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My fasting sugar dropped to It can do the same thing for you. We used amphetamine AMPH -induced sensitization and sensorimotor gating in rats, two preclinical procedures relevant to schizophrenia-related psychopathology, combined with in vivo single-unit neuronal electrophysiology recordings in the ventral tegmental area, and molecular analyses to characterize the actions of CBD directly in the nucleus accumbens shell NASh , a brain region that is the current target of most effective antipsychotics.
Our findings demonstrate a novel mechanism for the putative antipsychotic-like properties of CBD in the mesolimbic circuitry. We identify the molecular signaling pathways through which CBD may functionally reduce schizophrenia-like neuropsychopathology.
However, the mechanisms by which. The cannabis-derived phytochemical, cannabidiol CBD , has been shown to have pharmacotherapeutic efficacy for the treatment of schizophrenia. However, the mechanisms by which CBD may produce. CBD spray and MS spasticity symptoms: A randomized, placebo controlled long-term follow-up clinical trial with THC: CBD spray versus placebo demonstrated that it was not associated with cognitive decline, depression or significant mood changes after 12 months of treatment.
CBD oromucosal spray did not adversely influence standard driving ability in patients with moderate to severe MS spasticity. Other new long term observational data about the use of THC: Findings to date reinforce the efficacy and safety observed in Phase III clinical trials. It is of interest that in practice average dosages used by patients tended to be lower than those reported in clinical studies Thus, these new data support a positive benefit-risk relationship for THC: CBD oromucosal spray during longer-term use.
Symmetric corticobasal degeneration S- CBD. Corticobasal degeneration CBD is a neurodegenerative disease characterized pathologically by neuronal loss, gliosis and tau deposition in neocortex, basal ganglia and brainstem. Typical clinical presentation is known as corticobasal syndrome CBS and involves the core features of progressive asymmetric rigidity and apraxia, accompanied by other signs of cortical and extrapyramidal dysfunction.
Asymmetry is also emphasized on neuroimaging. Clinical records were reviewed and quantitative volumetric analysis of symmetric atrophy on head MRI using atlas based parcellation was performed.
Subjects were classified as S- CBD if no differences had been observed between right- and left-sided cortical or extrapyramidal signs or symptoms. Five cases 2 female met criteria for S- CBD. None had limb dystonia, myoclonus, apraxia or alien limb phenomena.
CBD can have a symmetric presentation, clinically and radiologically, in which typical features of CBS, such as limb apraxia, myoclonus, dystonia and alien limb phenomenon, may be absent. Copyright c Elsevier Ltd. Human Gingival Mesenchymal Stem Cells hGMSCs are multipotential cells that can expand and differentiate in culture under specific and standardized conditions.
In the present study, we have investigated whether in vitro pre-treatment of hGMSCs with Cannabidiol CBD can influence their expression profile, improving the therapeutic potential of this cell culture. In conclusion, the present study will provide a new simple and reproducible method for preconditioning hGMSCs with CBD , before transplantation, as an interesting strategy for improving the hGMSCs molecular phenotype, reducing the risk of immune or inflammatory reactions in the host, and in parallel, for increasing their survival and thus, their long-term therapeutic efficacy.
Impact of enzymatic and alkaline hydrolysis on CBD concentration in urine. A sensitive and specific analytical method for cannabidiol CBD in urine was needed to define urinary CBD pharmacokinetics after controlled CBD administration, and to confirm compliance with CBD medications including Sativex-a cannabis plant extract containing 1: Non-psychoactive CBD has a wide range of therapeutic applications and may also influence psychotropic smoked cannabis effects.
Solid-phase extraction isolated and concentrated analytes prior to GC-MS. Enzyme-hydrolyzed urine specimens exhibited more than a fold CBD concentration increase compared to alkaline and non-hydrolyzed specimens. This method can be applied for urinary CBD quantification and further pharmacokinetics characterization following controlled CBD administration.
A sensitive and specific analytical method for cannabidiol CBD in urine was needed to define urinary CBD pharmacokinetics after controlled CBD administration, and to confirm compliance with CBD medications including Sativex—a cannabis plant extract containing 1: Alzheimer's disease AD is a neurodegenerative disease, in which the primary etiology remains unknown. AD shows oxidative stress and chronic inflammation.
Cannabidiol CBD is a non-psychotomimetic phytocannabinoid from Cannabis sativa plant. CBD attenuates oxidative stress and diminishes mitochondrial dysfunction and reactive oxygen species generation. For permissions, please e-mail: Diabetic retinopathy is characterized by blood-retinal barrier BRB breakdown and neurotoxicity.
These pathologies have been associated with oxidative stress and proinflammatory cytokines, which may operate by activating their downstream target p38 MAP kinase. In the present study, the protective effects of a nonpsychotropic cannabinoid, cannabidiol CBD , were examined in streptozotocin-induced diabetic rats after 1, 2, or 4 weeks.
