Article

Cannabidiol Claims and Misconceptions

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  • CReDO Science
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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.

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... Outro constituinte importante da cannabis é o CBD mencionado acima, que se liga ao CB1 / CB2 receptores com afinidade muito baixa e sem efeitos psicotomiméticos, as pesquisas, afirmam, no entanto, que o CBD parece ter efeitos psicofarmacológicos, uma vez que administração está associada a alguns efeitos benéficos sobre a ansiedade e outras condições, como esquizofrenia, vício e possivelmente até depressão. Sugere que "o CBD deveria ser preferencialmente rotulado como "não intoxicante" e sem reforço associado, desejo, uso compulsivo etc 16,18 . ...
... A controvérsia sobre os benefícios da cannabis medicinal e principalmente sobre o uso dos extratos da planta em crianças está em andamento 18 . Na maioria dos países do mundo, a cannabis, medicinal ou não, é atualmente ilegal. ...
... Apesar da falta de dados clínicos convincentes sobre a eficácia dos canabinóides no tratamento do TEA, o tratamento com canabinóides parece ser relativamente seguro em adultos e crianças 18,43 . No entanto, efeitos nocivos dos canabinóides foram relatados, alguns deles devido a produtos contaminados que não estavam sob supervisão regulatória 21 . ...
Article
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O Transtorno do Espectro Autista (TEA) é caracterizado por déficits persistentes na comunicação social, padrões restritos e repetitivos de comportamento, interesses ou atividades e, muitas vezes, deficiências intelectuais. O TEA possui várias comorbidades prevalentes, como distúrbios do sono, distúrbio do déficit de atenção/hiperatividade e epilepsia. Existe um interesse crescente em canabinóides, especialmente canabidiol (CBD), como monoterapia ou tratamento complementar para os principais sintomas e comorbidades do TEA. No entanto, a ação neural do CBD, sua relevância e eficácia para o TEA, ainda permanece em discussão. O objetivo deste trabalho foi empreender uma revisão de literatura sobre estudos que tratem dos efeitos do uso de Cannabis sativa (cannabis). no indivíduo com TEA. Foram encontrados 45 estudos nas bases de dados PubMed, MEDLINE e LILACS , dos quais, apenas 5 conformaram-se com os critérios de aceitação, com os descritores: Cannabis AND Autism Spectrum Disorder. Observamos que são necessários estudos adicionais para examinar os prós e contras do CBD e outros canabinóides no TEA, antes que eles sejam estabelecidos como tratamento para sintomas e comorbidades do TEA. Nenhum dos trabalhos apresentam dados clínicos ou pré-clínicos convincentes que demonstrem a eficácia e segurança da cannabis medicinal, incluindo o CBD.
... Cannabidiol (CBD) is a non-psychoactive and non-intoxicating cannabinoid compound found primarily in hemp plants' leaves and inflorescence. It is a 21-carbon terpenophenolic compound that is produced when a cannabidiolic acid (CBDA) precursor is decarboxylated ( Figure 1) [1,2]. CBD has recently gained much attention from the pharmaceuticals industry because of the versatile potential utilization of these compounds including for epilepsy, as well as for its cancer anti-inflammatory, analgesic, antioxidant, antimicrobial, neuro-protective, and anticonvulsant properties [2][3][4][5]. ...
... It is a 21-carbon terpenophenolic compound that is produced when a cannabidiolic acid (CBDA) precursor is decarboxylated ( Figure 1) [1,2]. CBD has recently gained much attention from the pharmaceuticals industry because of the versatile potential utilization of these compounds including for epilepsy, as well as for its cancer anti-inflammatory, analgesic, antioxidant, antimicrobial, neuro-protective, and anticonvulsant properties [2][3][4][5]. Cannabinoid compounds, including cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), are derived from their precursor, cannabigerolic acid (CBGA). THC/THC acid (THCA) and CBD/CBDA are the subsequent synthesized products of CBGA. ...
... THC/THC acid (THCA) and CBD/CBDA are the subsequent synthesized products of CBGA. The THCA and CBDA compounds are decarboxylated to THC and CBD, respectively, when exposed to heat and light [2]. ...
Article
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Cannabidiol (CBD) is a non-psychoactive cannabinoid compound found in hemp plants that has recently sparked interest in the biomedical and food industries. CBD is a natural decarboxylated product of cannabidiolic acid (CBDA). In this study, processing parameters were developed to enhance the decarboxylation process of CBDA in hemp leaves using hot-melt extrusion (HME). The hemp leaves were formulated with two different acid-based polymers, namely ascorbic acid (AA) and ascorbyl palmitate (AP), before the HME. The results showed that the carboxylation process of CBDA was increased by at least 2.5 times in the extrudate leaves and the content of the CBD was four times higher when formulated with AP (2800 µg/g) compared with the raw leaves (736 µg/g). The total phenolic and total flavonoid content, as well as the DPPH antioxidant capacity, were higher in the AP formulated extrudate. At the same time, the Δ9-tetrahydrocannabinol (THC) content was reduced by half in the extrudate compared with the raw leaves. It was also observed that double HME processing did not increase the decarboxylation process. It was concluded that the HME process significantly improved the conversion rate of CBDA to CBD in formulated hemp leaves with a reduced THC content.
... Unlike Δ 9 -tetrahydrocannabinol (THC), CBD has no undesired psychoactive side effects that would pose a risk of drug abuse. CBD is therefore of particular interest for pharmaceutical use [1]. Various pharmacological effects of CBD are already known or under investigation including antiepileptic, anti-inflammatory, antioxidative or neuroprotective activity [2]. ...
... rel. Increase in Density = (Density (x%) − Density (0%))/(x%) (1) In the nominator, the difference of the density of soybean oil with the corresponding CBD content and that of the CBD-free soybean oil was calculated. Subsequently, to be able to compare the resulting values, they were normalized to the CBD content (x%). ...
Article
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In this study, the general processability of cannabidiol (CBD) in colloidal lipid carriers was investigated. Due to its many pharmacological effects, the pharmaceutical use of this poorly water-soluble drug is currently under intensive research and colloidal lipid emulsions are a well-established formulation option for such lipophilic substances. To obtain a better understanding of the formulability of CBD in lipid emulsions, different aspects of CBD loading and its interaction with the emulsion droplets were investigated. Very high drug loads (>40% related to lipid content) could be achieved in emulsions of medium chain triglycerides, rapeseed oil, soybean oil and trimyristin. The maximum CBD load depended on the type of lipid matrix. CBD loading increased the particle size and the density of the lipid matrix. The loading capacity of a trimyristin emulsion for CBD was superior to that of a suspension of solid lipid nanoparticles based on trimyristin (69% vs. 30% related to the lipid matrix). In addition to its localization within the lipid core of the emulsion droplets, cannabidiol was associated with the droplet interface to a remarkable extent. According to a stress test, CBD destabilized the emulsions, with phospholipid-stabilized emulsions being more stable than poloxamer-stabilized ones. Furthermore, it was possible to produce emulsions with pure CBD as the dispersed phase, since CBD demonstrated such a pronounced supercooling tendency that it did not recrystallize, even if cooled to −60 °C.
