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Cannabidiol Claims and Misconceptions
Abstract
Once a widely ignored phytocannabinoid, cannabidiol now attracts great therapeutic interest, especially in epilepsy and cancer. As with many rising trends, various myths and misconceptions have accompanied this heightened public interest and intrigue. This forum article examines and attempts to clarify some areas of contention.
... CBD is reported not to have any psychoactive or psychotropic effects unlike THC 5,6 . Russo (2017) views this as an inaccurate claim since CBD has been reported to produce pharmacological benefits on mental health disorders such as schizophrenia, depression, anxiety and addiction 10,11 . ...
... A study by García-Gutiérrez et al., (2020) reported that CBD does not have sedating properties and Russo (2017) explained that products containing CBD may be sedating but pure CBD does not produce sedation 3,11 . Sedation and somnolence are listed as very common adverse effects which can occur with use of Epidyolex®/ Epidiolex® which consists of 100mg pure CBD, indicated for treatment-resistant epilepsies 12 . ...
... A study by García-Gutiérrez et al., (2020) reported that CBD does not have sedating properties and Russo (2017) explained that products containing CBD may be sedating but pure CBD does not produce sedation 3,11 . Sedation and somnolence are listed as very common adverse effects which can occur with use of Epidyolex®/ Epidiolex® which consists of 100mg pure CBD, indicated for treatment-resistant epilepsies 12 . ...
Background: Cannabidiol (CBD) is one of the main cannabinoids present in the cannabis plant. The demand for CBD grew over time with more individuals consuming CBD products due to its potential therapeutic properties. Objectives: To assess the knowledge and perceptions of Maltese members of the public and health care professionals (HCPs) about CBD, one of the main cannabinoids present in the cannabis plant. Methods: Surveys aiming to assess the knowledge and perception of the public and HCPs about CBD were developed, validated and disseminated. Results: Four hundred members of the public and 150 HCPs completed questionnaires. Ninety-six percent of participants (n=384) agreed that CBD has a therapeutic effect. Respondents from the general public were mostly knowledgeable about CBD and its use, had positive perceptions in relation to CBD and like HCPs, feel more comfortable if CBD is recommended by HCPs. HCPs were not so knowledgeable about certain aspects on CBD. One hundred and twelve HCPs were not aware that there is only one FDA/EMA approved CBD-based product. HCPs would feel comfortable in prescribing CBD products for pain and insomnia and the majority of them (55%; n=83) believe that CBD has mostly an analgesic effect. Social stigma associated with the use of CBD and potential judgement of HCPs were barriers to CBD use. Conclusion: Increased research, knowledge and availability of prescribing information and guidelines related CBD use might lead to an increased willingness of HCPs to recommend CBD and lead to a decrease in potential barriers associated with its use. Keywords: Cannabidiol, positive perceptions, pain and insomnia
... Discuss the legal status of cannabis and its derivatives in various regions and countries. Highlight any recent changes in legislation related to the use of cannabis in cosmetic and skincare products [48]. • Distinction between hemp and marijuana. ...
... • Distinction between hemp and marijuana. Explore how regulations differentiate between hemp-derived and marijuana-derived products [48]. Explain the significance of the THC content in cannabis products and its impact on legality. ...
Biotechnology, as an interdisciplinary scientific field, is crucial in identifying the valuable active ingredients of plants. Their application extends beyond medical and pharmaceutical formulations to encompass cosmetics, in which these natural substances play a significant role. This article aimed to investigate the potential advantages of integrating cannabis-derived compounds into skincare cosmetic formulations. Their therapeutic efficacy on diverse dermatoses was emphasised. The diverse applications of cannabinoids and terpenes in cosmetic formulations were also examined. Scientific report analysis confirms the beneficial effects of cannabis-derived compounds, including cannabidiol and seed oil, in enhancing skin health and addressing inflammation and dermatological issues. The potential of cannabis-derived compounds in creating novel and effective cosmeceutical products was emphasised.
... CBD is frequently mischaracterized as non-psychoactive or non-psychotropic. However, these labels are inaccurate as it has pharmacological effects for anxiety, depression and addiction [13]. CBD should, instead, be characterized as non-intoxicating compared to THC since it lacks the craving and compulsive use that would be indicative of a drug of abuse [13]. ...
... However, these labels are inaccurate as it has pharmacological effects for anxiety, depression and addiction [13]. CBD should, instead, be characterized as non-intoxicating compared to THC since it lacks the craving and compulsive use that would be indicative of a drug of abuse [13]. The number of CBD oils, tinctures and vaporization liquids marketed to consumers has increased recently as many people see it as a safe alternative to using products containing ∆ 9 -THC. ...
The use of plant-based medicine dates back centuries, and cannabis (Cannabis sativa) is one such plant that has been used medicinally and illicitly. Although cannabis contains hundreds of cannabinoids and other natural products, its potential medicinal use was largely ignored by modern researchers due to the legal restrictions and heavy regulations introduced in the 1930s. As restrictions on cannabis access have eased since the 1990s there is renewed interest in the research of cannabinoids and the other components in the cannabis plant. The focus of this review article is an overview of cannabis and the analytical challenges in the quality control and biological analysis. The pharmacological effects of psychoactive cannabinoids, delta-9-tetrahydrocannabinol (Δ9-THC) and delta-8-trans- tetrahydrocannabinol (Δ8-THC) is discussed, along with an abundant non-intoxicating cannabinoid, cannabidiol (CBD). The analytical methods for the quality control assays of cannabis products include gas chromatography and liquid chromatography coupled to different detectors, including mass spectrometry. This review will highlight various analytical methods for the quality control of cannabis products and the quantitation of cannabinoids in biological matrices for forensics and toxicology.
... The former is responsible for the 'high' provoked by cannabis use and is associated with a risk of dependence. In contrast, CBD does not have a high affinity for brain cannabinoid receptor 1 and is 'non-intoxicating' [1]. Although CBD may have anxiolytic properties [2] a World Health Organization review concluded that CBD "exhibits no effects indicative of any abuse or dependence potential", has a good safety profile, and that "there is no evidence of recreational use of CBD or any public health-related problems associated with the use of pure CBD" [3]. ...
... Our results from this first assessment of CBD use prevalence in France have several implications. First, the fact that 10% of the study population declared using CBD makes the regulation of CBD-based products in Franceand EU in general-an urgent issue, especially in light of reports of adulteration and mislabelling [12,14,40], as well as misinformation [1,36] and drug-testing issues [41]. Second, we identified different profiles of users so creating segmented markets may help consumers find the most suitable CBD-based products for their specific needs. ...
Background
Cannabidiol (CBD), a safe, non-intoxicating cannabis component, is growing in popularity in Europe and worldwide. However, CBD EU regulation is blurry, and consequent labelling and product quality issues may have implications for public health. There is therefore a need to assess the prevalence and perceived harmfulness of CBD use in EU countries, as well as to characterise CBD users. We aimed to do so in the French population.
Methods
In December 2021, an online survey was conducted in a sample respecting the French adult population structure for key demographic variables. Sociodemographic, behavioural and CBD perception data were collected. Three separate regressions were performed to identify correlates of i) having heard of CBD, ii) using CBD, iii) perceived harmfulness of CBD. A hierarchical classification was also performed to identify profiles of CBD users.
Results
The study sample comprised 1969 adults, of whom 69.2% had heard of CBD and 10.1% used it. Less than half (46.8%) of the former considered it harmful. Having heard of CBD was associated with younger age, being born in France, tobacco use, and cannabis use. CBD use was associated with younger age, tobacco use, cannabis use, poor self-reported general health status, and positive perception of alternative medicines. Cluster analysis revealed four different CBD user profiles based on socio-demographics and behavioural characteristics.
Conclusion
Ten percent of the adults in this French study used CBD, and several user profiles emerged. Our results indirectly advocate clearer European CBD regulations to ensure safe and high-quality products.
... Other findings support the hypothesis that CBD modulates THC activity through mechanisms independent of CB1 receptor involvement [14]. CBD seems to be an indirect activator of the CB1 receptor through the increase in endogenous cannabinoid anandamide levels, and it has also been identified as a negative allosteric modulator of the same receptor [15]. Other experiments suggest that CBD could act as an inverse agonist or antagonist of the cannabinoid type 2 receptor (CB2R) [16]. ...
... In a recent study of the behavioral profile of CBD (15,30, and 60 mg/kg; i.p.) as a potential drug of abuse evaluated in C57BL/6J mice, it failed to induce conditioned place preference (CPP), a form of conditioning test used to evaluate motivational effects. In the same group of experiments, spontaneous withdrawal symptoms and motor activity in the OF were also examined 12 h after the last i.p. ...
Cannabidiol (CBD) is the second cannabinoid, in order of importance after Δ9-tetrahydrocannabinol (THC), from Cannabis sativa. Unlike THC, CBD does not cause psychotomimetic effects, and although these compounds have the same chemical formula, their pharmacological characteristics are not equivalent. Preclinical studies suggest that CBD has anti-inflammatory, analgesic, anxiolytic, antiemetic, anticonvulsant, and antipsychotic properties and influences the sleep–wake cycle. The evaluation of effects on spontaneous motor activity is crucial in experimental pharmacology, and the careful measurement of laboratory animal movement is an established method to recognize the effects of stimulant and depressant drugs. The potential influence of CBD on locomotor activity has been investigated through numerous in vivo experiments. However, there is no clear picture of the impact of CBD on these issues, even though it is administered alone for medical uses and sold with THC as a drug for pain caused by muscle spasms in multiple sclerosis, and it was recently licensed as a drug for severe forms of infantile epilepsy. On this basis, with the aim of developing deeper knowledge of this issue, scientific data on CBD’s influence on locomotor activity are discussed here. We conducted research using PubMed, Scopus, Google Scholar, and a search engine for literature between January 2009 and December 2021 on life sciences and biomedical topics using the keywords “motor activity”, “locomotor activity”, and “locomotion” in combination with “cannabidiol”. In this article, we discuss findings describing the effects on locomotor activity of the CBD precursor cannabidiolic acid and of CBD alone or in combination with THC, together with the effects of CBD on locomotor modifications induced by diseases and on locomotor changes induced by other substances.
... In addition to THC, there is also considerable research being conducted into CBD, one of the most prominent (alongside THC) cannabinoids that occur naturally within the genus cannabis sativa. Similar to THC, CB D is a metabolite that requires decarboxylation to transform from its natural state of cannabidiolic acid or CB DA (Russo, 2017). First isolated in 1940 (Adams et al., 1940), over the last couple of decades evidence has been starting to accrue that suggests CBD has medicinal potential for a range of ailments. ...
... Fifth, while research into the therapeutic potential of CBD is slowly evolving (e.g. Russo, 2017) (WADA, 2019), it is apparent that similarly focussed research is necessary. The emerging relationship between cannabis consumption and fitness was briefly explored in a paper by the author and can be found in Appendix F of the book (Subritzky, 2018). ...