Retinal cell death was determined by terminal dUTP nick-end labeling assay; BRB function by quantifying extravasation of bovine serum albumin-fluorescein; and oxidative stress by assays for lipid peroxidation, dichlorofluorescein fluorescence, and tyrosine nitration.
Experimental diabetes induced significant increases in oxidative stress, retinal neuronal cell death, and vascular permeability. These results demonstrate that CBD treatment reduces neurotoxicity, inflammation, and BRB breakdown in diabetic animals through activities that may involve inhibition of p38 MAP kinase. Asthma represents a public health problem and traditionally is classified as an atopic disease, where the allergen can induce clinical airway inflammation, bronchial hyperresponsiveness, and reversible obstruction of airways.
Studies have demonstrated the presence of T-helper 2 lymphocytes in the lung of patients with asthma. These cells are involved in cytokine production that regulates immunoglobulin synthesis.
Asthma was induced in 8-week-old Wistar rats by ovalbumin OVA. CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL levels. CBD seems to be a potential new drug to modulate inflammatory response in asthma. Several publications have suggested increasing cannabis potency over the last decade, which, together with lower amounts of cannabidiol CBD , could contribute to an increase in adverse effects after cannabis smoking.
This study aimed to investigate the relationship between THC- and CBD concentrations in blood samples among cannabis users, and to compare cannabinoid concentrations with the outcome of a clinical test of impairment CTI and between traffic accidents and non-accident driving under the influence of drugs DUID -cases. Seizure sample analysis did not reveal high potency cannabis products, and while CBD content appeared high in hashish, it was almost absent in marijuana.
Purified Cannabidiol , the main non-psychotropic component of Cannabis sativa, alone, counteracts neuronal apoptosis in experimental multiple sclerosis.
Multiple Sclerosis MS is a global concern disease leading to a progressive, chronic and demyelinating condition, affecting the central nervous system CNS. The present study was designed to test the effects of intraperitoneal administration of cannabidiol CBD , the main non-psychotropic cannabinoid of Cannabis sativa CS , in an experimental model of MS. The aim is to evaluate the capability of CBD administration to thwart the cascade of mediators involved in MS-induced apoptosis.
After immunization, mice were observed daily for signs of EAE and weight loss. Disease signs were evaluated using a standardized scoring system. Moreover, CBD interferes with pp21 axis activation. As results, the absence of tissue apobody formation in spinal cord tissues of EAE-mice treated with CBD was established.
Most of therapeutic properties of CS are currently ascribed to the psychotropic effects of phenylterpenoid delta-9 tetrahydrocannabinol. We have demonstrated that, alone, purified CBD possesses an anti-apoptotic power against the neurodegenerative processes underlying MS development. This represents an interesting new profile of CBD that could lead to its introduction in the clinical management of MS. Cannabinoids have been shown to exert anti-inflammatory activities in various in vivo and in vitro experimental models as well as ameliorate various inflammatory degenerative diseases.
However, the mechanisms of these effects are not completely understood. Using the BV-2 mouse microglial cell line and lipopolysaccharide LPS to induce an inflammatory response, we studied the signaling pathways engaged in the anti-inflammatory effects of cannabinoids as well as their influence on the expression of several genes known to be involved in inflammation.
The cannabinoid anti-inflammatory action does not seem to involve the CB1 and CB2 cannabinoid receptors or the abn- CBD -sensitive receptors. The anxiolytic effects of cannabidiol in chronically stressed mice are mediated by the endocannabinoid system: Role of neurogenesis and dendritic remodeling.
Repeated injections of cannabidiol CBD , the major non-psychotomimetic compound present in the Cannabis sativa plant, attenuate the anxiogenic effects induced by Chronic Unpredictable Stress CUS. The specific mechanisms remain to be fully understood but seem to involve adult hippocampal neurogenesis and recruitment of endocannabinoids. Golgi staining and immunofluorescence revealed that these effects were associated with an increase in hippocampal neurogenesis and spine density in the dentate gyrus of the hippocampus.
Cannabidiol , a Cannabis sativa constituent, as an antipsychotic drug. A high dose of delta9-tetrahydrocannabinol, the main Cannabis sativa cannabis component, induces anxiety and psychotic-like symptoms in healthy volunteers. These effects of delta9-tetrahydrocannabinol are significantly reduced by cannabidiol CBD , a cannabis constituent which is devoid of the typical effects of the plant. Studies in animal models and in healthy volunteers clearly suggest an anxiolytic-like effect of CBD.
