Efficacy and adverse event profile of cannabidiol and medicinal cannabis for treatment-resistant epilepsy: Systematic review and meta-analysis.

Posted on by

“This paper aimed to systematically examine the efficacy and adverse event (AE) profile of cannabidiol and medicinal cannabis by analyzing qualitative and meta-analytic data.

According to the results, a statistically meaningful effect of cannabidiol compared with placebo was observed (p < 0.00001). When comparing treatment with cannabidiol or medicinal cannabis, significance was not found for the AE profile (p = 0.74). As AEs for cannabidiol were more common under short-term than under long-term treatment (p < 0.00001), this approach was favorable in the long term.

Furthermore, cannabidiol is more effective than placebo, regardless of the etiology of epileptic syndromes and dosage.

Overall, the AE profile did not differ across treatments with cannabidiol or medicinal cannabis, though it did differ favorably for long-term than for short-term treatment.”

https://www.ncbi.nlm.nih.gov/pubmed/31731110

“CBD treatments were effective compared with placebo, regardless of the dose administered. •The safety analysis is related to tolerable SEs found in studies with both CBD and medicinal CNB. •There was a greater tendency for adverse events in short-term treatment compared with long-term treatment.”

https://www.epilepsybehavior.com/article/S1525-5050(19)30862-5/fulltext

Cannabis Use, a Self-Management Strategy Among Australian Women With Endometriosis: Results From a National Online Survey.

Posted on by

Journal of Obstetrics and Gynaecology Canada Home“This study sought to determine the prevalence, tolerability, and self-reported effectiveness of cannabis in women with endometriosis.

A total of 484 responses were included for analysis, with 76% of the women reporting the use of general self-management strategies within the last 6 months. Of those using self-management, 13% reported using cannabis for symptom management. Self-reported effectiveness in pain reduction was high (7.6 of 10), with 56% also able to reduce pharmaceutical medications by at least half. Women reported the greatest improvements in sleep and in nausea and vomiting. Adverse effects were infrequent (10%) and minor.

Women report good efficacy of cannabis in reducing pain and other symptoms, with few adverse effects reported.”

https://www.ncbi.nlm.nih.gov/pubmed/31722852

https://www.jogc.com/article/S1701-2163(19)30808-4/fulltext

Cannabidiol Protects Dopaminergic Neuronal Cells from Cadmium.

Posted on by

ijerph-logo“The protective effect of cannabidiol (CBD), the non-psychoactive component of Cannabis sativa, against neuronal toxicity induced by cadmium chloride (CdCl2 10 μM) was investigated in a retinoic acid (RA)-differentiated SH-SY5Y neuroblastoma cell line.

CBD (1 μM) was applied 24 h before and removed during cadmium (Cd) treatment. In differentiated neuronal cells, CBD significantly reduced the Cd-dependent decrease of cell viability, and the rapid reactive oxygen species (ROS) increase.

CBD significantly prevented the endoplasmic reticulum (ER) stress (GRP78 increase) and the subcellular distribution of the cytochrome C, as well as the overexpression of the pro-apoptotic protein BAX. Immunocytochemical analysis as well as quantitative protein evaluation by western blotting revealed that CBD partially counteracted the depletion of the growth associated protein 43 (GAP43) and of the neuronal specific class III β-tubulin (β3 tubulin) induced by Cd treatment.

These data showed that Cd-induced neuronal injury was ameliorated by CBD treatment and it was concluded that CBD may represent a potential option to protect neuronal cells from the detrimental effects of Cd toxicity.”

https://www.ncbi.nlm.nih.gov/pubmed/31718076

https://www.mdpi.com/1660-4601/16/22/4420

Study protocol for a randomised, double-blind, placebo-controlled study evaluating the Efficacy of cannabis-based Medicine Extract in slowing the disease pRogression of Amyotrophic Lateral sclerosis or motor neurone Disease: the EMERALD trial.

Posted on by

Image result for bmj open“Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no known cure and with an average life expectancy of 3-5 years post diagnosis.

The use of complementary medicine such as medicinal cannabis in search for a potential treatment or cure is common in ALS.

Preclinical studies have demonstrated the efficacy of cannabinoids in extending the survival and slowing of disease progression in animal models with ALS.

There are anecdotal reports of cannabis slowing disease progression in persons with ALS (pALS) and that cannabis alleviated the symptoms of spasticity and pain.”

https://www.ncbi.nlm.nih.gov/pubmed/31719072

https://bmjopen.bmj.com/content/9/11/e029449

Cell Suspensions of Cannabis sativa (var. Futura): Effect of Elicitation on Metabolite Content and Antioxidant Activity.