Contents at a glance
At a time when cannabis legalisation is spreading across an increasing number of jurisdictions globally, this book cuts across the noise and presents a factual account of issues faced by regulators in the real-world context of Colorado. It can be read as an evidence-based handbook for regulators and should be a first port of call for anyone interested in the legalisation of cannabis.
In January 2014, Colorado implemented a commercial cannabis market for pleasure - the first jurisdiction globally to implement a regulated, adult-use cannabis supply chain from seed-to-sale. It was reported as an historic occasion that presaged a grand social and economic experiment in drug legalisation.
Including analysis of hundreds of pages of government documents, almost 1000 media articles, and interviews in the field with over 30 senior government officials, industry executives, and front-line public health representatives, this book is the definitive account of real-world cannabis policy implementation.
The cannabis academic public health literature is examined prodigiously including its potential for harm and benefit together with alternative regulatory approaches. The book also features a number of papers published in academic journals based on the PhD research of the author. The commodification of cannabis vs the craft approach together with the entanglement of the medical and recreational markets are two of many topical themes discussed in detail.
Multiple recommendations relevant for other jurisdictions considering the legalisation of cannabis are presented. Recognising the limitations of harm reduction approaches that cannot conceptually conceive beneficial aspects of cannabis consumption, a new framework, the spectrum of wellness is proposed as an alternative in Appendix 1 of the book.
... Recent studies have highlighted CBD's ability to inhibit tumor growth, induce apoptosis, and suppress metastasis in preclinical models of breast cancer [6]. CBD exerts its effects through multiple mechanisms, including modulation of the endocannabinoid system, induction of apoptosis, inhibition of cell proliferation, and suppression of metastasis [6,7]. It interacts with cannabinoid receptors (CB1 and CB2) and non-cannabinoid receptors such as TRPV1 and PPARγ, contributing to its anticancer properties [8]. ...
Background
Breast cancer is one of the most prevalent cancers worldwide, posing significant challenges due to its heterogeneity and the emergence of drug resistance. Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis sativa, has recently gained attention for its potential therapeutic effects in breast cancer.
Objective
This review aims to evaluate the antitumor effects of CBD in breast cancer treatment by synthesizing preclinical and clinical evidence, elucidating its mechanisms of action, and exploring its translational potential.
Methods
A systematic review was conducted following PRISMA guidelines. A comprehensive search was performed across PubMed, Google Scholar, Web of Science, and Scopus databases, using keywords such as “Cannabidiol,” “CBD,” “Breast Cancer,” “Therapeutic Agent,” and “Antitumor Effects.” A total of 1,191 articles were initially identified. After duplicate removal and eligibility screening, 34 studies published between 1998 and 2025 were selected, including in vitro, in vivo, and clinical investigations. Studies were assessed based on PRISMA recommendations, considering inclusion criteria such as CBD’s impact on apoptosis, cell proliferation, tumor progression, and molecular mechanisms.
Results
CBD demonstrated significant anticancer effects, including induction of apoptosis, inhibition of cell proliferation, suppression of metastasis, and modulation of the tumor microenvironment. Mechanistically, CBD modulates key pathways such as PI3K/Akt, mTOR, and PPARγ and interacts with CB1, CB2, and non-cannabinoid receptors. Preclinical studies showed CBD’s efficacy, particularly in triple-negative breast cancer (TNBC), while limited clinical trials highlighted its potential as an adjunct to conventional therapies.
Conclusion
CBD offers a promising therapeutic approach for breast cancer, especially for aggressive subtypes like TNBC. However, challenges such as variability in study design, lack of standardized protocols, and limited clinical validation hinder its clinical application. Future research should focus on conducting robust clinical trials, identifying predictive biomarkers, and optimizing combinatorial therapies to integrate CBD into personalized cancer treatment strategies.
... This growing array of computational tools includes a range of approaches such as machine learning algorithms, molecular modeling techniques, and quantitative structureactivity relationship (QSAR) models [28], [29]. These advancements allow researchers to gain deeper insights into the interactions between molecules and their targets, thereby enhancing the prediction of biological activity and guiding drug discovery efforts [8], [30]. ...
Accurate prediction of CB2 receptor ligand activity is pivotal for advancing drug discovery targeting this receptor, which is implicated in inflammation, pain management, and neurodegenerative conditions. Although conventional machine learning and deep learning techniques have shown promise, their limited interpretability remains a significant barrier to rational drug design. In this work, we introduce CB2former, a framework that combines a Graph Convolutional Network with a Transformer architecture to predict CB2 receptor ligand activity. By leveraging the Transformer's self attention mechanism alongside the GCN's structural learning capability, CB2former not only enhances predictive performance but also offers insights into the molecular features underlying receptor activity. We benchmark CB2former against diverse baseline models including Random Forest, Support Vector Machine, K Nearest Neighbors, Gradient Boosting, Extreme Gradient Boosting, Multilayer Perceptron, Convolutional Neural Network, and Recurrent Neural Network and demonstrate its superior performance with an R squared of 0.685, an RMSE of 0.675, and an AUC of 0.940. Moreover, attention weight analysis reveals key molecular substructures influencing CB2 receptor activity, underscoring the model's potential as an interpretable AI tool for drug discovery. This ability to pinpoint critical molecular motifs can streamline virtual screening, guide lead optimization, and expedite therapeutic development. Overall, our results showcase the transformative potential of advanced AI approaches exemplified by CB2former in delivering both accurate predictions and actionable molecular insights, thus fostering interdisciplinary collaboration and innovation in drug discovery.
... CBD bears a striking resemblance in structure to Δ9-tetrahydrocannabinol (THC), the primary psychoactive cannabinoid compound. Nevertheless, CBD does not elicit feelings of euphoria [24] and possesses a minimal risk of abuse [25]. It has been shown that D1 dopaminergic receptors (D1Rs) in the DG of the rat hippocampal DG mediate the inhibitory impact of CBD on METH rewarding effects [26]. ...
Methamphetamine (METH), a stimulant that is extremely addictive, directly affects the central nervous system. METH's abuse and consumption are directly linked to mental illnesses, psychosis, and behavioral and cognitive impairments. It may disrupt the reward system and dopaminergic transmission. METH's rewarding qualities are associated with a rise in dopamine. Additionally, cannabidiol (CBD), one of the primary cannabinoid components of the cannabis plant, significantly affects dopaminergic transmission and may aid in reward- and addiction-related behaviors. To shed light on the role of the D2-like dopamine receptor (D2R) in the hippocampal dentate gyrus (DG), the present study examined the effects of CBD on the acquisition and expression of the conditioned place preference (CPP) induced by METH. The function of D2R was ascertained by delivering Sulpiride microinjections, as a D2R antagonist Sulpiride (0.25, 1, and 4 μg/0.5 μL DMSO12%) into the DG. Moreover, an intracerebroventricular injection of CBD at a dose of 10 μg/5 μL for CPP acquisition and 50 μg/5 μL for CPP expression was given to rats. According to the current research, CBD dramatically reduced the acquisition and expression of CPP resulting from METH. However, Sulpiride suppressed the effect of CBD on METH-induced CPP acquisition and expression, with a greater impact on expression experiments. Ultimately, this study proposed that the expression experiment of METH-induced CPP appears to be heavily dependent on D2R in the DG.
... CBD has powerful interactions with several CYP450 enzymes that are involved in the metabolism of drugs. Moreover, it has been discovered that CBD works through a variety of intricate pharmacological processes, including the inhibition of endocannabinoid reuptake and GPR55, the action of TRPV1, and increased activity of serotonin 5-HT 1A receptor proteins [19,20]. ...
... [ [76][77][78] CBDA Rescued memory deficits and reduced amyloid-beta and Tau pathology in an Alzheimer's disease-like mouse model [79] Antioxidant, anti-inflammatory, analgesic effect [74,82] CBGA Exhibits antioxidant activity manifested in its ability to scavenge free radicals, to prevent the oxidation process, and to reduce metal ions [85] ...
Cannabis sativa, otherwise known as hemp, is discussed to highlight the various problems and prospects associated with its use as an herbal ingredient. The chemical composition of hemp, with classification based on cannabinoid contents, its biological activities, current global scenarios and legality issues, economic importance, and future prospects, are discussed.
... CBD has powerful interactions with several CYP450 enzymes that are involved in the metabolism of drugs. Moreover, it has been discovered that CBD works through a variety of intricate pharmacological processes, including the inhibition of endocannabinoid reuptake and GPR55, the action of TRPV1, and increased activity of serotonin 5-HT 1A receptor proteins [19,20]. ...
Cannabis sativa has long been used for neurological and psychological healing. Recently, cannabidiol (CBD) extracted from cannabis sativa has gained prominence in the medical field due to its non-psychotropic therapeutic effects on the central and peripheral nervous systems. CBD, also acting as a potent antioxidant, displays diverse clinical properties such as anticancer, antiinflammatory, antidepressant, antioxidant, antiemetic, anxiolytic, antiepileptic, and antipsychotic effects. In this review, we summarized the structural activity relationship of CBD with different receptors by both experimental and computational techniques and investigated the mechanism of interaction between related receptors and CBD. The discovery of structural activity relationship between CBD and target receptors would provide a direction to optimize the scaffold of CBD and its derivatives, which would give potential medical applications on CBD-based therapies in various illnesses.
Graphical Abstract
... It is mainly used for its THC (tetrahydrocannabinol) content, which is responsible for its intoxicating effects. More than 100 other cannabinoids including, CBD (cannabidiol), are non-intoxicating ( Figure 5) (Russo, 2017). ...
Background
Most Bantu ethnic groups in southern Africa utilize indigenous herbal medicines, some of which have psychoactive properties. Traditional medical practitioners (TMPs) commonly use them not only for divinatory purposes but to treat and manage mental and other illnesses. Unfortunately, the research on their results, risks, and benefits do not align. Little is known about their potential abuse among TMPs and community members in southern Africa. Herbal medicines are complex because whole plants are sometimes used, unlike in other treatments which use only one active ingredient. However, if the key mechanisms of action of these ethnomedicinal plants can be identified through socio-pharmacological research, useful botanical agents can be developed. A review of socio-pharmacological studies to evaluate the consequences of exposure to ethnomedicinal plants with psychoactive properties was conducted with the aim of identifying harm reduction strategies and investigating how the plants could be developed into useful botanicals.
Method
The search methods involved retrieval of records from PubMed/MEDLINE, Embase, Web of Science, Dissertations and Theses Global, and OpenGrey. The English language and human subjects were used as filters. In addition, some information was obtained from TMPs and community members.
Results
The following psychoactive plants were found to be commonly used or abused: Boophone disticha, Cannabis sativa, Datura stramonium, Leonotis leonurus, Psilocybe cubensis, and Sceletium tortuosum. The commercialization of Cannabis, L. leonurus, S. tortuosum, and Aspalathus is growing fast. The abuse liability of B. disticha, D. stramonium, and P. cubensis appears not to be appreciated. Five countries were found to have TMP policies and three with TMP Councils.
Conclusion
TMPs in the region are aware of the CNS effects of the identified psychoactive plants which can be explored further to develop therapeutic agents. There is a need to work closely with TMPs to reduce harm from the abuse of these plants.
