Are side effects of cannabidiol (CBD) products caused by tetrahydrocannabinol (THC) contamination?
Abstract and Figures
Cannabidiol (CBD)-containing products are widely marketed as over the counter products, mostly as food supplements, to avoid the strict rules of medicinal products. Side-effects reported in anecdotal consumer reports or during clinical studies were first assumed to be due to hydrolytic conversion of CBD to psychotropic Δ ⁹ -tetrahydrocannabinol (THC) in the stomach after oral consumption. However, research of pure CBD solutions stored in simulated gastric juice or subjected to various storage conditions such as heat and light with specific liquid chromatographic/tandem mass spectrometric (LC/MS/MS) and ultra-high pressure liquid chromatographic/quadrupole time-of-flight mass spectrometric (UPLC-QTOF) analyses was unable to confirm THC formation. Another hypothesis for the side-effects of CBD products may be residual THC concentrations in the products as contamination, because most of them are based on crude hemp extracts containing the full spectrum of cannabinoids besides CBD. Analyses of 67 food products of the German market (mostly CBD oils) confirmed this hypothesis: 17 products (25%) contained THC above the lowest observed adverse effects level (2.5 mg/day). Inversely, CBD was present in the products below the no observed adverse effect level. Hence, it may be assumed that the adverse effects of some commercial CBD products are based on a low-dose effect of THC and not due to effects of CBD itself. The safety, efficacy and purity of commercial CBD products is highly questionable, and all of the products in our sample collection showed various non-conformities to European food law such as unsafe THC levels, full-spectrum hemp extracts as non-approved novel food ingredients, non-approved health claims, and deficits in mandatory food labelling requirements. In view of the growing market for such lifestyle products, the effectiveness of the instrument of food business operators' own responsibility for product safety must obviously be challenged.
Figures - available via license: CC BY
Content may be subject to copyright.
... A key reason for choosing to initiate with a CBDpredominant variety was to prioritize safety as CBD is highly tolerable, does not induce euphoria, and has a low risk for adverse effects (Taylor et al. 2018;Larsen and Shahinas 2020). In addition, many CBDpredominant preparations contain a small percentage of THC (Bonn-Miller et al. 2017;Lachenmeier et al. 2020). It was decided that the maximum amount of THC allowed in a CBD-predominant product to be considered for these protocols would be 1:10 THC to CBD. ...
... It was decided that the maximum amount of THC allowed in a CBD-predominant product to be considered for these protocols would be 1:10 THC to CBD. Many global CBD-predominate products contain 0.-2% THC (Bonn-Miller et al. 2017;Corroon et al. 2020;Lachenmeier et al. 2020). ...
... Another deciding factor in choosing CBDpredominant as the initiating product was the fact that many CBD-predominant preparations contain a small percentage of THC (Bonn-Miller et al. 2017;Lachenmeier et al. 2020). If the ratio of THC to CBD is 1:20, a patient taking 40 mg of a CBD-predominant product is also receiving 2 mg of THC. ...
Background
Globally, medical cannabis legalization has increased in recent years and medical cannabis is commonly used to treat chronic pain. However, there are few randomized control trials studying medical cannabis indicating expert guidance on how to dose and administer medical cannabis safely and effectively is needed.
Methods
Using a multistage modified Delphi process, twenty global experts across nine countries developed consensus-based recommendations on how to dose and administer medical cannabis in patients with chronic pain.
Results
There was consensus that medical cannabis may be considered for patients experiencing neuropathic, inflammatory, nociplastic, and mixed pain. Three treatment protocols were developed. A routine protocol where the clinician initiates the patient on a CBD-predominant variety at a dose of 5 mg CBD twice daily and titrates the CBD-predominant dose by 10 mg every 2 to 3 days until the patient reaches their goals, or up to 40 mg/day. At a CBD-predominant dose of 40 mg/day, clinicians may consider adding THC at 2.5 mg and titrate by 2.5 mg every 2 to 7 days until a maximum daily dose of 40 mg/day of THC. A conservative protocol where the clinician initiates the patient on a CBD-predominant variety at a dose of 5 mg once daily and titrates the CBD-predominant dose by 10 mg every 2 to 3 days until the patient reaches their goals, or up to 40 mg/day. At a CBD-predominant dose of 40 mg/day, clinicians may consider adding THC at 1 mg/day and titrate by 1 mg every 7 days until a maximum daily dose of 40 mg/day of THC. A rapid protocol where the clinician initiates the patient on a balanced THC:CBD variety at 2.5–5 mg of each cannabinoid once or twice daily and titrates by 2.5–5 mg of each cannabinoid every 2 to 3 days until the patient reaches his/her goals or to a maximum THC dose of 40 mg/day.