... 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. ...
Article
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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.
... Cannabidiol (CBD) is one of the primary cannabinoids found in significant but variable concentrations in cannabinoid-based medicines (CBM). While structurally similar to Δ9-tetrahydrocannabinol (THC), CBD does not cause intoxication or euphoria (Russo 2017) and has showed considerable tolerability in humans with a low abuse potential (Chesney et al. 2020). This favorable safety profile has led to the recent mitigation of legal and regulatory barriers surrounding purified CBD products in several countries and recent increased interest in CBD treatments. ...
... CBD is widely touted as a panacea for a wide range of health problems and has been marketed as a dietary and "wellness" product (Russo 2017;Khalsa et al. 2020; Eisenstein 2019). CBD's potential effects as an add-on therapy have been studied for social anxiety disorders, schizophrenia, non-motor symptoms in Parkinson's disease, and substance use disorders (Bergamaschi et al. 2011;Crippa et al. 2019;McGuire et al. 2018;Millar et al. 2019;Prud'homme et al. 2015;Thiele et al. 2019;Leehey et al. 2020). ...
Article
Full-text available
Background Cannabidiol (CBD) is a primary component in the cannabis plant; however, in recent years, interest in CBD treatments has outpaced scientific research and regulatory advancement resulting in a confusing landscape of misinformation and unsubstantiated health claims. Within the limited results from randomized controlled trials, and lack of trust in product quality and known clinical guidelines and dosages, real-world evidence (RWE) from countries with robust regulatory frameworks may fill a critical need for patients and healthcare professionals. Despite growing evidence and interest, no real-world data (RWD) studies have yet investigated patients’ reports of CBD impact on symptom control in the common expression of pain, anxiety, depression, and poor wellbeing. The objective of this study is to assess the impact of CBD-rich treatment on symptom burden, as measured with a specific symptom assessment scale (ESAS-r). Methods This retrospective observational study examined pain, anxiety, depression symptoms, and wellbeing in 279 participants over 18 years old, prescribed with CBD-rich treatment at a network of clinics dedicated to medical cannabis in Quebec, Canada. Data were collected at baseline, 3 (FUP1), and 6 (FUP2) month after treatment initiation. Groups were formed based on symptom severity (mild vs moderate/severe) and based on changes to treatment plan at FUP1 (CBD vs THC:CBD). Two-way mixed ANOVAs were used to assess ESAS-r scores differences between groups and between visits. Results All average ESAS-r scores decreased between baseline and FUP1 (all p s < 0.003). The addition of delta-9-tetrahydrocannabinol (THC) during the first follow-up had no effect on symptom changes. Patients with moderate/severe symptoms experienced important improvement at FUP1 (all p s < 0.001), whereas scores on pain, anxiety, and wellbeing of those with mild symptoms actually increased. Differences in ESAS-r scores between FUP1 and FUP2 were not statistically different. Conclusion This retrospective observational study suggests CBD-rich treatment has a beneficial impact on pain, anxiety, and depression symptoms as well as overall wellbeing only for patients with moderate to severe symptoms; however, no observed effect on mild symptoms. The results of this study contribute to address the myths and misinformation about CBD treatment and demand further investigation.
... 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). ...
Book
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.
... At the same time, antineoplastic properties of cannabinoids have been also reported in numerous experimental cancer models (248,249). In contrast to tetrahydrocannabiol, CBD shows a low affinity for classical cannabinoid receptors CB1 and CB2 and has no undesirable effects on CNS (250). Consequently, its use in anticancer protocols is widely discussed (248)(249)(250)(251). On the other hand, the mechanism of CBD cytotoxicity is uncertain. ...
... In contrast to tetrahydrocannabiol, CBD shows a low affinity for classical cannabinoid receptors CB1 and CB2 and has no undesirable effects on CNS (250). Consequently, its use in anticancer protocols is widely discussed (248)(249)(250)(251). On the other hand, the mechanism of CBD cytotoxicity is uncertain. ...
Article
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Glucocorticoids (GCs) are a central component of multi-drug treatment protocols against T and B acute lymphoblastic leukemia (ALL), which are used intensively during the remission induction to rapidly eliminate the leukemic blasts. The primary response to GCs predicts the overall response to treatment and clinical outcome. In this review, we have critically analyzed the available data on the effects of GCs on sensitive and resistant leukemic cells, in order to reveal the mechanisms of GC resistance and how these mechanisms may determine a poor outcome in ALL. Apart of the GC resistance, associated with a decreased expression of receptors to GCs, there are several additional mechanisms, triggered by alterations of different signaling pathways, which cause the metabolic reprogramming, with an enhanced level of glycolysis and oxidative phosphorylation, apoptosis resistance, and multidrug resistance. Due to all this, the GC-resistant ALL show a poor sensitivity to conventional chemotherapeutic protocols. We propose pharmacological strategies that can trigger alternative intracellular pathways to revert or overcome GC resistance. Specifically, we focused our search on drugs, which are already approved for treatment of other diseases and demonstrated anti-ALL effects in experimental pre-clinical models. Among them are some “truly” re-purposed drugs, which have different targets in ALL as compared to other diseases: cannabidiol, which targets mitochondria and causes the mitochondrial permeability transition-driven necrosis, tamoxifen, which induces autophagy and cell death, and reverts GC resistance through the mechanisms independent of nuclear estrogen receptors (“off-target effects”), antibiotic tigecycline, which inhibits mitochondrial respiration, causing energy crisis and cell death, and some anthelmintic drugs. Additionally, we have listed compounds that show a classical mechanism of action in ALL but are not used still in treatment protocols: the BH3 mimetic venetoclax, which inhibits the anti-apoptotic protein Bcl-2, the hypomethylating agent 5-azacytidine, which restores the expression of the pro-apoptotic BIM, and compounds targeting the PI3K-Akt-mTOR axis. Accordingly, these drugs may be considered for the inclusion into chemotherapeutic protocols for GC-resistant ALL treatments.
... The most studied and well-known phytocannabinoids derived from the C sativa plant are THC and cannabidiol (CBD). 2 Table 2 summarizes their proposed mechanisms and psychoactivity. 2,[5][6][7][8][9][10][11][12][13][14][15] THC is the primary psychoactive component of marijuana and is responsible for the intoxicating "high" typically associated with marijuana use. CBD has different effects from THC and does not cause an intoxicating high on its own. ...
... Although the mechanism for THC is understood, the pharmacologic actions of CBD are less clear. 2,[5][6][7][8][9][10][11][12][13][14][15] Different components are present in various parts of the C sativa plant that are being extracted, and each ingredient has its own attributed effects. Isolate products purport to extract only certain phytocannabinoids from specific parts of the C sativa plant, producing a more purified product. ...
