Tag Archives: cannabinoid

Cannabidiol Treatment for Refractory Seizures in Sturge-Weber Syndrome.

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“Sturge-Weber syndrome results in leptomeningeal vascular malformations, medically refractory epilepsy, stroke(s), and cognitive impairments. Cannabidiol, a cannabinoid without psychoactive properties, has been demonstrated in preclinical models to possibly have anticonvulsant, antioxidant, and neuroprotective actions.

CONCLUSION:

This study suggests that cannabidiol may be well tolerated as adjunctive medication for seizure management and provides initial data supporting further study of cannabidiol in individuals with Sturge-Weber syndrome.”

https://www.ncbi.nlm.nih.gov/pubmed/28454984

Significant Tic Reduction in An Otherwise Treatment-Resistant Patient with Gilles de la Tourette Syndrome Following Treatment with Nabiximols.

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“Early anecdotal reports and preliminary studies suggested that cannabinoid-based medicines such as delta-9-tetrahydrocannabinol (THC) are effective in the treatment of Gilles de la Tourette syndrome (TS).

We report a single case study of a patient with otherwise treatment-resistant TS successfully treated with nabiximols.

Our results provide further evidence that treatment with nabiximols may be effective in the treatment of patients with TS.

Given the positive response exhibited by the patient highlighted in this report, further investigation of the effects of nabiximols is proposed on a larger group of patients in a clinical trial setting.”

 https://www.ncbi.nlm.nih.gov/pubmed/28445405

Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity

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“The cannabinoid CB2 receptor (CB2R) represents a promising therapeutic target for various forms of tissue injury and inflammatory diseases. There is a great interest in the development of selective type-2 cannabinoid receptor (CB2R) agonists as potential drug candidates for various pathophysiological conditions, which include chronic and inflammatory pain, pruritus, diabetic neuropathy and nephropathy, liver cirrhosis, and protective effects after ischaemic-reperfusion injury.” https://www.nature.com/articles/ncomms13958

“Pain relief without the high. Researchers at Leiden University led by Mario van der Stelt (Leiden Institute for Chemistry) have set ‘gold standards’ for developing new painkillers based on the medicinal effects of cannabis.”  https://www.sciencedaily.com/releases/2017/01/170104103916.htm

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Anti-inflammatory effects of the cannabidiol derivative dimethylheptyl-cannabidiol – studies in BV-2 microglia and encephalitogenic T cells

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“Preparations derived from Cannabis sativa (marijuana and hashish) have become widespread since ancient times, both as therapeutic agents and in recreational smoking.

Among the more than 60 phytocannabinoids identified in Cannabis extracts, the two most abundant are Δ9-tetrahydrocannabinol (THC), the major psychotropic constituent, and cannabidiol (CBD), the major non-psychoactive component.

Cannabinoids were shown to exert a wide range of therapeutic effects, and many of the cannabinoids, especially CBD, were shown to possess potent anti-inflammatory and immunomodulatory activities. In addition, it was shown that several cannabinoids have pro-apoptotic, neuroprotective, and antitumor properties

Dimethylheptyl-cannabidiol (DMH-CBD), a non-psychoactive, synthetic derivative of the phytocannabinoid cannabidiol (CBD), has been reported to be anti-inflammatory in RAW macrophages. Here, we evaluated the effects of DMH-CBD at the transcriptional level in BV-2 microglial cells as well as on the proliferation of encephalitogenic T cells.

The results show that DMH-CBD has similar anti-inflammatory properties to those of CBD. DMH-CBD downregulates the expression of inflammatory cytokines and protects the microglial cells by inducing an adaptive cellular response against inflammatory stimuli and oxidative injury. In addition, DMH-CBD decreases the proliferation of pathogenic activated TMOG cells.

Several CBD derivatives were also shown to have anti-inflammatory and anti-proliferative properties.

The results show that DMH-CBD induces similar anti-inflammatory, anti-proliferative, and stress response effects to those previously observed for CBD.”

https://www.degruyter.com/view/j/jbcpp.2016.27.issue-3/jbcpp-2015-0071/jbcpp-2015-0071.xml

CB1 cannabinoid receptor drives oocyte maturation and embryo development via PI3K/Akt and MAPK pathways.

