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A Review of Human Studies Assessing Cannabidiol's (CBD) Therapeutic Actions and Potential
Abstract
Cannabidiol (CBD) is a highly touted product for many different disorders among the lay press. Numerous CBD products are available, ranging from a US Food and Drug Administration (FDA)‐approved product called Epidiolex to products created for medical marijuana dispensaries and products sold in smoke shops, convenience stores, and over the Internet. The legal status of the non–FDA‐approved products differs depending on the source of the CBD and the state, while the consistency and quality of the non–FDA‐approved products vary markedly. Without independent laboratory verification, it is impossible to know whether the labeled CBD dosage in non–FDA‐approved CBD products is correct, that the delta‐9‐tetrahydrocannabinol content is <0.3%, and that it is free of adulteration and contamination. On the Internet, CBD has been touted for many ailments for which it has not been studied, and in those diseases with evaluable human data, it generally has weak or very weak evidence. The control of refractory seizures is a clear exception, with strong evidence of CBD's benefit. Acute CBD dosing before anxiety‐provoking events like public speaking and the chronic use of CBD in schizophrenia are promising but not proven. CBD is not risk free, with adverse events (primarily somnolence and gastrointestinal in nature) and drug interactions. CBD has been shown to increase liver function tests and needs further study to assess its impact on suicidal ideation.
... Extracts from Cannabis sativa, containing phytocannabinoids such as CBD and THC, have gained great interest recently. Phytocannabinoids are being explored for treating various disorders and diseases, such as epilepsy, anxiety, chronic pain, spasticity, Parkinson's disease, psychosis, aggression, attention deficit hyperactivity disorder (ADHD) and ASD [19,20]. While some studies have identified methodological limitations, such as small and heterogeneous cohorts, study design and lack of standardized doses [20], there is substantial evidence supporting the efficacy of phytocannabinoids in treating specific disorders. ...
... Phytocannabinoids are being explored for treating various disorders and diseases, such as epilepsy, anxiety, chronic pain, spasticity, Parkinson's disease, psychosis, aggression, attention deficit hyperactivity disorder (ADHD) and ASD [19,20]. While some studies have identified methodological limitations, such as small and heterogeneous cohorts, study design and lack of standardized doses [20], there is substantial evidence supporting the efficacy of phytocannabinoids in treating specific disorders. For instance, CBD's role in managing seizures has been extensively studied, with many randomized trials demonstrating significant reductions or even cessation of seizures in a significant portion of cases [19,20]. ...
... While some studies have identified methodological limitations, such as small and heterogeneous cohorts, study design and lack of standardized doses [20], there is substantial evidence supporting the efficacy of phytocannabinoids in treating specific disorders. For instance, CBD's role in managing seizures has been extensively studied, with many randomized trials demonstrating significant reductions or even cessation of seizures in a significant portion of cases [19,20]. Ongoing clinical use of CBD has further bolstered its reputation as a safe and effective alternative for individuals with epilepsy, with increasing demand from both children and adults with treatment-resistant seizures [19]. ...
Autism Spectrum Disorder (ASD) encompasses a wide range of neurodevelopmental conditions characterized by deficits in social interaction, communication and behavior. Current pharmacological options are limited and feature significant side effects. In this study, we conducted a retrospective, observational, and cross-sectional cohort study to evaluate the effects of Cannabidiol (CBD)-dominant, full-spectrum cannabis extract, containing Tetrahydrocannabinol (THC) in a ratio of 33:1 (CBD:THC), on non-syndromic children and adolescents (5–18 years old) with moderate to severe ASD. Thirty volunteers were recruited, underwent neuropsychological evaluations and were treated with individualized doses of CBD-dominant extract. Clinical assessments were conducted by the designated clinician. Additionally, parents or caregivers were independently interviewed to assess perceived treatment effects. We found significant improvements in various symptomatic and non-symptomatic aspects of ASD, with minimal untoward effects, as reported by both clinical assessments and parental perceptions. The observed improvements included increased communicative skills, attention, learning, eye contact, diminished aggression and irritability, and an overall increase in both the patient’s and family’s quality of life. Despite its limitations, our findings suggest that treatment with full-spectrum CBD-dominant extract may be a safe and effective option for core and comorbid symptoms of ASD, and it may also increase overall quality of life for individuals with ASD and their families.
... The market for the primary hemp-derived cannabinoid, CBD, has emerged in the health and wellness sector. Although clinical research on CBD is still in its infancy, emerging research has suggested that CBD may be beneficial in alleviating the symptoms of insomnia (Ranum et al., 2023), reducing stress and anxiety (Lookfong et al., 2023), and modulating inflammation (Pagano et al., 2023), among other medical uses (White, 2019). Hempderived cannabinoids are primarily sold in health and wellness products for human and pet consumption (Alvarenga et al., 2023;Wheeler et al., 2020) and cosmetic products (Jeong et al., 2019). ...
... Farmers who were growing floral hemp for CBD believed that CBD was a beneficial health and wellness product. Although the claims of health benefits of CBD may be exaggerated in digital spaces , clinical research has shown there to be beneficial properties of CBD for medical uses (Lookfong et al., 2023;Pagano et al., 2023;Ranum et al., 2023;White, 2019). ...
Recent legislative changes have opened new avenues of hemp production for farmers seeking to diversify their operations. With the availability of these opportunities comes the need to better understand the decision making processes of new hemp growers. The purpose of this study was to explore what motivated first-year hemp farmers to grow hemp and to better understand the resources they utilized for decision-making. Fifteen farmers engaged in one-on-one interviews, which were analyzed using qualitative research methods. Three distinct themes emerged that undergirded farmer motivations to grow hemp: personal characteristics, identified advantages of hemp as a crop, and trialability and compatibility. Additionally, four themes were central to the resources new hemp farmers sought out: grower networks, digital media, government-based resources, and print media. The findings of this study align with components of Rogers’ Diffusion of Innovation Theory and recent research related to hemp and hemp-based products. Based on these findings, we recommend developing and expanding educational resources for those interested in entering hemp production to aid in their decision-making process and assist them as they navigate their entry into hemp cultivation.
... Among these, delta-9tetrahydrocannabinol (THC) is the most prevalent cannabinoid, known for its intoxicating effects and therapeutic benefits in treating chemotherapy-induced nausea and vomiting, pain, and muscle spasticity (National Academies of Sciences, Engineering, and Medicine et al., 2017;Smith and Gruber, 2023). In contrast, cannabidiol (CBD), usually the second most abundant cannabinoid, is non-intoxicating and has been reported to have therapeutic effects for a variety of conditions such as seizure disorders, anxiety, pain, and inflammation (White, 2019). Moreover, growing number of clinical trials indicate that CBD presents antipsychotic properties that have an beneficial effects in patients with schizophrenia as well as in the people at clinical high risk for psychosis (Rohleder et al., 2016;McGuire et al., 2018;Leweke et al., 2021;Bhattacharyya et al., 2024). ...
... Consequently, their therapeutic use may influence the metabolism of other drugs through inhibition or induction of cytochrome complexes and/or p-glycoprotein transporter, as well as through addition of side effects (summarized in Table 1). However, limited human studies investigating the DDIs of cannabinoids with other prescribed medications have been documented in literature (Geffrey et al., 2015;Gaston et al., 2017;Morrison et al., 2019;White, 2019;Vázquez et al., 2020), with some being merely case reports (Grayson et al., 2017;Leino et al., 2019;Madden et al., 2020). Given the frequent use of psychotropic drugs and cannabinoids, DDI between those two groups of medicines should be a common phenomenon. ...
Aim
Our objective was to systematically assess the prevalence and clinical features of adverse events related to interactions between cannabinoids and psychotropic drugs through a retrospective chart review.
Methodology
1586 adverse event reports were assessed. Cases included in the analysis showed a high probability of a causal relationships between cannabinoid-psychotropic drug interactions and adverse events. Data extracted included age, sex, psychotropic drug, cannabinoid products, other medications, and the clinical outcomes and mechanisms of these interactions.
Results
Cannabinoids were involved in 8% of adverse events associated with the concomitant use of psychotropic drugs and other preparations. We identified 20 reports in which side effects presented a causal relationship with the use of psychotropic drugs and cannabinoids. Preparations containing 18% or more tetrahydrocannabinol (THC), presented significant side effects with the following antidepressants: mianserine (restless legs syndrome, urogenital pain, ventricular tachycardia), mirtazapine (pancreatitis, hyperhidrosis, arthralgia), quetiapine (myocarditis, renal failure, bradycardia, sialorrhea), haloperidol (ventricular arrhythmia, prolonged QTc), aripiprazole (prolonged QTc), ventricular tachycardia) and cariprazine (stomach pain, hepatotoxicity), sertraline (ataxia, hyperactivity, coma, hallucinations, anxiety, agitation, tachycardia, panic attacks, disorientation, headache, dizziness, blurry vision, severe emesis, xerostomia, dry eyes), trazodone (disorientation, memory impairment, sedation), fluvoxamine (tachycardia, tachypnoea, dysarthria, auditory hallucinations). Two out of 20 reports (10%) analyzed in our study was related with the simultaneous use of cannabidiol (CBD) oil and sertraline. Concomitant use of those substances was associated with the adverse events in form of diarrhea, emesis, fever and severe fatigue.
Conclusion
Clinicians need to closely monitor adverse events resulting from the combined use of cannabinoids and psychotropic medications. The accumulation of side effects and pharmacokinetic interactions (including CYP and p-glycoprotein inhibition) between these drugs can lead to clinically significant adverse outcomes.
... research has utilized rodents, humans, or in vitro models, and scientific literature on dogs and cats is beginning to emerge. 4 Cannabidiol is a non-competitive allosteric modulator of the G protein-coupled cannabinoid receptor 1 (CB1) and an inverse agonist of CB2, 5,6 key components of the endocannabinoid system. Whereas CB1 is mostly concentrated in the central nervous system and regulates neurotransmitter release, CB2 is mainly located in cells of the immune system (intestine, tonsils, spleen) and plays a role in controlling cytokine release. ...
... Whereas CB1 is mostly concentrated in the central nervous system and regulates neurotransmitter release, CB2 is mainly located in cells of the immune system (intestine, tonsils, spleen) and plays a role in controlling cytokine release. [5][6][7] The negative modulation of these receptors by CBD aids in homeostasis and attenuation of inflammation. Other receptors that CBD has been found to interact with in mammals include fatty acid hydrolase (FAAH; inhibits enzyme hydrolysis of anandamide), G-protein coupled receptor 55 (GPR55; bone metabolism), transient receptor potential vanilloid 1 (TRPV1; analgesic and antiepileptic), peroxisome proliferator-activated receptor gamma (PPARγ; anti-inflammatory and antioxidant), and serotonin 5-beta hydroxytryptamine receptors 1 and 3 (5-HT 1A and 5-HT 3A ; antidepressant and anxiolytic). ...
Background
Cannabidiol (CBD) has therapeutic potential in companion animals. Shorter‐term studies have determined that CBD is well tolerated in dogs with mild adverse effects and an increase in alkaline phosphatase (ALP) activity. There is need to assess CBD's long‐term tolerability.
Hypothesis
Determine the long‐term tolerability of CBD administered PO to healthy dogs for 36 weeks at dosages of 5 and 10 mg/kg body weight (BW)/day. Our hypothesis was that CBD would be well tolerated by dogs.
Methods
Eighteen healthy adult beagle dogs were randomly assigned to 3 groups of 6 each that received 0, 5, or 10 mg/kg BW/day CBD PO. Dogs were adapted to their housing for 3 weeks and received treatment for 36 weeks once daily with food. Adverse events (AEs) were recorded daily. Blood biochemistry profiles were monitored every 4 weeks. Data were analyzed as repeated measures over time using a mixed model, with significance at α = 0.05.
Results
The 0 and 5 mg/kg treatment groups had similar fecal scores, and the 10 mg/kg treatment group had higher frequency of soft feces. No other significant AEs were noted. An increase (P < .0001) in ALP activity occurred in groups that received CBD. Remaining blood variables were within reference range.
Conclusions and Clinical Importance
Chronic administration of CBD in healthy dogs at 5 mg/kg was better tolerated than 10 mg/kg, and both dosages caused an increase in ALP activity. Although our data does not indicate hepatic damage, it is recommended to monitor liver function in dogs receiving CBD chronically.
... Notably, the intake of high-fat/high-calorie meals led to a 4.85-fold increase in CBD plasma exposure (C max ), and a 4.2-fold increase in AUC (area under the curve) (Taylor et al., 2018). CBD is predominantly metabolized within the liver through the involvement of cytochrome P450 (CYP2C19 and CYP3A) as well as uridine 5′-diphosphoglucuronosyltransferase (UGT1A7, UGT1A9, and UGT2B7) (Jiang et al., 2011;White, 2019). Furthermore, CBD may be the inhibitor or inducer of several cytochrome P450 isoforms, which underscores a notable risk for potential drug interactions with CYP substrates. ...
... Previous literature shows that CBD inhibits neutrophil migration and infiltration in vivo and vitro (Mabou Tagne et al., 2019;Gómez et al., 2021;Robaina Cabrera et al., 2021). Thus, treatment with CBD may ameliorate excessive inflammatory responses involving neutrophils. ...
Intracerebral hemorrhage (ICH) is a subtype of stroke with a high mortality rate. Oxidative stress cascades play an important role in brain injury after ICH. Cannabidiol, a major non-psychotropic phytocannabinoids, has drawn increasing interest in recent years as a potential therapeutic intervention for various neuropsychiatric disorders. Here we provide a comprehensive review of the potential therapeutic effects of cannabidiol in countering oxidative stress resulting from ICH. The review elaborates on the various sources of oxidative stress post-ICH, including mitochondrial dysfunction, excitotoxicity, iron toxicity, inflammation, and also highlights cannabidiol’s ability to inhibit ROS/RNS generation from these sources. The article also delves into cannabidiol’s role in promoting ROS/RNS scavenging through the Nrf2/ARE pathway, detailing both extranuclear and intranuclear regulatory mechanisms. Overall, the review underscores cannabidiol’s promising antioxidant effects in the context of ICH and suggests its potential as a therapeutic option.
... Another highly prevalent cannabinoid is cannabidiol (CBD). CBD is non-intoxicating, though investigations of potential anxiolytic, antipsychotic, and anticonvulsant applications are promising (Amminger et al., 2022;Bhattacharyya et al., 2010;McGuire et al., 2018;White, 2019). Also present in cannabis are hundreds of other compounds, such as terpenes, and minor cannabinoids, concentrations of which vary between chemovars (Ferber et al., 2020). ...
... Skeptics of a causal hypothesis point out the dissociation between recent decades' significant increases in cannabis use and relatively stable global rates of schizophrenia diagnoses (Degenhardt, Hall, & Lynskey, 2003). However, recent work indicates elevated rates of first-episode psychosis in regions with predominantly high-potency cannabis (Di Forti et al., 2015, 2019. Moreover, limitations have been identified within existing prediction models, including gaps and lags in incidence data (Hickman, Vickerman, Macleod, Kirkbride, & Jones, 2007). ...