Article
Use of cannabidiol (CBD) products has become widespread due to the proposed medical benefits without the “high” of marijuana, with recent polling indicating that 1 in 7 Americans report using a CBD product. However, health care professionals have apprehension about whether these treatments are legal, safe, and effective. In this review, we provide a summary of the scientific evidence on CBD oil so that a nurse practitioner can guide patients to the safest and most beneficial products within today’s regulatory environment.
... [25][26][27][28][29] In contrast, the session emphasized the use of greater percentage strengths of CBD, as the potential benefits and safety profile as compared to THC is purported to be much more favorable. [29][30][31][32][33][34][35][36] Among surveyed participants, after receiving formal education by a pharmacist, these objectives were realized among naïve patients in particular, and to a lesser extent among current users (Table 5 & 6). ...
Article
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Objective: The primary objectives of this pre-post session study, was to evaluate the impact of a pharmacist-led education session on the perceived benefits and safety of cannabis among patients with chronic pain, as well as determine the influence of pharmacist education on the selection of safer cannabis products and dosage forms for medical use among patients. Methods: A retrospective analysis of completed pre-post session questionnaires was conducted among chronic pain patients attending a mandatory education session led by a pharmacist, prior to being authorized cannabis in clinic. All questionnaire data was analyzed using SPSS v. 25. Demographic and sample characteristics were reviewed using univariate analyses. Chi-Square tests were employed to determine if the group-based education significantly affected knowledge, perception of efficacy and safety of cannabis. Results: Of the 260 session participants, 203 completed pre-post session questionnaires. After the session, a majority of current cannabis users (33.8%) and cannabis naïve/past users (56.9%) reported they would use a low THC product in the future, and a majority of current users (54.5%) would use a high CBD product in the future. After education, participants were more likely to report cannabis as having the potential for addiction (chi-square =42.6, p <0.0001) and harm (chi-square =34.0, p <0.0001). Conclusions: Pharmacist counselling and education has the potential to influence patient selection and use of cannabis, from more harmful to safer products, as well as moderate the potential perceived benefits of use.
... THC is illegal in the US, but CBC derived from industrial hemp (< 0.3% THC) is legal, and MC is legal in many states. Research interest into CBD is increasing because of documented antiemetic, analgesic, alerting, antianxiety, anticonvulsant, antipsychotic, anti-inflammatory, and antioxidant properties (Russo, 2017). Many people are using widely available nonstandardized, overthe-counter CBD products to self-manage symptoms (Highet, Lesser, Johnson, & Kaur, 2020;Van-Dolah, Bauer, & Mauck, 2019). ...
Article
Full-text available
Purpose: Unlike therapy-related nausea and vomiting (chemotherapy or radiotherapy induced), nausea and vomiting (N/V) in patients with advanced cancer is often multicausal and thus presents unique challenges. Few professional guidelines address the palliative management of N/V, and those that do are insufficiently detailed to bolster clinical decision-making. Nonetheless, oncology advanced practitioners (APs) are frequently challenged to manage these high-impact symptoms. This requires collaborating with other oncology care providers and cultivating a knowledge base to educate and mentor professional colleagues to optimize N/V unrelated to treatment. Methods: Literature reviewed included current and classic articles that address the physiologic bases of N/V related to disease and with malignant bowel obstruction, agents used to alleviate nausea or N/V, and nonpharma-cologic adjunctive measures. This information was framed within palli-ative care and symptom management clinical experience. Results: This review article summarizes what is known about the neuropharmacol-ogy of N/V in advanced disease. Focused assessment, pharmacologic agents (antiemetics, central neuromodulators, and peripheral proki-netic agents), and nondrug adjunctive measures that may be useful for N/V are included. Conclusions: Managing N/V in advanced cancer is a quality-of-life imperative that requires persistence and interpro-fessional collaboration among oncology APs and other clinicians to personalize management. This work can change the perception that N/V related to progressive disease is frequently intractable to one that considers it as a manageable clinical challenge.
... The addition of other cannabinoids, such as CBD, may have an impact on the severity of neurocognitive impairment (Figures 2F,G) (69). One of the studies in this review, compared oromucosal spray formulations of THC vs. THC: CBD 1:1 vs. CBD vs. placebo and noted that participants in the THC: CBD group had less drowsiness, dysphoria, and euphoria ( Figure 2F) (42). ...
Article
Full-text available
While the recreational use of cannabis has well-established dose-dependent effects on neurocognitive and psychomotor functioning, there is little consensus on the degree and duration of impairment typically seen with medical marijuana use. Compared to recreational cannabis users, medical cannabis patients have distinct characteristics that may modify the presence and extent of impairment. The goal of this review was to determine the duration of acute neurocognitive impairment associated with medical cannabis use, and to identify differences between medical cannabis patients and recreational users. These findings are used to gain insight on how medical professionals can best advise medical cannabis patients with regards to automobile driving or safety-sensitive tasks at work. A systematic electronic search for English language randomized controlled trials (RCTs), clinical trials and systematic reviews (in order to capture any potentially missed RCTs) between 2000 and 2019 was conducted through Ovid MEDLINE and EMBASE electronic databases using MeSH terms. Articles were limited to medical cannabis patients using cannabis for chronic non-cancer pain or spasticity. After screening titles and abstracts, 37 relevant studies were subjected to full-text review. Overall, seven controlled trials met the inclusion/exclusion criteria and were included in the qualitative synthesis: six RCTs and one observational clinical trial. Neurocognitive testing varied significantly between all studies, including the specific tests administered and the timing of assessments post-cannabis consumption. In general, cognitive performance declined mostly in a THC dose-dependent manner, with steady resolution of impairment in the hours following THC administration. Doses of THC were lower than those typically reported in recreational cannabis studies. In all the studies, there was no difference between any of the THC groups and placebo on any neurocognitive measure after 4 h of recovery. Variability in the dose-dependent relationship raises the consideration that there are other important factors contributing to the duration of neurocognitive impairment besides the dose of THC ingested. These modifiable and non-modifiable factors are individually discussed.
... 46 While CBD is far less studied, it is a popular alternative therapy, and is particularly attractive to consumers as it is both fairly well-tolerated (causing mostly nonserious side effects) and nonintoxicating, with little or no abuse potential. 32,41 After the 2018 Farm Bill removed CBD products derived from hemp (Cannabis sativa with <0.3% D-9-tetrahydrocannabinol [THC]) from the Controlled Substances Act, 18 CBD products (eg, candies, cosmetics, soft-gels, tinctures) have flooded the marketplace. Some CBD manufacturers tout their products as wonder drugs, useful for numerous conditions such as Alzheimer's disease, epilepsy, anxiety, and cancer. 1 While the preclinical literature suggests that CBD has wide-ranging therapeutic activity (indeed, product claims are often based on preclinical data), 31,32 most of these findings have not been rigorously tested in large clinical trials, with the exception of CBD's anticonvulsant activity in the rare childhood epileptic conditions Dravet and Lennox Gastaut syndromes. ...