... Currently, in most parts of the world, it is also not a first-line treatment. Rather, eligible patients have not responded well to other medicines, or experience unacceptable side effects (Russo, 2017). While only a few are officially registered medicines, cannabis products for medical use are still required to meet certain quality standards. ...
Cannabis is now one of the most thoroughly studied and analyzed plant materials. More than 100 cannabinoids have been isolated and identified in cannabis along with the primary psychoactive component, Δ9-tetrahydrocannabinol (Δ9-THC). In addition to Δ9-THC, there are other components of cannabis that are medically beneficial. For example, cannabidiol (CBD) and cannabigerol (CBG) can moderate or influence the psychoactive effects of Δ9-THC. The raw cannabis plant consists of cannabinoids in their acidic form. When someone states that cannabinoids are in their "acidic form", they are referring to the chemical structure of the compound itself. A cannabinoid in its acidic form has a carboxyl group (-COOH) attached. While tetrahydrocannabinolic acid (THCA) is the non-psychoactive precursor to THC, it does not bind to the CB1 and CB2 receptors. Instead, it binds with other cannabinoids receptors in the endocannabinoid system. When THC is not decarboxylated, it is THCA. Although THCA possesses therapeutic effects, like anti-inflammatory and neuroprotective qualities, it is not in its most beneficial or psychoactive form. Decarboxylation is a chemical reaction that removes a carboxyl group (-COOH) and releases carbon dioxide (CO2). The two main catalysts for decarboxylation to occur are heat and time. High CBD strains tend to decarboxylate a bit slower than those with high THC content. Decarboxylate high CBD strains by baking them for 15-20 minutes at 149°C and decarboxylate high THC strains by baking them for 10-18 minutes at the same temperature (149°C) in the oven. Full decarboxylation may require more time to occur. It is important to keep tight temperature control applying cannabis to various technological applications. While heat is needed to decarboxylate the acids into the active form of cannabinoids our bodies can use, extreme temperatures can destroy many of the important plant materials that contribute to positive health outcomes, like terpenes.
... vestigations of CBG pharmacology identified interactions with various receptors (Fig. 1, Ref. [38]). CBG exhibited limited agonism/antagonism at cannabinoid type-1 (CB1R) and type-2 (CB2R) receptors and also acted as an agonist for α2-adrenoceptors and showed affinity for 5-hydroxytryptamine-1A receptors (5HT1AR) as antagonist [42]. CBG also activated TRPA1-mediated calcium elevation but antagonized menthol-or sicilian-induced calcium elevation through TRPM8 [43,44]. ...
Neurodegenerative disorders pose significant societal and individual burdens, marked by progressive degeneration of the nervous system. The limited efficacies of current treatments underscore the pressing need for innovative therapeutic approaches. Cannabigerol (CBG) is a cannabinoid derivative found in the plant genus Cannabis that is viewed as a molecule of therapeutic interest due to its unique pharmacological profile and interactions with the endocannabinoid system (ECS). This comprehensive review explores the therapeutic potential of CBG for the treatment of disorders of the nervous system, such as Alzheimer’s and Parkinson’s disease. Preclinical investigations have revealed that the neuroprotective properties of CBG involve ECS modulation, promoting neuronal survival, and mitigating neuroinflammation and oxidative stress. However, it should be acknowledged that
much of the research on the therapeutic potential of CBG is still in its early stages and primarily consists of in vitro and animal studies. Further clinical trials and research are needed to determine the efficacy and safety of CBG and the optimal dosing strategies required to treat neurodegenerative diseases. This review also explores the transformative potential of nanocarrier systems in CBG-centered therapies targeting neurodegenerative disorders and discusses the merits and demerits of various nanocarrier systems. This dual focus on the therapeutic potential of CBG and innovative distribution systems underscores the extent of the
investigative work required to advance neurodegenerative disease management.
... CBD can have interactions with several molecular targets, such as enzymes, nuclear receptors, ionotropic receptors, metabotropic receptors, etc. Hence, exploring the feasible signaling pathways that contribute to pharmacological effects is imperative [15][16][17][18]. ...
Cannabidiol (CBD), a cannabinoid that does not create psychoactive activities, has been identified as having a multitude of therapeutic benefits. This study delves into the chemical properties, pharmacokinetics, safety and toxicity, pharmacological effects, and most importantly, the association between the therapeutic potential of CBD and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. The relationship between Nrf2 and CBD is closely linked to certain proteins that are associated with cardiovascular dysfunctions, cancers, and neurodegenerative conditions. Specifically, Nrf2 is connected to the initiation and progression of diverse health issues, including nephrotoxicity, bladder-related diseases, oral mucositis, cancers, obesity, myocardial injury and angiogenesis, skin-related inflammations, psychotic disorders, neuropathic pain, Huntington's disease, Alzheimer's disease, Parkinson's disease, neuroinflammation, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis. The association between CBD and Nrf2 is a zone of great interest in the medical field, as it has the potential to significantly impact the treatment and prevention of wide-ranging health conditions. Additional investigation is necessary to entirely apprehend the mechanisms underlying this crucial interplay and to develop effective therapeutic interventions.
... It is novel to use cannabis as a source of biologically active ingredients in food (Shahbazi et al., 2020;Walker et al., 2021). Dietary models based on the use of cannabis in beverages, concentrated oils, encapsulated extracts, or oils have been developed (Blake & Nahtigal, 2019;Russo, 2017). Test data, predictive results, and final quantitative and qualitative assessments may help monitor the use of cannabinoids in food systems. ...
There are differing views on cannabis and phytocannabinoid usage in diverse domains of application. This review explores the advantages and drawbacks of using cannabis and phytocannabinoids, including their effects on human health, in addition to highlighting the need for precise and repeatable analytical methods for quantifying controlled phytocannabinoids in consumer cannabidiol (CBD) products and foods. The composition and characteristics of the phytochemicals found in cannabis, the advantages and disadvantages of controlled and uncontrolled phytocannabinoids, and the need for regulation and standardization in the use of cannabis and products containing phytocannabinoids are all covered in this review of the pertinent literature. Cannabinoids used illegally can have negative consequences, but controlled phytocannabinoids found in consumer CBD products are relatively safe and unlikely to cause any adverse effects. It is necessary to restrict the amount of CBD in foods and consumer products in order to ensure safety. To measure the amount of restricted phytocannabinoids in these products, accurate analytical techniques are also required. In order to increase the use of cannabis among consumers, more research is needed to improve our understanding of the bioavailability and metabolic pathways of these compounds. Furthermore, consumers want clear and uniform federal rules governing the amount of CBD in food products in order to ensure correct dosing. To promote safe and responsible use, cannabis and phytocannabinoids must be carefully considered, regulated, and standardized. It is necessary for consumers to have clear, consistent standards governing the percentage of CBD in their food products. As a result, they would know the exact amount of CBD in their products.
... O estudo demonstrou a emissão de pareceres favoráveis para o acesso ao CBD por via judicial, mesmo quando a prescrição estava fora das indicações terapêuticas conforme o registro do produto na Anvisa. A prescrição e a concessão judicial para uso off-label (fora das indicações dos produtos à base de CBD registrados na agência) podem estimular a divulgação do CBD como uma panaceia para uma ampla gama de problemas de saúde e tentativa de comercialização para outros fins, como dietético e de bem-estar 32 . ...
Este estudo analisou as ações judiciais de pacientes que solicitaram ao Sistema Único de Saúde produtos à base de canabidiol (CBD) durante o período de 2019 a 2022, descrevendo características sociodemográficas, clínicas e jurídicas. Trata-se de um estudo transversal composto pela avaliação das notas técnicas emitidas pelos Núcleos de Apoio Técnico do Judiciário (NatJus), que embasaram as decisões judiciais. Os dados foram obtidos do sistema e-NatJus, do Ministério da Justiça, utilizando técnicas de web scraping. Regressão logística foi empregada para estimar razões de chances com intervalos de 95% de confiança. Foram analisadas 1.115 notas técnicas das ações demandantes de CBD, das quais 54,7% dos pacientes eram do sexo masculino, com idade média de 18,4 anos, em sua maioria da Região Sul do país (38,8%), e 49,6% buscavam tratamento para epilepsia. Das ações com pareceres favoráveis, 28,8% não tinham evidências científicas, 26,5% pleitearam produtos sem registro na Agência Nacional de Vigilância Sanitária e 25,3% dos que tinham registro não estavam em conformidade com a indicação terapêutica. Os pacientes da Região Nordeste tiveram a chance de parecer favorável aumentada em 3 vezes; e os que tinham diagnóstico de epilepsia, em 2,3 vezes. Os pareceres técnicos que deram suporte aos magistrados para as decisões judiciais das demandas de pacientes por produtos à base de canabidiol no Brasil estavam, em sua maioria, em conformidade com evidências científicas, denotando a importância dos NatJus na qualificação do acesso a produtos medicinais no país.
... The cannabinoids, C21 terpenophenolic compounds, are considered as the leading class of Cannabis's pharmacological activity, being the ones responsible for interaction with the central nervous system's CB1 and CB2 receptors [1]. Among them, Δ9tetrahydrocannabinol (THC) is considered as the compound with the most notable psychoactive and pain relief effects [2]. However, the active form of THC does not occur at a significant concentration in the plants, being synthesized as Δ9-tetrahydrocannabinolic acid (THCA). ...
The decarboxylation of Δ9-tetrahydrocannabinolic acid (THCA) plays pivotal role in the potency of medical cannabis and its extracts. However, the literature data point out substantial variations in the process reaction rate and conversion efficacy due to variability of the temperature, heat transfer efficacy, raw material attributes, consequently resulting in incomplete decarboxylation, cannabinoid content decrease due to decomposition, evaporation, and possible side reactions. Our present work aims to draw attention to mid-infrared (MIR) spectroscopy for in-situ monitoring and decipher the THCA decarboxylation reaction in the solid state. The initial TG/DTG curves of THCA, for a first time outlined the solid-solid decarboxylation dynamics, defined the endpoint of the process and the temperature of the maximal conversion rate, which aided in the design of the further IR experiments. Temperature controlled IR spectroscopy experiments were performed on both THCA standard and cannabis flower by providing detailed band assignment and conducting spectra-structure correlations, based on the concept of functional groups vibrations. Moreover, a multivariate statistical analysis was employed to depict the spectral regions of utmost importance for the THCA→THC interconversion process. The principal component analysis model was reduced to two PCs, where PC1 explained 94.76% and 98.21% of the total spectral variations in the THCA standard and in the plant sample, respectively. The PC1 plot score of the THCA standard, as a function of the temperature, neatly complemented to the TG/DTG curve and enabled determination of rate constants for the decarboxylation reaction undertaken on several temperatures. Consequently, a progress in elucidation of kinetic models of THCA decarboxylation, fitting experimental data for both, solid state standard substance and a plant flower, was achieved. The results open the horizon to promote an appropriate process analytical technology (PAT) in the outgrowing medical cannabis industry.