Cannabis use is consistently associated with both increased incidence of frank psychotic disorders and acute exacerbations of psychotic symptoms in healthy individuals and people with psychosis spectrum disorders. Although there is uncertainty around causality, cannabis use may be one of a few modifiable risk factors for conversion to psychotic disorders in individuals with Clinical High Risk for Psychosis (CHR-P) syndromes, characterized by functionally impairing and distressing subthreshold psychotic symptoms. To date, few recommendations beyond abstinence to reduce adverse psychiatric events associated with cannabis use have been made. This narrative review synthesizes existing scientific literature on cannabis' acute psychotomimetic effects and epidemiological associations with psychotic disorders in both CHR-P and healthy individuals to bridge the gap between scientific knowledge and practical mental health intervention. There is compelling evidence for cannabis acutely exacerbating psychotic symptoms in CHR-P, but its impact on conversion to psychotic disorder is unclear. Current evidence supports a harm reduction approach in reducing frequency of acute psychotic-like experiences, though whether such interventions decrease CHR-P individuals' risk of conversion to psychotic disorder remains unknown. Specific recommendations include reducing frequency of use, lowering delta-9-tetrahydrocannabinol content in favor of cannabidiol-only products, avoiding products with inconsistent potency like edibles, enhancing patient-provider communication about cannabis use and psychotic-like experiences, and utilizing a collaborative and individualized therapeutic approach. Despite uncertainty surrounding cannabis' causal association with psychotic disorders, cautious attempts to reduce acute psychosis risk may benefit CHR-P individuals uninterested in abstinence. Further research is needed to clarify practices associated with minimization of cannabis-related psychosis risk.
... Given the current pharmacological interest, inherent legalities, and little data available for cannabinoids, we thought that it would be appropriate to investigate these molecules that also have a phenol ring in their basic structure. Increasing evidence indicates that certain cannabinoids are effective antioxidants, in addition to their therapeutic uses [54][55][56][57][58][59]. For this study, we have chosen eight phytocannabinoids (29,30,(43)(44)(45), and 48-50), which are important components in the Cannabis sativa plant, and two synthetic cannabinoids (46 and 47), all of which are being investigated for potential therapeutic uses. ...
... Given the current pharmacological interest, inherent legalities, and little data available for cannabinoids, we thought that it would be appropriate to investigate these molecules that also have a phenol ring in their basic structure. Increasing evidence indicates that certain cannabinoids are effective antioxidants, in addition to their thera peutic uses [54][55][56][57][58][59]. For this study, we have chosen eight phytocannabinoids (29,30,(43)(44)(45), and 48-50), which are important components in the Cannabis sativa plant, and two syn thetic cannabinoids (46 and 47), all of which are being investigated for potential therapeu tic uses. ...
We aim to develop a theoretical methodology for the accurate aqueous pKa prediction of structurally complex phenolic antioxidants and cannabinoids. In this study, five functionals (M06-2X, B3LYP, BHandHLYP, PBE0, and TPSS) and two solvent models (SMD and PCM) were combined with the 6-311++G(d,p) basis set to predict pKa values for twenty structurally simple phenols. None of the direct calculations produced good results. However, the correlations between the calculated Gibbs energy difference of each acid and its conjugate base, ΔGaq(BA)°=ΔGaqA−°−ΔGaq(HA)°, and the experimental aqueous pKa values had superior predictive accuracy, which was also tested relative to an independent set of ten molecules of which six were structurally complex phenols. New correlations were built with twenty-seven phenols (including the phenols with experimental pKa values from the test set), which were used to make predictions. The best correlation equations used the PCM method and produced mean absolute errors of 0.26–0.27 pKa units and R2 values of 0.957–0.960. The average range of predictions for the potential antioxidants (cannabinoids) was 0.15 (0.25) pKa units, which indicates good agreement between our methodologies. The new correlation equations could be used to make pKa predictions for other phenols in water and potentially in other solvents where they might be more soluble.
... Secondary metabolites such as cannabinoids and terpenes are now undergoing further investigation as potential lead compounds for further nutraceutical and pharmaceutical development. For example, it is well established that cannabinoids such as cannabidiol (CBD) and delta-9tetrahydrocannabinol (delta-9-THC) provide therapeutic effects through direct or indirect modulation of the body's naturally occurring endocannabinoid system [2]. The ongoing research of these compounds is justified by their numerous potential therapeutic and recreational uses, including analgesic, anti-inflammatory, and antioxidant effects [2]. ...
... For example, it is well established that cannabinoids such as cannabidiol (CBD) and delta-9tetrahydrocannabinol (delta-9-THC) provide therapeutic effects through direct or indirect modulation of the body's naturally occurring endocannabinoid system [2]. The ongoing research of these compounds is justified by their numerous potential therapeutic and recreational uses, including analgesic, anti-inflammatory, and antioxidant effects [2]. Other secondary metabolites determined in Cannabis sativa have not been thoroughly investigated, including stilbenes and flavonoids. ...
Cannabis sativa is a plant used for recreational and therapeutic purposes; however, many of the secondary metabolites in the plant have not been thoroughly investigated. Stilbenes are a class of compounds with demonstrated anti-inflammatory and antioxidant properties and are present in cannabis. Many stilbenes present in cannabis have been investigated for their therapeutic effects. Fourteen stilbenes have been identified to be present in cannabis, all of which are structurally dihydrostilbenoids, with half possessing a prenylated moiety. The stilbenes summarized in this analysis show varying degrees of therapeutic benefits ranging from anti-inflammatory, antiviral, and anti-cancer to antioxidant effects. Many of the identified stilbenes have been researched to a limited extent for potential health benefits. In addition, predictive in silico modeling was performed on the fourteen identified cannabis-derived stilbenes. This modeling provides prospective activity, pharmacokinetic, metabolism, and permeability data, setting the groundwork for further investigation into these poorly characterized compounds.
... Co-administration with other drugs alters blood levels of THC and CBD because THC is metabolized by cytochrome P450 (CYP), specifically CYP2C9, CYP2C19, and CYP3A4 (13)(14)(15)(16)(17). CBD, on the other hand, is metabolized by CYP2C19 and CYP3A4 (13). When THC and CBD are taken together with enzyme inducers, their blood levels decrease (18,19). Conversely, when THC and CBD are used alongside drugs that inhibit CYP450, especially CYP2C19 and CYP3A4, the levels of THC and CBD in the blood can increase to toxic levels (20,21). ...
Introduction: The prevalence of cancer patients seeking the Paisali formula from researchers in collaboration with Khu Muang Hospital during the year 2022 reflects the cancer patients’ inclination towards exploring herbal remedies for cancer treatment. Methods: This study aimed to investigate the effectiveness of the Paisali formula in alleviating vomiting and hematological toxicity in cancer patients using an experimental approach. The study comprised a total of 400 participants divided into two groups: an experimental group of 200 individuals receiving the Paisali drug and a control group of 200 individuals receiving a placebo. Throughout the study, toxicity levels were evaluated through laboratory blood tests conducted five times at 30-day intervals, and the results underwent independent t-test analysis. Results: The experimental group, which received 200 mg of Paisali, exhibited a statistically significant reduction in post-chemotherapy vomiting (p<0.00). Additionally, a comparison of blood test results before and after the administration of Paisali between the experimental and control groups revealed noteworthy differences in hydrogen ion concentration, hemoglobin levels, hematocrit, neutrophil count, alkaline phosphatase, aspartate transaminase, total bilirubin, and blood sugar values (p<0.00), as well as white blood cell values (p<0.02). These results suggest that the Paisali formula not only effectively reduced vomiting but also ameliorated hematological toxicity when compared to standard treatment alone. Conclusion: This study offers valuable insights into the potential advantages of incorporating the Paisali formula as an additional treatment option for managing chemotherapy-induced side effects in cancer patients. However, further research is necessary to comprehensively explore its mechanisms and long-term effects.
... Most cannabis products also contain cannabinoids other than THC that are of interest to researchers. For example, cannabidiol (CBD) is found in many cannabis products and is receiving growing research attention, in part owing to interest in its therapeutic potential [17][18][19][20], and to heterogeneity across clinical and preclinical evidence with respect to whether CBD attenuates or exacerbates the acute psychoactive effects of THC [21][22][23][24]. Further research is needed to clarify the acute effects of CBD, which requires survey methods for quantifying CBD use (akin to those emerging for quantifying THC use), the feasibility of which has yet to be established. ...
Aims
To establish the feasibility of using ecological momentary assessment (EMA) to estimate total quantities of Δ‐9‐tetrahydrocannabinol (THC) and cannabidiol (CBD) used across different forms of cannabis, and to assess the predictive validity of THC estimates for predicting acute cannabis‐related consequences.
Design
14‐day EMA using a smartphone application to assess cannabis use in real time.
Setting
Canada.
Participants
Targeted sample of n = 42 young adults (59.52% women, mean age 25 years) reporting frequent cannabis use.
Measurements
Surveys completed immediately prior to cannabis use assessed the quantities, THC content and CBD content of various forms of cannabis to be used in the current session; participants also uploaded photos of the cannabis product labels when available. Surveys administered at fixed times throughout the day (84.81% completion rate) assessed acute cannabis‐related consequences.
Findings
Participants completed a total of 786 pre‐cannabis surveys, of which 79.39% and 77.35% contained sufficient information to calculate total THC and CBD (in milligrams), respectively. High agreement was observed between participant‐entered THC and CBD contents and those shown in corresponding photos of cannabis product labels. Aggregating across all products used, participants reported using an average of 141.41 [standard deviation (SD) = 224.62, range = 0.00–2000.00] milligrams of THC (i.e. 28.28 standard five‐milligram units) and 7.53 (SD = 34.87, range = 0.00–484.22) milligrams of CBD per day. Multilevel models revealed that participants were more likely to report acute negative consequences following sessions when their estimated THC use was higher than their typical THC use. At the between‐person level, participants reporting more THC use on average across sessions were less likely to report negative consequences overall.
Conclusions
Using ecological momentary assessment to estimate total quantities of Δ‐9‐tetrahydrocannabinol and cannabidiol used across different forms of cannabis appears to be feasible, with preliminary predictive validity for acute negative cannabis‐related consequences.
... Tabela 3 -Estudos da Tabela 1 que relataram a melhora de SNM com o uso de Cannabis sativa em pacientes com DP. Costa et al., 2022;Crippa et al., 2019;Almeida et al., 2018;Deuel et al., 2020;Erga et al., 2022;Ferreira-Junior et al., 2020;Figura et al., 2022;Fraguas-Sánchez et al., 2018;Kolongowski et al., 2021;Lacroix et al., 2022;Mainka et al., 2018;Mechoulam et al., 2016;Oikonomou et al., 2022;Ortiz et al., 2022;Owusu et al., 2020;O'Sullivan et al., 2021;Paes-Colli et al., 2022;Patel et al., 2019;Pérez-Olives et al., 2021;Peres et al., 2018;Pisanti et al., 2017;Russo, 2018;Stasiłowicz et al., 2021;Suryadevara et al., 2017;Urbi et al., 2021;Velayudhan et al., 2021;Viana et al., 2022;White, 2019;Yan et al., 2021). Alguns estudos afirmam que houve melhora na cognição e na comunicação com doses diárias de 300mg de CDB (Chagas et al., 2014a;Díaz Rodríguez et al., 2023;Dash et al., 2020;Ferreira-Júnior et al., 2020;Kim et al., 2022). ...
Objetivo: Mapear e analisar as evidências disponíveis na literatura existente acerca da efetividade e segurança do uso da Cannabis sativa no tratamento dos Sintomas Não-Motores (SNM) da Doença de Parkinson (DP). Metodologia: Trata-se de uma revisão de escopo, com busca realizada nas bases de dados BVS Direct, EBSCO, Embase, PubMed e Scopus, sem limite temporal ou de idioma. Este processo foi norteado pela pergunta de pesquisa “Quais são as evidências da efetividade e segurança do uso terapêutico de Cannabis sativa no tratamento dos sintomas não-motores em pacientes com Doença de Parkinson?”. Resultados: Dos 2193 artigos encontrados, 90 estudos foram considerados elegíveis. Os estudos indicaram que a Cannabis sativa possui potencial para tratar diversos SNM, com melhora significativa da dor e distúrbios do sono, bem como melhora em manifestações neuropsiquiátricas e da qualidade de vida. As taxas de efeitos colaterais tendem a ser baixas e geralmente são classificados como leves e bem tolerados. No entanto, os resultados variam dependendo da dose utilizada, forma de administração do produto e composto canabinoide utilizado, sendo necessário mais estudos para avaliar a sua efetividade e segurança. Conclusão: O uso da Cannabis sativa pode melhorar os SNM, com potencial para impactar positivamente a qualidade de vida dos portadores de DP. Entretanto, mais estudos são necessários para garantir a efetividade e segurança dessa terapia complementar.
... Cannabidiol (CBD) is a non-intoxicating phytocannabinoid produced by cannabis and is dominant in the hemp variety, which is typically classified as having less than 0.3% ∆ 9 -THC [31]. CBD has been extensively studied for its anxiolytic properties [13,32], which have revealed that these anxiolytic effects are only achieved within a narrow dose-efficacy window [33][34][35][36]. This narrow dosing window may be difficult for people to achieve consistently, if at all, and perhaps has contributed to mixed results of CBD's anxiolytic efficacy in human trials [37]. ...
Volatile organic compounds, colloquially referred to as “terpenes”, have been proposed to impact the therapeutic qualities that are traditionally ascribed to cannabis. However, the contribution of these terpenes in anxiety, at relevant levels and exposure methods common with cannabis use, is lacking empirical assessment. We tested the anxiolytic properties of two prominent cannabis terpenes, linalool and β-myrcene, in male and female mice using short duration vapor pulls to model human inhalation when combusting flower or vaping cannabis oil. We observed sex differences in the locomotor effects in the open field and anxiolytic properties in the elevated plus maze of these terpenes that depended on their exposure characteristics. Both linalool and β-myrcene had anxiolytic effects in female mice when delivered in discrete vapor pulls over the course of 30 min. In male mice, only a single vapor hit containing linalool or β-myrcene had anxiolytic effects. The combination of sub-effective levels of linalool and the phytocannabinoid, cannabidiol (CBD), had synergistic anxiolytic effects in females, but these entourage effects between CBD and terpenes were absent with β-myrcene for females and for either terpene in males. Together, our findings reveal sex differences in the anxiolytic properties of common cannabis terpenes and highlight the potential benefits of unique combinations of CBD and terpenes in expanding the therapeutic dose window.
... Cannabidiol (CBD) is a non-intoxicating phytocannabinoid produced by cannabis and is dominant in the hemp variety, which is typically classified as having less than 0.3% Δ 9 -THC [30]. CBD has been extensively studied for its anxiolytic properties [13,31], which have revealed that these anxiolytic effects are only achieved within a narrow dose-efficacy window [32][33][34][35]. This narrow dosing window may be difficult for people to achieve consistently, if at all, and perhaps has contributed to mixed results of CBD's anxiolytic efficacy in human trials [36]. ...
Volatile organic compounds, colloquially referred to as “terpenes”, are proposed to impact the therapeutic qualities that are traditionally ascribed to cannabis. However, the contribution of these terpenes in anxiety, at relevant levels and exposure methods common with cannabis use, is lacking empirical assessment. We tested the anxiolytic properties of two prominent cannabis terpenes, linalool and β-myrcene, in male and female mice using short duration vapor pulls to model human inhalation when combusting flower or vaping cannabis oil. We observed sex differences in the locomotor effects and anxiolytic properties of these terpenes that depended on their exposure characteristics. Both linalool and β-myrcene had anxiolytic effects in female mice when delivered in discrete vapor pulls over the course of 30 minutes. In male mice, only a single vapor hit containing linalool or β-myrcene had anxiolytic effects. The combination of sub-effective levels of linalool and the phytocannabinoid, cannabidiol (CBD), had synergistic anxiolytic effects in females, but these Entourage Effects between CBD and terpenes were absent with β-myrcene for females and for either terpene in males. Together, our findings reveal sex differences in the anxiolytic properties of common cannabis terpenes and highlight the benefits of unique combinations of CBD and terpenes in expanding the therapeutic dose window.
