Tag Archives: cannabidiol

Single and combined effects of delta9 -tetrahydrocannabinol and cannabidiol in a mouse model of chemotherapy-induced neuropathic pain.

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British Journal of Pharmacology

“It has been suggested that the non-psychoactive phytocannabinoid cannabidiol (CBD) can impact the pharmacological effects of delta-9-tetrahydrocannabinol (THC). We tested the hypothesis that CBD and THC would significantly mitigate mechanical sensitivity in a mouse model of paclitaxel-induced neuropathic pain, and that CBD+THC combinations would produce synergistic effects. We also tested the hypothesis that CBD would attenuate oxaliplatin- and vincristine- induced mechanical sensitivity.

KEY RESULTS:

Both CBD and THC alone attenuated mechanical allodynia in mice treated with paclitaxel. Very low ineffective doses of CBD and THC were synergistic when given in combination. CBD also attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity, while THC significantly attenuated vincristine- but not oxaliplatin-induced mechanical sensitivity. The low dose combination significantly attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity.

CONCLUSIONS AND IMPLICATIONS:

CBD may be potent and effective at preventing the development of CIPN, and its clinical utility may be enhanced by co-administration of low doses of THC. These treatment strategies would increase the therapeutic window of Cannabis-based pharmacotherapies.”

https://www.ncbi.nlm.nih.gov/pubmed/28548225

http://onlinelibrary.wiley.com/doi/10.1111/bph.13887/abstract

Correlation Between Cannabidiol-Induced Reduction of Infarct Volume and Inflammatory Factors Expression in Ischemic Stroke Model.

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“Recent studies demonstrated that cannabidiol had neuroprotective property. There is some evidence about effective role of cannabidiol in reduction of ischemic damages. It has been reported that infarct size is influenced by various factors after MCAO, including inflammatory factors. The aim of the present study was to evaluate the effect of cannabidiol on infarction volume and correlation of infarct size with tumor necrosis factor receptor 1 (TNFR1), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression.

RESULTS:

The present results indicate that in the MCAO-induced cerebral ischemia, administration of cannabidiol (100 and 200 ng/rat) causes a significant reduction in infarction volume in comparison with the vehicle group. Also, there were significant correlations between decrease of regional infarct volume and TNFR1/NF-κB expression.

CONCLUSION:

The results of this study indicate that cannabidiol reduced cerebral infarction possibly through diminishing TNFR1/NF-κB-induced neurotoxicity in transient focal cerebral ischemia.”

 https://www.ncbi.nlm.nih.gov/pubmed/28539998
http://bcn.iums.ac.ir/article-1-708-en.html

Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome

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“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.)”

http://www.nejm.org/doi/10.1056/NEJMoa1611618

“Cannabinoids for Epilepsy — Real Data, at Last”  http://www.nejm.org/doi/full/10.1056/NEJMe1702205

“Cannabidiol (CBD) Significantly Reduces Convulsive Seizure Frequency in Dravet Syndrome (DS): Results of a Multi-center, Randomized, Double-blind, Placebo-controlled Trial (GWPCARE1)” http://files.shareholder.com/downloads/AMDA-1TW341/201889199x0x919787/73B57FA6-CD45-4ABB-8C89-87EFEA36B4ED/1332B_AES_Poster_Dravet_Part_B_.pdf

“EPILEPSY AND MARIJUANA: CANNABIS DRUG REDUCES DRAVET SYNDROME SEIZURES IN LARGE-SCALE CLINICAL TRIAL” http://www.newsweek.com/cannabis-marijuana-dravet-syndrome-epilepsy-clinical-trial-614982

“Study proves medicinal cannabis can help children with severe epilepsy, researchers say” http://www.abc.net.au/news/2017-05-25/scientific-study-medicinal-cannabis-helps-children-with-epilepsy/8556180
 
 
 

Cannabidiol in Medical Marijuana: Research Vistas and Potential Opportunities.

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“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 principle phytocannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) and CBD are the major pharmacologically active cannabinoids. The effect of CBD on brain systems as well as on phenomenological measures (e.g. cognitive function) are distinct and in many cases opposite to that of Δ9-THC.