Article
Cannabidiol (CBD) is widely advertised as helpful for chronic pain management but research is limited. Using a cross-sectional, anonymous survey, we examined patterns of naturalistic CBD use among individuals with fibromyalgia (FM) and other chronic pain conditions. Our objective was to better understand rates of CBD use, reasons for use and discontinuation, communication with healthcare professionals about CBD, and perceptions of CBD effectiveness and safety among people with FM. After excluding incomplete surveys, our study population consisted of N = 2701 participants with fibromyalgia, primarily in the United States. Overall, 38.1% reported never using CBD, 29.4% reported past CBD use, and 32.4% reported current CBD use. Past-year cannabis use was strongly associated with past or current CBD use. Those using CBD typically did so due to inadequate symptom relief, while those not using CBD typically cited safety concerns as their reason for not using CBD. Two-thirds of participants disclosed CBD use to their physician, although only 33% asked for physician advice on using CBD. Participants used CBD for numerous FM-related symptoms (most commonly pain), and generally reported slight to much improvement across symptom domains. Around half of participants reported side effects, which were typically minor. Our findings are limited by selection bias and our cross-sectional design, which prevents causal associations. In conclusion, CBD use is common among individuals with FM and many individuals using CBD report improvements across numerous FM-related symptoms. Our findings highlight the need for additional rigorous studies to better understand CBD's potential for FM management. Perspective: This article indicates that that CBD use is common among people with fibromyalgia, and the results suggest that many derive benefit from using CBD across multiple symptoms domains. Clinicians should discuss CBD use with fibromyalgia patients, and future studies are needed to rigorously assess CBD's therapeutic value for fibromyalgia symptoms.
... THC is a partial agonist of both CB1 and CB2 receptors and is responsible for the psychoactive, intoxicating effects of cannabis 20 whereas CBD does not appear to bind to these receptors at physiologically meaningful concentrations. Importantly, CBD is non-intoxicating and generally well tolerated 21 . One of the most Chemical compounds More than 500 chemical compounds: cannabinoids, terpenes, flavonoids. ...
... THC is illegal in the US, but CBC derived from industrial hemp (< 0.3% THC) is legal, and MC is legal in many states. Research interest into CBD is increasing because of documented antiemetic, analgesic, alerting, antianxiety, anticonvulsant, antipsychotic, anti-inflammatory, and antioxidant properties (Russo, 2017). Many people are using widely available nonstandardized, overthe-counter CBD products to self-manage symptoms (Highet, Lesser, Johnson, & Kaur, 2020;Van-Dolah, Bauer, & Mauck, 2019). ...
Article
Full-text available
Purpose: Unlike therapy-related nausea and vomiting (chemotherapy or radiotherapy induced), nausea and vomiting (N/V) in patients with advanced cancer is often multicausal and thus presents unique challenges. Few professional guidelines address the palliative management of N/V, and those that do are insufficiently detailed to bolster clinical decision-making. Nonetheless, oncology advanced practitioners (APs) are frequently challenged to manage these high-impact symptoms. This requires collaborating with other oncology care providers and cultivating a knowledge base to educate and mentor professional colleagues to optimize N/V unrelated to treatment. Methods: Literature reviewed included current and classic articles that address the physiologic bases of N/V related to disease and with malignant bowel obstruction, agents used to alleviate nausea or N/V, and nonpharmacologic adjunctive measures. This information was framed within palliative care and symptom management clinical experience. Results: This review article summarizes what is known about the neuropharmacology of N/V in advanced disease. Focused assessment, pharmacologic agents (antiemetics, central neuromodulators, and peripheral prokinetic agents), and nondrug adjunctive measures that may be useful for N/V are included. Conclusions: Managing N/V in advanced cancer is a quality-of-life imperative that requires persistence and interprofessional collaboration among oncology APs and other clinicians to personalize management. This work can change the perception that N/V related to progressive disease is frequently intractable to one that considers it as a manageable clinical challenge.
... Tetrahydrocannabinol (THC) and cannabidiol (CBD) are wellknown phytocannabinoids, considered as the most notable Cannabis components with pharmacological activity [5]. THC acts mostly as a CB1 receptor agonist, leading to its distinguished psychoactive and pain relief effects, while CBD works through a variety of pharmacological pathways, including inhibition of endocannabinoid reuptake, activation of transient receptor potential vanilloid 1 and G protein-coupled receptor 55 [6,7]. Considering their immense importance in the overall pharmacological activity, as well as the current Cannabis legislation restrictions, related to the THC content of some classes of Cannabis products, one could entitle the content of CBD and THC as critical quality parameters of Cannabis products. ...
Article
Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most notable Cannabis components with pharmacological activity and their content in the plant flowers and extracts are considered as critical quality parameters. The new Medical Cannabis industry needs to adopt the quality standards of the pharmaceutical industry, however, the variability of phytocannabinoids content in the plant material often exerts an issue in the inconsistency of the finished product quality parameters. Sampling problems and sample representativeness is a major limitation in the end-point testing, particularly when the expected variation of the product quality parameters is high. Therefore, there is an obvious need for the introduction of Process Analytical Technology (PAT) for continuous monitoring of the critical quality parameters throughout the production processes. Infrared spectroscopy is a promising analytical technique that is consistent with the PAT requirements and its implementation depends on the advances in instrumentation and chemometrics that will facilitate the qualitative and quantitative aspects of the technique. Our present work aims in highlighting the potential of mid-infrared (MIR) spectroscopy as PAT in the quantification of the main phytocannabinoids (THC and CBD), considered as critical quality/material parameters in the production of Cannabis plant and extract. A detailed assignment of the bands related to the molecules of interest (THC, CBD) was performed and the spectral features of the decarboxylation of native flowers were identified, and the acid forms (THCA, CBDA) specific bands were assigned and thoroughly explained. Further, multivariate models were constructed for the prediction of both THC and CBD content in extract and flower samples from various origins, and their prediction ability was tested on a separate sample set. Savitskzy-Golay smoothing and the second derivative of the native MIR spectra (1800-400 cm⁻¹ region) resulted in best-fit parameters. The PLS models presented satisfactory R2Y and RMSEP of 0.95 and 3.79% for THC, 0.99 and 1.44% for CBD in the Cannabis extract samples, respectively. Similar statistical indicators were noted for the Partial least-squares (PLS) models for THC and CBD prediction of decarboxylated Cannabis flowers (R2Y and RMSEP were 0.99 and 2.32% for THC, 0.99 and 1.33% for CBD respectively). The VIP plots of all models demonstrated that the THC and CBD distinctive band regions bared the highest importance for predicting the content of the molecules of interest in the respected PLS models. The complexity of the sample (plant tissue or plant extract), the variability of the samples regarding their origin and horticultural maturity, as well as the non-uniformity of the plant material and the flower-ATR crystal contact (in the case of Cannabis flowers) were governing the accuracy descriptors. Taking into account the presented results, ATR-MIR should be considered as a promising PAT tool for THC and CBD content estimation, in terms of critical material and quality parameters for Cannabis flowers and extracts.