... Conversely, in vivo and in vitro studies using animals or animalderived cells suggest many therapeutic uses of CBD including treatment for non-alcoholic fatty liver disease (NAFLD) (Chen et al., 2018;Silvestri et al., 2015), liver steatosis (Yang et al., 2014), cardiomyopathy (Hao et al., 2015), inflammation (Juknat et al., 2012), liver fibrosis (Lim et al., 2011), and neurological injury (Ryan et al., 2009;Sun et al., 2017). In humans, CBD has been proposed as a treatment for various conditions such as anxiety, chronic pain, sleep disorders, neurological disorders, and diabetes (Arnold et al., 2023;Consroe et al., 1991;Crippa et al., 2021;Jadoon et al., 2016;White, 2019). ...
... The discovery of endocannabinoid receptors (CBR) has shed light on the endocannabinoid system (ECS), a complex signalling network involved in various physiological functions, such as pain modulation, immune response, appetite regulation, and mood control [4][5][6]. Furthermore, the activation of endocannabinoid receptors (CBRs) has been associated in the therapeutic management of various medical conditions, including cancer, anxiety disorders, chronic pain, neurodegenerative diseases, and other health complications [7][8][9]. ...
This study provides a comprehensive analysis of the conformational dynamics of pseudo-endocannabinoid receptors (p-CBRs) CB1 and CB2 in response to ligand binding. The ligands studied include N-arachidonoyl dopamine (NADA), Cannabidiol (CBD), known agonists (FUB-MDMB and E3R), and inverse agonists (Taranabant and AM630). Using homology models based on crystal structures (PDB ID: 5U09 for CB1 and 5ZTY for CB2), molecular docking, and molecular dynamics (MD) simulations, the research validates the structural integrity and dynamic behaviours of these pseudo-receptors. Induced-fit docking revealed NADA as having the highest binding affinity for both receptors, with docking scores of −13.92 kcal/mol for CB1 and −13.32 kcal/mol for CB2, facilitated by key hydrogen bond interactions. MD simulations over 250 ns at ~298 K showed successful equilibration, indicating the most stable interaction for NADA, thereby further validating the models. CB1 and CB2 exhibited distinct conformational responses to ligands, with Cα RMSD and Cα RMSF analyses suggesting a more rigid binding pocket for CB1 and a flexible binding pocket for CB2. These findings highlight the significance of receptor behaviour and dynamics in the development of cannabinoid-based therapeutics, supporting the potential of CBD and NADA as modulators for CB1 and CB2, respectively.
... Traditional approaches to speech learning often focus on technical aspects such as intonation, posture and language use. However, this approach often fails to address the psychological barriers that learners may face, such as anxiety and self-confidence (White, 2019). Given the complexity of the challenges faced by learners in developing their public speaking skills, there is a need to develop a more holistic and inclusive learning approach, which should not only teach effective speaking techniques, but also help learners overcome the psychological barriers they may face (Linares, 2020). ...
Background. The effectiveness of oral corrective feedback (OCF) in language learning is influenced by learners’ comprehension and response to various OCF techniques. Therefore, it is essential for teachers to consider learners’ preferences for OCF strategies. Purpose. this study aims to investigate the use of ARIAS Model on speech learning. This research will explore the effectiveness of this approach in helping learners overcome challenges in public speaking and improve their speaking skills with more confidence and conviction. Method. This research used a qualitative method with a descriptive approach. Data collection techniques included interviews, observations, and questionnaires filled out by 21 students. Results. The results showed that the use of the ARIAS model significantly improved students’ clarity (85%), intonation (80%), and expression (90%) in speech. In addition, 95% of students gave positive responses to the ARIAS model, indicating its acceptance and effectiveness in speech learning. Conclusion. This study concludes that the ARIAS model is a comprehensive and effective approach to develop public speaking skills, help students overcome psychological barriers, and improve their speech skills with more confidence and convincing. However, technical challenges such as technological infrastructure must be overcome to ensure optimal implementation. The findings support the importance of integrating the ARIAS model in the Indonesian language learning curriculum to improve students’ communication skills.
... In addition, flgA has been demonstrated to serve as a transcriptional factor and is noted to be a pre-requirement for flgC expression. Among the dozens of phytocannabinoids, Cannabidiol (CBD), the non-psychoactive constituent, has captured the interest of several researchers globally due to its alleged pharmacological qualities, such as its anxiolytic, anti-inflammatory and analgesic properties [10]. Contrary to delta-9tetrahydrocannabinol (THC), CBD is free from any psychotic effects, making it suitable for treating patients with zero or minimal feelings of "high" associated with traditional cannabis use [11]. ...
Salmonella Typhimurium is a typical Gram-Negative bacterium associated with food-borne illness threatening public health. This pathogen is reported to have caused millions of infections and thousands of hospitalizations yearly in the United States alone. Salmonella Typhimurium has a sophisticated array of virulent factors, including its flagella, that contribute significantly to its pathogenicity. Cannabidiol (CBD), the non-psychoactive component of the cannabis plant, has attracted the interest of many researchers recently because of its antimicrobial properties. With the growing interest in exploring CBD’s antimicrobial properties, we, in this study, have delved into unravelling how prolonged exposure of Salmonella Typhimurium to CBD influences the expression of the flgA gene. We hypothesized that the exposure of Salmonella Typhimurium to CBD may result in flgA upregulation, causing the bacteria to withstand various stresses and potentially enhance its survival rates and pathogenicity. We have employed several assays, such as mRNA expression, motility assays, pH induction assays, nutrient starvation interventions, and biofilm analysis, to explore the influence of CBD on the pathophysiology of Salmonella Typhimurium. Our findings reveal that CBD-resistant strains exhibit enhanced resilience to extreme pH levels and motility and survive poorly under nutrient starvation, with more robust biofilm formation compared to the susceptible strains. The results contribute to the broader comprehension of CBD resistance mechanisms in bacteria. This work provides insight into the potential therapeutic interventions for controlling CBD-resistant bacterial infections. This study also underscores the essence of exploring novel alternative antimicrobial agents to tackle the ever-persistence of bacterial antibiotic resistance.
... 9 In addition, other noncannabinoid receptors were found as targets of CBD. 10 The therapeutic benefits of the use of CBD have been extensively investigated by different studies, where CBD has been proven to display therapeutic properties for a variety of psychiatric disorders having antioxidant, antitumoral, anti-inflammatory, neuroprotective, and painrelieving properties. [11][12][13][14][15][16] Recently, there has been a growing interest in the use of CBD as a therapeutic agent or as a coadjuvant treatment for symptoms and comorbidities related to neurodevelopmental disorders and in particular autism spectrum disorders (ASD). [17][18][19][20] These and other cannabinoids can have a synergic action with other molecules contained in C. sativa and exert therapeutic effects for different psychiatric and neurological diseases. ...
Objective: Cannabis sativa is the most used recreational drug worldwide. In recent years, there has been a growing interest in the potential therapeutic benefits of medicinal cannabis to treat a variety of psychiatric and neurological conditions. In particular, cannabidiol (CBD), a nonpsychoactive cannabis constituent, has been investigated for its potential prosocial effects on behavior, although the molecular mechanisms underlying this effect are still largely unknown. The aim of this study was to investigate the effect of a C. sativa oil CBD rich (CS oil) on social interaction and ultrasonic communication in mice. Study Design: Twenty-seven adult male mice (B6; 129P F2) were treated daily with vehicle or CS oil for 2 weeks. At Day 14, mice were tested for behavior (social interaction test and ultrasonic communication). Forty minutes before the behavioral tests, mice were exposed to intranasal treatment with vehicle or the oxytocin receptor antagonist, L-371,257. After behavioral tests, VH- and CS oil-treated mice were sacrificed, RNA was extracted from the hypothalamus and used for quantitative Real Time-PCR experiments. Results: We found that a 2-week treatment with the CS oil on mice exerted a prosocial effect associated with an increase in ultrasonic vocalizations. These effects were inhibited by pretreating mice with an oxytocin receptor antagonist. In addition, at the molecular level, we found that CS oil treatment caused a significant increase in oxytocin and a decrease in oxytocin receptor expression levels in the brain hypothalamus. Conclusion: Our results suggest that CS oil promotes social behavior by acting on oxytocin pathway.
... CBD is reportedly associated with a wide variety of potential health benefits, while Δ9-THC is the major psychoactive component in the cannabis plant. 2,3 Most commercial products are therefore expected to contain CBD and no THC. South African consumers in particular, have access to a wide range of cannabis-derived products offered by retail outlets and informal traders. ...
... The genetic basis of DS is largely attributed to heterozygous mutations in the NaV1.1 alpha subunit of voltage-gated sodium ion channels encoded by the SCN1A gene [6,7]. These mutations result in the loss of function of NaV1.1 channels, which is critical for normal brain function and leads to seizures and epilepsy [8,9]. In some cases, these pathogenic SCN1A variants can be inherited, while in others, de novo mutations occur [10,11]. ...
Background
Dravet Syndrome (DS) is a rare and severe form of childhood epilepsy that is often refractory to conventional antiepileptic drugs. Emerging evidence suggests that Cannabidiol (CBD) offer therapeutic benefits for DS. This review aims to evaluate the efficacy and safety of CBD in pediatric patients with DS based on data from ten clinical trials.
Methods
A review was conducted to identify clinical trials assessing the efficacy and safety of CBD in pediatric patients diagnosed with DS. PubMed, MEDLINE, Scopus, Web of Science, and relevant grey literature were systematically searched for relevant articles up to October 2023, and clinical trials within the last 10 years were included. The search strategy incorporated controlled vocabulary terms and keywords related to "Cannabidiol," "Dravet Syndrome," and "pediatric patients."
Results
The analysis revealed promising efficacy outcomes. Notably, CBD demonstrated substantial reductions in seizure frequency, with some patients achieving seizure freedom. The findings emphasised the consistency of CBD's efficacy across different patient subgroups. The safety profile of CBD was generally acceptable, with adverse events often being manageable.
Conclusion
This review consolidates evidence from multiple clinical trials, affirming the potential of CBD as a promising treatment option for pediatric patients with DS. While further research is needed to address existing knowledge gaps, CBD's efficacy and acceptable safety profile make it a valuable addition to the therapeutic tools for DS.
... CBD's ability to inhibit inducible nitric oxide synthase (iNOS) protein expression and activation of nuclear factor kappa B (NF-K B) in the brain shows its neuroprotective tendencies (Bhunia et al. 2022;Ekiner et al. 2022). While extensive studies on the systemic therapeutic effects of CBD in the body have been done (Britch et al. 2021;Peng et al. 2022;White 2019), the potential of this phyto-cannabinoid on neurological/neuropsychiatric disorders requires further exploration regarding its effect on neuroinflammation that occurs as a consequence of these disorders. In addition to reviewing the therapeutic properties of CBD, and evaluating its potential as an anti-inflammatory agent, particularly in neurological/neuropsychiatric disorders, this article primarily identifies and states mechanisms through which CBD can help minimize inflammation caused by cytokine release. ...
Background
The treatment of diverse diseases using plant-derived products is actively encouraged. In the past few years, cannabidiol (CBD) has emerged as a potent cannabis-derived drug capable of managing various debilitating neurological infections, diseases, and their associated complications. CBD has demonstrated anti-inflammatory and curative effects in neuropathological conditions, and it exhibits therapeutic, apoptotic, anxiolytic, and neuroprotective properties. However, more information on the reactions and ability of CBD to alleviate brain-related disorders and the neuroinflammation that accompanies them is needed.
Main body
This narrative review deliberates on the therapeutic and remedial prospects of CBD with an emphasis on neurological and neuropsychiatric disorders. An extensive literature search followed several scoping searches on available online databases such as PubMed, Web of Science, and Scopus with the main keywords: CBD, pro-inflammatory cytokines, and cannabinoids. After a purposive screening of the retrieved papers, 170 (41%) of the articles (published in English) aligned with the objective of this study and retained for inclusion.
Conclusion
CBD is an antagonist against pro-inflammatory cytokines and the cytokine storm associated with neurological infections/disorders. CBD regulates adenosine/oxidative stress and aids the downregulation of TNF-α, restoration of BDNF mRNA expression, and recovery of serotonin levels. Thus, CBD is involved in immune suppression and anti-inflammation. Understanding the metabolites associated with response to CBD is imperative to understand the phenotype. We propose that metabolomics will be the next scientific frontier that will reveal novel information on CBD’s therapeutic tendencies in neurological/neuropsychiatric disorders.
... Unlike delta-9-tetrahydrocannabinol (Δ9-THC), CBD is not high inducing nor does it lead to impairment of cognitive function (e.g., impaired memory; Zamarripa et al., 2022). CBD is U.S. Food and Drug Administration approved for the treatment of two rare and severe forms of epilepsy (i.e., Lennox-Gastaut syndrome, Dravet syndrome; U.S. Food and Drug Administration, 2023) and is widely touted as a putative therapeutic aid for various health conditions, though many findings are inconsistent across the literature (e.g., reduce stress and anxiety, improve sleep quality; Babson et al., 2017;Bolsoni et al., 2022;Sholler et al., 2020;Skelley et al., 2020;White, 2019). Moreover, CBD-containing products, including those combined with caffeine (e.g., CBD-infused coffee), are increasingly available and are commonly used among young adults (Moltke & Hindocha, 2021). ...
Caffeine and cannabidiol (CBD) are commonly consumed by the general population, particularly among young adults; however, there is little research on the simultaneous effects of caffeine and CBD. The present study aimed to examine the simultaneous self-reported effects of caffeine and CBD in young healthy adults. Participants (N = 54) who reported daily caffeine use (>200 mg) attended one experimental session via Zoom and were assigned randomly to receive caffeine (200 mg) combined with either a placebo or CBD (25, 50, 80, 160, or 240 mg). Participants completed subjective drug effects measures at baseline and then ingested caffeine and their assigned CBD dose. Throughout the 140-min session, participants completed self-report measures. The primary outcomes of this study were measures of general drug effects and anxiety. After caffeine and CBD administration, few effects were observed in self-reported measures of general drug effects. No negative effects emerged as a result of combined caffeine and CBD administration. These results should be interpreted cautiously given the preliminary nature and variability in outcomes. The present study findings suggest that combinations of the tested doses of caffeine and CBD do not alter subjective drug effects; further, no negative effects emerged, providing preliminary safety evidence for using these products simultaneously. Further research is needed to examine the simultaneous and/or interactive nature of caffeine and CBD on other caffeine-induced outcomes (e.g., cognition and physiological effects) and will be critical for informing future regulatory decisions regarding caffeine: CBD mixtures.
... O THC foi identificado como o principal canabinoide responsável pelo efeito psicotrópico da cannabis, portanto, é encontrado em altas concentrações na índica (> 0,3%) e baixas concentrações na sativa (< 0,3%). O CBD foi citado como um constituinte não intoxicante da planta de cannabis com potencial valor terapêutico 9 . ...
