Approximately one-third of people with epilepsy will experience treatment-resistance which is defined as failure of adequatetrials 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 grow facility 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 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 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. Despite these concerns, ethanol is commonly used as a solventin 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.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 grow system 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 apopulation 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 .