Conclusions
In summary, using a modified Delphi process, expert consensus-based recommendations were developed on how to dose and administer medical cannabis for the treatment of patients with chronic pain.
... The post marketing safety assessment showed gastrointestinal effects as most commonly reported adverse effect 12 . We have included this information and several more studies into the two newer versions (version 3; v3 13 and version 4; v4 14 ) of our article 2 to strengthen our arguments. Besides the mentioned human evidence, experimental research in vivo and in vitro resulted in concerns about hepatotoxicity 15 , teratogenicity 16 , and gut inflammation 17 . ...
... This practice is clearly in favour of the food business operator (FBO) because -as the EIHA correctly states -a major part of total THC may be comprised by THCA 1 . We have updated our article to clarify this issue on several instances and to avoid future misunderstandings 13 . ...
An interesting and valuable discussion has arisen from our recent article (Lachenmeier et al., 2020) and we are pleased to have the opportunity to expand on the various points we made. Equally important, we wish to correct several important misunderstandings that were made by Kruse and Beitzke (2020) on behalf of the European Industrial Hemp Association (EIHA) that possibly contributed to their concerns about the validity of our data, toxicological assessment and conclusions regarding regulatory status of cannabidiol (CBD) products. First and foremost, our study did only assess the risk of psychotropic Δ ⁹ -tetrahydrocannabinol (THC) without inclusion of non-psychotropic Δ ⁹ -tetrahydrocannabinolic acid (THCA). Secondly, as this article will discuss in more detail, there is ample evidence for adverse effects of CBD products, not only in paediatric patients, but also in adult users of over-the-counter CBD products (including inadvertent “high” effects). Thirdly, the exposure and risk assessment was conducted using up-to-date guidelines according to the European Food Safety Authority (EFSA) and the German Federal Institute for Risk Assessment (BfR). And finally, the current legal situation in the European Union, without approval of any hemp extract-containing product according to the Novel Food regulation, actually allows blanket statements that all such products are illegal on the market, and this indeed would imply a general ban on the use and marketing of such products as food or food ingredients until such an approval has been granted. We hope that this reassures the F1000Research readership regarding the validity of our results and conclusions. We are pleased, though, that the EIHA has acknowledged the fact that there are non-compliant CBD products available, but according to our data these are a substantial fraction of the market.
... Commercially available CBD products are largely unregulated and are not held to the quality control as FDA-approved medications, which can result in inconsistent dosing, safety, and therapeutic response predictability (Freeman et al., 2019b). Two studies found that a majority of sampled CBD products were mislabeled regarding their CBD content, and approximately a quarter of the products contained detectable amounts of THC (Bonn-Miller et al., 2017;Lachenmeier et al., 2019). ...
Cannabidiol (CBD) has become a fast-growing avenue for research in psychiatry, and clinicians are challenged with understanding the implications of CBD for treating mental health disorders. The goal of this review is to serve as a guide for mental health professionals by providing an overview of CBD and a synthesis the current evidence within major psychiatric disorders. PubMed and PsycINFO were searched for articles containing the terms “cannabidiol” in addition to major psychiatric disorders and symptoms, yielding 2,952 articles. Only randomized controlled trials or within-subject studies investigating CBD as a treatment option for psychiatric disorders (N=16) were included in the review. Studies were reviewed for psychotic disorders (n =6), anxiety disorders (n =3), substance use disorders (tobacco n= 3, cannabis n= 2, opioid n= 1), and insomnia (n= 1). There were no published studies that met inclusion criteria for alcohol or stimulant use disorder, PTSD, ADHD, autism spectrum disorder, or mood disorders. Synthesis of the CBD literature indicates it is generally safe and well tolerated. The most promising preliminary findings are related to the use of CBD in psychotic symptoms and anxiety. There is currently not enough high-quality evidence to suggest the clinical use of CBD for any psychiatric disorder.