Objective: To discuss the effects of CBD and THC on the athlete and their influences on the sport. Method: A literature review was carried out on Google Scholar, ScienceDirect, PubMed, and on the ResearchGate research network, as well as searches on the reference lists of pre-selected works on the subject, using as descriptors: cannabidiol, THC, athletes and sports to check state of the art. Publications in English were used. Research was carried out between April and November 2022. Results: CBD is used as an adjuvant for the treatment of disorders, providing antioxidant, analgesic, anti-inflammatory and neuroprotective properties in sports and clinical environments. Such benefits are observed both in the specific use of CBD, as well as in combination with THC. Conclusion: CBD and THC can exert physiological, biochemical and psychological effects that benefit athletes, however, studies with sportsmen are needed before definitive conclusions can be reached about the usefulness of CBD and THC effects to athletic performance.
DESCRIPTORS: Cannabidiol; THC; Athletes; Sports.
... [6][7][8] Observations to date have shown that CBD exerts a range of actions on the Table 1. [9][10][11][12][13][14] Such a comprehensive interaction is associated with the involvement of a number of signaling pathways; however, these have not yet been fully identified. Many hypotheses and potential relationships through which cannabinoids may act on the body are available in the literature. ...
Background:
Cannabis, more commonly known as marijuana or hemp, has been used for centuries to treat various conditions. Cannabis contains two main components cannabidiol (CBD) and tetrahydrocannabinol (THC). CBD, unlike THC, is devoid of psychoactive effects and is well tolerated by the human body but has no direct effect on the receptors of the endocannabid system, despite the lack of action on the receptors of the endocannabid system.
Objectives and methods:
We have prepared a literature review based on the latest available literature regarding the analgesic effects of CBD. CBD has a wide range of effects on the human body. In this study, we will present the potential mechanisms responsible for the analgesic effect of CBD. To the best of our knowledge, this is the first review to explore the analgesic mechanisms of CBD.
Results and conclusion:
The analgesic effect of CBD is complex and still being researched. CBD models the perception of pain by acting on G protein-coupled receptors. Another group of receptors that CBD acts on are serotonergic receptors. The effect of CBD on an enzyme of potential importance in the production of inflammatory factors such as cyclooxygenases and lipoxygenases has also been confirmed. The presented potential mechanisms of CBD's analgesic effect are currently being extensively studied.
... CBD is easily available and relatively cheap to produce which makes it a very attractive chemical compound that can be used in medicine. Observations to date have shown that CBD exerts a range of actions on the human body, including analgesic as well as anxiolytic, anti-oxidant, anti-inflammatory, anti-convulsant and even anti-psychotic effects [38,39,40,41,42,43,44]. Such a comprehensive interaction is associated with the ...
Introduction and objective:
Low back pain (LBP) is a major cause of disability and the main reason why individual patients need medical attention. Pharmacological treatment options for LBP are limited and are often associated with serious side-effects. This makes it necessary to search for new painkillers. One potential therapeutic agent is cannabidiol (CDB). Cannabidiol and tetrahydrocannabinol are the most researched components of cannabis, the plant more commonly known as marijuana or hemp. To the best of our knowledge, this is the first narrative review of the effects of CBD alone on acute and chronic back pain.
Review methods:
Based on the guidelines provided by the Primary Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA), the PubMed/ MEDLINE database was used to identify articles for analysis from the last 30 years. Due to the limited number of studies on this topic, all types of studies that met the inclusion criteria were included. After analysis, 10 studies were included in this review.
Brief description of the state of knowledge:
Currently, the use of medical marijuana continues to increase and the Food and Drug Administration (FDA) has already approved four cannabis-based drugs. Cannabidiol (CBD) is a relatively safe substance for humans and generally well tolerated. It is a substance that is easily available and often taken by patients with LBP.
Summary:
Evidence for the effectiveness of CBD in the treatment of acute low back pain is lacking. There was only one clinical trial conducted in the Emergency Department that showed no superiority of CBD over placebo in acute LBP. The majority of studies concern chronic rather than acute LBP. Although most of the results suggest a beneficial effect of cannabinoids in relieving chronic LBP, hard evidence is lacking. Rigorous randomized controlled trials are needed.
Aims
This study aimed to determine the effect of vaporized cannabidiol (CBD) on visual function and vehicle driving performance, given the growing popularity of CBD use worldwide.
Design
Randomized, double‐blind, placebo‐controlled cross‐over experimental study.
Setting
Laboratory of Vision Sciences and Applications, University of Granada, Spain.
Participants
Thirty participants were recruited through advertisements placed in the local newspaper and distributed among the university community. They had a mean age of 26.2 (6.2) years, and 70% were male. All of them were occasional users of CBD or cannabis, and held valid driving licenses.
Interventions
Three experimental sessions, conducted one week apart, in which a placebo, 15% CBD (16 mg) or 30% CBD (32 mg) was vaporized.
Measurements
The primary endpoint for driving performance was the overall driving performance score (ODPS). Secondary outcomes included visual function variables such as static and dynamic visual acuity, stereoacuity, contrast sensitivity, motion detection and other driving performance parameters such as mean speed, lateral vehicle control or reaction time.
Findings
Comparisons revealed no statistically significant changes in ODPS after vaporizing CBD at 15% or 30% compared with the placebo (χ ² = 0.479; P = 0.787). Visual function remained largely unchanged, with only a statistically significant decrease in motion detection (χ ² = 7.980; P = 0.018). Similarly, no statistically significant differences were found in driving performance secondary outcomes, such as the standard deviation of lateral lane position (χ ² = 0.068; P = 0.966), distance travelled outside the lane (χ ² = 2.530; P = 0.282), reaction time (χ ² = 1.000; P = 0.607), or collisions (χ ² = 0.987; P = 0.610). Additionally, correlations between ODPS and visual function did not yield statistically significant results.
Conclusions
Consumption of vaporized cannabidiol in 16 mg and 32 mg doses does not appear to affect simulated vehicle driving performance and visual function.
The synthetic utility of tetrabenzyl pyrophosphate for achieving chemoselective phosphorylation of phenols, as well as primary, secondary, and tertiary alcohols, is reported here. Additionally, we introduce a rapid, mild, and chemoselective debenzylation procedure, enabling access to phosphates in the presence of redox sensitive groups. Finally, stoichiometrically controlled monodebenzylation provides a versatile platform for late-stage divergent synthesis of phosphodiester and phosphoramidate chemical libraries.
Herbal medicines are becoming more popular as people seek holistic ways to manage their health. This article discusses how people are turning to natural products in addition to or as a substitute to conventional medicines, which has led to the revival of herbal medicines.
This review disseminates new developments in this industry, changes in the care delivery systems, and innovations in drug safety. Pharmaceuticals have brought innovative changes within their field of drug formation, new theories regarding medicine for individuals, and introducing biotechnologies. At the same time, patient care models are changing towards the more integrated and patient-oriented ones. Further, maintaining drug safety continues to be a critical focal point because the complexity of drug therapies continues to increase, and their potential adverse effects need to be minimized. This review, therefore, looks at these interconnections based on current literature, research findings, and case studies in a bid to give an overall vision of the evolution of modern pharmaceuticals and how their advancement impacts the delivery of healthcare.
The increasing use of Cannabis sativa products for medicinal, dietary, and recreational purposes has raised concerns about mycotoxin contamination in cannabis and hemp. Mycotoxins persist in these products’ post-processing, posing health risks via multiple exposure routes. This study investigated cytotoxic and genotoxic interactions between cannabidiol (CBD) and the mycotoxin citrinin (CIT) using human cell models: SH-SY5Y, HepG2, HEK293, and peripheral blood lymphocytes. IC50 values and membrane disruption were initially assessed, followed by an evaluation of genotoxicity in lymphocytes using the Comet Assay and Cytokinesis Blocked Micronucleus Cytome Assay. Obtained findings demonstrate that cell-type sensitivity varied across treatments, with combined CBD and CIT exposure exhibiting distinct interactions. Lactate dehydrogenase (LDH) release remained minimal, suggesting cytotoxicity did not stem from membrane disruption but likely involved intracellular pathways. In lymphocytes, CBD alone produced negligible cyto/genotoxic effects and weak antiproliferative responses, whereas CIT displayed clear toxic impacts. DNA damage indicates that CIT may induce genome instability through indirect mechanisms rather than direct DNA interaction, with evidence of potential aneuploidic effects from the CBMN Cyt Assay. Combined exposure led to a reduction in CIT-induced DNA and cytogenetic damage, suggesting CIT’s potential interference with the beneficial properties of CBD. These results provide a foundation for further toxicological assessments and highlight the necessity of standardized mycotoxin monitoring in cannabis-derived products.
Background: Emerging evidence supports cannabidiol (CBD) as a promising therapeutic compound for various health conditions, despite its approval as a medication (product for medical purposes) remaining restricted to a limited range of clinical indications. Simultaneously, the regulation of cannabis-derived products for medicinal and recreational use has expanded their global market availability to meet local community demands. This scenario presents a complex challenge for clinicians, researchers, and industry, as the global appeal of therapeutic uses of CBD is growing more rapidly than the scientific evidence supporting its safety and effectiveness. Outcomes: A narrative review was conducted to discuss the best evidence regarding the pharmacological profile of CBD, its efficacy, and safety within the context of regulation and perspectives on the development of new cannabinoid-based drugs. Key articles addressing the various facets of this issue were selected for comprehensive analysis. Conclusions: Clinicians and researchers may face unique challenges in understanding the pharmacological profile of CBD and the prospects for developing its clinical indications, given the heterogeneity of clinical terminologies and the quality and composition of cannabis-based medical products available on the market. More basic and clinical research that complies with regulatory agencies’ testing guidelines, such as good manufacturing practices (GMPs), good laboratory practices (GLPs), and good clinical practices (GCPs), is needed to obtain approval for CBD or any other cannabinoid as a therapeutic for broader clinical indications.
Modern drugs are popular due to their role in emergency medicine however their roles are limited in chronic diseases due to their long-term usage and associated side effects. Various research have been conducted on nutraceuticals for prophylactic and therapeutic use. Significant role of micronutrients in diseases management has also been identified. Nutraceuticals are supplements with nutritional and medicinal value having proper dosage forms. Nutraceuticals work in synergy and support the pharmacokinetics, for example, vitamin D with K2, vitamin D with calcium, curcumin in combination with boswellic acid, and many such other combinations. Ayurveda nutraceuticals are also now emerging and making contribution in Asian market. Nutraceuticals are not tightly regulated in most part of the world; however, some countries like Japan have regulation in place to regulate nutraceuticals under Food for Specified Health Uses (FOSHU), whereas the USA regulates it under Dietary Supplement Health and Education Act of 1994. Currently nutraceutical is being utilized as adjuvant to existing therapies to reduce the reactive oxygen species in cancer, diabetes, rheumatoid arthritis, hypertension, and other diseases having significant inflammation and oxidative stress.
The non‐psychoactive cannabinoids cannabidiol (CBD) and cannabidiolic acid (CBDA) are available on the market in different forms, mostly for their anti‐inflammatory and potential analgesic properties. These substances are prohibited during equine competitions. CBD and CBDA are naturally present in hemp straw, commonly used as a bedding substitute for wheat straw. Unfortunately, horses can eat it, which therefore could lead to a possible risk of positive findings for CBD/CBDA in biological samples after doping control tests. The goals of this study were, first, to provide recommendations on the use of hemp straw before competition and, second, to assess if discrimination between hemp bedding exposure and CBD oil administration is possible. Several CBD equine in vivo studies have been conducted, including one on hemp straw used as bedding and one after administration of CBD oil by topical and sublingual routes. In hemp straw, CBDA was detected in higher quantities than CBD, and other cannabinoids have been observed. After hemp straw exposure, CBDA was also detected in higher quantities than CBD in all urine samples. It appeared that hemp straw should not be used as bedding for equine competition except if a delay of at least 48 h is respected. Regarding the CBD oil product analysis, CBD was the main compound detected. After administration, 7‐hydroxy CBD was identified in the urine. In conclusion, based on these data, we highlighted that it could be possible to discriminate the exposure of a horse to hemp straw from an administration of a CBD oil product thanks to the main presence of CBDA.
Introduction: Competing risk methods are time- to-event analyses that take into account events likely to modify or prevent a subject from achieving the primary endpoint. The objective of our study was to investigate risk factors for the occurrence of the first serious and/or unexpected adverse drug reaction (ADR) in patients enrolled in the STATIS ANRS 12290 trial.
Material and methods: This was a secondary multivar- iate analytical study of STATIS data carried out from January to June 2023. The Cox and Fine and Gray models were used to search for factors associated with the occurrence of ADR.
Results: At the end of a median follow-up period of 48 weeks, the overall cumulative incidence of ADR was 10/100 pers-weeks, higher in arm 2 than in arm 1 (15/100 pers-weeks vs. 5.5/100 pers-weeks, P < 0.001). The Kaplan–Meier method and the Fine and Gray method using death as a competing risk retained the following factors: treatment arm (system- atic vs. guided) [CsHRa = 2.64 vs. sHRa = 2.69], Kar- nofsky score [CsHRa = 0.49 vs. sHRa = 0.53], HIV viral load [CsHRa = 1.88 vs. sHRa = 1.90], and ASAT level [CsHRa and sHRa = 1.08]. Because of the similar proportion of deaths in the two treatment groups (48 vs. 46 deaths) and the use of a univariate model, Fine and Gray’s method gave results identical to those of the tra- ditional Cox model.
Discussion/conclusion: The use of Fine and Gray’s method in addition to the traditional Cox proportional hazards method can indicate whether the presence of a competing risk, which depends on the outcome, mod- ifies the risk estimate.
Introduction: Kabran01, a traditional medicinal recipe is proposed by the traditional healers for treatment of diabetes in Côte d’Ivoire without scientific proof of its tolerance in humans. The aim of our work was to carry out acute toxicity tests at 2000 and 5000 mg/kg of Kabran01.
Material and methods: Kabran01’s recipe includes the fresh leaves of 12 Ivorian medicinal plants, which are ground in water, then dried. For this study, 50 g dried Kabran01 is decocted, macerated with distilled water or with a hydroalcoholic solution (30/70). The aqueous extracts were lyophilized. The hydroalcoholic extract was evaporated at 40�C in a circulating air oven. The study was conducted in OECD 423 guidelines. Physical signs and mortality were investigated. Blood samples were collected, and different biochemical and haemato- logical parameters were measured. Histopathological examinations were carried out of vital organs from all rats.
Results: The administration of Kabran01 (2000 mg/kg or 5000 mg/kg, bw) did not induced physicals modifica- tions. It not induced modifications in rat’s body weight, water, and food consumption. The administration of infused and hydroalcoholic Kabran01 at these doses significantly increased the relative masses of pancreas, kidney, and heart of rats (p<0.05). Also, histological examinations showed that the Kabran01 exerted mini- mal alterations at the level of the different organs observed under the microscope. Indeed, Kabran01 decocted caused minimal ectasia of the heart and mini- mal steatosis of the liver. Its infusion and hydroalcoholic extract caused moderate pycnosis and steatosis of the liver and ectasia. In addition, the hydroalcoholic extract caused minimal atrophy and ectasia of the pancreas and minimal dilatation of the renal tubules. Discussion/Conclusion: The Kabran01 recipe is mildly toxic, with slight organic damage to the liver and kidneys.
This HPLC-DAD method allows a selective, accurate and precise quantification of cannabigerol, cannabidiol, cannabinol and cannabichromene. It demonstrated to be applicable to pre-clinical studies and therapeutic drug monitoring of cannabidiol.