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. Disparate findings and reports related to effects of cannabis consumption reflect differential relative concentration of Δ9-THC and CBD.

Existing literature, notwithstanding its deficiencies, provides empirical support for the hypothesis that CBD may exert beneficial effects on brain effector systems/substrates subserving domain-based phenomenology. Interventional studies with purified CBD are warranted with a call to target-engagement proof-of-principle studies using the research domain criteria (RDoC) framework.” https://www.ncbi.nlm.nih.gov/pubmed/28501518

http://www.sciencedirect.com/science/article/pii/S1043661817303559

Evaluation of Cannabidiol in Animal Seizure Models by the Epilepsy Therapy Screening Program (ETSP).

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Neurochemical Research

“Cannabidiol (CBD) is a cannabinoid component of marijuana that has no significant activity at cannabinoid receptors or psychoactive effects. There is considerable interest in CBD as a therapy for epilepsy.

Almost a third of epilepsy patients are not adequately controlled by clinically available anti-seizure drugs (ASDs). Initial studies appear to demonstrate that CBD preparations may be a useful treatment for pharmacoresistant epilepsy.

The National Institute of Neurological Disorders and Stroke (NINDS) funded Epilepsy Therapy Screening Program (ETSP) investigated CBD in a battery of seizure models using a refocused screening protocol aimed at identifying pharmacotherapies to address the unmet need in pharmacoresistant epilepsy. Applying this new screening workflow, CBD was investigated in mouse 6 Hz 44 mA, maximal electroshock (MES), corneal kindling models and rat MES and lamotrigine-resistant amygdala kindling models.

Following intraperitoneal (i.p.) pretreatment, CBD produced dose-dependent protection in the acute seizure models; mouse 6 Hz 44 mA (ED50 164 mg/kg), mouse MES (ED50 83.5 mg/kg) and rat MES (ED50 88.9 mg/kg). In chronic models, CBD produced dose-dependent protection in the corneal kindled mouse (ED50 119 mg/kg) but CBD (up to 300 mg/kg) was not protective in the lamotrigine-resistant amygdala kindled rat. Motor impairment assessed in conjunction with the acute seizure models showed that CBD exerted seizure protection at non-impairing doses.

The ETSP investigation demonstrates that CBD exhibits anti-seizure properties in acute seizure models and the corneal kindled mouse. However, further preclinical and clinical studies are needed to determine the potential for CBD to address the unmet needs in pharmacoresistant epilepsy.”  https://www.ncbi.nlm.nih.gov/pubmed/28478594

 https://link.springer.com/article/10.1007%2Fs11064-017-2287-8

Cannabidiol decreases bone resorption by inhibiting RANK/RANKL expression and pro-inflammatory cytokines during experimental periodontitis in rats.

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“Cannabidiol (CBD) is a cannabinoid component from Cannabis sativa that does not induce psychotomimetic effects and possess anti-inflammatory properties.  In the present study we tested the effects of CBD in a periodontitis experimental model in rats. Morphometrical analysis of alveolar bone loss demonstrated that CBD-treated animals presented a decreased alveolar bone loss. These results indicate that CBD may be useful to control bone resorption during progression of experimental periodontitis in rats.” https://www.ncbi.nlm.nih.gov/pubmed/19070683

http://www.sciencedirect.com/science/article/pii/S1567576908003469

Cannabidiol administration reduces sublesional cancellous bone loss in rats with severe spinal cord injury.

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“Patients with spinal cord injury (SCI) undergo severe loss of bone mineral below the level of lesion, and data on available treatment options after SCI is scarce.

The aim of this work was to investigate the therapeutic effect of cannabidiol (CBD), a non-psychoactive cannabis, on sublesional bone loss in a rat model of SCI.

