Tag Archives: cannabidiol

Safety and efficacy of nabiximols on spasticity symptoms in patients with motor neuron disease (CANALS): a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.

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The Lancet Neurology

“Spasticity is a major determinant of disability and decline in quality of life in patients with motor neuron disease.

Cannabinoids have been approved for symptomatic treatment of spasticity in multiple sclerosis. We investigated whether cannabinoids might also reduce spasticity in patients with motor neuron disease.

Nabiximols was well tolerated, and no participants withdrew from the double-blind phase of the study. No serious adverse effects occurred.

INTERPRETATION:

In this proof-of-concept trial, nabiximols had a positive effect on spasticity symptoms in patients with motor neuron disease and had an acceptable safety and tolerability profile.”

https://www.ncbi.nlm.nih.gov/pubmed/30554828

https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(18)30406-X/fulltext

Chemical characterization of leaves, male and female flowers from spontaneous cannabis (Cannabis sativa var. spontanea) growing in Hungary.

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“Cannabis sativa var. spontanea is a spontaneous form of hemp with a low content of psychoactive cannabinoids and can be considered as a valuable source of other phytoconstituents to be used in nutraceuticals or for their health promoting properties.

Chemical data on this hemp variety are rather scarce. In this paper we report a comprehensive phytochemical characterization of leaves, male and female inflorescences of C. sativa var. spontanea growing wild in Hungary.

The results indicated that female inflorescence essential oil contains high amounts of the CB2 agonists (E)-caryophyllene (28.3%) and cannabidiol (CBD) (24.9%), whereas leaves and male inflorescence essential oils contained lower amounts of both compounds. HPLC-MS allowed to quantify CBD and CBD-A in the ethyl acetate extracts from leaves, male and female inflorescences; they were 0.3, 0.8 and 0.9%, and 0.2, 0.3 and 0.4%, respectively. Flavonoids were formed by C-glycosides and glucuronic acids of kaempferol and apigenin, with a total content of 3.8, 6.1 and 7.8 mg/g in methanolic extracts from leaves, male and female inflorescences, respectively.

Based on these results, C. sativa var. spontanea may represent an important source of CB2 agonists and bioflavonoids to be used in nutraceuticals, cosmetics and pharmaceuticals.”

https://www.ncbi.nlm.nih.gov/pubmed/30548994

https://onlinelibrary.wiley.com/doi/abs/10.1002/cbdv.201800562

Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series.

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“Cannabidiol (CBD) is a non-psychotomimetic cannabinoid compound that is found in plants of the genus Cannabis. Preclinical research has suggested that CBD may have a beneficial effect in rodent models of post-traumatic stress disorder (PTSD). This effect is believed to be due to the action of CBD on the endocannabinoid system. CBD has seen a recent surge in research regarding its potential value in a number of neuro-psychiatric conditions. This is the first study to date examining the clinical benefit of CBD for patients with PTSD.

RESULTS:

From the total sample of 11 patients, 91% (n = 10) experienced a decrease in PTSD symptom severity, as evidenced by a lower PCL-5 score at 8 weeks than at their initial baseline. The mean total PCL-5 score decreased 28%, from a mean baseline score of 51.82 down to 37.14, after eight consecutive weeks of treatment with CBD. CBD was generally well tolerated, and no patients discontinued treatment due to side effects.

CONCLUSIONS:

Administration of oral CBD in addition to routine psychiatric care was associated with PTSD symptom reduction in adults with PTSD. CBD also appeared to offer relief in a subset of patients who reported frequent nightmares as a symptom of their PTSD. Additional clinical investigation, including double-blind, placebo-controlled trials, would be necessary to further substantiate the response to CBD that was observed in this study.”

https://www.ncbi.nlm.nih.gov/pubmed/30543451

https://www.liebertpub.com/doi/10.1089/acm.2018.0437

Cannabis-based products for pediatric epilepsy: A systematic review.