... In unklaren Grenzfällen, die der Lebensmittelüberwachung bekannt werden, könnten die Vorgänge zur Prüfung der Betäubungsmitteleinstufung an die dafür zuständige Behörde abgegeben werden. Eine generelle Abgabe aller Fälle erscheint nach dem Urteil des BGH allerdings nicht mehr zweckmäßig.Unsere Untersuchungsergebnisse[27] im Vergleich mit den Modellrechnungen inTabelle 2 zeigen, dass die THC-Gehalte in Hanfprodukten, mit Ausnahme von Einzelfällen, durch die relativ hohen notwendigen Verzehrsmengen in der Regel nicht zum Missbrauch zu Rauschzwecken geeignet sind. Die seit Jahren aus Überwachungskrei-Ob Kalorien, Vitamine oder Aminosäuren, in Austern, Parmesan, Nudeln, Pastinake oder Truthahn -hier steht's. ...
Produkte mit Hanfextrakt sind als neuartige Lebensmittel ohne Zulassung weiter nicht verkehrsfähig. Der Europäische Gerichtshof schließt aber die Einstufung von Cannabidiol als Betäubungsmittel aus. Für Hanfblätter und -blüten muss laut BGH ein Missbrauch zu Rauschzwecken ausgeschlossen werden, jedoch ist dann gegebenenfalls eine Abgabe auch an Endverbraucher möglich.
... Cannabidiol (CBD)-based products are proliferating in countries with different legislation regarding the use of cannabis-based products (Walker et al., 2020). Concerns about the safety of CBD-based products have been raised (Lachenmeier et al., 2019). Given the high risk of misleading information and subsequent confusion about CBD's legal status and its effects, there is a need to elucidate motivations and patterns of use among CBD users. ...
Background
Cannabidiol and cannabidiol-based products are proliferating in many countries. This recent and rapid diffusion prompts investigating the reasons for its use.
Methods
We analyzed data from an online survey among cannabidiol users in the French general population ( n = 1166) selected for their interest in such products. We described the reported reasons for using cannabidiol. We performed logistic regressions to identify the correlates of declaring well-being and other specific reasons for using cannabidiol. We also provided descriptive data regarding the cannabidiol patterns of use.
Results
Well-being was the most cited primary reason for use (27% of the sample). Declaring well-being as a primary reason for using cannabidiol was inversely associated with cigarette smoking, cannabis use, and employment. Among cannabidiol users reporting well-being as their primary reason for use, stress and sleep improvements were the most-cited specific reasons. In the whole study sample, the most common modes of use were smoking cannabidiol-rich cannabis (61%) and ingesting cannabidiol oil sublingually (19%).
Conclusions
In a sample of cannabidiol users from France, well-being was the most-cited primary reason for use, and smoking was the first route of administration. Further research is needed to clarify to what extent expected effects are scientifically sound and to understand country-related specificities regarding patterns of use.
... Il est donc possible d'avoir une présence ou des concentrations supérieures de ce composé par rapport aux spécifications affichées sur le produit [93]. Cela peut mener à une intoxication au 9-THC [94] ou à un contrôle antidopage positif à cette molécule et aux autres cannabinoïdes interdits [95]. La composition du produit est donc un élément important à prendre en compte lors de l'utilisation du CBD et notamment avec les produits dit « full spectrum » (i.e. ...
Résumé
Objectifs
Dans cet article, nous souhaitons faire le point sur les différentes propriétés du cannabidiol (CBD) potentiellement intéressantes pour le sportif.
Actualités
Le CBD est, avec le Δ9-tetrahydrocannabinol, l’un des phytocannabinoïdes les plus abondants du Cannabis Sativa L. Avec la levée de l’interdiction en 2018 du CBD par l’Agence mondiale anti-dopage, il est probable que les sportifs se tournent davantage vers les produits au CBD dérivés du Cannabis Sativa L.
Perspectives et projets
Des études précliniques sur le CBD ont montré des effets anxiolytiques, analgésiques, anti-inflammatoires, neuroprotecteurs mais également sur le sommeil. Ces propriétés pourraient être intéressantes dans la gestion des blessures, des commotions, de l’anxiété et des troubles du sommeil. Si le CBD paraît être une molécule sûre, les effets secondaires indésirables existent bel et bien et notamment pour les produits non réglementés.
Conclusion
Le manque de preuves scientifiques et le trop peu d’études cliniques appliquées aux sportifs ne permettent pas, pour le moment, de recommander l’utilisation du CBD aux athlètes.
Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid and hemp derivative increasingly used in food. Illegal in food at the U.S. federal level, but legal in some states, the CBD-infused food product market has grown substantially, prompting government concerns regarding potential safety risks. CBD foods are a growing market that is driven by increasing demand from producers and consumers and that is governed by an inconsistent and evolving legal framework. This systematic review of research and regulations identified how legality relates to safety. The research also included an emphasis on dose, a key factor for determining safety in foods. Statutes and guidance documents were reviewed from a selection of jurisdictions with existing or proposed legalized CBD in food to determine what restrictions are used relative to safety, including dose and related standards for food. A search of scientific literature was conducted to evaluate what is known about safe dose in food applications and determine what information is still needed to inform a standard or regulated limit. Findings were analyzed to determine risks and what research and regulations are needed to address them. Legal jurisdictions do little to safeguard consumers against potential risks associated with CBD in food because they focus primarily on warnings and prohibiting health claims. Warning and labeling requirements lack consistency. More concerning is the absence of standards for dose in food or for the composition of the CBD used. Further, there is limited and incomplete information to inform such standards.
Highlights:
Pain is common among athletes at all levels and the treatment of pain can be a challenging and frustrating task. The team physician needs a fundamental knowledge of analgesic strategies as it relates to athletes. It is important to understand the mechanism of action, side effect profile/associated complications, incidence of and indications for use, as well as the controversies associated with the most common analgesic medications used in sports medicine. Several “in vogue” treatment modalities, including cannabidiol, are also becoming more commonly used and are worth discussion.
Cannabis is one of the oldest cultivated plant, which has been used by humankind for thousands of years due to its biological properties and a wide range of applications. In total, hemp plants contain over 500 different substances while the characteristic components are the cannabinoids. The most important cannabinoids are (-)-Δ⁹-trans-tetrahydrocannabinol (Δ⁹-THC), cannabidiol (CBD), and cannabinol (CBN – the latter being an oxidation product resulting from Δ⁹-THC). In the course of recent years, a paradigm shift has taken place with regard to the use of products and ingredients derived from hemp, especially CBD. Thus, an ever-increasing number of products containing CBD are on the market; this ranges from classic CBD oil to CBD chewing gum and even CBD shampoo. Despite an increasing presence of these products in the market, the regulation of cannabinoids in these products is very inconsistent in different countries, except for Δ⁹-THC whose limit is 0.2% for many products and many countries. The enormous abundance of CBD-containing products calls for the development of new analytical techniques that allow a reliable and quick determination of the main cannabinoids usually found in hemp. This seems all the more necessary since previous examinations of CBD oils often revealed a difference between the declared amount and the actual content of the ingredients. Many methods usually applied to determine cannabinoids are rather time-consuming and associated with high costs. In this study, we developed and validated a sensitive, simple, reliable as well as fast method for the determination of CBN, CBD and Δ⁹-THC in commercially available CBD oils using high-performance thin-layer chromatography (HPTLC) combined with electrospray ionization mass spectrometry (ESI-MS). Thus, for this method, a recovery rate of ≥90% was determined. This procedure enables both qualitative and quantitative analyses of CBN, CBD and Δ⁹-THC in CBD oils of different matrices such as hempseed oil, olive oil or sunflower oil. Thus, this method is a helpful and fast tool to investigate a broad variety of commercially available CBD oils.
Cannabidiol (CBD)-containing products are widely marketed as over the counter products, mostly as food supplements. Adverse effects reported in anecdotal consumer reports or during clinical studies were first assumed to be due to hydrolytic conversion of CBD to psychotropic Δ ⁹ -tetrahydrocannabinol (Δ ⁹ -THC) in the stomach after oral consumption. However, research of pure CBD solutions stored in simulated gastric juice or subjected to various storage conditions such as heat and light with specific liquid chromatographic/tandem mass spectrometric (LC/MS/MS) and ultra-high pressure liquid chromatographic/quadrupole time-of-flight mass spectrometric (UPLC-QTOF) analyses was unable to confirm THC formation. Another hypothesis for the adverse effects of CBD products may be residual Δ ⁹ -THC concentrations in the products as contamination, because most of them are based on hemp extracts containing the full spectrum of cannabinoids besides CBD. Analyses of 181 food products of the German market (mostly CBD oils) confirmed this hypothesis: 21 products (12%) contained Δ ⁹ -THC above the lowest observed adverse effect level (2.5 mg/day). Inversely, CBD was present in the products below the no observed adverse effect level. Hence, it may be assumed that the adverse effects of some commercial CBD products are based on a low-dose effect of Δ ⁹ -THC and not due to effects of CBD itself. The safety, efficacy and purity of commercial CBD products is highly questionable, and all of the products in our sample collection showed various non-conformities to European food law such as unsafe Δ ⁹ -THC levels, hemp extracts or CBD isolates as non-approved novel food ingredients, non-approved health claims, and deficits in mandatory food labelling requirements. In view of the growing market for such lifestyle products, the effectiveness of the instrument of food business operators' own responsibility for product safety and regulatory compliance must obviously be challenged, and a strong regulatory framework for hemp products needs to be devised.