The antipsychotic-like properties of CBD have been investigated in animal models using behavioral and neurochemical techniques which suggested that CBD has a pharmacological profile similar to that of atypical antipsychotic drugs. The results of two studies on healthy volunteers using perception of binocular depth inversion and ketamine-induced psychotic symptoms supported the proposal of the antipsychotic-like properties of CBD. In addition, open case reports of schizophrenic patients treated with CBD and a preliminary report of a controlled clinical trial comparing CBD with an atypical antipsychotic drug have confirmed that this cannabinoid can be a safe and well-tolerated alternative treatment for schizophrenia.
Future studies of CBD in other psychotic conditions such as bipolar disorder and comparative studies of its antipsychotic effects with those produced by clozapine in schizophrenic patients are clearly indicated. Could cannabidiol be used as an alternative to antipsychotics? Individuals with this disorder often present signs such as hallucination, anxiety, reduced attention, and social withdrawal. Although antipsychotic drugs remain the cornerstone of schizophrenia treatment, they are associated with severe side effects.
Recently, the endocannabinoid system ECS has emerged as a potential therapeutic target for pharmacotherapy that is involved in a wide range of disorders, including schizophrenia. Since its discovery, a lot of effort has been devoted to the study of compounds that can modulate its activity for therapeutic purposes.
Among them, cannabidiol CBD , a non-psychoactive component of cannabis, shows great promise for the treatment of psychosis, and is associated with fewer extrapyramidal side effects than conventional antipsychotic drugs. The overarching goal of this review is to provide current available knowledge on the role of the dopamine system and the ECS in schizophrenia, and to discuss key findings from animal studies and clinical trials investigating the antipsychotic potential of CBD.
Cannabidiol in medical marijuana: Research vistas and potential opportunities. The high and increasing prevalence of medical marijuana consumption in the general population invites the need for quality evidence regarding its safety and efficacy.
Herein, we synthesize extant literature pertaining to the phytocannabinoid cannabidiol CBD and its brain effects. The effect of CBD on brain systems as well as on phenomenological measures e. Cannabidiol is without euphoriant properties, and exerts antipsychotic, anxiolytic, anti-seizure, as well as anti-inflammatory properties. It is essential to parcellate phytocannabinoids into their constituent moieties as the most abundant cannabinoid have differential effects on physiologic systems in psychopathology measures.
Interventional studies with purified CBD are warranted with a call to target-engagement proof-of-principle studies using the research domain criteria RDoC framework.
Cannabidiol CBD has been traditionally used in Cannabis -based preparation, however historically, it has received far less interest as a single drug than the other components of Cannabis.
Currently, CBD generates considerable interest due to its beneficial neuroprotective, antiepileptic, anxiolytic, antipsychotic, and anti-inflammatory properties. Therefore, the CBD scaffold becomes of increasing interest for medicinal chemists. This review provides an overview of the chemical structure of natural and synthetic CBD derivatives including the molecular targets associated with these compounds.
A clear identification of their biological targets has been shown to be still very challenging. Cannabidiol CBD has been traditionally used in Cannabis-based preparation, however historically, it has received far less interest as a single drug than the other components of Cannabis. Cannabidiol inhibits angiogenesis by multiple mechanisms.
The non-psychoactive cannabinoid cannabidiol CBD effectively inhibits the growth of different types of tumours in vitro and in vivo and down-regulates some pro-angiogenic signals produced by glioma cells. As its anti-angiogenic properties have not been thoroughly investigated to date, and given its very favourable pharmacological and toxicological profile, here, we evaluated the ability of CBD to modulate tumour angiogenesis.
These effects were associated with the down-modulation of several angiogenesis-related molecules. Its dual effect on both tumour and endothelial cells supports the hypothesis that CBD has potential as an effective agent in cancer therapy.
Several studies have demonstrated anti-proliferative and pro-apoptotic actions of cannabinoids on various tumours, together with their anti-angiogenic properties. Firstly, we evaluated the effect of CBD on human umbilical vein endothelial cell HUVEC proliferation and viability - through [3- 4,5-dimethylthiazolyl -2,5-diphenyltetrazolium bromide] assay and FACS analysis - and in vitro motility - both in a classical Boyden chamber test and in a wound-healing assay.
This study reveals that CBD inhibits angiogenesis by multiple mechanisms. Mechanisms of cannabidiol neuroprotection in hypoxic-ischemic newborn pigs: The mechanisms underlying the neuroprotective effects of cannabidiol CBD were studied in vivo using a hypoxic-ischemic HI brain injury model in newborn pigs. Therefore we investigated, in Wistar rats, effects of pulmonary, oral and subcutaneous sc. While cannabinoid serum and brain levels rapidly peaked and diminished after pulmonary administration, sc.
In contrast, oral CBD produced mild hyperlocomotion. In conclusion, oral administration yielded the most pronounced behavioural effects which corresponded to the highest brain levels of cannabinoids. Of central importance was the novel finding that THC can be detected in serum and brain after administration of CBD alone which, if confirmed in humans and given the increasing medical use of CBD -only products, might have important legal and forensic ramifications.