Posted on by

molecules-logo“Cannabis sativa L. is one of the most-studied species for its phytochemistry due to the abundance of secondary metabolites, including cannabinoids, terpenes and phenolic compounds. In the last decade, fiber-type hemp varieties have received interest for the production of many specialized secondary metabolites derived from the phenylpropanoid pathway. The interest in these molecules is due to their antioxidant activity.

Since secondary metabolite synthesis occurs at a very low level in plants, the aim of this study was to develop a strategy to increase the production of such compounds and to elucidate the biochemical pathways involved. Therefore, cell suspensions of industrial hemp (C. sativa L. var. Futura) were produced, and an advantageous elicitation strategy (methyl jasmonate, MeJA) in combination with precursor feeding (tyrosine, Tyr) was developed.

The activity and expression of phenylalanine ammonia-lyase (PAL) and tyrosine aminotransferase (TAT) increased upon treatment. Through 1H-NMR analyses, some aromatic compounds were identified, including, for the first time, 4-hydroxyphenylpyruvate (4-HPP) in addition to tyrosol. The 4-day MeJA+Tyr elicited samples showed a 51% increase in the in vitro assay (2,2-diphenyl-1-picrylhydrazyl, DPPH) radical scavenging activity relative to the control and a 80% increase in the cellular antioxidant activity estimated on an ex vivo model of human erythrocytes.

Our results outline the active metabolic pathways and the antioxidant properties of hemp cell extracts under the effect of specific elicitors.”

https://www.ncbi.nlm.nih.gov/pubmed/31717508

https://www.mdpi.com/1420-3049/24/22/4056

Short- and Long-Term Effects of Cannabis on Headache and Migraine.

Posted on by

“Use of cannabis to alleviate headache and migraine is relatively common, yet research on its effectiveness remains sparse.

We sought to determine whether inhalation of cannabis decreases headache and migraine ratings as well as whether gender, type of cannabis (concentrate vs. flower), THC, CBD, or dose contribute to changes in these ratings. Finally, we explored evidence for tolerance to these effects.

Archival data were obtained from StrainprintTM, a medical cannabis app that allows patients to track symptoms before and after using different strains and doses of cannabis. Latent change score models and multilevel models were used to analyze data from 12,293 sessions where cannabis was used to treat headache and 7,441 sessions where cannabis was used to treat migraine.

There were significant reductions in headache and migraine ratings after cannabis use.

Men reported larger reductions in headache than women and use of concentrates was associated with larger reductions in headache than flower. Further, there was evidence of tolerance to these effects.

Perspective: Inhaled cannabis reduces self-reported headache and migraine severity by approximately 50%. However, its effectiveness appears to diminish across time and patients appear to use larger doses across time, suggesting tolerance to these effects may develop with continued use.”

https://www.ncbi.nlm.nih.gov/pubmed/31715263

“Headache and migraine ratings were reduced by nearly 50% after using cannabis.”

https://www.jpain.org/article/S1526-5900(19)30848-X/fulltext

NICE recommends cannabis based drugs for epilepsy and multiple sclerosis

Posted on by

Image result for the bmj journal“In final appraisal documents the UK National Institute for Health and Care Excellence has recommended the use of cannabidiol with clobazam for treating seizures associated with two rare and severe forms of epilepsy: Lennox-Gastaut syndrome and Dravet syndrome.

The decision comes after NICE initially rejected the use of cannabidiol in draft appraisal documents released in August because of concerns over a lack of data on the drug’s long term effectiveness.

However, in its latest documents NICE has recommended the drug for people aged 2 or over, reporting that clinical trials had shown that, in comparison with usual care, cannabidiol reduced the number of drop and non-drop seizures and the number of convulsive and non-convulsive seizures.

The final appraisal documents are out for consultation until 27 November, and final approval is expected on 18 December.

The documents were released alongside NICE’s final guideline on cannabis based medicinal products. In this, NICE also recommends the use of nabiximols for patients with multiple sclerosis.”

https://www.ncbi.nlm.nih.gov/pubmed/31712197

https://www.bmj.com/content/367/bmj.l6453

Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: a prospective cohort study.

Posted on by

Publication Cover “Chronic pain is highly prevalent in most of the industrialized nations around the world. Despite the documented adverse effects, opioids are widely used for pain management. Cannabinoids, and specifically Cannabidiol, is proposed as an opioid alternative, having comparable efficacy with better safety profile.

Objectives: We aim to investigate the impact of full hemp extract cannabidiol (CBD) on opioid use and quality of life indicators among chronic pain patients.