This study discovered the impact of high-tunnel (i.e., unheated greenhouse) and open-field production on two industrial hemp cultivars (SB1 and CJ2) over their yield parameters, cannabinoid development, and volatile profiles. Development of neutral cannabinoids (CBD, THC, and CBC), acidic cannabinoids (CBDA, THCA, and CBCA), and total cannabinoids during floral maturation were investigated. The volatile profiles of hemp flowers were holistically compared via HS-SPME-GC/MS. Findings indicated a high tunnel as an efficient practice for achieving greater total weight, stem number, and caliper, especially in the SB1 cultivar. Harvesting high-tunnel-grown SB1 cultivars during early flower maturation could obtain a high CBD yield while complying with THC regulations. Considering the volatile profiles, hemp flowers mainly consisted of mono- and sesquiterpenoids, as well as oxygenated mono- and sesquiterpenoids. Volatile analysis revealed the substantial impact of cultivars on the volatile profile compared to the production systems.
Bioactive substances derived from plants, created by them for defense, are known as phytochemicals. Alkaloids, glycosides, polyphenols, terpenes and terpenoids, phytosterols, cannabinoids and carotenoids are the different categories of phytochemicals. Schizophrenia is associated with changes in the structure of the brain, decrease of dendritic spines from pyramidal neurons in the cortex, loss of gray matter and enlarged ventricles. Hallucinations, delusions, disorganized behavior and amotivation are some symptoms of schizophrenia. Phytochemicals are a key component of the management of schizophrenia. Alkaloids can operate as cholinergic agonists on muscarinic receptors and improve memory deficits. Glycosides target ErbB signaling, inhibit D3/D4 receptors and change dopamine and serotonin metabolism. Because of their anti-inflammatory, antioxidant and anti-apoptotic properties, polyphenols display neuroprotective and anti-schizophrenic activity. Terpenes and terpenoids act on the glutamate and dopamine pathways and inhibit glycinergic action. Cannabinoids have an anti-schizophrenic effect plus boost GABAergic activity and prevent serotonin uptake. Phytosterols have antipsychotic potential by blocking ketamine-induced biochemical, histological and behavioral changes. Because they regulate brain-derived neurotrophic factor (BDNF), carotenoids show significant potential for treating a variety of central nervous system problems. They are also an excellent antipsychotic medication.
Cannabis sativa L., a plant historically utilized for textile fibers, oil, and animal feed, is progressively being recognized as a potential food source. This review elucidates the nutritional and functional attributes of hemp and cannabidiol (CBD) within the context of food science. Hemp is characterized by the presence of approximately 545 secondary metabolites, among which around 144 are bioactive cannabinoids of primary importance. The study looks in detail at the nutritional components of cannabis and the potential health benefits of CBD, encompassing anti-inflammatory, anxiolytic, and antipsychotic effects. The review deals with the legislation and potential applications of hemp in the food industry and with the future directions of cannabis applications as well. The paper emphasizes the need for more scientific investigation to validate the safety and efficacy of hemp components in food products, as current research suggests that CBD may have great benefits for a wide range of consumers.
Cannabidiol (CBD) has been used in diseases that affect the central nervous system. Its effects on the peripheral synapses are of great interest, since endocannabinoid receptors are expressed in muscles. CBD (0.3 mM) was analysed using mammalian and avian neuromuscular preparations, through myographic techniques in complementary protocols. Mammalian cells were examined by light microscopy while exogenous acetylcholine (40 µM) and potassium chloride (100 mM) were added into avian preparations, before and at the end of experiments. Pharmacological tools such as atropine (2 µM), polyethylene glycol (PEG 400, 20 µM), Ca2+ (1.8 mM), F55-6 (20 µg/mL), and nifedipine (1.3 mM) were assessed with CBD. In mice, CBD causes a facilitatory effect and paralysis, whereas in avian, paralysis. Concluding, CBD is responsible for activated or inhibited channels, for ACh release via muscarinic receptor modulation, and by the inhibition of nicotinic receptors leading to neuromuscular blockade, with no damage to striated muscle cells.
Introduction
Preclinical and experimental research have provided promising evidence that medicinal cannabis may be efficacious in the treatment of posttraumatic stress disorder (PTSD). However, implementation of medicinal cannabis into routine clinical therapies may not be straightforward.
Areas covered
In this review, we describe some of the clinical, practical, and safety challenges that must be addressed for cannabis-based treatment of PTSD to be feasible in a real-world setting. These issues are especially prevalent if medicinal cannabis is to be combined with trauma-focused psychotherapy.
Expert opinion
Future consideration of the clinical and practical considerations of cannabis use in PTSD therapy will be essential to both the efficacy and safety of the treatment protocols that are being developed. These issues include dose timing and titration, potential for addiction, product formulation, windows of intervention, and route of administration. In particular, exposure therapy for PTSD involves recall of intense emotions, and the interaction between cannabis use and reliving of trauma memories must be explored in terms of patient safety and impact on therapeutic outcomes.
Cannabidiol (CBD) is a plant-derived cannabinoid found in cannabis and hemp plants with broad psychopharmacologic effects and poorly understood mechanisms of action that may include anti-oxidant and anti-inflammatory properties and CNS modulation of endocannabinoid, glutamatergic, and serotonergic neurotransmission. This article reviews existing data on the safety and efficacy of CBD for mental and physical health indications in the pediatric population and for psychiatric disorders in adults, with a focus on clinical trials. Searches of PubMed and PsycINFO for articles through October 2021 focused on clinical trials on “cannabidiol” and “seizure” or “psychiatry” in youth and adults, identifying 686 articles that were then screened and evaluated for relevance. Research into the safety and efficacy of CBD led to the United States Food and Drug Administration's approval of Epidolex, a purified pharmaceutical-grade CBD medicine, for treating drug-resistant seizures in Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis complex. Beyond treatment for rare seizure disorders, CBD has received growing public interest in recent years as a “natural” treatment for various other medical and psychiatric conditions, resulting in a rapidly expanding multi-billion-dollar US market for CBD dietary/health supplements and a growing number of Americans reporting regular use. However, the growing demand and broad claims of purported benefits have greatly outpaced the body of literature substantiating its use. Further, limited safety data in pediatric populations, drug-to-drug interactions between CBD and prescribed medications, and issues related to mislabeling and contamination have blunted enthusiasm for CBD in the pediatric healthcare community and indicate a need for additional research.
Aging is usually considered a key risk factor associated with multiple diseases, such as neurodegenerative diseases, cardiovascular diseases and cancer. Furthermore, the burden of age-related diseases has become a global challenge. It is of great significance to search for drugs to extend lifespan and healthspan. Cannabidiol (CBD), a natural nontoxic phytocannabinoid, has been regarded as a potential candidate drug for antiaging. An increasing number of studies have suggested that CBD could benefit healthy longevity. Herein, we summarized the effect of CBD on aging and analyzed the possible mechanism. All these conclusions may provide a perspective for further study of CBD on aging.
Objective:
Cannabidiol (CBD), one of the non-psychotomimetic compounds of Cannabis sativa, causes anxiolytic-like effects in animals, with typical bell-shaped dose-response curves. No study, however, has investigated whether increasing doses of this drug would also cause similar curves in humans. The objective of this study was to compare the acute effects of different doses of CBD and placebo in healthy volunteers performing a simulated public speaking test (SPST), a well-tested anxiety-inducing method.
Method:
A total of 57 healthy male subjects were allocated to receive oral CBD at doses of 150 mg (n=15), 300 mg (n=15), 600 mg (n=12) or placebo (n=15) in a double-blind procedure. During the SPST, subjective ratings on the Visual Analogue Mood Scale (VAMS) and physiological measures (systolic and diastolic blood pressure, heart rate) were obtained at six different time points.
Results:
Compared to placebo, pretreatment with 300 mg of CBD significantly reduced anxiety during the speech. No significant differences in VAMS scores were observed between groups receiving CBD 150 mg, 600 mg and placebo.
Conclusion:
Our findings confirm the anxiolytic-like properties of CBD and are consonant with results of animal studies describing bell-shaped dose-response curves. Optimal therapeutic doses of CBD should be rigorously determined so that research findings can be adequately translated into clinical practice.
In just a few years, cannabidiol (CBD) has become immensely popular around the world. After initially being discovered as an effective self-medication for Dravet syndrome in children, CBD is now sold and used to treat a wide range of medical conditions and lifestyle diseases. The cannabinoid CBD, a non-psychoactive isomer of the more infamous tetrahydrocannabinol (THC), is available in a growing number of administration modes, but the most commonly known is CBD oil. There are currently dozens, if not hundreds, of producers and sellers of CBD oils active in the market, and their number is increasing rapidly. Those involved vary from individuals who prepare oils on a small scale for family and (Facebook) friends to compounding pharmacies, pharmaceutical companies, and licensed cannabis producers. Despite the growing availability of CBD, many uncertainties remain about the legality, quality, and safety of this new “miracle cure.” As a result, CBD is under scrutiny on many levels, ranging from national health organizations and agricultural lobbyists to the WHO and FDA. The central question is whether CBD is simply a food supplement, an investigational new medicine, or even a narcotic. This overview paper looks into the known risks and issues related to the composition of CBD products, and makes recommendations for better regulatory control based on accurate labeling and more scientifically supported health claims. The intention of this paper is to create a better understanding of the benefits versus the risks of the current way CBD products are produced, used, and advertised.
Rationale:
Preliminary evidence suggests that cannabidiol (CBD) may be effective in the treatment of neurodegenerative disorders; however, CBD has never been evaluated for the treatment of cognitive impairments associated with schizophrenia (CIAS).
Objective:
This study compared the cognitive, symptomatic, and side effects of CBD versus placebo in a clinical trial.
Methods:
This study was a 6-week, randomized, placebo-controlled, parallel group, fixed-dose study of oral CBD (600 mg/day) or placebo augmentation in 36 stable antipsychotic-treated patients diagnosed with chronic schizophrenia. All subjects completed the MATRICS Consensus Cognitive Battery (MCCB) at baseline and at end of 6 weeks of treatment. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and biweekly.
Results:
There was no main effect of time or drug on MCCB Composite score, but a significant drug × time effect was observed (p = 0.02). Post hoc analyses revealed that only placebo-treated subjects improved over time (p = 0.03). There was a significant decrease in PANSS Total scores over time (p < 0. 0001) but there was no significant drug × time interaction (p = 0.18). Side effects were similar between CBD and placebo, with the one exception being sedation, which was more prevalent in the CBD group.
Conclusions:
At the dose studied, CBD augmentation was not associated with an improvement in MCCB or PANSS scores in stable antipsychotic-treated outpatients with schizophrenia. Overall, CBD was well tolerated with no worsening of mood, suicidality, or movement side effects.
Trial registration:
https://clinicaltrials.gov/ct2/show/NCT00588731.
Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL). Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies. Mean age of participants was 16.1 years (range 0.5–55 years). Cannabidiol (CBD) 20 mg/kg/day was more effective than placebo at reducing seizure frequency by 50%+(relative risk (RR) 1.74, 95% CI 1.24 to 2.43, 2 RCTs, 291 patients, low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating). The number needed to treat for one person using CBD to experience 50%+ seizure reduction was 8 (95% CI 6 to 17). CBD was more effective than placebo at achieving complete seizure freedom (RR 6.17, 95% CI 1.50 to 25.32, 3 RCTs, 306 patients, low GRADE rating), and improving QoL (RR 1.73, 95% CI 1.33 to 2.26), however increased risk of AEs (RR 1.24, 95% CI 1.13 to 1.36) and SAEs (RR 2.55, 95% CI 1.48 to 4.38). Pooled across 17 observational studies, 48.5% (95% CI 39.0% to 58.1%) of patients reported 50%+ reductions in seizures; in 14 observational studies 8.5% (95% CI 3.8% to 14.5%) were seizure-free. Twelve observational studies reported improved QoL (55.8%, 95% CI 40.5 to 70.6); 50.6% (95% CI 31.7 to 69.4) AEs and 2.2% (95% CI 0 to 7.9) SAEs. Pharmaceutical-grade CBD as adjuvant treatment in paediatric-onset drug-resistant epilepsy may reduce seizure frequency. Existing RCT evidence is mostly in paediatric samples with rare and severe epilepsy syndromes; RCTs examining other syndromes and cannabinoids are needed.
PROSPERO registration number
CRD42017055412.
The interest in cannabis-based products for the treatment of refractory epilepsy has skyrocketed in recent years. Marijuana and other cannabis products with high content in Δ(9) - tetrahydrocannabinol (THC), utilized primarily for recreational purposes, are generally unsuitable for this indication, primarily because THC is associated with many undesired effects. Compared with THC, cannabidiol (CBD) shows a better defined anticonvulsant profile in animal models and is largely devoid of adverse psychoactive effects and abuse liability. Over the years, this has led to an increasing use of CBD-enriched extracts in seizure disorders, particularly in children. Although improvement in seizure control and other benefits on sleep and behavior have been often reported, interpretation of the data is made difficult by the uncontrolled nature of these observations. Evidence concerning the potential anti-seizure efficacy of cannabinoids reached a turning point in the last 12 months, with the completion of three high-quality placebo-controlled adjunctive-therapy trials of a purified CBD product in patients with Dravet syndrome and Lennox-Gastaut syndrome. In these studies, CBD was found to be superior to placebo in reducing the frequency of convulsive (tonic-clonic, tonic, clonic, and atonic) seizures in patients with Dravet syndrome, and the frequency of drop seizures in patients with Lennox-Gastaut syndrome. For the first time, there is now class 1 evidence that adjunctive use of CBD improves seizure control in patients with specific epilepsy syndromes. Based on currently available information, however, it is unclear whether the improved seizure control described in these trials was related to a direct action of CBD, or was mediated by drug interactions with concomitant medications, particularly a marked increased in plasma levels of N-desmethylclobazam, the active metabolite of clobazam. Clarification of the relative contribution of CBD to improved seizure outcome requires re-assessment of trial data for the subgroup of patients not comedicated with clobazam, or the conduction of further studies controlling for the confounding effect of this interaction.
Objective:
Research in both animals and humans indicates that cannabidiol (CBD) has antipsychotic properties. The authors assessed the safety and effectiveness of CBD in patients with schizophrenia.
Method:
In an exploratory double-blind parallel-group trial, patients with schizophrenia were randomized in a 1:1 ratio to receive CBD (1000 mg/day; N=43) or placebo (N=45) alongside their existing antipsychotic medication. Participants were assessed before and after treatment using the Positive and Negative Syndrome Scale (PANSS), the Brief Assessment of Cognition in Schizophrenia (BACS), the Global Assessment of Functioning scale (GAF), and the improvement and severity scales of the Clinical Global Impressions Scale (CGI-I and CGI-S).
Results:
After 6 weeks of treatment, compared with the placebo group, the CBD group had lower levels of positive psychotic symptoms (PANSS: treatment difference=-1.4, 95% CI=-2.5, -0.2) and were more likely to have been rated as improved (CGI-I: treatment difference=-0.5, 95% CI=-0.8, -0.1) and as not severely unwell (CGI-S: treatment difference=-0.3, 95% CI=-0.5, 0.0) by the treating clinician. Patients who received CBD also showed greater improvements that fell short of statistical significance in cognitive performance (BACS: treatment difference=1.31, 95% CI=-0.10, 2.72) and in overall functioning (GAF: treatment difference=3.0, 95% CI=-0.4, 6.4). CBD was well tolerated, and rates of adverse events were similar between the CBD and placebo groups.
Conclusions:
These findings suggest that CBD has beneficial effects in patients with schizophrenia. As CBD's effects do not appear to depend on dopamine receptor antagonism, this agent may represent a new class of treatment for the disorder.