... [1,2] Archaeologists discovered traces of cannabis seeds in Siberia dating as far back as 3000 BC. [3] Cannabis was used recreationally up until 1961 when it was included as a controlled substance in the United Nations' Single Convention on Narcotic Drugs. [4,5] Recently about 33 states in the United States have legalized the use of cannabis for recreational and medicinal use. [6] Cannabis remains the most widely used drug globally, with an estimated 188 million people having used the drug. ...
The use of cannabis for medical purposes has been a subject for discussion for so many years. Cannabis as a source of medical treatment first came to light in the 19th century. However, origins of cultivation of marijuana as a medical plant can be traced back to thousands of years. Attempts to completely legalize the use of cannabis for medical purposes are strongly contested in many places due to some of its negative effects on users physically, psychologically, and socially. This review is aimed to discuss the mechanism of action and pharmacogenetics of cannabinoids to elucidate its uses as medicine as well as negative effects. Online searches on the following database: Google Scholar, PubMed, Biomed Central, and SciELO were done. An attempt was made to review articles with keywords such as cannabis, cannabinoid receptors, genes, and medical marijuana. This review has highlighted with evidence the importance of genomic profiling to prevent side effects associated with predisposing genes for the benefit of patients who are medical candidates for medicinal cannabis use. Medical profiling via cannabinoid gene expression studies of patients who are medical candidates of cannabis could prevent the negative effects associated with its use.
... Currently, Cannabis-derived products are used as the common ingredients in skin care products such as body oils, moisturizers, lotions, and lip balms, but scientific research on the topical safety and usefulness of the formulations are scarce (Anwar et al., 2006;Stella et al., 2019). Recently, the endocannabinoid system was found, which comprises receptors, ligands, and enzymes that are broadly expressed in the brain and the periphery, where they operate to achieve stability in many homeostatic processes (Russo & Guy, 2006;Russo, 2017;Vaidya et al., 2022). ...
Cannabis sativa L. is a flowering plant in the family Cannabaceae, and has been cultivated since ancient times for its fibres, oils, resins, dried inflorescences, and leaves. It can be used for a variety of industrial purposes. Over the years, the therapeutic and pharmacological efficacy of its phytoconstituents is shown in a variety of human diseases and health. The use and exploitation of the plant have sparked controversy; however, there are recent legalizations of its use for medical and other purposes in many countries within the corresponding legislative framework. In addition to this legalization, C. sativa is encouraging the very rapid growth of the cannabis oriented pharmaceutical industry. This chapter summarized recent developments in the science of C. sativa and its products about their industrial application, while also addressing gaps in the existing knowledge and future research directions for this high-value multi-use, and potential industrial plant with universal benefits.
... Interpretation of these findings is further complicated by the suggestion that CBD is not, by itself, sedating. Although cannabis high in CBD can produce lethargy (Crippa et al., 2004;Pearce et al., 2014;Zhornitsky & Potvin, 2012), it has been argued (Russo, 2011(Russo, , 2016(Russo, , 2017) that those effects actually are caused by the terpene βmyrcene, which often co-occurs with CBD. And because concentrations of β-myrcene vary considerably among strains, it follows that sedating properties of these strains, and possibly the crash risk, may vary as well. ...
Background:
β-myrcene, one of the most common terpenes found in cannabis, has been associated with sedation. We propose that β-myrcene contributes to driving impairment even in the absence of cannabinoids.
Aim:
To conduct a double-blind, placebo-controlled crossover pilot study of the effect of β- myrcene on performance on a driving simulator.
Method:
A small sample (n=10) of participants attended two experimental sessions, one in which they were randomized to receive 15 mg of pure β-myrcene in a capsule versus a canola oil control. Each session, participants completed a baseline block and three follow-up blocks on a STISIM driving simulator.
Results:
β-myrcene was associated with statistically significant reductions in speed control and increased errors on a divided attention task. Other measures did not approach statistical significance but fit the pattern of results consistent with the hypothesis that β-myrcene impairs simulated driving.
Conclusions:
This pilot study produced proof-of-principle evidence that the terpene β-myrcene, an agent commonly found in cannabis, can contributes to impairment of driving-related skills. Understanding how compounds other than THC affect driving risk will strengthen the field's understanding of drugged driving.
... Occasionally, novel polymorphisms of commonly known fALS genes produce sALS, as do oligogenic reasons that are becoming more well-identified (Song et al 2022a, b;Leblond et al. 2014). Also, ALS has a wide range of those first symptoms, including fasciculations and weakness in the legs, arms, limbs, and neck, and difficulties in chewing swallowing, and speaking, but it really stems from nerve cell death, which causes involuntary and voluntary muscle disruption (Russo 2017). The majority of sALS and fALS cases are connected to prion-like agglomeration of wild-type (WT) and mutated SOD1 in nerve cells, accompanied by proliferation of nerve fibers (Sironi 2022;Kerman et al. 2010;Stern and Lambert 2007;Münch et al. 2011;Lee and Kim 2015;Ayers et al. 2016). ...
Amyotrophic lateral sclerosis (ALS) is a rare, cumulative neurological deteriorating disease that disturbs the neurons (nerve cells) that control voluntary muscle movement (those muscles we choose to move). Currently, the Food and Drug Administration (FDA) approved drugs such as Radicava, Rilutek, Tiglutik, Exservan, and Nuedexta to treat ALS. Given the wide range of pharmaceutical applications of heterocyclic compounds, especially those containing the nitrogen ring systems such as pyridine, pyrimidine, and indole. These molecular frameworks have piqued the interest of medicinal chemists for further investigation in a variety of diseases. We have found several review works done on this research topic. Until now, no reviews published on the nitrogen heterocycles for treating ALS. This review examines the major causes of ALS, a brief history of medications that have been used to treat it so far, and the most recent breakthroughs in nitrogen ring systems for treating ALS. The novelty of this study provides insights on several effective synthetic techniques for nitrogen-based heterocyclic medications that operate as potent anti-inflammatory treatments and guard against ALS. KEY POINTS: • Pharmacological activity of heterocyclic compounds. • Neurodegenerative diseases and their drawbacks are discussed in detail. • Recent survey of nitrogen heterocycles in treating ALS disease are highlighted.
... 36 CBD on the other hand is described as a ''nonintoxicating,'' anticonvulsive, anxiolytic, and anti-inflammatory cannabinoid, with no significant drug abuse liability. 37 Recent studies documenting the therapeutic virtues of CBD have promoted research into nonintoxicating cannabinoids, therefore, justifying the recent interest in CBD as a potential therapeutic molecule. 7,19,36,38 Advancement made in the field of synthetic chemistry has paved the way toward the development of more potent and selective synthetic cannabinoids using Phytocannabinoids as a framework (e.g., more HU-308) ( Table 2). ...
Introduction: Cannabidiol (CBD) is the second most abundant Phytocannabinoid in Cannabis extracts. CBD has a binding affinity for several cannabinoid and cannabinoid-associated receptors. Epidiolex (oral CBD solution) has been lately licensed by the Food and Drug Administration (FDA) for the treatment of pediatric epileptic seizures. Methods: In this review, we discussed the most promising applications of CBD for chronic inflammatory conditions, namely CBD's anti-inflammatory effects during inflammatory bowel disease, coronavirus disease (antiviral effect), brain pathologies (neuroprotective and anti-inflammatory properties), as well as CBD immunomodulatory and antitumoral activities in the tumor microenvironment. Special focus was shed on the main therapeutic mechanisms of action of CBD, particularly in the control of the immune system and the endocannabinoid system. Results: Findings suggest that CBD is a potent immunomodulatory drug as it has manifested immunosuppressive properties in the context of sterile inflammation (e.g., inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative diseases), and immunoprotective effects during viral infections (e.g. COVID-19) Similarly, CBD has exhibited a selective response toward cancer types by engaging different targets and signaling pathways. These results are in favor of the primary function of the endocannabinoid system which is homeostatic maintenance. Conclusion: The presented evidence suggests that the endocannabinoid system is a prominent target for the treatment of inflammatory and autoimmune diseases, rheumatoid diseases, viral infections, neurological and psychological pathologies, and cancer. Moreover, the antitumoral activities of CBD have been suggested to be potentially used in combination with chemo- or immunotherapy during cancer. However, clinical results are still lacking, which raises a challenge to apply translational cannabis research to the human immune system.
... This is especially crucial for hemp growers, as they need to adhere to regulations concerning legal threshold levels of THC. The hemp inflorescence is traditionally considered to contain mainly cannabidiol (CBD) (Stoa, 2017), a biologically active and non-intoxicating cannabinoid (Russo, 2017), and only trace amounts of THC the primary psychoactive component of cannabis. Irrespective of the botanical distinction of hemp, in numerous countries throughout the world, the level of THC in the inflorescences at harvest is the sole factor that differentiates legally between hemp and drug-type cannabis. ...
Recent studies highlight the therapeutic virtues of cannabidiol (CBD). Furthermore, due to their molecular enriched profiles, cannabis inflorescences are biologically superior to a single cannabinoid for the treatment of various health conditions. Thus, there is flourishing demand for Cannabis sativa varieties containing high levels of CBD. Additionally, legal regulations around the world restrict the cultivation and consumption of tetrahydrocannabinol (THC)-rich cannabis plants for their psychotropic effects. Therefore, the use of cannabis varieties that are high in CBD is permitted as long as their THC content does not exceed a low threshold of 0.3%–0.5%, depending on the jurisdiction. These chemovars are legally termed ‘hemp’. This controlled cannabinoid requirement highlights the need to detect low levels of THC, already in the field. In this review, cannabis profiling and the existing methods used for the detection of cannabinoids are firstly evaluated. Then, selected valuable biosensor technologies are discussed, which suggest portable, rapid, sensitive, reproducible, and reliable methods for on-site identification of cannabinoids levels, mainly THC. Recent cutting-edge techniques of promising potential usage for both cannabis and hemp analysis are identified, as part of the future cultivation and agricultural improvement of this crop.
... For this definition, we look to the World Health Organization; "Any substance that affects mental processes when ingested" is considered to be psychoactive [41]. All forms of cannabidiol have been demonstrated to alter serotonin levels, which affects the mental process by providing a sense of contentment [42,43]. If the government has patented a form of cannabidiol that does not alter serotonin levels when intromitted, it is unique in the cannabinoid world. ...
This disquisition provides historical context illustrating the psychosocial, political, and bureaucratic barriers to applying a biomolecular approach to substance use disorders, focusing on what are arguably the most stigmatized molecules in America. It provides a biomolecular treatment strategy designed to mitigate multiple types of addiction by influencing the dopamine and serotonin neurotransmitters' activity through phytocannabinoid supplementation of the endocannabinoid system and proposes a strategy for circumventing the bureaucratic obstacles.
... The bestknown cannabinoids are THC and cannabidiol (CBD). In contrast to THC, CBD is regarded as non-intoxicating [10], while exerting various other effects. CBD is, for example, licensed for the treatment of rare forms of childhood epilepsy [11][12][13][14]. ...
