β-Caryophyllene (BCP) ameliorates MPP+ induced cytotoxicity.

Posted on May 2, 2018 by David

Biomedicine & Pharmacotherapy

“Parkinson’s disease (PD) is one of the most common neurodegenerative diseases resulting from the continuous death of dopaminergic neurons in substantia nigra. MPP+ (1-methyl-4-phenylpyridinium) has been reported to be a major neurotoxin causing neurotoxic insults on dopaminergic neurons in humans.

β-Caryophyllene (BCP), an important cannabinoid derived from the essential oils of different species, has displayed pharmacological properties in different kinds of tissues and cells. However, neuroprotective effects of BCP in PD haven’t been reported before.

Our results indicate that treatment with MPP+ in SH-SY5Y cells led to a significant decrease in cell viability, which was restored by BCP. Additionally, BCP suppressed MPP+-induced release of lactic dehydrogenase (LDH) and the generation of reactive oxygen species (ROS). In contrast, BCP treatment restored the reduction in mitochondrial membrane potential (MMP) induced by MPP+. BCP treatment increased intracellular GSH and GPx activity.

Also, we found that the antioxidant effects of BCP against MPP+- induced neurotoxicity are dependent on cannabinoid receptor type 2 (CB2R). Moreover, our results indicated that BCP prevented MPP+-induced apoptosis of SH-SY5Y through inhibiting the up-regulation of cleaved Caspase-3, Bax, and restoring the expression of Bcl-2. Besides, BCP markedly suppressed HO-1 activation and c-Jun N-terminal Kinase (JNK) phosphorylation.

We conclude that BCP might act as a promising therapeutic agent against MPP+ toxicity in neuronal cells.”

https://www.ncbi.nlm.nih.gov/pubmed/29710667

https://www.sciencedirect.com/science/article/abs/pii/S0753332217370269

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934

The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration.

Posted on April 27, 2018 by David

“There is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis.

The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users.

CONCLUSIONS:

Chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/29689485

https://www.drugandalcoholdependence.com/article/S0376-8716(18)30184-4/fulltext

Palatability and oral cavity tolerability of THC:CBD oromucosal spray and possible improvement measures in multiple sclerosis patients with resistant spasticity: a pilot study.

Posted on April 24, 2018 by David

“Complaints about Δ⁹-tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (Sativex^®; GW Pharma Ltd, Sailsbury, UK) in the management of multiple sclerosis spasticity include unpleasant taste and oral mucosal anomalies.

This pilot study assessed the use of sugar-free chewing gum and/or a refrigerated bottle of THC:CBD oromucosal spray to mitigate these effects.

RESULTS:

Taste perception in patients receiving chewing gum ± cold bottle intervention (Groups A and C combined) was significantly (p = 0.0001) improved from baseline to week 4 while maintaining spasticity control.

CONCLUSION:

Patient comfort, satisfaction and treatment adherence may benefit from these interventions.”

https://www.ncbi.nlm.nih.gov/pubmed/29683408

https://www.futuremedicine.com/doi/10.2217/nmt-2017-0056

Prolonged Cannabidiol Treatment Effects on Hippocampal Subfield Volumes in Current Cannabis Users.

Posted on April 24, 2018 by David

Cannabis and Cannabinoid Research cover image

“Chronic cannabis use is associated with neuroanatomical alterations in the hippocampus. While adverse impacts of cannabis use are generally attributed to Δ⁹-tetrahydrocannabinol, emerging naturalistic evidence suggests cannabidiol (CBD) is neuroprotective and may ameliorate brain harms associated with cannabis use, including protection from hippocampal volume loss. 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.

Results: No change was observed in left or right hippocampus as a whole. However, left subicular complex (parasubiculum, presubiculum, and subiculum) volume significantly increased from baseline to post-treatment (p=0.017 uncorrected) by 1.58% (Cohen’s d=0.63; 2.83% in parasubiculum). 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.

Conclusions: 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 brain structural harms conferred by chronic cannabis use. Furthermore, these outcomes suggest that CBD may be a useful adjunct in treatments for cannabis dependence and may be therapeutic for a range of clinical disorders characterized by hippocampal pathology (e.g., schizophrenia, Alzheimer’s disease, and major depressive disorder).”

https://www.ncbi.nlm.nih.gov/pubmed/29682609

“In conclusion, our findings are the first to demonstrate an ameliorating effect of CBD treatment upon brain structural harms characteristic of regular cannabis use. Furthermore, these results speak to the potential for CBD treatment to restore hippocampal pathology in a range of clinical populations (e.g., schizophrenia, Alzheimer’s disease, and major depressive disorder).”

https://www.liebertpub.com/doi/10.1089/can.2017.0047

Hemp shows potential for treating ovarian cancer

Posted on April 23, 2018 by David

“Researchers demonstrate hemp’s ability to slow cancer growth and uncover mechanism for its cancer-fighting ability.

Results from some of the first studies to examine hemp’s ability to fight cancer show that it might one day be useful as plant-based treatment for ovarian cancer. Hemp is part of the same cannabis family as marijuana but doesn’t have any psychoactive properties or cause addiction.