... Cannabidiol (CBD), the main non-psychoactive component of Cannabis plants (Russo, 2017), has a terpenophenolic structure hydroxylated at carbons 1 and 3 (Jones et al., 1977). This structure gives CBD lipophilic properties, which allow its passage across the blood-brain barrier (Calapai et al., 2020). ...
Article
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Experimental evidence indicates that cannabidiol (CBD) induces anxiolytic and antiepileptic effects through the activation of 5-HT 1A receptors. These receptors are coupled to G i/o proteins and induce inhibitory effects. At present, the interaction of CBD with 5-HT 1A receptors in the human brain is unknown. The aim of this study focused on evaluating the interaction between CBD and 5-HT 1A receptors in cell membranes obtained from the hippocampus and temporal neocortex of autopsies and patients with drug-resistant mesial temporal lobe epilepsy (DR-MTLE). Cell membranes were isolated from the hippocampus and temporal neocortex of a group of patients with DR-MTLE who were submitted to epilepsy surgery ( n = 11) and from a group of autopsies ( n = 11). The [ ³ H]-8-OH-DPAT binding assay was used to determine the pharmacological interaction of CBD with 5-HT 1A receptors. The [ ³⁵ S]-GTPγS assay was used to investigate the CBD-induced activation of G i/o proteins through its action on 5-HT 1A receptors.The CBD affinity (p K i ) for 5-HT 1A receptors was similar for autopsies and patients with DR-MTLE (hippocampus: 4.29 and 4.47, respectively; temporal neocortex: 4.67 and 4.74, respectively). Concerning the [ ³⁵ S]-GTPγS assay, no statistically significant changes were observed for both hippocampal and neocortical tissue ( p > 0.05) at low CBD concentrations (1 pM to 10 μM). In contrast, at high concentrations (100 μM), CBD reduced the constitutive activity of G i/o proteins of autopsies and DR-MTLE patients (hippocampus: 39.2% and 39.6%, respectively; temporal neocortex: 35.2% and 24.4%, respectively). These changes were partially reversed in the presence of WAY-100635, an antagonist of 5-HT 1A receptors, in the autopsy group (hippocampus, 59.8%, p < 0.0001; temporal neocortex, 71.5%, p < 0.0001) and the group of patients with DR-MTLE (hippocampus, 53.7%, p < 0.0001; temporal neocortex, 68.5%, p < 0.001). Our results show that CBD interacts with human 5-HT 1A receptors of the hippocampus and temporal neocortex. At low concentrations, the effect of CBD upon G i/o protein activation is limited. However, at high concentrations, CBD acts as an inverse agonist of 5-HT 1A receptors. This effect could modify neuronal excitation and epileptic seizures in patients with DR-MTLE.
... CBD has a good safety profile, lacking drug abuse associated reinforcement, craving or compulsive consumption. These factors contribute to its elaborated research and pose a significant regulatory advantage [5][6][7][8]. ...
Article
Recent advances in the research of medicinal cannabis has placed the non-intoxicating cannabinoid cannabidiol (CBD) at the front of many investigations. The reasons behind this popularity is the compound’s therapeutic properties, alongside a safe profile of administration lacking addictive properties such as euphoric state of mind and characterized with a wide dosing range. Oral administration of CBD is challenging due to poor solubility in the gastro-intestinal system and susceptibility to extensive first pass metabolism. As a result, the practice in clinic and investigational trials is to administer cannabinoids in edible oils or oil-based solutions. Nonetheless, reported pharmacokinetics of cannabinoids and CBD in particular are not uniform among research groups and are affected by the vehicle of administration. The purpose of the work presented here is to investigate oral absorption processes of synthetic CBD when given in different oral formulations in healthy volunteers. The study design was a three way, blind, cross-over single administration study of 12 healthy male volunteers. CBD was administered in powder form, dissolved in sesame oil and in self-nano-emulsifying drug delivery system (SNEDDS). Administration of CBD in lipid-based vehicles resulted in a significant increase in Cmax and AUC of CBD, as compared to powder form. Overall plasma exposure of CBD did not differ between sesame oil vehicle and the SNEDDS formulation. However, administration of CBD in pure oil resulted in two absorption behaviors of early and delayed absorption among subjects, as opposed to SNEDDS platform that resulted in a uniform early absorption profile. Results of this trial demonstrate the importance of solubilization process of lipophilic drugs such as CBD and demonstrated the ability of the nano formulation to achieve a reliable, predictable PK profile of the drug. These findings offer a standardized oral formulation for the delivery of cannabinoids and contribute data for the growing field of cannabinoid PK.
... 1. CBD has been reported to demonstrate broad activity against dozens of macromolecular targets, as well as in numerous cell culture assays, often with different authors reporting different EC50/IC50 values or ranges [17,18]. Though arguably a subjective term, one might reasonably consider the reported activity of CBD to be promiscuous and characteristic of a so called "dirty drug" [19]. While it has been argued by some that such broad activity should not be considered ab initio as an unfavorable attribute of a screening "hit", such behavior is not generally considered desirable of a drug candidate and can even be indicative of nonspecific and thus unpredictable macromolecular interactions of limited or null value [4,20]. ...
Article
Decades of research have discovered a broad variety of interesting in vitro activities resulting from cannabinoid exposure. Recent investigations of cannabidiol, however, present a potential explanation for these findings, which relies on the nonspecific effects of colloidal dispersions as opposed to those of specific drug interactions with macromolecular targets. This perspective raises the question of how false-positive assay results arising from such colloidal interference may permeate the field of cannabinoid pharmacology. It further suggests a direction for future research with the intent of identifying true pharmacological interactions that might be more efficiently developed into therapeutic targets.
... A schematic pathway is depicted in Figure 1. In particular, CBDA light-and/or heat-induced decarboxylation provides cannabidiol, recently defined as "a pharmacologic agent of wondrous diversity, an absolute archetypal dirty drug" [16]. catalyzes Claisen-like condensation between n-hexanoyl-CoA and three nucleophilic malonyl-CoA. ...
Article
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Cannabidiolic acid (CBDA) is the main phytocannabinoid in fiber and seed-oil hemp (Cannabis sativa L.) plants, but its potential health-related capabilities have been masked for years by a greater scientific interest towards its neutral derivative cannabidiol (CBD). This review aims to collect from the literature and critically discuss all the information about this molecule, starting from its biosynthesis, and focusing on its bioactivity, as an anti-inflammatory, anti-emetic, anti-convulsant, and anti-cancerogenic drug. Furthermore, in the awareness that, despite its multiple bioactive effects, currently poor efforts have been made to achieve its reliable purification, herein, we propose a relatively simple, fast, and inexpensive procedure for its recovery from pollen of industrial hemp cultivars. Spectroscopic and spectrometric techniques allowed us to unequivocally identify pure isolated CBDA and to distinguish it from the constitutional isomer tetrahydrocannabinolic acid (THCA-A).
