contained 4.9 times higher than the acceptable limit of bifenthrin . No other sample tested above the toxicity limit for any other pesticide. A large proportion of samples had inconclusive results for at least one pesticide: 21 samples had inconclusive results for 25/76 pesticides, four samples had inconclusive results for 35/76 pesticides, three samples for 26/76 pesticides, and one sample for 71/76 pesticides .This current analysis of ‘artisanal’ cannabis samples administered to children with epilepsy in the Australian community found potentially unsafe levels of residual solvents, mainly ethanol, in approximately one quarter of the cannabis drying rack samples tested. In the manufacture of artisanal cannabis preparations, the incomplete evaporation of ethanol and other solvents prior to reconstitution with an oil-based diluent can lead to consumers ingesting higher amounts of residual solvents than anticipated, particularly if products are taken at high doses and/or for prolonged periods of time. There are legitimate concerns around the potential harmful effects of ethanol on the developing brain, as well as the fact that alcohol consumption, particularly chronic and/or acute use of considerably large amounts of alcohol , and sudden alcohol withdrawal, can increase the risk of seizures. Other alcohol-related factors for increased seizure risk include impaired sleep quality and interactions with antiepileptic drugs. The effect of chronic low-level ethanol exposure on seizure frequency and neurodevelopment of children has not been systematically evaluated, with the current literature mostly focused on acute poisonings, fetal alcohol syndrome/effects or extrapolated from preclinical studies.

Children and adolescents exposed to serum ethanol concentrations of >0.125 mg/L may be asymptomatic or present with mild symptoms such as drowsiness, dizziness, and ataxia, while a serum ethanol concentration of 50–100 mg/dL is considered a toxic dose in an infant or young child, with >100 mg/dL associated with central nervous system depression, vital sign abnormalities, and increased mortality in children. Despite these concerns, ethanol is commonly used as a solvent in many oral liquid preparations for pediatric populations to improve drug solubility and/or as a diluent. According to ICH guidelines, ethanol and isopropanol are ‘Class 3 solvents’ which are regarded as less toxic and of lower risk to human health. Such solvents may be administered in concentrations higher than the toxicity limit provided this is underpinned by good manufacturing practice or other quality-based requirements. In fact, the FDA-approved CBD-containing medication Epidiolex , which is prescribed to treat rare childhood epilepsies, contains 79 mg/mL of ethanol, equivalent to 10% v/v anhydrous ethanol. With Epidiolex typically dosed at up to 10 mL/day , it can be deduced that relatively small amounts of ethanol are ingested by patients relative to a single USA standard drink which contains 14 g of ethanol. The maximal amount of any extract consumed in the present study was 16 mL/day. As with the calculations for Epidiolex above, we conclude that in the ‘worst-case scenario’ presented in the current study, a child may have consumed 16 mL of a solution containing 25.1% ethanol, equivalent to 3 g/day of ethanol. The World Health Organization states that ethanol content in over-the-counter medications should be less than 0.5% in children less than 6 years old, <5% for children 6–12 years old and less than 10% for children over 12 years. Of the 17 samples that were above the toxicity limit, 12 were between 0.5 and 5%, two between 5 and 10%, and three exceeded 10%. The average age of the children and adolescents with epilepsy in our study was 8.8 4.6 years suggesting that some children were ingesting higher than appropriate levels of ethanol. However, it is reassuring that 71% of the samples tested contained less than 5% of ethanol content and this concentration is suitable for children aged 6–12 years according to WHO guidelines. In addition to these high concentrations of residual solvents in some samples, one sample also tested above the safety limit for bifenthrin, an insecticide used in cannabis cultivation that can be toxic to human health if used inappropriately. The exact implications of this observation are unclear, but it suggests that pesticide contamination is a legitimate concern which requires further investigation across a larger set of samples.