Cannabis sativa ( C. sativa ) is commonly chemically classified based on its Δ ⁹ -tetrahydrocannabinol (THC) and cannabidiol (CBD) content ratios. However, the plant contains nearly 150 additional cannabinoids, referred to as minor cannabinoids. Minor cannabinoids are gaining interest for improved plant and product characterization, e.g., for medical use, and bioanalytical questions in the medico-legal field. This study describes the development and validation of an analytical method for the elucidation of minor cannabinoid fingerprints, employing liquid chromatography coupled to high-resolution mass spectrometry. The method was used to characterize inflorescences from 18 different varieties of C. sativa , which were cultivated under the same standardized conditions. Complementing the targeted detection of 15 cannabinoids, untargeted metabolomics employing in silico assisted data analysis was used to detect additional plant ingredients with focus on cannabinoids. Principal component analysis (PCA) was used to evaluate differences between varieties. The overall purpose of this study was to examine the ability of targeted and non-targeted metabolomics using the mentioned techniques to distinguish cannabis varieties from each other by their minor cannabinoid fingerprint. Quantitative determination of targeted cannabinoids already gave valuable information on cannabinoid fingerprints as well as inter- and intra-variety variability of cannabinoid contents. The untargeted workflow led to the detection of 19 additional compounds. PCA of the targeted and untargeted datasets revealed further subgroups extending commonly applied phenotype classification systems of cannabis. This study presents an analytical method for the comprehensive characterization of C. sativa varieties.
Graphical abstract
... In Europe, hemp was defined as Cannabis sativa plants containing less than 0.2% of the intoxicating cannabinoid Δ9-tetrahydrocannabinol (THC), but recent changes to laws and the adoption of the new Common Agricultural Policy have increased this to less than 0.3%. This figure is less than 0.3% in North America and Asia (Russo, 2017;Hammami et al., 2021). Drug-type Cannabis plants are grown for their high levels of the intoxicating THC and are commonly referred to as marijuana. ...
Hemp (Cannabis sativa L.) is a multipurpose crop with many important uses including medicine, fibre, food and biocomposites. This plant is currently gaining prominence and acceptance for its valuable applications. Hemp is grown as a cash crop for its novel cannabinoids which are estimated to be a multibillion-dollar downstream market. Hemp cultivation can play a major role in carbon sequestration with good CO2 to biomass conversion in low input systems and can also improve soil health and promote phytoremediation. The recent advent of genome editing tools to produce non-transgenic genome-edited crops with no trace of foreign genetic material has the potential to overcome regulatory hurdles faced by genetically modified crops. The use of Artificial Intelligence - mediated trait discovery platforms are revolutionizing the agricultural industry to produce desirable crops with unprecedented accuracy and speed. However, genome editing tools to improve the beneficial properties of hemp have not yet been deployed. Recent availability of high-quality Cannabis genome sequences from several strains (cannabidiol and tetrahydrocannabinol balanced and CBD/THC rich strains) have paved the way for improving the production of valuable bioactive molecules for the welfare of humankind and the environment. In this context, the article focuses on exploiting advanced genome editing tools to produce non-transgenic hemp to improve the most industrially desirable traits. The challenges, opportunities and interdisciplinary approaches that can be adopted from existing technologies in other plant species are highlighted.
... The phytocannabinoid Δ 9 -tetrahydrocannabinol (THC) is predominantly responsible for the experienced mental high felt by consumers of cannabis products, 1,2 whereas cannabidiol (CBD), a further wellknown cannabinoid, is regarded as non-intoxicating, 3 while thought to exert other effects including anticonvulsive, anti-inflammatory, mildly sedative, and anxiolytic properties. [4][5][6] Cannabinol (CBN), a non-enzymatically generated degradation product from THC, 7,8 can also be found in trace amounts in cannabis products. ...
Introduction:
Cannabis is the most frequently consumed illegal substance worldwide. More recently, an increasing number of legal cannabis-products low in psychoactive Δ9 -tetrahydrocannabinol (THC), but high in non-intoxicating cannabidiol (CBD) are being more widely consumed. While the detection and quantification of THC and its metabolites in biological matrices is an important forensic-toxicological task, additional detection of CBD is also important, for example when examining the plausibility of consumer's statements. This report describes the method validation for the quantitative determination of THC and its two major metabolites, 11-hydroxy-THC (OH-THC) and 11-nor-9-carboxy-THC (THC-COOH), as well as CBD and cannabinol (CBN) in whole blood and urine.
Method:
The method employs automated on-line solid phase extraction coupled to gas chromatography tandem mass spectrometry (GC-MS/MS). The method was fully validated according to guidelines of the Swiss Society of Legal Medicine (SGRM) and the Society of Toxicological and Forensic Chemistry (GTFCh).
Results:
The method fulfilled the validation criteria regarding analytical limits, accuracy and precision, extraction efficacy, and sample stability. Limits of detection (LOD) and quantification (LOQ) in whole blood and urine were 0.15 ng/mL and 0.3 ng/mL, respectively, for THC, OH-THC and CBD, 0.1 ng/mL and 0.2 ng/mL, respectively, for CBN, and 1.0 ng/mL and 3.0 ng/mL, respectively, for THC-COOH.
Conclusion:
The fully validated and automated method allows sensitive and robust measurement of cannabinoids in whole blood and urine. Detection of CBD provides additional information regarding consumed products.
... One potential option is cannabidiol. Cannabidiol (CBD), the non-intoxicating component of the cannabis sativa plant (Russo, 2017), does not alter subjective experience in the same way as ∆ 9tetrahydrocannabinol (THC). Data suggest that CBD can reduce inflammation, mitigate seizure frequency, prevent neural degeneration, and decrease other concerns in both clinical and preclinical studies (Devinsky et al., 2016;Gu et al., 2019;Iuvone et al., 2009;Karl et al., 2017;Ribeiro et al., 2015;Scuderi et al., 2009). ...
Background: Nearly one-third of American adults receive an anxiety disorder diagnosis in their lifetimes. Although evidence-based anxiety interventions exist, these treatments might have limited availability and efficacy. Though preliminary evidence supports the use of cannabidiol (CBD) to alleviate anxiety, no prior work investigates individuals’ expectancies about CBD’s impact on anxiety.
Methods: The present study examines relevant anxiety symptoms and expectancies about CBD’s effects in a sample of 455 CBD-using adults recruited from Amazon’s MTurk platform.
Results: Participants reported moderate anxiety without the influence of CBD. Moreover, they expected global and symptom-level anxiolytic effects of CBD. Anxiety scores positively covaried with usual cannabis intoxication, providing support for a self-medication hypothesis. Results revealed a positive relation between anxiety symptoms and expectancies about CBD’s anxiolytic properties; those who were most anxious expected more CBD-related relief. CBD consumption decreased as age increased, but showed little variation with other demographic variables.
Conclusions: Overall, individuals appear to hold positive expectancies about CBD’s anxiolytic potential. Results support placebo-controlled randomized clinical trials for CBD as an anxiolytic.
... The cannabinoids, C21 terpenophenolic compounds, are considered as the leading class of cannabis's pharmacological activity, being the ones responsible for interaction with the central nervous system's CB1 and CB2 receptors [1]. Among them, D9tetrahydrocannabinol (THC) is considered to exert the most notable psychoactive and pain relief effects [2]. However, the active form of THC does not occur at a significant concentration in the plants, being synthesized as D9-tetrahydrocannabinolic acid (THCA). ...
The decarboxylation of Δ9-tetrahydrocannabinolic acid (THCA) plays pivotal role in the potency of medical cannabis and its extracts. Our present work aims to draw attention to mid-infrared (MIR) spectroscopy to in-situ monitor and decipher the THCA decarboxylation reaction in the solid state. The initial TG/DTG curves of THCA, for a first time, outlined the solid–solid decarboxylation dynamics, defined the endpoint of the process and the temperature of the maximal conversion rate, which aided in the design of the further IR experiment. Temperature controlled IR spectroscopy experiments were performed on both THCA standard and cannabis flower by providing detailed band assignment and conducting spectra-structure correlations, based on the concept of functional groups vibrations. Moreover, a multivariate statistical analysis was employed to address the spectral regions of utmost importance for the THCA → THC interconversion process. The principal component analysis model was reduced to two PCs, where PC1 explained 94.76% and 98.21% of the total spectral variations in the THCA standard and in the plant sample, respectively. The PC1 plot score of the THCA standard, as a function of the temperature, neatly complemented to the TG/DTG curves and enabled determination of rate constants for the decarboxylation reaction undertaken on several selected temperatures. The predictive capability of MIR was further demonstrated with PLS (R2X = 0.99, R2Y = 0.994 and Q2 = 0.992) using thermally treated flower samples that covered broad range of THCA/THC content. Consequently, a progress in elucidation of kinetic models of THCA decarboxylation in terms of fitting the experimental data for both, solid state standard substance and a plant flower, was achieved. The results open the horizon to promote an appropriate process analytical technology (PAT) in the outgrowing medical cannabis industry.
... It is an important ‗entourage compound' in the sense that it decreases the side effects of THC, thereby increasing the safety profile of cannabis extracts [18] . In fact, in its physiologically meaningful dosage it binds to neither CB1 nor CB2 receptors, thereby bypassing all the psychoactive actions of THC [19] . Incidentally, CBDA blocks the transporter protein for endocannabinoids, which has a high affinity to fatty acids, which in turn prolongs the activation of the CB1 receptor [20,21] . ...
Millions of Americans use cannabis for medical purposes including but not limited to pain, nausea, mood changes and appetite stimulation. The use of cannabinoid in the palliative care setting is a relatively new trend. Given the fact that a patient receiving palliative care is not necessarily approaching death, the increasing need for palliative care as the American population ages, this literature review was compiled in order to examine the potential efficacy of cannabis in treating the mental health comorbidities of palliative care patients. We attempted to create the most comprehensive report on cannabinoid use in palliative psychiatry. It summarizes the most recently published science on cannabinoid use in palliative care patients and its impact on mood and anxiety symptoms. The mechanism of action of cannabinoids on their associated receptors was elucidated, as were the pharmacological roles that specific molecules in cannabinoids, like cannabidiolic acid and terpenes, play in cannabinoids’ overall efficacy. The legal impediments to widespread cannabis use were also explored. While the potential efficacy of cannabinoids has proven to be mixed, more research is necessary to ensure that a potentially vital resource in treating palliative care patients does not go underutilized.
... On the other hand, some other studies have evidenced CBD as a negative allosteric modulator, i.e., it could reduce the affinity or efficacy of an orthosteric ligand [102]. As a liposoluble substance, CBD shows low oral bioavailability (13-19%), but it quickly overcomes the blood-brain barrier (BBB) when used as an injectable [100,103,104]. The mechanism of action of CBD (3) remains unclear [105], and one hypothesis is that CBD (3) does not have specific receptors [106,107] but it is capable of modulating concomitantly more than one receptor, and exerts an agonist effect on transient receptor potential ion channels (TRPV1, TRPV2, TRPA1 e TRPM8) [108,109], which forces some authors to describe CBD (3) as a potential multitarget drug candidate [110,111]. ...