There is growing consumer demand for cannabidiol (CBD), a constituent of the cannabis plant, due to its purported medicinal benefits for myriad health conditions.¹ Viscous plant-derived extracts, suspended in oil, alcohol (tincture), or vaporization liquid, represent most of the retail market for CBD. Discrepancies between federal and state cannabis laws have resulted in inadequate regulation and oversight, leading to inaccurate labeling of some products.² To maximize sampling and ensure representativeness of available products, we examined the label accuracy of CBD products sold online, including identification of present but unlabeled cannabinoids.
Introduction: Cannabidiol (CBD) is a nonpsychoactive constituent of whole plant cannabis that has been reported to reduce anxiety-like behaviors in both pre-clinical and human laboratory studies. Yet, no controlled clinical studies have demonstrated its ability to reduce negative mood or dampen responses to negative emotional stimuli in humans. The objective of this study was to investigate the effects of CBD on responses to negative emotional stimuli, as a model for its potential anxiety-reducing effects.
Materials and Methods: The study used a double-blind, placebo (PLB)-controlled, within-subjects design in which 38 healthy, drug-free participants consumed oral CBD (300, 600, and 900 mg) or PLB before completing several behavioral tasks selected to assess reactivity to negative stimuli. Dependent measures included emotional arousal to negative and positive visual stimuli, perceptual sensitivity to emotional facial expressions, attentional bias toward emotional facial expressions, and feelings of social rejection. In addition, subjective drug effects and physiological data were also gathered during each experimental session to assess drug effects.
Discussion: CBD did not dampen responses to negative emotional stimuli and did not affect feelings of social rejection. The high dose of CBD (900 mg) marginally reduced attentional bias toward happy and sad facial expressions, and produced a slight increase in late-session heart rate. CBD did not produce detectable subjective effects or alterations in mood or anxiety.
Conclusion: These findings indicate that CBD has minimal behavioral and subjective effects in healthy volunteers, even when they are presented with emotional stimuli. Further research into the behavioral and neural mechanisms of CBD and other phytocannabinoids is needed to ascertain the clinical function of this drug.
The purpose of this study was to investigate whether the anxiolytic effect of cannabidiol (CBD) in humans follows the same pattern of an inverted U-shaped dose-effect curve observed in many animal studies. Sixty healthy subjects of both sexes aged between 18 and 35 years were randomly assigned to five groups that received placebo, clonazepam (1 mg), and CBD (100, 300, and 900 mg). The subjects were underwent a test of public speaking in a real situation (TPSRS) where each subject had to speak in front of a group formed by the remaining participants. Each subject completed the anxiety and sedation factors of the Visual Analog Mood Scale and had their blood pressure and heart rate recorded. These measures were obtained in five experimental sessions with 12 volunteers each. Each session had four steps at the following times (minutes) after administration of the drug/placebo, as time 0: -5 (baseline), 80 (pre-test), 153 (speech), and 216 (post-speech). Repeated-measures analyses of variance showed that the TPSRS increased the subjective measures of anxiety, heart rate, and blood pressure. Student-Newman-Keuls test comparisons among the groups in each phase showed significant attenuation in anxiety scores relative to the placebo group in the group treated with clonazepam during the speech phase, and in the clonazepam and CBD 300 mg groups in the post-speech phase. Clonazepam was more sedative than CBD 300 and 900 mg and induced a smaller increase in systolic and diastolic blood pressure than CBD 300 mg. The results confirmed that the acute administration of CBD induced anxiolytic effects with a dose-dependent inverted U-shaped curve in healthy subjects, since the subjective anxiety measures were reduced with CBD 300 mg, but not with CBD 100 and 900 mg, in the post-speech phase.
Background: Cannabidiol (CBD)-based treatments for several diseases, including Tourette’s syndrome, multiple sclerosis, epilepsy, movement disorders and glaucoma, are proving to be benefcial and the scientifc clinical background of the drug is continuously evolving.
Objectives: To investigate the short-term effect of CBDenriched hemp oil for relieving symptoms and improving the life quality (QOL) in young girls with adverse drug effects (ADRs) following human papillomavirus (HPV) vaccine.
methods: In this spontaneous spontaneous anecdotal, retrospective, “compassionate-use,” observational, open-label study, 12 females (age 12–24 years) with severe somatoform and dysautonomic syndrome following HPV vaccination were given sublingual CBD-rich hemp oil drops, 25 mg/kg per day supplemented by 2–5 mg/ml CBD once a week until a maximum dose of 150 mg/ml CBD per day was reached over a 3 month period. Patients’ quality of life was evaluated using the medical outcome short-form health survey questionnaire (Sf-36).
Results: Two patients dropped out due to iatrogenic adverse events and another two patients stopped the treatment early due to lack of any improvement. Sf-36 showed signifcant benefts in the physical component score (P < 0.02), vitality (P < 0.03) and social role functioning (P < 0.02) after the treatment. The administration of hemp oil also signifcantly reduced body pain according to the Sf-36 assessment. No significant differences from the start of treatment to severalmonths post-treatment were detected in role limitations due to emotional reactions (P = 0.02).
Conclusions: This study demonstrated the safety and tolerability of CBD-rich hemp oil and the primary effIcacy endpoint. Randomized controlled trials are warranted to characterize the safety profle and effcacy of this compound.
Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear.
To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids.
Twenty-eight databases from inception to April 2015.
Randomized clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome.
Study quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by 2 reviewers. Where possible, data were pooled using random-effects meta-analysis.
Patient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs.
A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio [OR], 3.82 [95% CI, 1.55-9.42]; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 [95% CI, 0.99-2.00]; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference [WMD], -0.46 [95% CI, -0.80 to -0.11]; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, -0.36 [95% CI, -0.69 to -0.05]; 7 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination.
There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.
The enactment of California's Proposition 215 stipulates that patients may use marijuana for medical reasons, provided that it is recommended by a physician. Yet, medical marijuana patients risk being stigmatized for this practice. This article examines the way in which medical marijuana patients perceive and process stigma, and how it affects their interactions and experiences with others. Eighteen semi-structured interviews of medical marijuana patients were carried out using a semi-structured interview guide. Most patients circumvented their own physicians in obtaining a recommendation to use medicinal marijuana, and also used a host of strategies in order to justify their medical marijuana use to family, friends, and colleagues in order to stave off potential stigma. The stigmatization of medical marijuana thus has a profound effect on how patients seek treatment, and whether they seek medical marijuana treatment at all.
Acute administration of the primary psychoactive constituent of cannabis, Δ-9-tetrahydrocannabinol (THC), impairs human facial affect recognition, implicating the endocannabinoid system in emotional processing. Another main constituent of cannabis, cannabidiol (CBD), has seemingly opposite functional effects on the brain. This study aimed to determine the effects of THC and CBD, both alone and in combination on emotional facial affect recognition. 48 volunteers, selected for high and low frequency of cannabis use and schizotypy, were administered, THC (8mg), CBD (16mg), THC+CBD (8mg+16mg) and placebo, by inhalation, in a 4-way, double-blind, placebo-controlled crossover design. They completed an emotional facial affect recognition task including fearful, angry, happy, sad, surprise and disgust faces varying in intensity from 20% to 100%. A visual analogue scale (VAS) of feeling 'stoned' was also completed. In comparison to placebo, CBD improved emotional facial affect recognition at 60% emotional intensity; THC was detrimental to the recognition of ambiguous faces of 40% intensity. The combination of THC+CBD produced no impairment. Relative to placebo, both THC alone and combined THC+CBD equally increased feelings of being 'stoned'. CBD did not influence feelings of 'stoned'. No effects of frequency of use or schizotypy were found. In conclusion, CBD improves recognition of emotional facial affect and attenuates the impairment induced by THC. This is the first human study examining the effects of different cannabinoids on emotional processing. It provides preliminary evidence that different pharmacological agents acting upon the endocannabinoid system can both improve and impair recognition of emotional faces.
Copyright © 2014. Published by Elsevier B.V.
Introduction:
Parkinson's disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no neuroprotective treatments for PD have been found to date, the endocannabinoid system has emerged as a promising target.
Methods:
From a sample of 119 patients consecutively evaluated in a specialized movement disorders outpatient clinic, we selected 21 PD patients without dementia or comorbid psychiatric conditions. Participants were assigned to three groups of seven subjects each who were treated with placebo, cannabidiol (CBD) 75 mg/day or CBD 300 mg/day. One week before the trial and in the last week of treatment participants were assessed in respect to (i) motor and general symptoms score (UPDRS); (ii) well-being and quality of life (PDQ-39); and (iii) possible neuroprotective effects (BDNF and H(1)-MRS).
Results:
We found no statistically significant differences in UPDRS scores, plasma BDNF levels or H(1)-MRS measures. However, the groups treated with placebo and CBD 300 mg/day had significantly different mean total scores in the PDQ-39 (p = 0.05).
Conclusions:
Our findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities; however, studies with larger samples and specific objectives are required before definitive conclusions can be drawn.
Impairments in cognitive ability and widespread pathophysiological changes caused by neurotoxicity, neuroinflammation, oxidative damage, and altered cholesterol homeostasis are associated with Alzheimer's disease (AD). Cannabidiol (CBD) has been shown to reverse cognitive deficits of AD transgenic mice and to exert neuroprotective, anti-oxidative, and anti-inflammatory properties in vitro and in vivo. Here we evaluate the preventative properties of long-term CBD treatment in male AβPPSwe/PS1ΔE9 (AβPP × PS1) mice, a transgenic model of AD. Control and AD transgenic mice were treated orally from 2.5 months of age with CBD (20 mg/kg) daily for 8 months. Mice were then assessed in the social preference test, elevated plus maze, and fear conditioning paradigms, before cortical and hippocampal tissues were analyzed for amyloid load, oxidative damage, cholesterol, phytosterols, and inflammation. We found that AβPP × PS1 mice developed a social recognition deficit, which was prevented by CBD treatment. CBD had no impact on anxiety or associative learning. The prevention of the social recognition deficit was not associated with any changes in amyloid load or oxidative damage. However, the study revealed a subtle impact of CBD on neuroinflammation, cholesterol, and dietary phytosterol retention, which deserves further investigation. This study is the first to demonstrate CBD's ability to prevent the development of a social recognition deficit in AD transgenic mice. Our findings provide the first evidence that CBD may have potential as a preventative treatment for AD with a particular relevance for symptoms of social withdrawal and facial recognition.
Inflammation in the central nervous system (CNS) is a complex process that involves a multitude of molecules and effectors, and it requires the transmigration of blood leukocytes across the blood-brain barrier (BBB) and the activation of resident immune cells. Cannabidiol (CBD), a non-psychotropic cannabinoid constituent of Cannabis sativa, has potent anti-inflammatory and immunosuppressive properties. Yet, how this compound modifies the deleterious effects of inflammation in TMEV-induced demyelinating disease (TMEV-IDD) remains unknown. Using this viral model of multiple sclerosis (MS), we demonstrate that CBD decreases the transmigration of blood leukocytes by downregulating the expression of vascular cell adhesion molecule-1 (VCAM-1), chemokines (CCL2 and CCL5) and the proinflammatory cytokine IL-1β, as well as by attenuating the activation of microglia. Moreover, CBD administration at the time of viral infection exerts long-lasting effects, ameliorating motor deficits in the chronic phase of the disease in conjunction with reduced microglial activation and pro-inflammatory cytokine production. Adenosine A2A receptors participate in some of the anti-inflammatory effects of CBD, as the A2A antagonist ZM241385 partially blocks the protective effects of CBD in the initial stages of inflammation. Together, our findings highlight the anti-inflammatory effects of CBD in this viral model of MS, and demonstrate the significant therapeutic potential of this compound for the treatment of pathologies with an inflammatory component.
This Phase I study aimed to assess the potential drug-drug interactions (pharmacokinetic [PK] and safety profile) of Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (Sativex (®), nabiximols) in combination with cytochrome P450 (CYP450) inducer (rifampicin) or inhibitors (ketoconazole or omeprazole). Thirty-six healthy male subjects were divided into three groups of 12, and then randomized to one of two treatment sequences per group. Subjects received four sprays of THC/CBD (10.8/10 mg) alongside single doses of the CYP3A and 2C19 inducer rifampicin (600 mg), CYP3A inhibitor ketoconazole (400 mg) or CYP2C19 inhibitor omeprazole (40 mg). Plasma samples were analyzed for CBD, THC and its metabolite 11-hydroxy-THC (11-OH-THC). A single dose of four sprays of THC/CBD spray (10.8/10 mg) following repeated doses of rifampicin (600 mg) reduced the Cmax and AUC of all analytes. Cmax reduced from 2.94 to 1.88 ng/mL (-36%), 1.03 to 0.50 ng/mL (-52%) and 3.38 to 0.45 ng/mL (-87%) for THC, CBD and 11-OH-THC, respectively compared to single dose administration of THC/CBD spray alone. Ketoconazole co-administration with THC/CBD spray had the opposite effect, increasing the Cmax of the respective analytes from 2.65 to 3.36 ng/mL (+27%), 0.66 to 1.25 ng/mL (+89%) and 3.59 to 10.92 ng/mL (+204%). No significant deviations in Cmax or AUC for any analyte were observed when THC/CBD spray was co-administered with omeprazole. THC/CBD spray was well tolerated by the study subjects both alone and in combination with rifampicin, ketoconazole and omeprazole. Evaluation of the PKs of THC/CBD spray alone and in combination with CYP450 inhibitors/inducers suggests that all analytes are substrates for the isoenzyme CYP3A4, but not CYP2C19. On the basis of our findings, there is likely to be little impact on other drugs metabolized by CYP enzymes on the PK parameters of THC/CBD spray, but potential effects should be taken into consideration when co-administering THC/CBD spray with compounds which share the CYP3A4 pathway such as rifampicin or ketoconazole.
Trials registration:
NCT01323465.
Rationale
Whilst Cannabidiol (CBD), a non-psychotomimetic cannabinoid, has been shown to enhance extinction learning in rats, its effects on fear memory in humans have not previously been studied.
Objectives
We employed a Pavlovian fear-conditioning paradigm in order to assess the effects of CBD on extinction and consolidation.
Method
Forty-eight participants were conditioned to a coloured box (CS) with electric shocks (UCS) in one context and were extinguished in a second context. Participants received 32 mg of CBD either following before or after extinction in a double-blind, placebo-controlled design. At recall, 48 h later, participants were exposed to CSs and conditioning contexts before (recall) and after (reinstatement) exposure to the UCS. Skin conductance and shock expectancy measures of conditioned responding were recorded throughout.
Results
Successful conditioning, extinction and recall were found in all three treatment groups. CBD given post-extinction enhanced consolidation of extinction learning as assessed by shock expectancy. CBD administered at either time produced trend level reduction in reinstatement of autonomic contextual responding. No acute effects of CBD were found on extinction.
Conclusions
These findings provide the first evidence that CBD can enhance consolidation of extinction learning in humans and suggest that CBD may have potential as an adjunct to extinction-based therapies for anxiety disorders.