In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson's disease, Alzheimer's disease, and rheumatoid arthritis. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.
Cannabis contains the psychoactive component delta9-tetrahydrocannabinol delta9-THC , and the non-psychoactive components cannabidiol CBD , cannabinol, and cannabigerol. It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta9-THC also mediates psychological effects through the activation of the CB1 receptor in the central nervous system.
In addition to the CB1 receptor agonists, cannabis also contains therapeutically active components which are CB1 receptor independent. The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Doxorubicin DOX is a widely used, potent chemotherapeutic agent; however, its clinical application is limited because of its dose-dependent cardiotoxicity. Cannabidiol CBD is a nonpsychotropic constituent of marijuana, which is well tolerated in humans, with antioxidant, antiinflammatory and recently discovered antitumor properties.
DOX-induced cardiomyopathy was characterized by increased myocardial injury elevated serum creatine kinase and lactate dehydrogenase levels , myocardial oxidative and nitrative stress decreased total glutathione content and glutathione peroxidase 1 activity, increased lipid peroxidation, 3-nitrotyrosine formation and expression of inducible nitric oxide synthase mRNA , myocardial cell death apoptotic and poly[ADP]-ribose polymerase 1 [PARP]-dependent and cardiac dysfunction decline in ejection fraction and left ventricular fractional shortening.
These data suggest that CBD may represent a novel cardioprotective strategy against DOX-induced cardiotoxicity, and the above-described effects on mitochondrial function and biogenesis may. Beale, Camilla; Broyd, Samantha J. Chronic cannabis use is associated with neuroanatomical alterations in the hippocampus. This study examined whether prolonged administration of CBD to regular cannabis users within the community could reverse or reduce the characteristic hippocampal harms associated with chronic cannabis use.
Participants were assessed at baseline and post- CBD treatment using structural magnetic resonance imaging. Automated longitudinal hippocampal segmentation was performed to assess volumetric change over the whole hippocampus and within 12 subfields. No change was observed in left or right hippocampus as a whole. Heavy cannabis users demonstrated marked growth in the left subicular complex, predominantly within the presubiculum, and right cornu ammonis CA 1 compared to lighter users.
Associations between greater right subicular complex and total hippocampal volume and higher plasma CBD concentration were evident, particularly in heavy users. Our findings suggest a restorative effect of CBD on the subicular and CA1 subfields in current cannabis users, especially those with greater lifetime exposure to cannabis.
While replication is required in a larger, placebo-controlled trial, these findings support a protective role of CBD against. Relevance to Alzheimer's Disease. Microglial activation is an invariant feature of Alzheimer's disease AD. On the other hand, the phytocannabinoid cannabidiol CBD has shown anti-inflammatory properties in different paradigms.
In contrast, 4-[4- 1,1-dimethylheptyl -2,6-dimethoxyphenyl]-6,6-dimethyl-bicyclo[3. All of the cannabinoids decreased lipopolysaccharide-induced nitrite generation, which was insensitive to cannabinoid antagonism. In summary, CBD is able to modulate microglial cell function in vitro and induce beneficial effects in an in vivo model of AD. Given that CBD lacks psychoactivity, it may represent a novel therapeutic approach for this neurological disease.
The immunosuppressive activity of cannabinoids has been well established. However, the underlying mechanisms are largely unknown. To view the other articles in this section visit http: Safety and side effects of cannabidiol , a Cannabis sativa constituent. Cannabidiol CBD , a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties.
However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline.
The keywords searched were "cannabinoids", " cannabidiol " and "side effects". Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters heart rate, blood pressure and body temperature , does not affect gastrointestinal transit and does not alter psychomotor or psychological functions.
Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters. Based on recent advances in cannabinoid administration in humans, controlled CBD may be safe in humans and animals.
However, further studies are needed to clarify these reported in vitro and in vivo side effects. Cannabidiol CBD is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity.
However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia.
In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F- CBD HUF 1 , is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity.
Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol. Aldose reductase ALR2 is a key enzyme involved in diabetic complications and the search for new aldose reductase inhibitors ARIs is currently very important.
The synthetic ARIs are often associated with deleterious side effects and medicinal and edible plants, containing compounds with aldose reductase inhibitory activity, could be useful for prevention and therapy of diabetic complications.
Non-psychotropic phytocannabinoids exert multiple pharmacological effects with therapeutic potential in many diseases such as inflammation, cancer, diabetes. Here, we have investigated the inhibitory effects of extracts and their fractions from two Cannabis sativa L.
A molecular docking study was performed to evaluate the interaction of these cannabinoids with the active site of ALR2 compared to known ARIs. The inhibitory activity of the fractions was greater for acidic cannabinoid-rich fractions. Comparative molecular docking results have shown a higher stability of the ALR2-cannabinoid acids complex than the other inhibitors.