Nowadays, neurodegenerative diseases (NDs), such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), represent a great challenge for different scientific fields, such as neuropharmacology, medicinal chemistry, molecular biology, and medicine, once all these pathologies remain incurable, with high socio-economic impacts and high costs for governmental health services. Due to their severity and multifactorial pathophysiological complexity, the available approved drugs for clinics have not yet shown adequate effectiveness in disease-modifying effects, with very restricting options in the therapeutic arsenal, which highlight the permanent need for continued drug discovery efforts in Academia and Industry. In this context, natural products, such as curcumin (1), resveratrol (2), and cannabidiol (CBD, 3) have been recognized as important sources of inspiration, promising chemical entities, prototype models, and starting materials for medicinal organic chemistry. Once their molecular architecture, multifunctional properties and single chemical diversity could address the discovery, optimization, and development of innovative drug candidates with improved pharmacodynamics and pharmacokinetics compared to the known drugs, there may be a real chance of discovering novel effective drugs to combat NDs. In this review, we report the most recent efforts of medicinal chemists worldwide, published in the scientific literature available in PubMed, SCOPUS, and Web of Sciences database, during the last 10 years of research devoted to the exploration of curcumin (1), resveratrol (2) and cannabidiol (CBD, 3) as starting materials or privileged scaffolds in the design of multi-target directed ligands (MTDLs) with potential therapeutic properties against NDs.
... 26 For example, most marijuana users in the United States believe that the drug is non-psychoactive. 27 Should adolescents in economically marginalised settings of South Africa, where illicit marijuana is cultivated and traded, hold onto some of these misconceptions, they could lead to sustained illicit marijuana use. ...
Background: Although various reasons for adolescent marijuana use have extensively been explored, contextual factors that sustain the practice in settings where the plant is illegally cultivated, especially in South Africa, remain a grey area.
Aim: We aimed to explore the contextual factors of sustained adolescent marijuana use in two illicit marijuana-growing settings of the Ingquza Hill Local Municipality of South Africa, based on the differential opportunity theory (DOT) and subcultural theory (SCT).
Setting: The study was conducted in two illicit marijuana-growing communities in the Ingquza Hill Local Municipality of the Eastern Cape Province of South Africa.
Methods: Exploratory qualitative research, using focus group discussions approach, was conducted amongst 37 participants, four focus groups and in two communities in the Ingquza Hill Municipality of the Eastern Cape Province of South Africa. Purposive and snowball sampling techniques were used to select the communities and participants, respectively. The data were analysed using a thematic content analysis approach and presented under various themes.
Results: Nine themes, grouped under two broad factors, DOT influences (availability and affordability of marijuana, idleness and means of dealing with personal problems) and SCT influences (peer conformity, the pleasure derived from marijuana smoking, manipulation of appetite, health reasons, for higher cognitive function and addiction), emerged from the analysis.
Conclusion: As marijuana has been identified to be a gateway drug for the use of other illicit drugs, its sustained usage amongst adolescents poses a health challenge to the user, community and the country’s healthcare system at large. Hence, there is the need to intensify adolescent marijuana use prevention campaigns in illicit marijuana-growing contexts of South Africa, focussing on the differential opportunities and subcultural inclinations that promote the behaviour in those contexts.
Introdução: A dor crônica é uma condição debilitante que afeta milhões, caracterizada por dor persistente por mais de três meses, decorrente de diversas causas, como doenças, lesões ou cirurgias. Ela impacta a qualidade de vida, comprometendo o bem-estar físico e emocional, muitas vezes resultando em ansiedade e depressão. O tratamento exige abordagem multidisciplinar, combinando medicamentos, terapias físicas e psicológicas. A conscientização pública e o acesso a tratamentos eficazes são essenciais para seu manejo. Objetivo: Assim, o presente estudo tem como objetivo compreender a aplicabilidade clínica do canabidiol (CBD) no tratamento da dor crônica. Metodologia: Trata-se, portanto, de uma revisão integrativa da literatura, que usou as bases de dados MEDLINE, PubMed e SciELO, com descritores específicos e coleta de dados de 2013 a 2024 para artigos originais. Ao final da seleção, foram analisados 11 documentos. Resultados: O CBD tem demonstrado eficácia significativa na redução da dor crônica, especialmente em condições como neuropatia, artrite e fibromialgia. Além de melhorar a qualidade de vida, promove benefícios no sono, função física e redução da ansiedade associada à dor. Estudos indicam que a eficácia do CBD pode variar de acordo com a dose, forma de administração (óleo, cápsulas, cremes) e duração do uso. Em geral, o CBD é bem tolerado, com efeitos adversos leves como fadiga, boca seca e alterações no apetite. No entanto, a resposta individual ao CBD e sua interação com outros medicamentos podem influenciar a eficácia e segurança, destacando a importância do acompanhamento médico no seu uso. Considerações Finais: O CBD possui potencial terapêutico significativo no tratamento da dor crônica, sendo capaz de reduzir a intensidade da dor, melhorar a qualidade do sono, diminuir a inflamação e aliviar o desconforto associado a diversas condições, como neuropatias e artrites. Futuras pesquisas devem focar em estudos comparativos e de longo prazo para estabelecer diretrizes terapêuticas baseadas em evidências robustas.
Introduction
Cannabis sativa is a highly versatile plant with a long history of cultivation and domestication. It produces multiple compounds that exert distinct and valuable therapeutic effects by modulating diverse biological systems, including the endocannabinoid system (ECS). Access to standardized, metabolically diverse, and reproducible C. sativa chemotypes and chemovars is essential for physicians to optimize individualized patient treatment and for industries to conduct drug‐discovery campaigns.
Objective
This study aimed to characterize and assess the phytochemical diversity of C. sativa chemotypes in diverse ecological regions of Colombia, South America.
Methodology
Ten cannabinoids and 23 terpenes were measured using liquid and gas chromatography, in addition to other phenotypic traits, in 156 C. sativa plants that were grown in diverse ecological regions in Colombia, a hotspot for global biodiversity.
Results
Our results reveal significant phytochemical diversity in Colombian‐grown C. sativa plants, with four distinct chemotypes based on cannabinoid profile. The significant amount of usually uncommon terpenes suggests that Colombia's environments may have unique capabilities that allow the plant to express these compounds. Colombia's diverse climates offer enormous cultivation potential, making it a key player in both domestic and international medicinal and recreational C. sativa trade.
Conclusion
These findings underscore Colombia's capacity to pioneer global C. sativa production diversification, particularly in South America with new emerging markets.
Introduction
Cannabidiol (CBD) is a non‐intoxicating cannabis compound found in diverse commercial products worldwide. However, its use may not be fully harmless. Accordingly, it is important to document the prevalence of CBD use and user characteristics in the general population.
Methods
We conducted a nationwide survey from a random sample of adults living in France using computer‐assisted telephone interviews between 2 March and 9 July 2022. We estimated the prevalence of CBD awareness and CBD use, and explored the different routes of administration. We also performed logistic regression models to identify factors associated with past‐year CBD use.
Results
Based on data from 3229 participants, we estimated that 71.0% (95% confidence interval) (69.0–73.0) of the French adult population had heard of CBD, and 10.1% (8.7–11.4) had used it in the previous year. Past‐year CBD use was associated with younger age, a higher educational level, not living in a middle‐sized urban unit, tobacco consumption and e‐cigarette use. The most common route of administration was smoking (56.1%).
Discussion and Conclusion
Past‐year CBD use prevalence in France appeared to be as high as that for cannabis. Proper prevention, regulation and control of CBD products is necessary to ensure that people have access to safe and high‐quality products. Reliable information on CBD should be sought and disseminated, especially regarding the harms associated with smoking the compound.
The production of essential oils by steam distillation is invariably associated with large amounts of organic waste which is normally disposed of or returned to the fields, although it may...
Introduction
Cannabinoids are increasingly popular in human and veterinary medicine and have been studied as an alternative treatment for a wide range of disorders. The goal of this study was to perform a pharmacokinetic analysis of oral cannabidiol (CBD)-/cannabidiolic acid (CBDA)-rich hemp oil (CBD/ArHO) in juvenile cynomolgus macaques (Macaca fascicularis).
Methods
After a 2 mg/kg CBD/ArHO pilot study, 4 and 8 mg/kg direct-to-mouth CBD/ArHO were administered (n = 4 per dose) once daily for 14 days and blood was collected at 0-, 0.5-, 1-, 2-, 4-, 8-, 12-, and 24-h, and on Days 7 and 14, to quantify serum cannabinoid concentrations by high-performance liquid chromatography–tandem mass spectrometry. Serum biochemistries and complete blood counts were performed on Days 0, 1, and 14.
Results
The maximum mean serum concentration (Cmax) of CBDA was 28.6–36.2 times that of CBD at 4 and 8 mg/kg. At 8 mg/kg, the Cmax of CBD was 1.4 times higher (p = 0.0721), and CBDA was significantly 1.8 times higher (p = 0.0361), than at 4 mg/kg. The maximum mean serum concentration of ∆⁹-tetrahydrocannabinol (THC) was 4.80 ng/mL at 8 mg/kg. Changes in serum biochemistries and complete blood counts over time were not clinically significant.
Discussion
Given the low serum CBD concentrations, the doses and frequency used in this study may be insufficient for a therapeutic effect of CBD in particular; therefore, clinical studies are needed to determine the therapeutic dose of CBD and CBDA for macaques, which may differ based on the disorder targeted.
Introduction:
Cannabis remains one of the most widely used illicit substances globally, with 188 million users in 2017. In the United States, nearly 50 million people are reported to have used cannabis in 2020. More research is needed because of the dramatic increase in cannabis use and the perception that its use has minimal risk.
Design:
The researchers used a retrospective design for this study.
Methods:
We used the Florida Department of Law Enforcement data from 2014 to 2020 for this study. We used descriptive statistics to report the characteristics of decedents whose cause of death (COD) was associated with cannabinoid (CB) and synthetic cannabinoid (SC) use. We used a general linear model with repeated measures to examine CB and SC death rate trends.
Results:
A total of 386 decedents' COD in Florida was associated with CB and SC use. Nearly 28% of decedents were 45-54 years, male (87.8%), and non-Hispanic whites (65.3%). One hundred percent of CB-related decedents died in urban counties. In rural counties, SC decedents accounted for 28.3% of deaths. Of decedents in rural counties, 39.9% were African American. Most decedents (with CB and SC use) died from accidents (98.7%), with 12.6% of cases involving cardiovascular-related illnesses.
Conclusion:
CBs and SCs as a COD pose a legitimate health problem to society. More people ages 45-54 died from CBs and SCs. Drug intoxications (from CBs and SCs) and motor vehicle collisions accounted for most of the accidents reported while under the influence of CBs and SCs. While most decedents from both CBs and SCs were non-Hispanic whites, a substantial proportion of African Americans died from SCs as a COD in rural counties. It is important that the public become aware of the risks for adverse effects of CB and SC. The public needs to be aware that CB and SC use can exacerbate cardiac-related conditions.