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“Evidence from high-quality randomized controlled trials (RCTs) suggests that cannabidiol probably reduces seizures among children with drug-resistant epilepsy (moderate certainty).”

https://www.ncbi.nlm.nih.gov/pubmed/30515765 

https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.14608

“Phytocannabinoids produce anticonvulsant effects through the endocannabinoid system, with few adverse effects.” https://www.ncbi.nlm.nih.gov/pubmed/25475762

Emerging drugs for the treatment of Dravet syndrome.

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“Dravet syndrome (DS) is an early-onset genetic developmental epileptic encephalopathy characterized by multiple seizure types which are refractory to antiseizure medication. There is an unmet need for effective and tolerable drugs to control different seizure types in DS types, with the aim of improving quality of life and preventing neurological impairment.

Areas covered: Narrative review of efficacy and tolerability of fenfluramine, cannabidiol (CBD), verapamil and modulators of serotonin signaling pathways (lorcaserin or trazodone) in the treatment of DS.

Expert Opinion/Commentary: A recent large randomized controlled-trial has shown that CBD is effective in the treatment of DS; preliminary data from the placebo-controlled trial on fenfluramine are also promising. Further studies are definitely required to evaluate the role of verapamil and modulators of serotonin signaling in DS. At present, drugs used to treat seizures in DS treat the symptoms of epilepsy rather than its cause(s). Future research should focus on elucidating the natural history of DS and whether appropriate treatment can have a beneficial impact on its disease course. A multidisciplinary, individualized approach to care of DS patients is required.”

https://www.ncbi.nlm.nih.gov/pubmed/30482063

https://www.tandfonline.com/doi/abs/10.1080/14728214.2018.1552937?journalCode=iemd20

Reefer madness or real medicine? A plea for incorporating medicinal cannabis in pharmacy curricula.

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Currents in Pharmacy Teaching and Learning

“Over the past twenty years, the acceptance and use of medicinal cannabis has increased in the United States. However, there is still a lack of education and comfort as it relates to the therapeutic uses of botanical cannabis and cannabidiol in pharmacy professional curricula. Professional training programs have failed to keep pace with the evolving national landscape and growing acceptance of this therapy.

PERSPECTIVE:

In this manuscript, the current landscape of pharmacy professional involvement in the dispensing and administration of medicinal cannabis throughout the United States is described. A concern exists that there is a knowledge gap among pharmacists and pharmacy students, as demonstrated by recent survey results, related to the pharmacology, dosing, administration, adverse effects, drug interactions, and monitoring of both medicinal and recreational cannabis use.

IMPLICATIONS:

While cannabis use is still considered illegal by the federal government, it is imperative pharmacy educators prepare the next generation of pharmacists to be knowledgeable on the safe and effective use and communication tactics related to cannabis. As a therapy garnering national attention with growing support for use, education on this topic must be included in pharmacy curricula and pharmacy continuing education.”

https://www.ncbi.nlm.nih.gov/pubmed/30497617

https://www.sciencedirect.com/science/article/abs/pii/S1877129717304860?via%3Dihub

Peripubertal cannabidiol treatment rescued behavioral and neurochemical abnormalities in MAM model of schizophrenia.

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 Neuropharmacology

“In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produced long-lasting behavioral alterations such as social withdrawal and cognitive impairment in the social interaction test and in the novel object recognition test, respectively. At molecular level, an increased cannabinoid receptor type-1 (CB1) mRNA and protein expression which might be due to a reduction in DNA methylation at gene promoter in the prefrontal cortex (PFC), coincided with deficits in the social interaction test and in the novel object recognition test in MAM rats. Both schizophrenia-like phenotype and altered transcriptional regulation of CB1 receptors were reversed by peripubertal treatment (from PND 19 to PND 39) with the non-psychotropic phytocannabinoid cannabidiol (30 mg/kg/day), or, in part, by treatment with the cannabinoid CB1 receptor antagonist/inverse agonist AM251 (0.5 mg/kg/day), but not with haloperidol (0.6 mg/kg/day). These results suggest that early treatment with cannabidiol may prevent both the appearance of schizophrenia-like deficits as well as CB1 alterations in the PFC at adulthood, supporting that peripubertal cannabidiol treatment might be protective against MAM insult.”