Cannabidiol (CBD) is a naturally occurring, non-psychotropic cannabinoid of the hemp plant Cannabis sativa L. and has been known to induce several physiological and pharmacological effects. While CBD is approved as a medicinal product subject to prescription, it is also widely sold over the counter (OTC) in the form of food supplements, cosmetics and electronic cigarette liquids. However, regulatory difficulties arise from its origin being a narcotic plant or its status as an unapproved novel food ingredient. Regarding the consumer safety of these OTC products, the question whether or not CBD might be degraded into psychotropic cannabinoids, most prominently tetrahydrocannabinol (THC), under in vivo conditions initiated an ongoing scientific debate. This feature review aims to summarize the current knowledge of CBD degradation processes, specifically the results of in vitro and in vivo studies. Additionally, the literature on psychotropic effects of cannabinoids was carefully studied with a focus on the degradants and metabolites of CBD, but data were found to be sparse. While the literature is contradictory, most studies suggest that CBD is not converted to psychotropic THC under in vivo conditions. Nevertheless, it is certain that CBD degrades to psychotropic products in acidic environments. Hence, the storage stability of commercial formulations requires more attention in the future.
Kurzfassung: Hanfhaltige Lebensmittel liegen voll im Trend. Großer Popularität erfreuen sich derzeit neuartige Nahrungsergänzungsmittel mit Cannabisextrakt, für die vor allem mit dem nicht-psychotropen Cannabinoid Cannabidiol (CBD) und dessen vermeintlich positiven Wir-kungen auf die Gesundheit geworben wird. Seit dem Aufkommen dieser CBD-Produkte werden durch die Lebensmittelüberwachungsbehörden extrem überhöhte ∆ 9-Tetrahydrocannabinol (THC)-Gehalte berichtet, die von klassischen Hanflebensmitteln nie erreicht wurden. Die An-wesenheit von THC in hanfbasierten Lebensmitteln hat neben der Problematik möglicher psy-chotroper Effekte auch Bedenken aufgeworfen, dass bei Drogentests positive Ergebnisse erhal-ten werden. Cannabis-positive Ergebnisse bei Blut-bzw. Urinuntersuchungen wurden bislang als ein Hinweis auf die Aufnahme von Cannabis, in der Form von Haschisch oder Marihuana, interpretiert und können daher unangenehme Folgen für den Betroffenen haben. In ersten Stu-dien nach Aufkommen der Hanflebensmittel wurden positive Ergebnisse bei forensisch-toxi-kologischen Tests auf Haschisch oder Marihuana nach dem Konsum von Hanfsamenöl und anderen Hanfsamenlebensmitteln beschrieben. Die verfügbare Literatur zeigt jedoch eine große Spanne, welche oralen THC-Gehalte gesichert zu einem positiven Drogentest führen würden. In der Regel ist ein negativer Befund bei einer Dosis von weniger als 0,1 mg/Tag wahrschein-lich. In eigenen Untersuchungen von CBD-Produkten (n=28) wird bei bestimmungsgemäßer Verwendung bei 43% der Produkte bereits eine THC-Dosis von mehr als 1 mg aufgenommen. Durch das Aufkommen zumeist illegal vertriebener CBD-Produkte mit teilweise sehr hohen THC-Gehalten wurde das Risiko eines positiven Drogentests somit wieder erhöht.