In conclusion, CBD administration attenuated SCI-induced sublesional cancellous bone loss.”

https://www.ncbi.nlm.nih.gov/pubmed/28479140

http://www.sciencedirect.com/science/article/pii/S0014299917303230

Compound found in cannabis helps ‘shrink’ four-year-old’s brain tumour

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Four-year-old William Frost from Newark

“The family of a four-year-old boy from Nottinghamshire are backing new research into whether a non-psychoactive compound found in cannabis can reduce paediatric brain cancer cells.

Experts from Nottingham’s Children’s Brain Tumour Research Centre, at The University of Nottingham, will test Cannabidiol (CBD) for its effects on paediatric brain tumours in youngsters. This research will form part of the pre-clinical phase of the evaluation of the potential use of cannabidiol in paediatric brain tumours” http://www.nottinghampost.com/compound-found-in-cannabis-helps-shrink-four-year-old-s-brain-tumour/story-30307458-detail/story.html

“Scientists plan study after Nottinghamshire boy’s tumour shrinks during cannabis compound treatment” https://nottstv.com/notts-scientists-treating-brain-tumours-with-cannabis-backed-by-four-year-old-boy-with-the-condition/
 
“Study looks at cannabis ingredient’s ability to help children’s tumours. UK research into cannabidiol (CBD) comes after surge in parents administering it to children without medical advice” https://www.theguardian.com/society/2017/may/02/study-cannabis-cannabidiol-cbd-ability-to-help-children-brain-tumours

 “Little boy’s aggressive brain tumour shrinks thanks to CANNABIS compound, his parents claim” https://www.thesun.co.uk/living/3472080/little-boys-aggressive-brain-tumour-shrinks-thanks-to-cannabis-his-parents-claimed/

“Little boy battling golf ball-sized brain tumour given new lease of life after being given a special OIL” http://www.mirror.co.uk/news/uk-news/little-boy-battling-golf-ball-10347423

 “Four-year-old brain cancer patient sees tumour shrink – thanks to cannabis oil”  http://metro.co.uk/2017/05/03/four-year-old-brain-cancer-patient-sees-tumour-shrink-thanks-to-cannabis-oil-6613034/
Four-year-old William was diagnosed with a brain tumour in 2014
http://www.thctotalhealthcare.com/category/brain-cancer/

Combined cannabinoid therapy via an oromucosal spray.

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“Extensive basic science research has identified the potential therapeutic benefits of active compounds extracted from the Cannabis sativa L. plant (the cannabinoids). It is recognized that a significant proportion of patients suffering with the debilitating symptoms of pain and spasticity in multiple sclerosis or other conditions smoke cannabis despite the legal implications and stigma associated with this controlled substance. GW Pharmaceuticals have developed Sativex (GW- 1000-02), a combined cannabinoid medicine that delivers and maintains therapeutic levels of two principal cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), via an oromucosal pump spray, that aims to minimize psychotropic side effects.”  https://www.ncbi.nlm.nih.gov/pubmed/16969427

“Sativex has proved to be well tolerated and successfully self-administered and self-titrated in both healthy volunteers and patient cohorts. Clinical assessment of this combined cannabinoid medicine has demonstrated efficacy in patients with intractable pain (chronic neuropathic pain, pain due to brachial plexus nerve injury, allodynic peripheral neuropathic pain and advanced cancer pain), rheumatoid arthritis and multiple sclerosis (bladder problems, spasticity and central pain), with no significant intoxication-like symptoms, tolerance or withdrawal syndrome.”  https://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summaryn_pr?p_JournalId=4&p_RefId=1021517

“Sativex(®) (nabiximols, USAN name) oromucosal spray contains the two main active constituents of Cannabis sativa, tetrahydrocannabinol and cannabidiol in a 1:1 molecular ratio, and acts as an endocannabinoid system modulator.”  https://www.ncbi.nlm.nih.gov/pubmed/21449855

“Abuse potential and psychoactive effects of δ-9-tetrahydrocannabinol and cannabidiol oromucosal spray (Sativex), a new cannabinoid medicine. Evidence to date suggests that abuse or dependence on Sativex is likely to occur in only a very small proportion of recipients.” https://www.ncbi.nlm.nih.gov/pubmed/21542664

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