Clinical relevance:
This study has clinical relevance to patient safety. CB and SC use contributes to motor vehicle accidents and can cause adverse effects including death.
Half of the harvested food is lost due to rots caused by microorganisms. Plants emit various volatile organic compounds (VOCs) into their surrounding environment, and the VOC profiles of healthy crops are altered upon infection. In this study, a whole-cell bacterial biosensor was used for the early identification of potato tuber soft rot disease caused by the pectinolytic bacteria Pectobacterium in potato tubers. The detection is based on monitoring the luminescent responses of the bacteria panel to changes in the VOC profile following inoculation. First, gas chromatography-mass spectrometry (GC-MS) was used to specify the differences between the VOC patterns of the inoculated and non-inoculated potato tubers during early infection. Five VOCs were identified, 1-octanol, phenylethyl alcohol, 2-ethyl hexanol, nonanal, and 1-octen-3-ol. Then, the infection was detected by the bioreporter bacterial panel, firstly measured in a 96-well plate in solution, and then also tested in potato plugs and validated in whole tubers. Examination of the bacterial panel responses showed an extensive cytotoxic effect over the testing period, as seen by the elevated induction factor (IF) values in the bacterial strain TV1061 after exposure to both potato plugs and whole tubers. Moreover, quorum sensing influences were also observed by the elevated IF values in the bacterial strain K802NR. The developed whole-cell biosensor system based on bacterial detection will allow more efficient crop management during postharvest, storage, and transport of crops, to reduce food losses.
The need to develop and improve accounting in the Republic of Azerbaijan is due to a number of external and internal factors. The country's accession to the ongoing and deepening economic integration in the world, the strengthening of foreign investment flows, the expansion of enterprises' relations with foreign companies, the improvement of accounting, reporting and analysis, and the development of international standards are external factors that determine adaptation. In the emerging single economic area, in international markets, it is the information provided by accounting, analysis, auditing and reporting. The formation of this information in a way that everyone can understand is consistent with the theoretical and methodological foundations of global accounting and reporting, including accounting, analysis and reporting on current assets.
However, it is theoretically and practically incorrect to attribute the need to improve the accounting and analysis of current assets and bring them into line with international standards solely on external factors. The point is that the existing system of accounting, analysis and reporting in this area has certain shortcomings and deficiencies from a theoretical, methodological and practical point of view. In general, the current state of accounting, analysis and reporting of short-term assets does not fully correspond to the modern dynamics and characteristics of a market economy, and its development. Thus, it becomes an objective necessity to conduct a comprehensive study of the current state of accounting, analysis and reporting of current assets in the country, to improve it and bring it in line with international standards.
Cannabis (Cannabis sativa L.) has a rich history of human use, and the therapeutic importance of compounds produced by this species is recognized by the medical community. The active constituents of cannabis, collectively called cannabinoids, encompass hundreds of distinct molecules, the most well-characterized of which are tetrahydrocannabinol (THC) and cannabidiol (CBD), which have been used for centuries as recreational drugs and medicinal agents. As a first step to establish a cannabis breeding program, we initiated this study to describe the HPLC-measured quantity of THC and CBD biochemistry profiles of 161 feral pistillate cannabis plants from 20 geographical regions of Iran. Our data showed that Iran can be considered a new region of high potential for distribution of cannabis landraces with diverse THC and CBD content, predominantly falling into three groups, as Type I = THC-predominant, Type II = approximately equal proportions of THC and CBD (both CBD and THC in a ratio close to the unity), and Type III = CBD-predominant. Correlation analysis among two target cannabinoids and environmental and geographical variables indicated that both THC and CBD contents were strongly influenced by several environmental–geographical factors, such that THC and CBD contents were positively correlated with mean, min and max annual temperature and negatively correlated with latitude, elevation, and humidity. Additionally, a negative correlation was observed between THC and CBD concentrations, suggesting that further studies to unravel these genotype × environment interactions (G × E interactions) are warranted. The results of this study provide important pre-breeding information on a collection of cannabis that will underpin future breeding programs.
Good sleep is vital for good health, and poor sleep, in particular insomnia, is associated with a range of poor health outcomes. Sleep disorders are common and a key reason why people self-medicate with cannabis. We have two key biological mechanisms which work together to regulate our sleep-wake cycle, the processes of sleep-wake homeostasis and our circadian rhythms. The endocannabinoid system is involved in the circadian sleep-wake cycle, including maintenance and promotion of sleep, and may provide the link between the circadian regulation systems and the physiological process of sleep. Cannabis has been used for centuries to treat sleep disorders. Preclinical and clinical evidence indicate that cannabidiol and tetrahydrocannabinol may have a role to play in the treatment of sleep disorders.
Medical use of Cannabis (or hemp) began thousands of years ago. In the 20th century, mechanisms of action were demonstrated with the discovery of its active substances, the phytocannabinoids, and its pharmacological targets, the endocannabinoid system. This system is composed of receptors, endogenous substances, and enzymes, and it participates in the modulation of physiological mechanisms in several species, including dogs. Studies indicate that changes in this system may contribute to the genesis of some diseases. Therefore, the use of substances that act on its components may help in the treatment of these diseases. The main phytocannabinoids described are Δ9−tetrahydrocannabinol (THC) and cannabidiol (CBD). In humans, the benefits of using CBD in several diseases have been demonstrated. The popularization of this type of treatment has also reached veterinary medicine, which on one hand was related to an increase in adverse event records, but on the other also allowed reports of anecdotal evidences of its effectiveness and safety in animals. Clinical studies published so far indicate that the use of CBD in dogs can be safe at given doses and can contribute to osteoarthritis and idiopathic epilepsy treatments. Clinical and pre-clinical studies and case reports were reviewed in this report to identify the main characteristics of hemp-based therapies in dogs, including its pharmacokinetics, pharmacodynamics, safety, and efficacy in the treatment of diseases.
Despite therapeutic use dating back thousands of years, there are still significant gaps among healthcare professionals, patients, and the public regarding the understanding of cannabis, its components, and their pharmacological and potential therapeutic benefits. Cannabis continues to gain popularity, especially in the last 10 years such that demands for policy evolution, needs for additional research, and requests for medical training cannot be ignored. Medical professionals are increasingly exposed to patients who request advice regarding medical cannabis treatments. Consequently, there is an important opportunity to learn from other countries’ experiences and acknowledge that limited academic training might affect proper and informed recommendations for medical cannabis applications. Starting from the general aspects of the cannabis plant, this chapter described its main characteristics and the terminology used to describe various elements. Such fundamental understanding is essential to support future learning of the clinical application of cannabinoid-based medicines.
Increasing patient interest in cannabinoid-based treatments is creating a significant demand for medical education. Without formalized access to such training, patients are often using cannabis or cannabis products without medical support or supervision. Additionally, regulatory restrictions have limited legal access to regulated cannabinoid-based treatments. Consequently, there is a growing need to develop clinical guidelines for cannabinoid safe and responsible prescription. Despite a paucity of high-quality evidence, pain management has been a common indication for the use of cannabis-based medicines. Most research has utilized prescription or pharmaceutical cannabinoids such as nabilone, dronabinol, and nabiximols, leaving the safety and efficacy of natural cannabis products to require further clinical research development. Healthcare practitioners (HCPs) seek opportunities to learn about the fundamentals of cannabis-based medicines, including available methods of administration, product formulations, and available evidence. HCPs should be able to recognize the main therapeutic properties and clinical differences between delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). The proposed systematic approach for medical cannabis use is based on existing practical recommendations and clinical experience from countries where cannabis has been approved. Specific guidance will assist HCPs to decide whether a patient is a candidate or not for cannabinoid therapy. Finally, key steps and essential information will support chemotype selection, starting dose, titration regimen, cannabinoid method of administration, and treatment monitoring. HCPs should be aware of potential adverse effects associated with cannabinoid therapy and monitor patients in regular follow-up appointments. Patient education to address expectations and common misconceptions will be crucial to clarify treatment objectives and to support beneficial patient outcomes.
This overview covers a wide range of cannabis topics, initially examining issues in dispensaries and self-administration, plus regulatory requirements for production of cannabis-based medicines, particularly the Food and Drug Administration “Botanical Guidance.” The remainder pertains to various cannabis controversies that certainly require closer examination if the scientific, consumer, and governmental stakeholders are ever to reach consensus on safety issues, specifically: whether botanical cannabis displays herbal synergy of its components, pharmacokinetics of cannabis and dose titration, whether cannabis medicines produce cyclo-oxygenase inhibition, cannabis-drug interactions, and cytochrome P450 issues, whether cannabis randomized clinical trials are properly blinded, combatting the placebo effect in those trials via new approaches, the drug abuse liability (DAL) of cannabis-based medicines and their regulatory scheduling, their effects on cognitive function and psychiatric sequelae, immunological effects, cannabis and driving safety, youth usage, issues related to cannabis smoking and vaporization, cannabis concentrates and vape-pens, and laboratory analysis for contamination with bacteria and heavy metals. Finally, the issue of pesticide usage on cannabis crops is addressed. New and disturbing data on pesticide residues in legal cannabis products in Washington State are presented with the observation of an 84.6% contamination rate including potentially neurotoxic and carcinogenic agents. With ongoing developments in legalization of cannabis in medical and recreational settings, numerous scientific, safety, and public health issues remain.
Introduction: In recent research, orally administered cannabidiol (CBD) showed a relatively high incidence of somnolence in a pediatric population. Previous work has suggested that when CBD is exposed to an acidic environment, it degrades to Δ⁹-tetrahydrocannabinol (THC) and other psychoactive cannabinoids. To gain a better understanding of quantitative exposure, we completed an in vitro study by evaluating the formation of psychoactive cannabinoids when CBD is exposed to simulated gastric fluid (SGF).
Methods: Materials included synthetic CBD, Δ⁸-THC, and Δ⁹-THC. Linearity was demonstrated for each component over the concentration range used in this study. CBD was spiked into media containing 1% sodium dodecyl sulfate (SDS). Samples were analyzed using chromatography with UV and mass spectrometry detection. An assessment time of 3 h was chosen as representative of the maximal duration of exposure to gastric fluid.
Results: CBD in SGF with 1% SDS was degraded about 85% after 60 min and more than 98% at 120 min. The degradation followed first-order kinetics at a rate constant of −0.031 min⁻¹ (R²=0.9933). The major products formed were Δ⁹-THC and Δ⁸-THC with less significant levels of other related cannabinoids. CBD in physiological buffer performed as a control did not convert to THC. Confirmation of THC formation was demonstrated by comparison of mass spectral analysis, mass identification, and retention time of Δ⁹-THC and Δ⁸-THC in the SGF samples against authentic reference standards.
Conclusions: SGF converts CBD into the psychoactive components Δ⁹-THC and Δ⁸-THC. The first-order kinetics observed in this study allowed estimated levels to be calculated and indicated that the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a physiological response. Delivery methods that decrease the potential for formation of psychoactive cannabinoids should be explored.