These results may have some relevance for the possible use of C. Accumulating evidence suggests that cannabidiol CBD may be an effective and safe anxiolytic agent and potentially also an antidepressant. The objective of this study was to further examine these properties of CBD using the 'depressive-like' Wistar-Kyoto WKY rat, focusing on the drug's effect on anhedonia-like behaviors.
These findings extend the limited knowledge on the antidepressant effect of CBD , now shown for the first time in a genetic animal model of depression. These results suggest that CBD may be beneficial for the treatment of clinical depression and other states with prominent anhedonia. Cannabidiol in humans-the quest for therapeutic targets. Cannabidiol CBD , a major phytocannabinoid constituent of cannabis, is attracting growing attention in medicine for its anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties.
However, up to this point, a comprehensive literature review of the effects of CBD in humans is lacking. The aim of the present systematic review is to examine the randomized and crossover studies that administered CBD to healthy controls and to clinical patients.
Both monotherapy and combination studies e. A total of 34 studies were identified: Potential pharmacokinetic and pharmacodynamic explanations for these results are discussed. Cannabidiol -induced apoptosis in primary lymphocytes is associated with oxidative stress-dependent activation of caspase We recently reported that cannabidiol CBD exhibited a generalized suppressive effect on T-cell functional activities in splenocytes directly exposed to CBD in vitro or isolated from CBD -administered mice.
To investigate the potential mechanisms of CBD effects on T cells, we characterized the pro-apoptotic effect of CBD on primary lymphocytes. The apoptosis of splenocytes was markedly enhanced following CBD exposure in a time- and concentration-dependent manner, as evidenced by nuclear hypodiploidity and DNA strand breaks.
Pretreatment of splenocytes with a cell-permeable inhibitor for caspase-8 significantly attenuated, in a concentration-dependent manner, CBD -mediated apoptosis, but not ROS production. Collectively, the present study demonstrated that the apoptotic effect of CBD in primary lymphocytes is closely associated with oxidative stress-dependent activation of caspase CBD is a constituent of some strains of recreational cannabis but its content is highly variable.
This study was undertaken to determine if CBD could reverse hypothermia or hypolocomotor effects caused by THC in rats. Additional experiments determined the effects of pretreatment with the cannabinoid CB1 receptor antagonist SR rimonabant.
CBD did not attentuate THC-induced hypothermia or hypolocomotion but instead exaggerated these effects in some conditions. There is no evidence from this study that elevated CBD content in cannabis could provide protection from the physiological effects of THC, in rats. Pharmacological properties of cannabidiol in the treatment of psychiatric disorders: 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.
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.
Cannabidiol as potential treatment in refractory pediatric epilepsy. In recent years there has been great scientific and public interest focused on the therapeutic potential of compounds derived from cannabis for the treatment of refractory epilepsy in children. From in vitro and in vivo studies on animal models, cannabidiol CBD appears to be a promising anticonvulsant drug with a favorable side-effect profile. In humans, CBD efficacy and safety is not supported by well-designed trials and its use has been described by anecdotal reports.
It will be necessary to investigate CBD safety, pharmacokinetics and interaction with other anti-epileptic drugs AEDs alongside performing double-blinded placebo-controlled trials in order to obtain conclusive data on its efficacy and safety in children.
Does cannabidiol have a role in the treatment of schizophrenia? Schizophrenia is a debilitating psychiatric disorder which places a significant emotional and economic strain on the individual and society-at-large.
Unfortunately, currently available therapeutic strategies do not provide adequate relief and some patients are treatment-resistant. In this regard, cannabidiol CBD , a non-psychoactive constituent of Cannabis sativa, has shown significant promise as a potential antipsychotic for the treatment of schizophrenia.
However, there is still considerable uncertainty about the mechanism of action of CBD as well as the brain regions which are thought to mediate its putative antipsychotic effects. We argue that further research on CBD is required to fast-track its progress to the clinic and in doing so, we may generate novel insights into the neurobiology of schizophrenia.
Cannabidiol normalizes caspase 3, synaptophysin, and mitochondrial fission protein DNM1L expression levels in rats with brain iron overload: We have recently shown that chronic treatment with cannabidiol CBD was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats.
Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson's and Alzheimer's, and has been related to cognitive deficits in animals and human subjects. Deficits in synaptic energy supply have been linked to neurodegenerative diseases, evidencing the key role played by mitochondria in maintaining viable neural cells and functional circuits.
It has also been shown that brains of patients suffering from neurodegenerative diseases have increased expression of apoptosisrelated proteins and specific DNA fragmentation. Here, we have analyzed the expression level of brain proteins involved with mitochondrial fusion and fission mechanisms DNM1L and OPA1 , the main integral transmembrane protein of synaptic vesicles synaptophysin , and caspase 3, an apoptosis-related protein, to gain a better understanding of the potential of CBD in restoring the damage caused by iron loading in rats.