... Among these, phytocannabinoids represent the most interesting and most thoroughly studied class of compounds as they are endowed of a wide range of pharmacological activities. In particular, (−)-trans-Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and (−)-transcannabidiol (CBD) are the best known phytocannabinoids ( Fig. 1), with the former characterized by the intoxicant psychotropic activity typical of cannabis [4][5][6], and the latter void of such effect but known for its anti-inflammatory, anti-oxidant, anti-convulsant, and other numerous properties [7][8][9][10][11][12][13][14][15]. Although legal restrictions limit the use of cannabis and its psychotropic constituents in research and clinic [16,17], they have been recognized as valuable treatments for several therapeutic indications, including glaucoma, Tourette syndrome, and neuropathic pain [7,[18][19][20][21]. ...
Article
The chemical analysis of cannabis potency involves the qualitative and quantitative determination of the main phytocannabinoids: Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), cannabigerol (CBG), cannabichromene (CBC), etc. Although it might appear as a trivial analysis, it is rather a tricky task. Phytocannabinoids are present mostly as carboxylated species at the aromatic ring of the resorcinyl moiety. Their decarboxylation caused by heat leads to a greater analytical variability due to both reaction kinetics and possible decomposition. Moreover, the instability of cannabinoids and the variability in the sample preparation, extraction, and analysis, as well as the presence of isomeric forms of cannabinoids, complicates the scenario. A critical evaluation of the different analytical methods proposed in the literature points out that each of them has inherent limitations. The present review outlines all the possible pitfalls that can be encountered during the analysis of these compounds and aims to be a valuable help for the analytical chemist. Graphical abstract
... The clinical literature contrasts with results of rodent studies of CIPN that uniformly support the antinociceptive efficacy of cannabinoids such as THC (12)(13)(14) and the phytocannabinoid CBD (15)(16)(17) [for reviews, see (18,19)]. THC binds to CB 1 receptors in the brain, whereas CBD, which lacks these psychoactive properties, engages a myriad of diverse targets but shows little affinity for cannabinoid receptors [for a review, see (20)]. However, the validity of animal models of pathological pain has also been questioned (21). ...
Article
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Background Efficacy of inhaled cannabis for treating pain is controversial. Effective treatment for chemotherapy-induced neuropathy represents an unmet medical need. We hypothesized that cannabis reduces neuropathic pain by reducing functional coupling in the raphe nuclei. Methods We assessed the impact of inhalation of vaporized cannabis plant (containing 10.3% Δ⁹-tetrahydrocannabinol (THC)/0.05% cannabidiol (CBD)) or placebo cannabis on brain resting state BOLD functional connectivity and pain behavior induced by paclitaxel in rats. Rats received paclitaxel to produce chemotherapy-induced peripheral neuropathy (CIPN) or its vehicle. Behavioral and imaging studies were performed after neuropathy was established and stable. Images were registered to, and analyzed, using a 3D MRI rat atlas providing site-specific data on over 168 different brain areas. Results Prior to vaporization, paclitaxel produced cold allodynia. Inhaled vaporized cannabis increased cold withdrawal latencies relative to pre-vaporization or placebo cannabis, consistent with THC-induced antinociception. In paclitaxel-treated rats, the midbrain serotonergic system, comprising the dorsal and median raphe, showed hyperconnectivity to cortical, brainstem, and hippocampal areas, consistent with nociceptive processing. Inhalation of vaporized cannabis uncoupled paclitaxel-induced hyperconnectivity patterns. No such changes in connectivity or cold responsiveness were observed following placebo cannabis vaporization. Conclusion Inhaled vaporized cannabis plant uncoupled brain resting state connectivity in the raphe nuclei, normalizing paclitaxel-induced hyperconnectivity to levels observed in vehicle-treated rats. Inhaled vaporized cannabis produced antinociception in both paclitaxel- and vehicle-treated rats. Our studies elucidate neural circuitry implicated in the therapeutic effects of THC and support a role for functional imaging studies in animals in guiding indications for future clinical trials.
... 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. ...
Article
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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.
... 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. ...
Article
Full-text available
Dysfunction of the dopamine system has been proposed to explain clinical manifestations of ADHD. ADHD patients have been demonstrated to lack appropriate dopamine levels. The neurotransmitter dopamine is commonly associated with the brain’s pleasure system, providing a feeling of enjoyment and motivation to perform specific tasks. The endocannabinoid system has been implicated in various dopamine-deficiency-related disorders, including ADHD. A complex interaction between the endocannabinoid system and dopamine production has been experimentally demonstrated. The endocannabinoid primarily responsible for the release of dopamine is anandamide and increasing the concentrations of this molecule has demonstrated therapeutic value in treating ADHD. In this review article, synthetic and natural exogenous and endogenous methods for increasing anandamide concentrations are described.
... 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). ...
Article
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.
... Cannabidiol (CBD) has attracted widespread interest as a nonintoxicating alternative to traditional cannabinoid-based analgesics (Russo, 2017). CBD has shown a good safety profile and low abuse potential in humans (Corroon & Phillips, 2018;Iffland & Grotenhermen, 2017;Pisanti et al., 2017; World Health Organization Expert Committee on Drug Dependence, 2018). ...
Article
Despite its frequent use for pain relief, no experimental pain research has tested the analgesic effects of cannabidiol (CBD) in humans. The goal of this study was to experimentally test the effects of CBD and expectancies for receiving CBD on human pain reactivity. Using a crossover, 2 × 2 factorial balanced placebo design, drug administration (given inactive substance or given active CBD) and verbal instruction sets (told inactive substance or told active CBD) were experimentally manipulated. Fifteen healthy adults each completed four separate experimental sessions. Participants were randomly assigned to different counterbalanced manipulation conditions at each session: control (told inactive—given inactive); expectancy (told active CBD—given inactive); drug (told inactive—given active CBD); and expectancy + drug (told active CBD—given active CBD). Primary outcomes were pain threshold, tolerance, intensity, unpleasantness, conditioned pain modulation (CPM), and offset analgesia (OA). There was a significant main effect of instructions on OA, such that the OA response was significantly larger when participants were told that they received CBD, regardless of drug content. Pain unpleasantness was significantly reduced in the drug, expectancy, and expectancy + drug conditions, relative to the control condition. The drug and expectancy conditions separately improved CPM, whereas the expectancy + drug and control conditions produced the lowest CPM change scores. We did not detect significant effects for pain threshold, tolerance, or intensity. Our results indicated that separate pain outcomes can be differentially affected by CBD and/or expectancies for receiving CBD. Future investigations of the psychological and pharmacological mechanisms underlying CBD analgesia are warranted. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
... 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). ...
Article
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] . ...
Article
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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.
... 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. ...
Article
Full-text available
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.
... 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. ...
Article
Full-text available
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.
... They are biosynthesized mainly from olivetolic acid, which is transformed to cannabigerolic acid or CBGA, which are transformed by either THCA and CBDA synthase to finally give Cannabidiol acid (CBDA) or tetrahydrocannabinol acid (THCA) respectively as shown in Figure 17.3. Other types of cannabinoids are derived from these 2 main components [40,41]. ...