At the time the ‘PELICAN’ study was collecting samples from participants , legal pathways to accessing medical cannabis in Australia were still evolving and highly bureaucratic, time-consuming, and expensive for patients. This represents a time in history when consumers had few alternatives to accessing medicinal cannabis and, artisanal ‘black market’ cannabis products, by comparison, were cheaper and easier to access. There are now better legal options available for accessing medicinal cannabis that avoid the concerns identified with unregulated products. In Australia, Epidiolex is now a registered and government-subsidized medicine for the treatment of Dravet syndrome and Lennox– Gastaut syndrome and an array of other CBD-containing products are available on prescription via schemes overseen by the Therapeutic Goods Administration. Despite this, the use of artisanal cannabis products will undoubtedly continue because of the perception that artisanal products are more effective and/or better tolerated than pharmaceutical-grade cannabis products , and that the addition of D9 -THC and minor cannabinoids may harness a supposed ‘entourage effect’ that enhances overall efficacy. To-date, no randomized, controlled studies have compared pharmaceutical-grade CBD against artisanal cannabis preparations in a population with epilepsy, although preclinical studies are starting to shed light on the pharmacological interactions between cannabis constituents. Meanwhile, in North America, concerns continue around an overall lack of mandatory testing of cannabis products to ensure patients are obtaining safe, quality-controlled product from licensed producers. Several recent reports have described cannabis-derived products contaminated with microbes, heavy metals, pesticides, and other toxins. The potential risk of contaminants in artisanal cannabis preparations, in addition to the variability in cannabinoid content and labeling accuracy, are legitimate concerns for consumer safety. Although the samples collected in the current study were intended for the treatment of seizures in children with epilepsy, it is possible that any individual seeking ‘CBD-rich’ artisanal products for treatment of a medical condition could be susceptible to purchasing contaminated products. The use of artisanal products accessed without prescription evades the necessary medical and regulatory oversight to ensure the patient’s suitability for medicinal cannabis and subsequent monitoring for safety and adverse events. Such products are unlikely to be optimized for safety or efficacy, indicating a need for improved patient access to safe, planting racks quality-controlled prescribed products from licensed manufacturers.Cannabis consumption is estimated at 192 million users in 2018 which equals 3.9 per cent of the world community aged between 15 and 64 years.

Cannabis use represents the most commonly illicit drug intake worldwide, with around 3.8% one-year prevalence worldwide and 5% in North Africa.Cannabis use may lead to adverse health effects such as heart attacks, brain development issues, lung tissues damage and psychiatric comorbidities; It is also responsible for the decline of cannabis users’ living conditions and other social consequences such as poor schooling or week work performance, family violence stigmatisation, social discrimination and criminality. In addition, cannabis users, victims of social discrimination, are often challenged by many health system challenges such as poor and inequitable access to healthcare, qualified human resource shortage and lack of social and assistance to quit drug use. Recently, ensuring timely access to medical care and adequate support and assistance for cannabis users has become an important concern for policy makers and health system stakeholders. More specifically, increased attention has been placed in using information and communication technologies to promote access to quality health care services for cannabis users and help them overcome major health system barriers and better connect with appropriate health services. Available evidence supports the effectiveness of mobile health technologies in improving patients adherence to treatment and ensuring better symptom monitoring by health professionals. For technology users, m-Health or mobile health is the visible part of ICT iceberg. It is defined as “medical and public health practices relying on mobile devices, such as cell phones, patient monitoring systems, personal digital assistants and other wireless devices“. m-Health has benefited from the rise of digital technologies and the emergence of increasingly innovative and intuitive portable technological tools. m-Health interventions range from sending simple text messages to complex telemedicine practices using connected mobile devices and m-Health applications associated or not with sensors. Over 340 mobile and ready-to-wear devices are made available to users around the world, and more than 325,000 m-Health applications are currently available on the main commercial virtual stores “Google app” and “Apple iOS”, this number estimated at 160,000 in 2015, has doubled after two years with more than 200 mobile apps added every day. m-Health intervention have proved appropriate in managing chronic diseases, by allowing useful functionalities for both patients, and health workers. They are also useful in monitoring epidemics and allowing remote health data collection. Therefore, m-Health interventions may play a key role in the fight against cannabis intake issues.

However, little evidence exists on the functionality, usability and effectiveness of m-Health intervention for cannabis use addiction. In response, we carried out a scoping review that aims at exploring technical and functional characteristics of available m-Health-apps intended for non-medical Cannabis Use and Dependence . We aimed more specifically to identify mobile applications used as m-Health interventions, describe their characteristics and discuss evaluation outputs of CUD-focused apps. The rest of the paper is structured as follows. Section 2 presents the research methodology. General, technical and functional characteristics of CUD m-Health intervention apps are provided in Section 3 along with evaluation approaches. These results are discussed in Section 4 in terms of usability. The conclusions are included in Section 5. Tobacco companies have long employed numerous tactics to advertise their products to youth and young adults , and young people who report viewing tobacco advertisements are at greater risk for tobacco use initiation, progression to regular use, and development of nicotine dependence. As a result, the 1998 Tobacco Master Settlement Agreement limited the marketing of tobacco products in ways that might entice underaged youth to use them and movies, use of cartoon characters such as “Joe Camel”. However, following passage of the MSA, more subtle product placement strategies continued to be used in TV and movie productions with tobacco products featured as a part of the plot or character development.