Cannabidiol (CBD) is a non-psychoactive cannabinoid, widely marketed to athletes for claimed effects such as decreased anxiety, fear memory extinction, anti-inflammatory properties, relief of pain and for post-exercise recovery. The World Anti-Doping Agency (WADA) has excluded CBD from its list of prohibited substances. Nevertheless, caution is currently advised for athletes intending to use the compound—except CBD, all other cannabinoids are still on the prohibited list. CBD products, specifically non-medicinal, so-called full-spectrum cannabis extracts, may contain significant levels of these substances, but also contaminations of tetrahydrocannabinol (THC) (>2.5 mg/day in >30% of products on the German market) potentially leading to positive doping tests. Labelled claims about CBD content and absence of THC are often false and misleading. Contaminations with the psychoactive THC can result in adverse effects on cognition and, in general, the safety profile of CBD with respect to its toxicity is a controversial topic of discussion. For these reasons, we would currently advise against the use of over-the-counter CBD products, especially those from dubious internet sources without quality control.
Zusammenfassung
Seit dem 1996 aufgehobenen Anbauverbot für Pflanzen der Spezies Cannabis sativa L. (sog. Faserhanf) mit geringem Gehalt des psychoaktiven Inhaltsstoffs Δ9-Tetrahydrocannabinol (THC) wird eine Vielzahl daraus hergestellter Lebensmittel angeboten. Als Beurteilungshilfe für die amtliche Lebensmittelüberwachung werden in dieser Übersichtsarbeit alle Aspekte von Hanf als Lebensmittel diskutiert, eine Einführung in die Botanik der Hanfpflanze gegeben und die aktuelle Gesetzeslage in Deutschland und der Europäischen Union dargestellt. Forensisch-toxikologische Aspekte insbesondere hinsichtlich des Einflusses von Hanflebensmitteln auf Drogentests werden beschrieben und eine Übersicht über die analytischen Möglichkeiten zur Absicherung der THC-Richtwerte gegeben. Abschließend werden Vorschläge für die lebensmittelchemische und rechtliche Beurteilung von Hanflebensmitteln gemacht. Neue Aspekte in diesem Update betreffen insbesondere sog. Cannabidiol (CBD)-Öle und deren Novel-Food-Status. Seit 1998 wurde ein Rückgang der THC-Konzentrationen für mehrere Produktgruppen beobachtet. Die von der EU vorgeschriebene Verwendung von zertifiziertem Hanfsamen und die verstärkte Kontrolle der Hersteller haben offensichtlich zu einem deutlichen Rückgang der THC-Konzentrationen in Hanflebensmitteln geführt. Der maximale THC-Gehalt in derzeit verfügbaren traditionellen Hanflebensmitteln ist zehn- bis hundertfach niedriger als in den Studien der 1990er-Jahre. Es ist zu beachten, dass frühere GC-Studien immer die Summe von THC und THC-Säuren bestimmten. In den letzten Jahren liefern LC-MS-Methoden Informationen über den spezifischen Gehalt an THC in Hanfprodukten. Dennoch wurden seitdem immer noch Lebensmittel mit inakzeptablen THC-Gehalten vorgefunden, was zu einer ganzen Reihe von öffentlichen Warnungen im EU-Schnellwarnsystem für Lebens- und Futtermittel (RASFF) führte. Daher ist eine kontinuierliche Qualitätskontrolle erforderlich, um den THC-Wert niedrig zu halten. Dazu gehört sowohl die Verwendung von Sorten mit niedrigem THC-Gehalt als auch die richtige Saatgutreinigung. Jüngstes Interesse gilt dem CBD, das wegen seiner vermeintlich günstigen gesundheitlichen Eigenschaften vermarktet wird. Während natürliche Gehalte in den oben genannten Lebensmitteln toleriert werden, werden reine CBD-Extraktprodukte entweder als Arzneimittel oder als sogenanntes Novel Food behandelt, die beide vor dem Inverkehrbringen zugelassen werden müssen. Nicht-traditionelle Hanf-Extraktprodukte weisen zudem häufig so hohe THC-Konzentrationen auf, dass die Produkte als gesundheitsschädlich beurteilt werden müssen.