We found that CBD rescued iron-induced effects, bringing hippocampal DNM1L, caspase 3, and synaptophysin levels back to values comparable to the control group.
Our results suggest that iron affects mitochondrial dynamics, possibly trigging synaptic loss and apoptotic cell death and indicate that CBD should be considered as a potential molecule with memory-rescuing and neuroprotective properties to be used in the treatment of cognitive deficits observed in neurodegenerative disorders.
We have previously reported that cannabidiol CBD lowers the incidence of diabetes in young non-obese diabetes-prone NOD female mice. In the present study we show that administration of CBD to 11—14 week old female NOD mice, which are either in a latent diabetes stage or with initial symptoms of diabetes, ameliorates the manifestations of the disease.
In addition, the level of the proinflammatory cytokine IL produced by splenocytes was significantly reduced, whereas the level of the anti-inflammatory IL was significantly elevated following CBD -treatment. Histological examination of the pancreata of CBD -treated mice revealed more intact islets than in the controls.
Our data strengthen our previous assumption that CBD , known to be safe in man, can possibly be used as a therapeutic agent for treatment of type 1 diabetes. Controlled clinical trial of cannabidiol in Huntington's disease. Based on encouraging preliminary findings, cannabidiol CBD , a major nonpsychotropic constituent of Cannabis, was evaluated for symptomatic efficacy and safety in 15 neuroleptic-free patients with Huntington's Disease HD.
A comparison of the effects of CBD and placebo on chorea severity and other therapeutic outcome variables, and on a Cannabis side effect inventory, clinical lab tests and other safety outcome variables, indicated no significant p greater than 0.
Cannabidiol promotes browning in 3T3-L1 adipocytes. Recruitment of the brown-like phenotype in white adipocytes browning and activation of existing brown adipocytes are currently being investigated as a means to combat obesity. Thus, a wide variety of dietary agents that contribute to browning of white adipocytes have been identified. The present study was designed to investigate the effects of cannabidiol CBD , a major nonpsychotropic phytocannabinoid of Cannabis sativa, on induction of browning in 3T3-L1 adipocytes.
These data suggest possible roles for CBD in browning of white adipocytes, augmentation of lipolysis, thermogenesis, and reduction of lipogenesis. In conclusion, the current data suggest that CBD plays dual modulatory roles in the form of inducing the brown-like phenotype as well as promoting lipid metabolism. Thus, CBD may be explored as a potentially promising therapeutic agent for the prevention of obesity. The current study examined sex differences in CBD modulation of THC-induced antinociception, hypolocomotion, and metabolism.
These results suggest that CBD may enhance THC's antinociceptive and hypolocomotive effects, primarily prolonging THC's duration of action; however, these effects were small and inconsistent across experiments. Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol.
Colon cancer is a major public health problem. Cannabis-based medicines are useful adjunctive treatments in cancer patients. CBD botanical drug substance, on colorectal cancer cell proliferation and in experimental models of colon cancer in vivo. In vivo, the effect of CBD BDS was examined on the preneoplastic lesions aberrant crypt foci , polyps and tumours induced by the carcinogenic agent azoxymethane AOM as well as in a xenograft model of colon cancer in mice. The results may have some clinical relevance for the use of Cannabis-based medicines in cancer patients.
The cannabis constituent cannabidiol CBD possesses anxiolytic and antipsychotic properties. During treatment and 48 h after withdrawal we measured behaviour, whole blood CBD concentrations and autoradiographic receptor binding.
Altered pharmacokinetics in mutant mice could not explain our findings since no genotype differences existed in CBD blood concentrations. Here we demonstrate that Nrg1 modulates acute and long-term neurobehavioural effects of CBD , which does not reverse the schizophrenia-relevant phenotypes.
Distinct neurobehavioural effects of cannabidiol in transmembrane domain neuregulin 1 mutant mice. The surgical technique has evolved since then and several studies have concluded that Laparoscopic common bile duct exploration LCBDE procedures are superior to sequential endolaparoscopic treatment in terms of both clinical and economical outcomes, Cuschieri et al.
Here we present our series from January to March In a retrospective study from January to March , we performed laparoscopic cholecystectomies, out of which patients underwent intraoperative cholangiogram and patients eventually had CBD exploration.
Choledochoduodenosotomy was done in 2 patients. Patients were followed regularly at six monthly intervals with a range of six months to three years of follow-up. There were no major complications like bile leak or pancreatitis. There were no cases of retained stones or intraabdominal infection.
Primary closure of choledochotomy in select patients is a. Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation? The Cannabis sativa plant has been used to treat various physiological and psychiatric conditions for millennia.
Current research is focused on isolating potentially therapeutic chemical constituents from the plant for use in the treatment of many central nervous system disorders.