Community-based studies suggest that cannabis products that are high in Δ(9)-tetrahydrocannabinol (THC) but low in cannabidiol (CBD) are particularly hazardous for mental health. Laboratory-based studies are ideal for clarifying this issue because THC and CBD can be administered in pure form, under controlled conditions. In a between-subjects design, we tested the hypothesis that pre-treatment with CBD inhibited THC-elicited psychosis and cognitive impairment. Healthy participants were randomised to receive oral CBD 600mg (n=22) or placebo (n=26), 210 min ahead of intravenous (IV) THC (1.5 mg). Post-THC, there were lower PANSS positive scores in the CBD group, but this did not reach statistical significance. However, clinically significant positive psychotic symptoms (defined a priori as increases ≥3 points) were less likely in the CBD group compared with the placebo group, odds ratio (OR)=0.22 (χ(2)=4.74, p<0.05). In agreement, post-THC paranoia, as rated with the State Social Paranoia Scale (SSPS), was less in the CBD group compared with the placebo group (t=2.28, p<0.05). Episodic memory, indexed by scores on the Hopkins Verbal Learning Task-revised (HVLT-R), was poorer, relative to baseline, in the placebo pre-treated group (-10.6±18.9%) compared with the CBD group (-0.4%±9.7 %) (t=2.39, p<0.05). These findings support the idea that high-THC/low-CBD cannabis products are associated with increased risks for mental health.
Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but moderately inhibits the degradation of the endocannabinoid anandamide. We previously reported that an elevation of anandamide levels in cerebrospinal fluid inversely correlated to psychotic symptoms. Furthermore, enhanced anandamide signaling let to a lower transition rate from initial prodromal states into frank psychosis as well as postponed transition. In our translational approach, we performed a double-blind, randomized clinical trial of cannabidiol vs amisulpride, a potent antipsychotic, in acute schizophrenia to evaluate the clinical relevance of our initial findings. Either treatment was safe and led to significant clinical improvement, but cannabidiol displayed a markedly superior side-effect profile. Moreover, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia.
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.
The effects of ipsapirone and cannabidiol (CBD) on healthy volunteers submitted to a simulated public speaking (SPS) test were compared with those of the anxiolytic benzodiazepine diazepam and placebo. Four independent groups of 10 subjects received, under a double-blind design, placebo or one of the following drugs: CBD (300 mg), diazepam (10 mg) or ipsapirone (5 mg). Subjective anxiety was evaluated through the Visual Analogue Mood Scale (VAMS) and the State-trait Anxiety Inventory (STAI). The VAMS anxiety factor showed that ipsapirone attenuated SPS-induced anxiety while CBD decreased anxiety after the SPS test. Diazepam, on the other hand, was anxiolytic before and after the SPS test, but had no effect on the increase in anxiety induced by the speech test. Only ipsapirone attenuated the increase in systolic blood pressure induced by the test. Significant sedative effects were only observed with diazepam. The results suggest that ipsapirone and CBD have anxiolytic properties in human volunteers submitted to a stressful situation.
Generalized Social Anxiety Disorder (SAD) is one of the most common anxiety conditions with impairment in social life. Cannabidiol (CBD), one major non-psychotomimetic compound of the cannabis sativa plant, has shown anxiolytic effects both in humans and in animals. This preliminary study aimed to compare the effects of a simulation public speaking test (SPST) on healthy control (HC) patients and treatment-naïve SAD patients who received a single dose of CBD or placebo. A total of 24 never-treated patients with SAD were allocated to receive either CBD (600 mg; n=12) or placebo (placebo; n=12) in a double-blind randomized design 1 h and a half before the test. The same number of HC (n=12) performed the SPST without receiving any medication. Each volunteer participated in only one experimental session in a double-blind procedure. Subjective ratings on the Visual Analogue Mood Scale (VAMS) and Negative Self-Statement scale (SSPS-N) and physiological measures (blood pressure, heart rate, and skin conductance) were measured at six different time points during the SPST. The results were submitted to a repeated-measures analysis of variance. Pretreatment with CBD significantly reduced anxiety, cognitive impairment and discomfort in their speech performance, and significantly decreased alert in their anticipatory speech. The placebo group presented higher anxiety, cognitive impairment, discomfort, and alert levels when compared with the control group as assessed with the VAMS. The SSPS-N scores evidenced significant increases during the testing of placebo group that was almost abolished in the CBD group. No significant differences were observed between CBD and HC in SSPS-N scores or in the cognitive impairment, discomfort, and alert factors of VAMS. The increase in anxiety induced by the SPST on subjects with SAD was reduced with the use of CBD, resulting in a similar response as the HC.
The last decade has seen increasing evidence of dysfunctions in the endogenous cannabinoid system in schizophrenia and of its relationship with the typical cognitive impairment of the disorder. Studies in animal models, healthy volunteers, and psychotic patients clearly suggest an antipsychotic-like effect of cannabidiol. This study investigated the effects of cannabidiol on selective attention in 28 schizophrenic patients using the Stroop Color Word Test and on these patients' electrodermal responsiveness to auditive stimuli.
The subjects attended two experimental sessions, the first one without the administration of drugs. In the second session the subjects were divided into three groups that received either a single dose of cannabidiol 300 mg or cannabidiol 600 mg or placebo.
The three groups did not differ significantly with respect to electrodermal measures in the two experimental sessions. When the first and second sessions were compared improved performance was found in all three groups, with patients who received placebo and cannabidiol 300 mg performing better than those who received cannabidiol 600 mg.
The single, acute administration of cannabidiol seems to have no beneficial effects on the performance of schizophrenic patients in the Stroop Color Word Test, although the hypothesis that chronic administration may lead to improvement cannot be disregarded.
Delta-9-tetrahydrocannabinol (Delta-9-THC) and Cannabidiol (CBD), the two main ingredients of the Cannabis sativa plant have distinct symptomatic and behavioral effects. We used functional magnetic resonance imaging (fMRI) in healthy volunteers to examine whether Delta-9-THC and CBD had opposite effects on regional brain function. We then assessed whether pretreatment with CBD can prevent the acute psychotic symptoms induced by Delta-9-THC. Fifteen healthy men with minimal earlier exposure to cannabis were scanned while performing a verbal memory task, a response inhibition task, a sensory processing task, and when viewing fearful faces. Subjects were scanned on three occasions, each preceded by oral administration of Delta-9-THC, CBD, or placebo. BOLD responses were measured using fMRI. In a second experiment, six healthy volunteers were administered Delta-9-THC intravenously on two occasions, after placebo or CBD pretreatment to examine whether CBD could block the psychotic symptoms induced by Delta-9-THC. Delta-9-THC and CBD had opposite effects on activation relative to placebo in the striatum during verbal recall, in the hippocampus during the response inhibition task, in the amygdala when subjects viewed fearful faces, in the superior temporal cortex when subjects listened to speech, and in the occipital cortex during visual processing. In the second experiment, pretreatment with CBD prevented the acute induction of psychotic symptoms by Delta-9-tetrahydrocannabinol. Delta-9-THC and CBD can have opposite effects on regional brain function, which may underlie their different symptomatic and behavioral effects, and CBD's ability to block the psychotogenic effects of Delta-9-THC.
The object of the experiment was to verify whether cannabidiol (CBD) reduces the anxiety provoked by delta 9-THC in normal volunteers, and whether this effect occurs by a general block of the action of delta 9-THC or by a specific anxiolytic effect. Appropriate measurements and scales were utilized and the eight volunteers received, the following treatments in a double-blind procedure: 0.5 mg/kg delta 9-THC, 1 mg/kg CBD, a mixture containing 0.5 mg/kg delta 9-THC and 1 mg/kg CBD and placebo and diazepam (10 mg) as controls. Each volunteer received the treatments in a different sequence. It was verified that CBD blocks the anxiety provoked by delta 9-THC, however this effect also extended to marihuana-like effects and to other subjective alterations induced by delta 9-THC. This antagonism does not appear to be caused by a general block of delta 9-THC effects, since no change was detected in the pulse-rate measurements. Several further effects were observed typical of CBD and of an opposite nature to those of delta 9-THC. These results suggest that the effects of CBD, as opposed to those of delta 9-THC, might be involved in the antagonism of effects between the two cannabinoids.
Objectives: To determine whether plant-derived cannabis medicinal extracts (CME) can alleviate neurogenic symptoms unresponsive to standard treatment, and to quantify adverse effects.
Design: A consecutive series of double-blind, randomized, placebo-controlled single-patient cross-over trials with two-week treatment periods.
Setting: Patients attended as outpatients, but took the CME at home.
Subjects: Twenty-four patients with multiple sclerosis (18), spinal cord injury (4), brachial plexus damage (1), and limb amputation due to neurofibromatosis (1).
Intervention: Whole-plant extracts of delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), 1:1 CBD:THC, or matched placebo were self-administered by sublingual spray at doses determined by titration against symptom relief or unwanted effects within the range of 2.5–120 mg/24 hours.
Measures used: Patients recorded symptom, well-being and intoxication scores on a daily basis using visual analogue scales. At the end of each two-week period an observer rated severity and frequency of symptoms on numerical rating scales, administered standard measures of disability (Barthel Index), mood and cognition, and recorded adverse events.
Results: Pain relief associated with both THC and CBD was significantly superior to placebo. Impaired bladder control, muscle spasms and spasticity were improved by CME in some patients with these symptoms. Three patients had transient hypotension and intoxication with rapid initial dosing of THC-containing CME.
Conclusions: Cannabis medicinal extracts can improve neurogenic symptoms unresponsive to standard treatments. Unwanted effects are predictable and generally well tolerated. Larger scale studies are warranted to confirm these findings.
Animal and human studies have suggested that cannabidiol (CBD) may possess anxiolytic properties, but how these effects are mediated centrally is unknown. The aim of the present study was to investigate this using functional neuroimaging. Regional cerebral blood flow (rCBF) was measured at rest using (99m)Tc-ECD SPECT in 10 healthy male volunteers, randomly divided into two groups of five subjects. Each subject was studied on two occasions, 1 week apart. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. SPECT images were acquired 90 min after drug ingestion. The Visual Analogue Mood Scale was applied to assess subjective states. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping (SPM). CBD significantly decreased subjective anxiety and increased mental sedation, while placebo did not induce significant changes. Assessment of brain regions where anxiolytic effects of CBD were predicted a priori revealed two voxel clusters of significantly decreased ECD uptake in the CBD relative to the placebo condition (p<0.001, uncorrected for multiple comparisons). These included a medial temporal cluster encompassing the left amygdala-hippocampal complex, extending into the hypothalamus, and a second cluster in the left posterior cingulate gyrus. There was also a cluster of greater activity with CBD than placebo in the left parahippocampal gyrus (p<0.001). These results suggest that CBD has anxiolytic properties, and that these effects are mediated by an action on limbic and paralimbic brain areas.
Cannabidiol (CBD) represents a new promising drug due to a wide spectrum of pharmacological actions. In order to relate CBD clinical efficacy to its pharmacological mechanisms of action, we performed a bibliographic search on PUBMED about all clinical studies investigating the use of CBD as a treatment of psychiatric symptoms. Findings to date suggest that (a) CBD may exert antipsychotic effects in schizophrenia mainly through facilitation of endocannabinoid signalling and cannabinoid receptor type 1 antagonism; (b) CBD administration may exhibit acute anxiolytic effects in patients with generalised social anxiety disorder through modification of cerebral blood flow in specific brain sites and serotonin 1A receptor agonism; (c) CBD may reduce withdrawal symptoms and cannabis/tobacco dependence through modulation of endocannabinoid, serotoninergic and glutamatergic systems; (d) the preclinical pro-cognitive effects of CBD still lack significant results in psychiatric disorders. In conclusion, current evidences suggest that CBD has the ability to reduce psychotic, anxiety and withdrawal symptoms by means of several hypothesised pharmacological properties. However, further studies should include larger randomised controlled samples and investigate the impact of CBD on biological measures in order to correlate CBD's clinical effects to potential modifications of neurotransmitters signalling and structural and functional cerebral changes.
Background
Cannabidiol has been used for treatment-resistant seizures in patients with severe early-onset epilepsy. We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the Lennox–Gastaut syndrome, a severe developmental epileptic encephalopathy.
Methods
In this double-blind, placebo-controlled trial conducted at 30 clinical centers, we randomly assigned patients with the Lennox–Gastaut syndrome (age range, 2 to 55 years) who had had two or more drop seizures per week during a 28-day baseline period to receive cannabidiol oral solution at a dose of either 20 mg per kilogram of body weight (20-mg cannabidiol group) or 10 mg per kilogram (10-mg cannabidiol group) or matching placebo, administered in two equally divided doses daily for 14 weeks. The primary outcome was the percentage change from baseline in the frequency of drop seizures (average per 28 days) during the treatment period.
Results
A total of 225 patients were enrolled; 76 patients were assigned to the 20-mg cannabidiol group, 73 to the 10-mg cannabidiol group, and 76 to the placebo group. During the 28-day baseline period, the median number of drop seizures was 85 in all trial groups combined. The median percent reduction from baseline in drop-seizure frequency during the treatment period was 41.9% in the 20-mg cannabidiol group, 37.2% in the 10-mg cannabidiol group, and 17.2% in the placebo group (P=0.005 for the 20-mg cannabidiol group vs. placebo group, and P=0.002 for the 10-mg cannabidiol group vs. placebo group). The most common adverse events among the patients in the cannabidiol groups were somnolence, decreased appetite, and diarrhea; these events occurred more frequently in the higher-dose group. Six patients in the 20-mg cannabidiol group and 1 patient in the 10-mg cannabidiol group discontinued the trial medication because of adverse events and were withdrawn from the trial. Fourteen patients who received cannabidiol (9%) had elevated liver aminotransferase concentrations.
Conclusions
Among children and adults with the Lennox–Gastaut syndrome, the addition of cannabidiol at a dose of 10 mg or 20 mg per kilogram per day to a conventional antiepileptic regimen resulted in greater reductions in the frequency of drop seizures than placebo. Adverse events with cannabidiol included elevated liver aminotransferase concentrations. (Funded by GW Pharmaceuticals; GWPCARE3 ClinicalTrials.gov number, NCT02224560.)
Background:
Chronic pain is a major therapeutic problem in kidney transplant patients owing to nephrotoxicity associated with nonsteroidal antiiflammatory drugs. Benefits in chronic pain treatment with cannabidiol (CBD) have been reported. This study assesses the effect, safety, and possible drug interactions in kidney transplant patients treated with CBD for chronic pain.
Methods:
We assessed patients who asked to receive CBD for pain treatment. Doses were increased from 50 to 150 mg twice a day for 3 weeks. Creatinine, blood count, liver function, liver enzymes, and drug levels were determined every 48 hours the first week and then once a week thereafter.
Results:
We assessed 7 patients with a mean age of 64.5 years (range, 58-75 years). CBD initial dose was 100 mg/d, CBD dose reduction to 50 mg/d has been done on day 4 to patient 1 for persistent nausea. Tacrolimus dose reduction in patient 3 was undertaken on days 4, 7, and 21 owing to persisting elevated levels (even before CBD) and itching, and on day 21 in patient 5. Tacrolimus levels decreased in patient 2 but were normal in the control 1 week later. Patients on cyclosporine were stable. Adverse effects were nausea, dry mouth, dizziness, drowsiness, and intermittent episodes of heat. CBD dose decrease was required in 2 patients. Two patients had total pain improvement, 4 had a partial response in the first 15 days, and in 1 there was no change.
Conclusions:
During this follow-up, CBD was well-tolerated, and there were no severe adverse effects. Plasma levels of tacrolimus were variable. Therefore, longer follow-up is required.
Background:
Previous studies have suggested that cannabidiol has anxiolytic and antipsychotic properties, raising hopes that cannabidiol will translate to the psychiatric clinic. Cannabidiol may be particularly useful for anxiety and paranoia in those at-risk of major mental illness.