Summary
In 1996, the prohibition of the cultivation of plants of the species Cannabis sativa L. (so-called fibre hemp) with minor content of the psychoactive Δ9-tetrahydrocannabinol (THC) was lifted. Nowadays, a wide variety of hemp food products is offered on the market. As a help for evaluation of such products, this review article provides the official food control with information on all aspects of hemp as foodstuff. An introduction to the botany of the hemp plant and the current law situation in Germany and the European Union is presented. In particular, the forensic-toxicological aspects regarding the influence of hemp food on drug tests are described. Furthermore, an overview of the analytic techniques used to verify compliance with the guidance values is given. Finally, suggestions for the food regulatory and food chemical evaluation of hemp food products are made. New aspects in this update concern so-called cannabidiol (CBD) oils and their novel food status. Since 1998, a decrease in the THC concentrations for several product groups has been observed. The prescribed use of certified hemp seed by the EU and the increase of controls on manufactur-ers have obviously led to a significant decline of THC concentrations in hemp food products. The maximum THC content in currently purchasable traditional hemp food products is ten- to a hundred-fold lower than those found in the studies of the 1990s. It is of note that earlier GC studies always consider the sum of THC and THC-acids. In the last years, LC-MS methods provide information about the isolated content of THC in hemp products. Nevertheless, food products with inacceptable THC contents were still observed since then, which led to a series of public warnings in the EU Rapid Alert System for Food and Feed (RASFF). Therefore, ongoing quality control is needed to maintain low THC levels. This includes both the use of low THC varieties and proper seed cleaning. Recent interest surrounds CBD, which is purported for various health properties. While natural contents in the above-mentioned food products are tolerated, pure CBD extract products are either treated as medicines or as so-called novel food, which both need to be approved before being placed on the market. In addition, nontraditional hemp extract products often exhibited extreme THC concentrations, which must be evaluated as hazardous to health.
Cannabidiol (CBD)-containing products are widely marketed as over the counter products, mostly as food supplements, to avoid the strict rules of medicinal products. Side-effects reported in anecdotal consumer reports or during clinical studies were first assumed to be due to hydrolytic conversion of CBD to psychoactive Δ ⁹ -tetrahydrocannainol (THC). However, research of pure CBD solutions stored in simulated gastric juice or subjected to various storage conditions such as heat and light with specific liquid chromatographic/tandem mass spectrometric (LC/MS/MS) and ultra-high pressure liquid chromatographic/quadrupole time-of-flight mass spectrometric (UPLC-QTOF) analyses was unable to confirm THC formation. Another hypothesis for the side-effects of CBD products may be residual THC concentrations in the products as contamination, because most of them are based on crude hemp extracts containing the full spectrum of cannabinoids besides CBD. Analyses of 28 food products of the German market containing hemp extract as an ingredient (mostly CBD oils) confirmed this hypothesis: 10 products (36%) contained THC above the lowest observed adverse effects level (2.5 mg/day). Inversely, CBD was present in the products below the no observed adverse effect level. Hence, it may be assumed that the adverse effects of some commercial CBD products are based on a low-dose effect of THC and not due to effects of CBD itself. The safety, efficacy and purity of commercial CBD products is highly questionable, and all of the products in our sample collection showed various non-conformities to European food law such as unsafe THC levels, full-spectrum hemp extracts as non-approved novel food ingredients, non-approved health claims, and deficits in mandatory food labelling requirements. In view of the growing market for such lifestyle products, the effectiveness of the instrument of food business operators' own responsibility for product safety must obviously be challenged.
Access to cannabis and cannabinoid products is increasing worldwide for recreational and medicinal use. Two primary compounds within cannabis plant matter, Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD), are both psychoactive, but only THC is considered intoxicating. There is significant interest in potential therapeutic properties of these cannabinoids and of CBD in particular. Some research has suggested that CBD may ameliorate adverse effects of THC, but this may be dose dependent as other evidence suggests possible potentiating effects of THC by low doses of CBD. We conducted a randomised placebo controlled trial to examine the acute effects of these compounds alone and in combination when administered by vaporisation to frequent and infrequent cannabis users. Participants (n = 36; 31 male) completed 5 drug conditions spaced one week apart, with the following planned contrasts: placebo vs CBD alone (400 mg); THC alone (8 mg) vs THC combined with low (4 mg) or high (400 mg) doses of CBD. Objective (blind observer ratings) and subjective (self-rated) measures of intoxication were the primary outcomes, with additional indices of intoxication examined. CBD showed some intoxicating properties relative to placebo. Low doses of CBD when combined with THC enhanced, while high doses of CBD reduced the intoxicating effects of THC. The enhancement of intoxication by low-dose CBD was particularly prominent in infrequent cannabis users and was consistent across objective and subjective measures. Most effects were significant at p < .0001. These findings are important to consider in terms of recommended proportions of THC and CBD in cannabis plant matter whether used medicinally or recreationally and have implications for novice or less experienced cannabis users.
Trial registration: ISRCTN Registry Identifier: ISRCTN24109245.