https://www.ncbi.nlm.nih.gov/pubmed/30496751

https://www.sciencedirect.com/science/article/pii/S0028390818308761?via%3Dihub

Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain

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“Clinical studies indicate that cannabidiol (CBD), the primary nonaddictive component of cannabis that interacts with the serotonin (5-HT)1A receptor, may possess analgesic and anxiolytic effects.

Overall, repeated treatment with low-dose CBD induces analgesia predominantly through TRPV1 activation, reduces anxiety through 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/30157131

https://insights.ovid.com/crossref?an=00006396-900000000-98870

Cannabidiol reduces airway inflammation and fibrosis in experimental allergic asthma.

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European Journal of Pharmacology

“Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Asthma remains a major public health problem and, at present, there are no effective interventions capable of reversing airway remodelling.

Cannabidiol (CBD) is known to exert immunomodulatory effects through the activation of cannabinoid-1 and -2 (CB1 and CB2) receptors located in the central nervous system and immune cells, respectively. However, as the role of CBD on airway remodelling and the mechanisms of CB1 and CB2 aren’t fully elucidated, this study was designed to evaluate the effects of cannabidiol in this scenario.

Allergic asthma was induced in Balb/c mice exposed to ovalbumin, and respiratory mechanics, collagen fibre content in airway and alveolar septa, cytokine levels, and CB1 and CB2 expression were determined. Moreover, expressions of CB1 and CB2 in induced sputum of asthmatic individuals and their correlation with airway inflammation and lung function were also evaluated.

CBD treatment, regardless of dosage, decreased airway hyperresponsiveness, whereas static lung elastance only reduced with high dose. These outcomes were accompanied by decreases in collagen fibre content in both airway and alveolar septa and the expression of markers associated with inflammation in the bronchoalveolar lavage fluid and lung homogenate. There was a significant and inverse correlation between CB1levels and lung function in asthmatic patients.

CBD treatment decreased the inflammatory and remodelling processes in the model of allergic asthma. The mechanisms of action appear to be mediated by CB1/CB2 signalling, but these receptors may act differently on lung inflammation and remodelling.”

https://www.ncbi.nlm.nih.gov/pubmed/30481497

https://www.sciencedirect.com/science/article/pii/S0014299918306836?via%3Dihub

Novel inverse agonists for the orphan G protein-coupled receptor 6.

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“The orphan G protein-coupled receptor 6 (GPR6) displays unique promise as a therapeutic target for the treatment of neuropsychiatric disorders due to its high expression in the striatopallidal neurons of the basal ganglia.

GPR6, along with closely related orphan receptors GPR3 and GPR12, are phylogenetically related to CB1 and CB2 cannabinoid receptors.

In the current study, we performed concentration-response studies on the effects of three different classes of cannabinoids: endogenous, phyto-, and synthetic, on both GPR6-mediated cAMP accumulation and β-arrestin2 recruitment. In addition, structure-activity relationship studies were conducted on cannabidiol (CBD), a recently discovered inverse agonist for GPR6.

We have identified four additional cannabinoids, cannabidavarin (CBDV), WIN55212-2, SR141716A and SR144528, that exert inverse agonism on GPR6. Furthermore, we have discovered that these cannabinoids exhibit functional selectivity toward the β-arrestin2 recruitment pathway.

These novel, functionally selective inverse agonists for GPR6 can be used as research tools and potentially developed into therapeutic agents.”

https://www.ncbi.nlm.nih.gov/pubmed/30480157