Of particular interest is the primary nonpsychoactive constituent cannabidiol CBD. Here we review preclinical and clinical data outlining the therapeutic efficacy of CBD for the treatment of motivational disorders such as drug addiction, anxiety, and depression. Across studies, findings suggest promising treatment effects and potentially overlapping mechanisms of action for CBD in these disorders and indicate the need for further systematic investigation of the viability of CBD as a psychiatric pharmacotherapy.
Cannabidiol CBD is the main non-psychotropic component of the glandular hairs of Cannabis sativa. It displays a plethora of actions including anticonvulsive, sedative, hypnotic, antipsychotic, antiinflammatory and neuroprotective properties. However, it is well established that CBD produces its biological effects without exerting significant intrinsic activity upon cannabinoid receptors.
For this reason, CBD lacks the unwanted psychotropic effects characteristic of marijuana derivatives, so representing one of the bioactive constituents of Cannabis sativa with the highest potential for therapeutic use. The present review reports the pharmacological profile of CBD and summarizes results from preclinical and clinical studies utilizing CBD , alone or in combination with other phytocannabinoids, for the treatment of a number of CNS disorders.
Thapa, Dinesh; Cairns, Elizabeth A. Abstract Background and Purpose: Corneal injury can result in dysfunction of corneal nociceptive signaling and corneal sensitization. Activation of the endocannabinoid system has been reported to be analgesic and anti-inflammatory. Gamma-irradiation enhances apoptosis induced by cannabidiol , a non-psychotropic cannabinoid, in cultured HL myeloblastic leukemia cells. Apoptosis was determined by staining with bisBenzimide and propidium iodide.
Human monocytes from normal individuals were resistant to either cannabinoids or gamma-irradiation. Caspase-3 activation was observed after the cannabinoid treatment, and may represent a mechanism for the apoptosis.
Our data suggest a possible new approach to treatment of AML. Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Objective To present a summary of current scientific evidence about the cannabinoid, cannabidiol CBD with regards to their relevance to epilepsy and other selected neuropsychiatric disorders. Methods We summarize the presentations from a conference in which invited participants reviewed relevant aspects of the physiology, mechanisms of action, pharmacology and data from studies with animal models and human subjects.
Results Cannabis has been used to treat disease since ancient times. CBD is anticonvulsant in many acute animal models but there is limited data in chronic models. CBD has neuroprotective and anti-inflammatory effects. CBD appears to be well tolerated in humans but small and methodologically limited studies of CBD in human epilepsy have been inconclusive.
More recent anecdotal reports of high-ratio CBD: Significance CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction and neonatal hypoxic-ischemic encephalopathy. However, we lack data from well-powered double-blind randomized, controlled studies on the efficacy of pure CBD for any disorder.
Initial dose-tolerability and double-blind randomized, controlled studies focusing on target intractable epilepsy populations such as patients with. Clinical experience with THC: CBD oromucosal spray in patients with multiple sclerosis-related spasticity.
Over a month timeframe, THC: CBD spray was initiated in patients. Mean follow-up was 9 months. CBD spray was used as add-on therapy in 95 patients and as monotherapy in 25 patients to achieve best-possible therapeutic results. CBD spray for less than 60 days. Main reasons for treatment discontinuation were: No new safety signals were noted with THC: CBD spray during the evaluation period. CBD spray was effective and well tolerated as add-on therapy or as monotherapy in a relevant proportion of patients with resistant MS spasticity.
Cannabidiol effects in the prepulse inhibition disruption induced by amphetamine. The information processing appears to be deficient in schizophrenia.
Prepulse inhibition PPI , which measures the inhibition of a motor response by a weak sensory event, is considered particularly useful to understand the biology of information processing in schizophrenia patients. Drugs that facilitate dopaminergic neurotransmission such as amphetamine induce PPI disruption in human and rodents.
Clinical and neurobiological findings suggest that the endocannabinoid system and cannabinoids may be implicated in the pathophysiology and treatment of schizophrenia. Cannabidiol CBD , a non-psychotomimetic constituent of the Cannabis sativa plant, has also been reported to have potential as an antipsychotic.
Since one possible mechanism of CBD action is the facilitation of endocannabinoid-mediated neurotransmission through anandamide, we tested the effects of an anandamide hydrolysis inhibitor URB in the amphetamine-induced PPI disruption. Pretreatment with CBD attenuated the amphetamine-disruptive effects on PPI test after systemic or intra-accumbens administration. Similar effects were also found with the inhibitor of anandamide hydrolysis.
These results corroborate findings indicating that CBD induces antipsychotic-like effects. In addition, they pointed to the nucleus accumbens as a possible site of these effects. The increase of anandamide availability may be enrolled in the CBD effects. THC for the treatment of multiple sclerosis. THC dose ratio tested. THC dose ratios of 1: When administered alone, CBD did not produce effects in either procedure. These results suggest that CBD , when administered with THC at therapeutically relevant ratios, may ameliorate aversive effects e.