Objective:
Since 2014, cannabidiol (CBD) has been administered to patients with treatment-resistant epilepsies (TREs) in an ongoing expanded-access program (EAP). We report interim results on the safety and efficacy of CBD in EAP patients treated through December 2016.
Methods:
Twenty-five US-based EAP sites enrolling patients with TRE taking stable doses of antiepileptic drugs (AEDs) at baseline were included. During the 4-week baseline period, parents/caregivers kept diaries of all countable seizure types. Patients received oral CBD starting at 2-10 mg/kg/d, titrated to a maximum dose of 25-50 mg/kg/d. Patient visits were every 2-4 weeks through 16 weeks and every 2-12 weeks thereafter. Efficacy endpoints included the percentage change from baseline in median monthly convulsive and total seizure frequency, and percentage of patients with ≥50%, ≥75%, and 100% reductions in seizures vs baseline. Data were analyzed descriptively for the efficacy analysis set and using the last-observation-carried-forward method to account for missing data. Adverse events (AEs) were documented at each visit.
Results:
Of 607 patients in the safety dataset, 146 (24%) withdrew; the most common reasons were lack of efficacy (89 [15%]) and AEs (32 [5%]). Mean age was 13 years (range, 0.4-62). Median number of concomitant AEDs was 3 (range, 0-10). Median CBD dose was 25 mg/kg/d; median treatment duration was 48 weeks. Add-on CBD reduced median monthly convulsive seizures by 51% and total seizures by 48% at 12 weeks; reductions were similar through 96 weeks. Proportion of patients with ≥50%, ≥75%, and 100% reductions in convulsive seizures were 52%, 31%, and 11%, respectively, at 12 weeks, with similar rates through 96 weeks. CBD was generally well tolerated; most common AEs were diarrhea (29%) and somnolence (22%).
Significance:
Results from this ongoing EAP support previous observational and clinical trial data showing that add-on CBD may be an efficacious long-term treatment option for TRE.
In just a few years, cannabidiol (CBD) has become immensely popular around the world. After initially being discovered as an effective self-medication for Dravet syndrome in children, CBD is now sold and used to treat a wide range of medical conditions and lifestyle diseases. The cannabinoid CBD, a non-psychoactive isomer of the more infamous tetrahydrocannabinol (THC), is available in a growing number of administration modes, but the most commonly known is CBD oil. There are currently dozens, if not hundreds, of producers and sellers of CBD oils active in the market, and their number is increasing rapidly. Those involved vary from individuals who prepare oils on a small scale for family and (Facebook) friends to compounding pharmacies, pharmaceutical companies, and licensed cannabis producers. Despite the growing availability of CBD, many uncertainties remain about the legality, quality, and safety of this new “miracle cure.” As a result, CBD is under scrutiny on many levels, ranging from national health organizations and agricultural lobbyists to the WHO and FDA. The central question is whether CBD is simply a food supplement, an investigational new medicine, or even a narcotic. This overview paper looks into the known risks and issues related to the composition of CBD products, and makes recommendations for better regulatory control based on accurate labeling and more scientifically supported health claims. The intention of this paper is to create a better understanding of the benefits versus the risks of the current way CBD products are produced, used, and advertised.
In this contribution, I summarize recent trends of cannabis use in Europe and their public health implications. The first trend refers to an increase of treatment demand for cannabis problems by 76% while prevalence of cannabis use remained largely stable in the same period, based on available data. There are good reasons to assume that this trend reflects increases in the prevalence of cannabis use disorders, however, data to support this claim are not available. Potential drivers for a rising prevalence of cannabis use disorders comprise changes in consumption patterns and increasing levels of THC in available cannabis products. While an increasing prevalence of cannabis use disorders seem likely, the estimates of the Global Burden of Disease studies suggest the opposite. The second trend refers to an emerging market for cannabidiol (CBD) products in European countries, where regulations on CBD are lacking. Given the lack of data on users of CBD products, it can hardly be assessed if current abstainers will initiate using other cannabis products after trying CBD products for medicinal or recreational purposes. However, regulations should be implemented and enforced in order to make CBD products safer for consumers, for instance by ensuring reliable potency levels and by reducing the presence of toxic substances through quality control measures. In summary, a substantial transition of the epidemiology of cannabis use is under way, accompanied by changes in potency, treatment demand and new products. In order to assess the public health implications of this transition, data on population exposure of specific cannabinoids are required.