Based on evidence that the therapeutic properties of Cannabis preparations are not solely dependent on the presence of Δ9-tetrahydrocannabinol (THC), pharmacological studies have been recently carried out with other plant cannabinoids (phytocannabinoids), particularly cannabidiol (CBD) and Δ9-tetrahydrocannabivarin (THCV). Results from some of these studies have fostered the view that CBD and THCV modulate the effects of THC via direct blockade of cannabinoid type-1 (CB1) receptors, thus behaving like first generation CB1 inverse agonists, such as rimonabant. Here we review in vitro and ex vivo mechanistic studies of CBD and THCV, and synthesize data from these studies in a meta-analysis. Synthesized data regarding mechanisms are then used to interpret results from recent preclinical animal studies and clinical trials. The evidence indicates that CBD and THCV are not rimonabant-like in their action, and thus appear very unlikely to produce unwanted central nervous system effects. They exhibit markedly disparate pharmacological profiles particularly at CB1 receptors: CBD is a very low affinity CB1 ligand which can nevertheless affect CB1 activity in vivo in an indirect manner, whilst THCV is a high affinity CB1 ligand and potent antagonist in vitro and yet only occasionally produces effects in vivo resulting from CB1 antagonism. THCV also has high affinity for CB2 and signals as a partial agonist, a departure from both CBD and rimonabant. These cannabinoids illustrate how in vitro mechanistic studies do not always predict in vivo pharmacology, and underlie the necessity of testing compounds in vivo before drawing any conclusion on their functional activity at a given target.
Rationale:
Animal and humans studies suggest that the two main constituents of cannabis sativa, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have quite different acute effects. However, to date the two compounds have largely been studied separately.
Objective:
To evaluate and compare the acute pharmacological effects of both THC and CBD in the same human volunteers.
Methods:
A randomised, double-blind, cross-over, placebo controlled trial was conducted in 16 healthy male subjects. Oral THC 10 mg or CBD 600 mg or placebo was administered in three consecutive sessions, at one-month interval. Physiological measures and symptom ratings were assessed before, and at 1, 2 and 3 hours post drug administration. The area under the curve (AUC) between baseline and 3 hours, and the maximum absolute change from baseline at 2 hours were analysed by one-way repeated measures analysis of variance, with drug condition (THC or CBD or placebo) as the factor.
Results:
Relative to both placebo and CBD, administration of THC was associated with anxiety, dysphoria, positive psychotic symptoms, physical and mental sedation, subjective intoxication (AUC and effect at 2 hours: p < 0.01), an increase in heart rate (p < 0.05). There were no differences between CBD and placebo on any symptomatic, physiological variable.
Conclusions:
In healthy volunteers, THC has marked acute behavioural and physiological effects, whereas CBD has proven to be safe and well tolerated.
Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe by the US Food and Drug Administration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits ng·mL -1. They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed on phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus). Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index. Methods for investigating entourage effects in future experiments will be proposed. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant.
This study examined the effect of Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on brain activation during a motor inhibition task.
Functional magnetic resonance imaging and behavioural measures were recorded while 15 healthy volunteers performed a Go/No-Go task following administration of either THC or CBD or placebo in a double-blind, pseudo-randomized, placebo-controlled repeated measures within-subject design.
Relative to placebo, THC attenuated activation in the right inferior frontal and the anterior cingulate gyrus. In contrast, CBD deactivated the left temporal cortex and insula. These effects were not related to changes in anxiety, intoxication, sedation, and psychotic symptoms.
These data suggest that THC attenuates the engagement of brain regions that mediate response inhibition. CBD modulated function in regions not usually implicated in response inhibition.
Background:
Almost a third of patients with epilepsy have a treatment-resistant form, which is associated with severe morbidity and increased mortality. Cannabis-based treatments for epilepsy have generated much interest, but scientific data are scarce. We aimed to establish whether addition of cannabidiol to existing anti-epileptic regimens would be safe, tolerated, and efficacious in children and young adults with treatment-resistant epilepsy.
Methods:
In this open-label trial, patients (aged 1-30 years) with severe, intractable, childhood-onset, treatment-resistant epilepsy, who were receiving stable doses of antiepileptic drugs before study entry, were enrolled in an expanded-access programme at 11 epilepsy centres across the USA. Patients were given oral cannabidiol at 2-5 mg/kg per day, up-titrated until intolerance or to a maximum dose of 25 mg/kg or 50 mg/kg per day (dependent on study site). The primary objective was to establish the safety and tolerability of cannabidiol and the primary efficacy endpoint was median percentage change in the mean monthly frequency of motor seizures at 12 weeks. The efficacy analysis was by modified intention to treat. Comparisons of the percentage change in frequency of motor seizures were done with a Mann-Whitney U test.
Results:
Between Jan 15, 2014, and Jan 15, 2015, 214 patients were enrolled; 162 (76%) patients who had at least 12 weeks of follow-up after the first dose of cannabidiol were included in the safety and tolerability analysis, and 137 (64%) patients were included in the efficacy analysis. In the safety group, 33 (20%) patients had Dravet syndrome and 31 (19%) patients had Lennox-Gastaut syndrome. The remaining patients had intractable epilepsies of different causes and type. Adverse events were reported in 128 (79%) of the 162 patients within the safety group. Adverse events reported in more than 10% of patients were somnolence (n=41 [25%]), decreased appetite (n=31 [19%]), diarrhoea (n=31 [19%]), fatigue (n=21 [13%]), and convulsion (n=18 [11%]). Five (3%) patients discontinued treatment because of an adverse event. Serious adverse events were reported in 48 (30%) patients, including one death-a sudden unexpected death in epilepsy regarded as unrelated to study drug. 20 (12%) patients had severe adverse events possibly related to cannabidiol use, the most common of which was status epilepticus (n=9 [6%]). The median monthly frequency of motor seizures was 30·0 (IQR 11·0-96·0) at baseline and 15·8 (5·6-57·6) over the 12 week treatment period. The median reduction in monthly motor seizures was 36·5% (IQR 0-64·7).
Interpretation:
Our findings suggest that cannabidiol might reduce seizure frequency and might have an adequate safety profile in children and young adults with highly treatment-resistant epilepsy. Randomised controlled trials are warranted to characterise the safety profile and true efficacy of this compound.
Funding:
GW Pharmaceuticals, Epilepsy Therapy Project of the Epilepsy Foundation, Finding A Cure for Epilepsy and Seizures.
Cannabidiol has been reported to act as an antagonist of cannabinoid agonists at type 1 cannabinoid receptors (CB1 ). We hypothesized that cannabidiol can inhibit cannabinoid agonist activity through negative allosteric modulation of CB1 .
CB1 internalization, arrestin2 recruitment, and PLCβ3 and ERK1/2 phosphorylation, were quantified in HEK 293A cells heterologously expressing CB1 and in the STHdh(Q7/Q7) cell model of striatal neurons endogenously expressing CB1 . Cells were treated with 2-arachidonylglycerol or Δ(9) -tetrahydrocannabinol alone and in combination with different concentrations of cannabidiol.
Cannabidiol reduced the efficacy and potency of 2-arachidonylglycerol and Δ(9) -tetrahydrocannabinol on PLCβ3- and ERK1/2-dependent signaling in cells heterologously (HEK 293A) or endogenously (STHdh(Q7/Q7) ) expressing CB1 . By reducing arrestin2 recruitment to CB1 , cannabidiol treatment prevented CB1 internalization. The allosteric activity of cannabidiol depended upon polar residues being present at positions 98 and 107 in the extracellular amino-terminus.
Cannabidiol behaved as a non-competitive negative allosteric modulator of CB1 . Allosteric modulation, in conjunction with non-CB1 effects, may explain the in vivo effects of cannabidiol. Allosteric modulators of CB1 have the potential to treat central nervous system and peripheral disorders while avoiding the adverse effects associated with orthosteric agonism or antagonism of CB1 . This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Plasma levels of cannabidiol (CBD) were ascertained weekly in 14 Huntington's disease patients undergoing a double-blind, placebo-controlled, crossover trial of oral CBD (10 mg/kg/day=about 700 mg/day) for 6 weeks. The assay procedure involved trimethylsilyl (TMS) derivatization of CBD and the internal standard delta-6-tetrahydrocannabinol (THC), capillary column gas chromatography, ion trap mass spectroscopy in positive ion chemical ionization mode using isobutane, and calculations of CBD levels based on peak ion intensity of the 387 M+H peak of delta-6-THC-TMS and the 459 M+H peak of CBD-2TMS. The sensitivity of the assay was about 500 pg/ml, and the precision was about 10–15%. Mean plasma levels of CBD ranged from 5.9–11.2 ng/ml over the 6 weeks of CBD administration. CBD levels averaged 1.5 ng/ml one week after CBD was discontinued, and were virtually undetectable thereafter. The elimination half-life of CBD was estimated to be about 2–5 days, and there were no differences between genders for half-life or CBD levels. Additionally, no plasma delta-1-THC, the major psychoactive cannabinoid of marijuana, was detected in any subject.
The effects of cannabis extracts on nocturnal sleep, early-morning performance, memory, and sleepiness were studied in 8 healthy volunteers (4 males, 4 females; 21 to 34 years). The study was double-blind and placebo-controlled with a 4-way crossover design. The 4 treatments were placebo, 15 mg Delta-9-tetrahydrocannabinol (THC), 5 mg THC combined with 5 mg cannabidiol (CBD), and 15 mg THC combined with 15 mg CBD. These were formulated in 50:50 ethanol to propylene glycol and administered using an oromucosal spray during a 30-minute period from 10 pm. The electroencephalogram was recorded during the sleep period (11 pm to 7 am). Performance, sleep latency, and subjective assessments of sleepiness and mood were measured from 8:30 am (10 hours after drug administration). There were no effects of 15 mg THC on nocturnal sleep. With the concomitant administration of the drugs (5 mg THC and 5 mg CBD to 15 mg THC and 15 mg CBD), there was a decrease in stage 3 sleep, and with the higher dose combination, wakefulness was increased. The next day, with 15 mg THC, memory was impaired, sleep latency was reduced, and the subjects reported increased sleepiness and changes in mood. With the lower dose combination, reaction time was faster on the digit recall task, and with the higher dose combination, subjects reported increased sleepiness and changes in mood. Fifteen milligrams THC would appear to be sedative, while 15 mg CBD appears to have alerting properties as it increased awake activity during sleep and counteracted the residual sedative activity of 15 mg THC.
Even high doses of oral cannabidiol do not cause THC-like effects in humans.
- Grotenhermen F.
Grotenhermen, F. et al. (2017) Even high doses of oral
cannabidiol do not cause THC-like effects in humans.
Cannabis Cannabinoid Res. (in press)
International control of cannabis.
- Mead A.P.
Mead, A.P. (2014) International control of cannabis. In
Handbook of Cannabis (Pertwee, R.G., ed.), pp. 44-64,
Oxford University Press