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“Endocannabinoids have been recognized as mediators of practically all reproductive events in mammals. However, little is known about the role of this system in oocyte maturation.

In a mouse model, we observed that activation of the cannabinoid receptor (CB)1during in vitro oocyte maturation modulated the phosphorylation status of Akt and ERK1/2 and enhanced the subsequent embryo production. In the absence of the CB1 receptor, in vivo oocyte maturation was impaired and embryo development delayed. The CB2receptor was unable to rescue these effects. Finally, we confirmed abnormal oocyte maturation rather than impaired embryonic transport through the oviduct in CB1 knockouts.

Our data suggest that cannabinoid agonists may be useful in vitro maturation supplements. For in vitro fertilization patients intolerant to gonadotropins, this could be a promising and only option.”

https://www.ncbi.nlm.nih.gov/pubmed/28428264

Neurological aspects of medical use of cannabidiol.

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“Cannabidiol (CBD) is among the major secondary metabolites of Cannabis devoid of the delta-9-tetra-hydrocannabinol psychoactive effects. It is a resorcinol-based compound with a broad spectrum of potential therapeutic properties, including neuroprotective effects in numerous pathological conditions. CBD neuroprotection is due to its antioxidant and antiinflammatory activi-ties and the modulation of a large number of brain biological targets (receptors, channels) involved in the development and maintenance of neurodegenerative diseases.

OBJECTIVE:

Aim of the present review was to describe the state of art about the pre-clinical research, the potential use and, when existing, the clinical evidence related to CBD in the neurological field.

RESULTS:

Laboratory and clinical studies on the potential role of CBD in Parkinson’s disease (PD), Alzheimer’s disease (AD), multiple sclerosis (MS), Huntington’s disease (HD), amyotrophic lateral sclerosis ALS), cerebral ischemia, were examined.

CONCLUSIONS:

Pre-clinical evidence largely shows that CBD can produce beneficial effects in AD, PD and MS patients, but its employment for these disorders needs further confirmation from well designed clinical studies. CBD pre-clinical demonstration of antiepileptic activity is supported by recent clinical studies in human epileptic subjects resistant to standard antiepileptic drugs showing its potential use in children and young adults affected by refractory epilepsy. Evidence for use of CBD in PD is still not supported by sufficient data whereas only a few studies including a small number of patients are available.”

https://www.ncbi.nlm.nih.gov/pubmed/28412918

Report from a Survey of Parents Regarding the Use of Cannabidiol (Medicinal cannabis) in Mexican Children with Refractory Epilepsy.

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“Structured online surveys were used to explore the experiences of the parents of children with refractory epilepsy using medicinal cannabis in Mexico during September 2016. The surveys, which were completed in full, were reviewed, and 53 cases of children aged between 9 months and 18 years were identified. Of these, 43 cases (82%) were from Mexico and 10 (18%) were from Latin American countries. Of the 43 Mexican cases, the diagnoses were as follows: 20 cases (47%) had Lennox-Gastaut syndrome (LGS); 13 cases (30%) had unspecified refractory epilepsy (URE); 8 cases (19%) had West syndrome (WS); 1 case (2%) had Doose syndrome (DS); and 1 case (2%) had Ohtahara syndrome (OS). In total, 47.1% of cases had previously been treated with 9 or more anticonvulsant therapies.

The parents reported a decrease in convulsions when cannabidiol was used in 81.3% of the cases; a moderate to significant decrease occurred in 51% of cases, and 16% of cases were free from seizure. The number of antiepileptic drugs being used was reduced in 9/43 (20.9%) cases. No serious adverse effects were reported, with only some mild adverse effects, such as increased appetite or changes in sleep patterns, reported in 42% of cases.”

https://www.ncbi.nlm.nih.gov/pubmed/28392943

Cannabidiol reduces lung injury induced by hypoxic-ischemic brain damage in newborn piglets.

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“Brain hypoxic-ischemic (HI) damage induces distant inflammatory lung damage in newborn pigs. We aimed to investigate the effects of cannabidiol (CBD) on lung damage in this scenario.