Methods:
Immersion in a controlled 3D virtual-reality scenario was used to assay persecutory ideation and anxiety in a sample of non-clinical volunteers ( n=32) pre-selected for high paranoid traits. Participants were randomised to receive oral cannabidiol (600 mg) or placebo 130 min prior to entering virtual-reality. Well-validated rating scales were used to assay persecutory thinking and anxiety. Salivary cortisol concentration, heart rate and blood pressure were measured over the course of the experimental session.
Results:
Immersion in the virtual-reality session elicited anxiety as indexed by the Beck's anxiety inventory ( p<0.005), and increased cortisol concentration ( p=0.05), heart rate ( p<0.05) and systolic blood pressure ( p<0.05). However, cannabidiol had no impact upon any of these effects, except for a strong trend to increase anxiety ( p=0.09). Cannabidiol had no effect on persecutory ideation as assayed by the Community Assessment of Psychic Experiences questionnaire or the State Social Paranoia Scale.
Conclusions:
In contrast to previous studies, there was no evidence of any benefits of cannabidiol on anxiety or persecutory ideation in healthy volunteers with high trait paranoia. However, a larger sample will be required for a definitive study.
Introduction: This literature survey aims to extend the comprehensive survey performed by Bergamaschi et al. in 2011 on cannabidiol (CBD) safety and side effects. Apart from updating the literature, this article focuses on clinical studies and CBD potential interactions with other drugs.
Results: In general, the often described favorable safety profile of CBD in humans was confirmed and extended by the reviewed research. The majority of studies were performed for treatment of epilepsy and psychotic disorders. Here, the most commonly reported side effects were tiredness, diarrhea, and changes of appetite/weight. In comparison with other drugs, used for the treatment of these medical conditions, CBD has a better side effect profile. This could improve patients' compliance and adherence to treatment. CBD is often used as adjunct therapy. Therefore, more clinical research is warranted on CBD action on hepatic enzymes, drug transporters, and interactions with other drugs and to see if this mainly leads to positive or negative effects, for example, reducing the needed clobazam doses in epilepsy and therefore clobazam's side effects.
Conclusion: This review also illustrates that some important toxicological parameters are yet to be studied, for example, if CBD has an effect on hormones. Additionally, more clinical trials with a greater number of participants and longer chronic CBD administration are still lacking.
Background
The Dravet syndrome is a complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate. We studied cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome.
Methods
In this double-blind, placebo-controlled trial, we randomly assigned 120 children and young adults with the Dravet syndrome and drug-resistant seizures to receive either cannabidiol oral solution at a dose of 20 mg per kilogram of body weight per day or placebo, in addition to standard antiepileptic treatment. The primary end point was the change in convulsive-seizure frequency over a 14-week treatment period, as compared with a 4-week baseline period.
Results
The median frequency of convulsive seizures per month decreased from 12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with placebo (adjusted median difference between the cannabidiol group and the placebo group in change in seizure frequency, −22.8 percentage points; 95% confidence interval [CI], −41.1 to −5.4; P=0.01). The percentage of patients who had at least a 50% reduction in convulsive-seizure frequency was 43% with cannabidiol and 27% with placebo (odds ratio, 2.00; 95% CI, 0.93 to 4.30; P=0.08). The patient’s overall condition improved by at least one category on the seven-category Caregiver Global Impression of Change scale in 62% of the cannabidiol group as compared with 34% of the placebo group (P=0.02). The frequency of total seizures of all types was significantly reduced with cannabidiol (P=0.03), but there was no significant reduction in nonconvulsive seizures. The percentage of patients who became seizure-free was 5% with cannabidiol and 0% with placebo (P=0.08). Adverse events that occurred more frequently in the cannabidiol group than in the placebo group included diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function tests. There were more withdrawals from the trial in the cannabidiol group.
Conclusions
Among patients with the Dravet syndrome, cannabidiol resulted in a greater reduction in convulsive-seizure frequency than placebo and was associated with higher rates of adverse events. (Funded by GW Pharmaceuticals; ClinicalTrials.gov number, NCT02091375.)
Over the past years, several lines of evidence support a therapeutic potential of Cannabis derivatives and in particular phytocannabinoids. Δ(9)-THC and cannabidiol (CBD) are the most abundant phytocannabinoids in Cannabis plants and therapeutic application for both compounds have been suggested. However, CBD is recently emerging as a therapeutic agent in numerous pathological conditions since devoid of the psychoactive side effects exhibited instead by Δ(9)-THC. In this review, we highlight the pharmacological activities of CBD, its cannabinoid receptor-dependent and -independent action, its biological effects focusing on immunomodulation, angiogenetic properties, and modulation of neuronal and cardiovascular function. Furthermore, the therapeutic potential of cannabidiol is also highlighted, in particular in nuerological diseases and cancer.
Objective:
Tuberous sclerosis complex (TSC) is an autosomal-dominant genetic disorder with highly variable expression. The most common neurologic manifestation of TSC is epilepsy, which affects approximately 85% of patients, 63% of whom develop treatment-resistant epilepsy. Herein, we evaluate the efficacy, safety, and tolerability of cannabidiol (CBD), a nonpsychoactive compound derived from the marijuana plant, as an adjunct to current antiepileptic drugs in patients with refractory seizures in the setting of TSC.
Methods:
Eighteen of the 56 patients who have enrolled in our current expanded-access study of cannabidiol for patients with treatment-resistant epilepsy carry a diagnosis of TSC. After an initial baseline period of 1 month, patients began treatment with CBD. The initial dose of 5 mg/kg/day was increased by 5 mg/kg/day every week up to a maximum dose of 50 mg/kg/day, if tolerated. Weekly seizure frequencies, percent change in seizure frequencies, and responder rates were calculated during the 2nd, 3rd, 6th, 9th, and 12th month of treatment with CBD.
Results:
The median weekly seizure frequency during the baseline period was 22.0 (interquartile range [IQR] 14.8-57.4), which decreased to 13.3 (IQR 5.1-22.1) after 3 months of treatment with cannabidiol. The median percent change in total weekly seizure frequency was -48.8% (IQR -69.1% to -11.1%) after 3 months of treatment. The 50% responder rates over the course of the study were 50%, 50%, 38.9%, 50%, and 50% after 2, 3, 6, 9, and 12 months of treatment with CBD, respectively. In patients taking clobazam concurrently with CBD (n = 12), the responder rate after 3 months of treatment was 58.3%, compared to 33.3% in patients not taking clobazam (n = 6). Twelve (66.7%) of 18 patients in this study experienced at least one adverse event thought possibly related to CBD; the most common adverse events were drowsiness (n = 8, 44.4%), ataxia (n = 5, 27.8%), and diarrhea (n = 4, 22.2%).
Significance:
Although double-blind, placebo-controlled trials are still necessary, these findings suggest that cannabidiol may be an effective and well-tolerated treatment option for patients with refractory seizures in TSC.
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.
Under an expanded access investigational new drug (IND) trial, cannabidiol (CBD) is being studied as a possible adjuvant treatment of refractory epilepsy in children. Of the 25 subjects in the trial, 13 were being treated with clobazam (CLB). Because CLB and CBD are both metabolized in the cytochrome P450 (CYP) pathway, we predicted a drug-drug interaction, which we evaluate in this article.
Thirteen subjects with refractory epilepsy concomitantly taking CLB and CBD under IND 119876 were included in this study. Demographic information was collected for each subject including age, sex, and etiology of seizures, as well as concomitant antiepileptic drugs (AEDs). CLB, N-desmethylclobazam (norclobazam; nCLB), and CBD levels were measured over the course of CBD treatment. CLB doses were recorded at baseline and at weeks 4 and 8 of CBD treatment. Side effects were monitored.
We report elevated CLB and nCLB levels in these subjects. The mean (± standard deviation [SD]) increase in CLB levels was 60 ± 80% (95% confidence interval (CI) [-2-91%] at 4 weeks); the mean increase in nCLB levels was 500 ± 300% (95% CI [+90-610%] at 4 weeks). Nine of 13 subjects had a >50% decrease in seizures, corresponding to a responder rate of 70%. The increased CLB and nCLB levels and decreases in seizure frequency occurred even though, over the course of CBD treatment, CLB doses were reduced for 10 (77%) of the 13 subjects. Side effects were reported in 10 (77%) of the 13 subjects, but were alleviated with CLB dose reduction.
Monitoring of CLB and nCLB levels is necessary for clinical care of patients concomitantly on CLB and CBD. Nonetheless, CBD is a safe and effective treatment of refractory epilepsy in patients receiving CLB treatment.
Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects.
This double-blind, placebo-controlled cross-over study of CBD, coadministered with intravenous fentanyl, was conducted at the Clinical Research Center in Mount Sinai Hospital, a tertiary care medical center in New York City. Participants were healthy volunteers aged 21 to 65 years with prior opioid exposure, regardless of the route. Blood samples were obtained before and after 400 or 800 mg of CBD pretreatment, followed by a single 0.5 (session 1) or 1.0 μg/kg (session 2) of intravenous fentanyl dose. The primary outcome was the Systematic Assessment for Treatment Emergent Events (SAFTEE) to assess safety and adverse effects. CBD peak plasma concentrations, time to reach peak plasma concentrations (tmax), and area under the curve (AUC) were measured.
SAFTEE data were similar between groups without respiratory depression or cardiovascular complications during any test session. After low-dose CBD, tmax occurred at 3 and 1.5 hours in sessions 1 and 2, respectively. After high-dose CBD, tmax occurred at 3 and 4 hours in sessions 1 and 2, respectively. There were no significant differences in plasma CBD or cortisol (AUC P = NS) between sessions.
Cannabidiol does not exacerbate adverse effects associated with intravenous fentanyl administration. Coadministration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse.
The endocannabinoid system (ECS) regulates multiple physiological processes, including cutaneous cell growth and differentiation. Here, we explored the effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland function and determined that CBD behaves as a highly effective sebostatic agent. Administration of CBD to cultured human sebocytes and human skin organ culture inhibited the lipogenic actions of various compounds, including arachidonic acid and a combination of linoleic acid and testosterone, and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels. Activation of TRPV4 interfered with the prolipogenic ERK1/2 MAPK pathway and resulted in the downregulation of nuclear receptor interacting protein-1 (NRIP1), which influences glucose and lipid metabolism, thereby inhibiting sebocyte lipogenesis. CBD also exerted complex antiinflammatory actions that were coupled to A2a adenosine receptor-dependent upregulation of tribbles homolog 3 (TRIB3) and inhibition of the NF-κB signaling. Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris.
What is known and objective:
Cannabidiol (CBD) is the main non-psychotropic component of the Cannabis sativa plant. REM sleep behaviour disorder (RBD) is a parasomnia characterized by the loss of muscle atonia during REM sleep associated with nightmares and active behaviour during dreaming. We have described the effects of CBD in RBD symptoms in patients with Parkinson's disease.
Cases summary:
Four patients treated with CBD had prompt and substantial reduction in the frequency of RBD-related events without side effects.
What is new and conclusion:
This case series indicates that CBD is able to control the symptoms of RBD.
The object of the experiment was to verify whether cannabidiol (CBD) reduces the anxiety provoked by ?9-TCH in normal volunteers, and whether this effect occurs by a general block of the action of ?9-TCH or by a specific anxiolytic effect. Appropriate measurements and scales were utilized and the eight volunteers received, the following treatments in a double-blind procedure: 0.5 mg/kg ?9-TCH, 1 mg/kg CBD, a mixture containing 0.5 mg/kg ?9-TCH and 1 mg/kg CBD and placebo and diazepam (10 mg) as controls. Each volunteer received the treatments in a different sequence. It was verified that CBD blocks the anxiety provoked by ?9-TCH, however this effect also extended to marihuanalike effects and to other subjective alterations induced by ?9-TCH. This antagonism does not appear to be caused by a general block of ?9-TCH effects, since no change was detected in the pulse-rate measurements. Several further effects were observed typical of CBD and of an opposite nature to those of ?9-TCH.
Based on previous observations that cannabidiol (CBD) blocks some effects of Δ9-tetrahydrocannabinol (Δ9-THC) in laboratory animals, the present work was carried out to study possible interaction between CBD and Δ9-THC in human beings. In a double blind procedure, 40 healthy male volunteers were assigned to 1 of 8 experimental groups, receiving per oral route, placebe, 30 mg Δ9-THC, 15 30 or 60 mg of CBD, and mixtures of 30 mg of Δ9-THC plus either 15, 30 or 60 mg of CBD respectively. Pulse rate, time production tasks and psychological logical reactions were measured at several time intervals after drug ingestion. 30 mg Δ9-THC alone increased pulse rate, disturbed time tasks and induced strong psychological reactions in the subjects. 15–60 mg of CBD alone provoked no effects. On the other hand, CBD was efficient in blocking most of the effects of Δ9-THC when both drugs were given together. CBD also decreased the anxiety component of Δ9-THC effects, in such a way that the subjects reported more pleasurable effects.
Understanding the structural and functional complexities of the transient receptor potential vanilloid receptor (TRPV1) is
essential to the therapeutic modulation of inflammation and pain. Because of its central role in initiating inflammatory processes
and integrating painful stimuli, there is an understandable interest in its pharmacological manipulation (sensitization/desensitization).
The present Highlight entitled “TRPV1 antagonists elevate cell surface populations of receptor protein and exacerbate TRPV1
mediated toxicities in human lung epithelial cells” describes how exposure to various antagonists produces TRPV1 sensitization
and proposes a possible mechanistic explanation to that sensitization.
Cannabis sativa is the source of a unique set of compounds known collectively as plant cannabinoids or phytocannabinoids. This review focuses on the manner with which three of these compounds, (−)-trans-Δ9-tetrahydrocannabinol (Δ9-THC), (−)-cannabidiol (CBD) and (−)-trans-Δ9-tetrahydrocannabivarin (Δ9-THCV), interact with cannabinoid CB1 and CB2 receptors. Δ9-THC, the main psychotropic constituent of cannabis, is a CB1 and CB2 receptor partial agonist and in line with classical pharmacology, the responses it elicits appear to be strongly influenced both by the expression level and signalling efficiency of cannabinoid receptors and by ongoing endogenous cannabinoid release. CBD displays unexpectedly high potency as an antagonist of CB1/CB2 receptor agonists in CB1- and CB2-expressing cells or tissues, the manner with which it interacts with CB2 receptors providing a possible explanation for its ability to inhibit evoked immune cell migration. Δ9-THCV behaves as a potent CB2 receptor partial agonist in vitro. In contrast, it antagonizes cannabinoid receptor agonists in CB1-expressing tissues. This it does with relatively high potency and in a manner that is both tissue and ligand dependent. Δ9-THCV also interacts with CB1 receptors when administered in vivo, behaving either as a CB1 antagonist or, at higher doses, as a CB1 receptor agonist. Brief mention is also made in this review, first of the production by Δ9-THC of pharmacodynamic tolerance, second of current knowledge about the extent to which Δ9-THC, CBD and Δ9-THCV interact with pharmacological targets other than CB1 or CB2 receptors, and third of actual and potential therapeutic applications for each of these cannabinoids.
British Journal of Pharmacology (2008) 153, 199–215; doi:10.1038/sj.bjp.0707442; published online 10 September 2007
Effectiveness and safety of antiepileptic medications in patients with epilepsy 11 12 Rockville, MD Agency for Healthcare Research and Quality
- Talati R Scholle
- O J Phung
Woman says she failed drug test after taking CBD oil
- Regant