Chapter
After decades of restriction of use of Cannabis and cannabinoid, there's increased realization of their importance as potential therapeutic agents. The extensive pharmacological studies revealed their ability to interact with several molecular targets which widen their application in treatment of different diseases, especially immunity related conditions, since they demonstrated a prominent role in the modulation of endocannabinoid systems. In this chapter we will review the role of endocannabinoid system in controlling immunological response. Also we will shed the light on the history, traditional uses and chemistry of cannabinoids and the reported molecular pharmacology of two important constituents of cannabis, Δ9‐Tetrahydrocannabinol and Cannabidiol which can give better insights on their implications on management of autoimmune diseases.
... 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]. ...
Article
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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
... 46 While CBD is far less studied, it is a popular alternative therapy, and is particularly attractive to consumers as it is both fairly well-tolerated (causing mostly nonserious side effects) and nonintoxicating, with little or no abuse potential. 32,41 After the 2018 Farm Bill removed CBD products derived from hemp (Cannabis sativa with <0.3% D-9-tetrahydrocannabinol [THC]) from the Controlled Substances Act, 18 CBD products (eg, candies, cosmetics, soft-gels, tinctures) have flooded the marketplace. Some CBD manufacturers tout their products as wonder drugs, useful for numerous conditions such as Alzheimer's disease, epilepsy, anxiety, and cancer. 1 While the preclinical literature suggests that CBD has wide-ranging therapeutic activity (indeed, product claims are often based on preclinical data), 31,32 most of these findings have not been rigorously tested in large clinical trials, with the exception of CBD's anticonvulsant activity in the rare childhood epileptic conditions Dravet and Lennox Gastaut syndromes. ...
Article
Cannabidiol (CBD) is widely advertised as helpful for chronic pain management but research is limited. We examined patterns of naturalistic CBD use among individuals with fibromyalgia (FM) and other chronic pain conditions. Our objective was to better understand CBD use among people with FM. We conducted an online, cross-sectional anonymous survey between April and May of 2020. After excluding incomplete surveys, our study population consisted of N = 2701 participants with fibromyalgia, primarily in the United States. We collected demographic and clinical information on demographics, and measured rates of CBD use, reasons for use and discontinuation, communication with healthcare professionals about CBD, and perceptions of CBD effectiveness and safety among people with FM. Overall, 38.1% reported never using CBD, 29.4% reported past CBD use, and 32.4% reported current CBD use. Past-year cannabis use was strongly associated with past or current CBD use. Those using CBD typically did so due to inadequate symptom relief, while those not using CBD typically cited safety concerns as their reason for not using CBD. Two-thirds of participants disclosed CBD use to their physician, although only 33% asked for physician advice on using CBD. Participants used CBD for numerous FM-related symptoms (most commonly pain), and generally reported slight to much improvement across symptom domains. Around half of participants reported side effects, which were typically minor. Our findings are limited by selection bias and our cross-sectional design, which prevents causal associations. CBD use is very common among individuals with FM and many individuals using CBD report improvements across numerous FM-related symptoms. Our findings highlight the need for additional rigorous studies to better understand CBD's potential for FM management. National Fibromyalgia Association provided funding to help recruit for this survey.
Conference Paper
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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.
Article
Aims To describe an outbreak of lung injuries in 2019 among people who vaped in the USA (type of injuries, persons afflicted, substances vaped, and cause of the injuries) and to analyse critically the regulatory responses of public health authorities and the media reporting of the outbreak. Methods Case studies of the reporting of the e‐cigarette or vaping product use associated lung injury (EVALI) outbreak. We examined data on the number of cases of lung injury provided by the US Centers for Disease Control (CDC), public advice on the causes of the outbreak provided by the CDC and the Food and Drug Administration (FDA), major media reports of the outbreak and proposed regulatory responses by governments in the USA, Australia and the United Kingdom. Results The CDC initially suggested that the cause of the outbreak was nicotine vaping because the outbreak followed a large increase in nicotine vaping among US adolescents. Case control studies revealed that the majority of cases had vaped illicit cannabis oils that were contaminated by vitamin E acetate. The CDC's public advice and the media were slow to report the evidence on the role of cannabis vaping. Popular government regulatory proposals – bans on sales of nicotine flavours and vaporisers – were based on the assumption that nicotine vaping was the cause of the outbreak. Conclusions Media reporting in the US, Australia, and the UK of the US Centers for Disease Control's analysis of the causes of the e‐cigarette or vaping product use associated lung injury (EVALI) outbreak contributed to regulatory over‐reactions to nicotine vaping by the public health community.
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In the last few years research into Cannabis and its constituent phytocannabinoids has burgeoned, particularly in the potential application of novel cannabis phytochemicals for the treatment of diverse illnesses related to neurodegeneration and dementia, including Alzheimer’s (AD), Parkinson’s (PD) and Huntington’s disease (HD). To date, these neurological diseases have mostly relied on symptomatological management. However, with an aging population globally, the search for more efficient and disease-modifying treatments that could delay or mitigate disease progression is imperative. In this context, this review aims to present a state of art in the research with cannabinoids and novel cannabinoid-based drug candidates that have been emerged as novel promising alternatives for drug development and innovation in the therapeutics of a number of diseases, especially those related to CNS-disturbance and impairment.
Article
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.
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Cannabis (marijuana) is one of the most consumed psychoactive substances in the world. The term marijuana is of Mexican origin. The primary cannabinoids that have been studied to date include cannabidiol and delta-9-tetrahydrocannabinol, which is responsible for most cannabis physical and psychotropic effects. Recently, the endocannabinoid system was discovered, which is made up of receptors, ligands and enzymes that are widely expressed in the brain and its periphery, where they act to maintain balance in several homeostatic processes. Exogenous cannabinoids or naturally-occurring phytocannabinoids interact with the endocannabinoid system. Marijuana must be processed in a laboratory to extract tetrahydrocannabinol and leave cannabidiol, which is the product that can be marketed. Some studies suggest cannabidiol has great potential for therapeutic use as an agent with antiepileptic, analgesic, anxiolytic, antipsychotic, anti-inflammatory and neuroprotective properties; however, the findings on cannabinoids efficacy and cannabis-based medications tolerability-safety for some conditions are inconsistent. More scientific evidence is required in order to generate recommendations on the use of medicinal cannabis.
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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.
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Renewed and sustained Cannabis chemistry exploration was initiated by Roger Adams at the University of Illinois Chemistry Department with cooperation from the Treasury Department Narcotics Laboratory in the early 1940’s. This partnership and time investment by both parties made practical sense. Adams was able to explore natural products chemistry and the Narcotics Laboratory began to clarify the chemistry mysteries of Cannabis. Minnesota wild hemp, often viewed as just a roadside weed, was employed as the critical botanical source. Based on its widespread cultivation during World War II, this was also a very pragmatic decision. Although the unique Illinois – Washington D. C. collaboration lasted only a few short years (1939–1942), the stunning results included the isolation and extensive characterization of cannabidiol, the structure elucidation and total synthesis of cannabinol as well as the identification of the tetrahydrocannabinol structure as an intoxicating pharmacophore. Furthermore, this research well prepared many junior chemists for prolific careers in both academia as well as industry, inspired the discoveries of later Cannabis investigators and also provided a successful model of a productive academic-government partnership.