RESULTS:

CBD prevented HI-induced deleterious effects on TLC and OI and reduced lung histological damage, modulating inflammation (decreased leukocyte infiltration and IL-1 concentration) and reducing protein content in BALF and EVLW. These effects were related to CBD-induced anti-inflammatory changes in the brain. HI did not increase oxidative stress in the lungs. In the lungs, WAY100635 blunted CBD’s beneficial effects on histological damage, IL-1 concentration and EVLW.

CONCLUSIONS:

CBD reduced brain HI-induced distant lung damage, with 5-HT1A receptor involvement in these effects. Whether CBD’s effects on lungs were due to anti-inflammatory effects on the brain or to direct effects on lungs remains to be elucidated.” https://www.ncbi.nlm.nih.gov/pubmed/28388598

“Hypoxic-ischemic brain injury is a diagnostic term that encompasses a complex constellation of pathophysiological and molecular injuries to the brain induced by hypoxia, ischemia, cytotoxicity, or combinations of these conditions. The typical causes of hypoxic-ischemic brain injury – cardiac arrest, respiratory arrest, near-drowning, near-hanging, and other forms of incomplete suffocation, carbon monoxide and other poisonous gas exposures, and perinatal asphyxia – expose the entire brain to potentially injurious reductions of oxygen (i.e., hypoxia) and/or diminished blood supply (ischemia).”  http://www.internationalbrain.org/articles/hypoxicischemic-brain-injury/

“Hypoxic-ischemic brain damage induces distant inflammatory lung injury in newborn piglets.” https://www.ncbi.nlm.nih.gov/pubmed/25950454

“Cannabidiol reduces lung injury induced by hypoxic-ischemic brain damage in newborn piglets.” https://www.ncbi.nlm.nih.gov/pubmed/28388598

Cannabinoid type 1 receptor-containing axons innervate NPY/AgRP neurons in the mouse arcuate nucleus.

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“Phytocannabinoids, such as THC and endocannabinoids, are well known to promote feeding behavior and to control energy metabolism through cannabinoid type 1 receptors (CB1R). However, the underlying mechanisms are not fully understood.

Generally, cannabinoid-conducted retrograde dis-inhibition of hunger-promoting neurons has been suggested to promote food intake, but so far it has not been demonstrated due to technical limitations.

Our immunohistochemical and ultrastructural study demonstrates the morphological substrate for cannabinoid-conducted feeding behavior via retrograde dis-inhibition of hunger-promoting AgRP/NPY neurons.”

https://www.ncbi.nlm.nih.gov/pubmed/28377876

Metabolic side effects induced by olanzapine treatment are neutralized by CB1 receptor antagonist compounds co-administration in female rats.

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“Weight gain is an important side effect of most atypical antipsychotic drugs such as olanzapine. Moreover, although many animal models with metabolic side effects have been well defined, the interaction with other pathways has to be considered.

The endocannabinoid system and the CB1 receptor (CB1R) are among the most promising central and peripheral targets involved in weight and energy balance.

In this study we developed a rat model based 15-days treatment with olanzapine that shows weight gain and an alteration of the blood parameters involved in the regulation of energy balance and glucose metabolism. Consequently, we analysed whether, and by which mechanism, a co-treatment with the novel CB1R neutral antagonist NESS06SM, could attenuate the adverse metabolic effects of olanzapine compared to the reference CB1R inverse agonist rimonabant.

Our results showed alterations of the cannabinoid markers in the nucleus accumbens and of orexigenic/anorexigenic markers in the hypothalamus of female rats treated with olanzapine. These molecular modifications could explain the excessive food intake and the resulting weight gain. Moreover, we confirmed that a co-treatment with CB1R antagonist/inverse agonist compounds decreased food intake and weight increment and restored all blood parameters, without altering the positive effects of olanzapine on behaviour. Furthermore, rimonabant and NESS06SM restored the metabolic enzymes in the liver and fat tissue altered by olanzapine.

Therefore, CB1 receptor antagonist/inverse agonist compounds could be good candidate agents for the treatment of weight gain induced by olanzapine.”

https://www.ncbi.nlm.nih.gov/pubmed/28377074