While this effect may be beneficial for therapeutic usage of a CBD: Cannabidiol reverses the reduction in social interaction produced by low dose Delta 9 -tetrahydrocannabinol in rats. While Delta 9 -tetrahydrocannabinol THC is the main psychoactive constituent of the cannabis plant, a non-psychoactive constituent is cannabidiol CBD. CBD has been implicated as a potential treatment of a number of disorders including schizophrenia and epilepsy and has been included with THC in a 1: This study investigated the effect of THC and CBD , alone or in combination, on some objective behaviours of rats in the open field.
Pairs of rats were injected with CBD or vehicle followed by THC or vehicle and behaviour in the open field was assessed for 10 min. However, the combination of high dose CBD and high dose THC significantly reduced social interaction between rat pairs, as well as producing a significant decrease in locomotor activity. Cannabidiol CBD , one of the most abundant Cannabis sativa-derived compounds, has been implicated with neuroprotective effect in several human pathologies. Until now, no undesired side effects have been associated with CBD.
In this study, we evaluated CBD 's neuroprotective effect in terminal differentiation mature and during neuronal differentiation neuronal developmental toxicity model of the human neuroblastoma SH-SY5Y cell line. A dose-response curve was performed to establish a sublethal dose of CBD with antioxidant activity 2. Moreover, no difference in antioxidant potential and neurite density was observed. When SH-SY5Y cells undergoing neuronal differentiation were exposed to CBD , no differences in antioxidant potential and neurite density were observed.
However, CBD potentiated the neurotoxicity induced by all redox-active drugs tested. Our data indicate that 2. Several studies have indicated that CBD displays neurobiological effects, including wake promotion.
Moreover, experimental evidence has shown that injections of CBD enhance wake-related compounds, such as monoamines dopamine, serotonin, epinephrine, and norepinephrine. However, no clear evidence is available regarding the effects of CBD on additional wake-related neurochemicals such as acetylcholine ACh. Altogether, these data demonstrate that CBD increases ACh levels in a brain region related to wake control.
This study is the first to show the effects of ACh levels in CBD -treated rats and suggests that the basal forebrain might be a site of action of CBD for wakefulness modulation.
The aim of this study was to compare the patterns of grey and white matter atrophy on MRI in autopsy confirmed progressive supranuclear palsy PSP and corticobasal degeneration CBD , and to determine whether the patterns vary depending on the clinical syndrome.
PSP and CBD subjects were also subdivided into those with a dominant dementia or extrapyramidal syndrome. PSP subjects showed brainstem atrophy with involvement of the cortex and underlying white matter. Frontoparietal grey and subcortical grey matter atrophy occurred in CBD. When subdivided, PSP subjects with an extrapyramidal syndrome had more brainstem atrophy and less cortical atrophy than CBD subjects with an extrapyramidal syndrome. PSP subjects with a dementia syndrome had more subcortical white matter atrophy than CBD subjects with a dementia syndrome.
Evidence for the efficacy and effectiveness of THC- CBD oromucosal spray in symptom management of patients with spasticity due to multiple sclerosis. This article reviews the current evidence for the efficacy and safety, with dizziness and fatigue as the most common treatment-related adverse events, being mostly mild to moderate in severity.
Results from both randomized controlled phase III studies involving about, MS patients or patient-years and recently published studies on everyday clinical practice involving more than patients or more than, patient-years are presented.
The aim of this review is to describe the historical development of research on cannabidiol. After the elucidation of the chemical structure of cannabidiol in , the initial studies showed that cannabidiol was unable to mimic the effects of Cannabis.
In the 's the number of publications on cannabidiol reached a first peak, having the research focused mainly on the interaction with delta9-THC and its antiepileptic and sedative effects. The following two decades showed lower degree of interest, and the potential therapeutic properties of cannabidiol investigated were mainly the anxiolytic, antipsychotic and on motor diseases effects.
The last five years have shown a remarkable increase in publications on cannabidiol mainly stimulated by the discovery of its anti-inflammatory, anti-oxidative and neuroprotective effects. These studies have suggested a wide range of possible therapeutic effects of cannabidiol on several conditions, including Parkinson's disease, Alzheimer's disease, cerebral ischemia, diabetes, rheumatoid arthritis, other inflammatory diseases, nausea and cancer.
In the last 45 years it has been possible to demonstrate that CBD has a wide range of pharmacological effects, many of which being of great therapeutic interest, but still waiting to be confirmed by clinical trials. Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes. 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.
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. The astrocytes have gained in recent decades an enormous interest as a potential target for neurotherapies, due to their essential and pleiotropic roles in brain physiology and pathology. The cannabinoid system and its ligands have been shown to interact and affect activities of astrocytes.
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