Results: Over half of chronic pain patients (53%) reduced or eliminated their opioids within 8 weeks after adding CBD-rich hemp extract to their regimens. Almost all CBD users (94%) reported quality of life improvements. The results indicated a significant relationship between CBD and PSQI (p = 0.003), and PEG (p = 0.006). There was a trend toward improvement but no significant relationship between CBD use and PHQ and PDI.

Conclusion: CBD could significantly reduce opioid use and improve chronic pain and sleep quality among patients who are currently using opioids for pain management.

Key Message: This is a prospective, single-arm cohort study for the potential role of cannabinoids as an alternative for opioids. The results indicate that using the CBD-rich extract enabled our patients to reduce or eliminate opioids with significant improvement in their quality of life indices.”

https://www.ncbi.nlm.nih.gov/pubmed/31711352

“Cannabis, the plant source of cannabinoids (CB), have been used for millennia for different purposes such as pain control and stress relief. Recent evidence highlights cannabinoids’ efficacy and safety for pain control. Besides its potential direct effects on pain, cannabinoids are suggested to have a role in reducing opioid intake. This study concludes that using CBD for chronic pain in patients using opioids has a significant effect on reducing opioid intake, reducing pain and improving quality of life (QoL). Over half of the participants who added CBD hemp extract reduced or eliminated opioids over the course of 8 weeks, and almost all CBD users reported improvements in QoL.”

https://www.tandfonline.com/doi/full/10.1080/00325481.2019.1685298

Cannabidiol as a potential treatment for psychosis

Posted on by

Image result for therapeutic advances in psychopharmacology“Accumulating evidence implicates the endocannabinoid system in the pathophysiology of psychosis.

If the endocannabinoid system plays a role in psychosis pathophysiology, it raises the interesting possibility that pharmacological compounds that modulate this system may have therapeutic value.

Cannabidiol (CBD), a phytocannabinoid constituent of Cannabis sativa, has been heralded as one such potential treatment.

Cannabidiol (CBD), a non-intoxicating constituent of the cannabis plant, has emerged as a potential novel class of antipsychotic with a unique mechanism of action.

In this review, we set out the prospects of CBD as a potential novel treatment for psychotic disorders.

In sum, CBD currently represents a promising potential novel treatment for patients with psychosis.”

https://journals.sagepub.com/doi/10.1177/2045125319881916

https://www.ncbi.nlm.nih.gov/pubmed/31741731

Tetrahydrocannabinolic acid A (THCA-A) reduces adiposity and prevents metabolic disease caused by diet-induced obesity.

Posted on by

Biochemical Pharmacology“Medicinal cannabis has remarkable therapeutic potential, but its clinical use is limited by the psychotropic activity of Δ9-tetrahydrocannabinol (Δ9-THC). However, the biological profile of the carboxylated, non-narcotic native precursor of Δ9-THC, the Δ9-THC acid A (Δ9-THCA-A), remains largely unexplored.

Here we present evidence that Δ9-THCA-A is a partial and selective PPARγ modulator, endowed with lower adipogenic activity than the full PPARγ agonist rosiglitazone (RGZ) and enhanced osteoblastogenic effects in hMSC. Docking and in vitro functional assays indicated that Δ9-THCA-A binds to and activates PPARγ by acting at both the canonical and the alternative sites of the ligand-binding domain. Transcriptomic signatures in iWAT from mice treated with Δ9-THCA-A confirmed its mode of action through PPARγ.

Administration of Δ9-THCA-A in a mouse model of HFD-induced obesity significantly reduced fat mass and body weight gain, markedly ameliorating glucose intolerance and insulin resistance, and largely preventing liver steatosis, adipogenesis and macrophage infiltration in fat tissues. Additionally, immunohistochemistry, transcriptomic, and plasma biomarker analyses showed that treatment with Δ9-THCA-A caused browning of iWAT and displayed potent anti-inflammatory actions in HFD mice.

Our data validate the potential of Δ9-THCA-A as a low adipogenic PPARγ agonist, capable of substantially improving the symptoms of obesity-associated metabolic syndrome and inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/31706843

“Δ9-THCA-A is a partial PPARγ ligand agonist with low adipogenic activity. Δ9-THCA-A enhances osteoblastogenesis in bone marrow derived mesenchymal stem cells. Δ9-THCA-A reduces body weight gain, fat mass, and liver steatosis in HFD-fed mice. Δ9-THCA-A improves glucose tolerance, insulin sensitivity, and insulin profiles in vivo. Δ9-THCA-A induces browning of iWAT and has a potent anti-inflammatory activity.”

https://www.sciencedirect.com/science/article/abs/pii/S0006295219303922?via%3Dihub