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CB1 is the most abundant GPCR found in the mammalian brain. It has garnered considerable attention as a potential therapeutic drug target. CB1 is involved in a wide range of physiological and psychiatric processes and has the potential to be targeted in a wide range of disease states. However, most of the selective and non-selective synthetic CB1 agonists and antagonists/inverse agonists developed to date are primarily used as research tools. No novel synthetic cannabinoids are currently in the clinic for use in psychiatric illness; synthetic analogues of the phytocannabinoid THC are on the market to treat nausea and vomiting caused by cancer chemotherapy, along with off-label use for pain. Novel strategies are being explored to target CB1, but with emphasis on the elimination or mitigation of the potential psychiatric adverse effects that are observed by central agonism/antagonism of CB1. New pharmacological options are being pursued that may avoid these adverse effects while preserving the potential therapeutic benefits of CB1 modulation. Allosteric modulation of CB1 is one such approach. In this review, we will summarize and critically analyze both the in vitro characterization and in vivo validation of CB1 allosteric modulators developed to date, with a focus on CNS therapeutic effects.
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The cannabinoid signaling system has recently garnered attention as a therapeutic target for numerous indications, and cannabinoids are now being pursued as new treatment options in diverse medical fields such as neurology, gastroenterology, pain management, and oncology. Cannabinoids are extremely hydrophobic and relatively unstable compounds, and as a result, formulation and delivery options are severely limited. Enzymatic glycosylation is a strategy to alter the physicochemical properties of small molecules, often improving their stability and aqueous solubility, as well as enabling site-specific drug targeting strategies. To determine if cannabinoids are a candidate for glycosylation, a library of glucosyltransferase (UGT) enzymes was screened for glycosylation activity towards various cannabinoids. The UGT76G1 enzyme from Stevia rebaudiana has been identified as having glucosyltransferase activity towards a broad range of cannabinoids. Compounds that were successfully glycosylated by UGT76G1 include the phytocannabinoids cannabidiol (CBD), Δ ⁹ -tetrahydrocannabinol (Δ ⁹ -THC), cannabidivarin (CBDV), and cannabinol (CBN), and the human endocannabinoids anandamide (AEA), 2-arachidonoyl-glycerol (2AG), 1-arachidonoyl-glycerol (1AG), and synaptamide (DHEA). Interestingly, UGT76G1 is able to transfer primary, secondary, and tertiary glycosylations at each acceptor of most of the cannabinoids tested. Additionally, Os03g0702000p, a glycosyltransferase from Oryza sativa , was able to transfer secondary glucose residues onto cannabinoid monoglycosides previously established by UGT76G1. This new class of cannabinoid-glycosides has been termed cannabosides. The compounds have greatly improved solubility in aqueous solutions. This increased aqueous solubility may enable new oral pharmaceutical delivery options for cannabinoids, as well as targeted delivery and release of cannabinoids within the intestines through glycoside prodrug metabolism.
Chapter
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.
Article
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.
Chapter
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.
Chapter
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.
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The COVID-19 pandemic has devastated the world, despite all efforts in infection control and treatment/vaccine development. Hospitals are currently overcrowded, with health statuses of patients often being hard to gauge. Therefore, methods for determining infection severity need to be developed so that high-risk patients can be prioritized, resources can be efficiently distributed, and fatalities can be prevented. Electrochemical prognostic biosensing of various biomarkers may hold promise in solving these problems as they are low-cost and provide timely results. Therefore, we have reviewed the literature and extracted the most promising biomarkers along with their most favorable electrochemical sensors. The biomarkers discussed in this paper are CRP, ILs, TNF-α, IFNs, glutamate, breath pH, lymphocytes, platelets, neutrophils and D-dimer. Metabolic syndrome is also discussed as a comorbidity for COVID-19 patients, as it increases infection severity and raises chances of becoming infected. Cannabinoids, especially CBD, are discussed as a potential adjunct therapy for COVID-19 as their medicinal properties may be desirable in minimizing the neurodegenerative or severe inflammatory damage caused by severe COVID-19 infection. Currently, hospitals are struggling to provide adequate care; thus, point-of-care electrochemical sensor development needs to be prioritized to provide an approximate prognosis for hospital patients. During and following the immediate aftermath of the pandemic, electrochemical sensors can also be integrated into wearable and portable devices to help patients monitor their recovery while returning to their daily lives. Beyond the COVID-19 pandemic, these sensors will also prove useful for monitoring inflammation-based diseases such as cancer and cardiovascular disease.
Conference Paper
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The discovery of the endocannabinoid system (ECS) has not only increased our understanding of the effects of plant cannabinoids, but also increased our understanding of human biochemistry as well as opened up avenues towards new therapeutic targets. Phytocannabinoids as well as their synthetic counterparts are known to engage with our endocannabinoid system ; hence our understanding of the basic biochemistry of this pivotal signaling system offers insights into beneficial and therapeutic uses of these molecules. There is a plethora of research data and scientific peer-reviewed papers on the topic of cannabinoids, the ECS and health/disease. Much data has been gathered from epidemiological and biomedical research, thus providing patients and medical professionals with good foundations for the use of cannabinoids in medicine. But understanding the biochemistry of the ECS and the role this signaling system plays in human physiology is the key to the proper use of these potent molecules.
Article
In the past, a variety of herbs were used in brewing, however only hops (Humulus lupulus) are now widely used as they contribute to the bitterness, flavour and microbiological stability of beer. After the abolition of prohibition of the cultivation of the Cannabis sativa L. species (the closest relative of H. lupulus), there are now beers infused with cannabis extracts made from all parts of the plant. The variety ‘hemp’ is used as it contains a minor concentration of the psychoactive Δ9‐tetrahydrocannabinol compared with marijuana. In this review, H. lupulus and C. sativa are compared and the opportunities and constraints for producing cannabis beers are discussed. © 2021 The Institute of Brewing & Distilling
Article
Cannabidiol (CBD) is the main cannabinoid naturally occurring in hemp. It has recently attracted the attention of the scientific community because of its numerous pharmacological activities. However, its legal status changes depending on whether it is either chemically synthesized or extracted from the plant: extracted CBD is a scheduled controlled substance, whereas synthetic CBD is not under control. In Europe, extracted CBD is excluded from the cosmetic ingredients of the CosIng database. Given the confusion surrounding these different forms of CBD, there is an urgent need for clarity to shed light from both a regulatory and a chemical point of view. The impurity profiles of synthetic and natural CBD differ and could currently represent the only means to distinguish the origin of this substance.
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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.
Article
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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.
Article
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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.
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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.
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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.
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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.
Article
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.
Article
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.
Article
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.
Article
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