“Hemp, like marijuana, contains therapeutically valuable components such as cannabidiol, cannabinol, and tetrahydrocannabinol,”

“Our findings from this research as well as prior research show that KY hemp slows ovarian cancer comparable to or even better than the current ovarian cancer drug Cisplatin,” said Turner. “Since Cisplatin exhibits high toxicity, we anticipate that hemp would carry less side effects.”

https://www.sciencedaily.com/releases/2018/04/180423155046.htm

“Hemp Shows Potential for Treating Ovarian Cancer” https://www.eurekalert.org/multimedia/pub/167927.php

“Studies show hemp’s potential for treating ovarian cancer” https://www.news-medical.net/news/20180424/Studies-show-hemps-potential-for-treating-ovarian-cancer.aspx

“Hemp shows potential for treating ovarian cancer” https://www.europeanpharmaceuticalreview.com/news/75103/hemp-treating-ovarian-cancer/

“Hemp portrays possibility for curing ovarian cancer” https://ebuzzcommunity.com/2018/04/hemp-portrays-possibility-for-curing-ovarian-cancer/

“Hemp Extract Inhibits Growth Of Ovarian Cancer, Research Finds” https://thefreshtoast.com/rx/hemp-extract-inhibits-growth-of-ovarian-cancer-research-finds/

Cannabidiol Based Medical Cannabis in Children with Autism- a Retrospective Feasibility Study

Posted on April 23, 2018 by David

“Objective: This retrospective study assessed safety, tolerability and efficacy of cannabidiol (CBD) based medical cannabis, as an adjuvant therapy, for refractory behavioral problems in children with ASD.

Background: Anecdotal evidence of successful cannabis treatment in children with autism spectrum disorder (ASD) are accumulating but formal studies are lacking.

Design/Methods: Sixty children with ASD (age = 11.8± 3.5, range 5.0–17.5; 77% low functioning; 83% boys) were treated with oral CBD and tetrahydrocannabinol (THC) at a ratio of 20:1. The dose was up-titrated to effect (maximal CBD dose − 10mg/kg/d). Tolerability and efficacy were assessed using a modified Liverpool Adverse Events Profile, the Caregiver Global Impression of Change (CGIC) scale, the Home Situations Questionnaire–Autism Spectrum Disorder (HSQ-ASD) and the Autism Parenting Stress Index (APSI).

Results: Following the cannabis treatment, behavioral outbreaks were much improved or very much improved (on the CGIC scale) in 61% of patients. The anxiety and communication problems were much or very much improved in 39% and 47% respectively. Disruptive behaviors, were improved by 29% from 4.74±1.82 as recorded at baseline on the HSQ-ASD to 3.36±1.56 following the treatment. Parents reported less stress as reflected in the APSI scores, changing by 33% from 2.04±0.77 to 1.37±0.59. The effect on all outcome measures was more apparent in boys with non-syndromic ASD. Adverse events included sleep disturbances (14%) irritability (9%) and loss of appetite (9%).

Conclusions: This preliminary study support the feasibility of CBD based medical cannabis as a promising treatment option for refractory behavioral problems in children with ASD. Based on these promising results, we have launched a large, double blind, placebo controlled cross-over trial with 120 participants (NCT02956226).”

http://n.neurology.org/content/90/15_Supplement/P3.318

Efficacy of CBD-enriched medical cannabis for treatment of refractory epilepsy in children and adolescents – An observational, longitudinal study.

Posted on April 21, 2018 by David

Cover image volume 40, Issue 5

“The objective of this observational study was to evaluate the efficacy of medical cannabis for the treatment of refractory epilepsy.

Fifty-seven patients (age 1-20 years) with epilepsy of various etiologies were treated with Cannabis oil extract (CBD/THC ratio of 20:1) for at least 3 months (Median follow up time-18 months). Forty-Six Patients were included in the efficacy analysis. Average CBD dose was11.4 mg/kg/d.

Twenty-six patients (56%) had ≤50% reduction in mean monthly seizure frequency. There was no statistically significant difference in response rate among various epilepsy etiologies, and cannabis strain used.

Younger age at treatment onset (<10 years) and higher CBD dose (>11 mg/kg/d) were associated with better response to treatment. Adverse reactions were reported in 46% of patients and were the main reason for treatment cessation.

Our results suggest that adding CBD-enriched cannabis extract to the treatment regimen of patients with refractory epilepsy may result in a significant reduction in seizure frequency according to parental reports.”

https://www.ncbi.nlm.nih.gov/pubmed/29674131

http://www.brainanddevelopment.com/article/S0387-7604(18)30112-8/fulltext

Dronabinol oral solution in the management of anorexia and weight loss in AIDS and cancer.

Posted on April 21, 2018 by David

“The true incidence of anorexia secondary to human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and cancer is not well classified owing to the fact that there is a lack of standardized definitions and recent clinical data in these settings.

Dronabinol, or Δ-9-tetrahydrocannabinol, is a synthetic molecule that closely mimics the action of Cannabis sativa L., a naturally occurring compound activated in the central nervous system by cannabinoid receptors.

Dronabinol exerts its effects by directly acting on the vomiting and appetite control centers in the brain, which in turn increases appetite and prevents vomiting.

In the USA, dronabinol is currently available in two dosage formulations – oral capsule and oral solution. While the oral capsule was initially approved by the US Food and Drug Administration in 1985, the recent approval of the oral solution in 2016 presents an “easy-to-swallow” alternative for patients using or intending to use dronabinol.

Dronabinol is indicated in adult patients with HIV/AIDS for the treatment of anorexia and weight loss. However, there is no approved indication in the setting of cancer-related anorexia and weight loss. This review aims at presenting available data on the use of oral dronabinol in the management of anorexia and weight loss in HIV/AIDS and cancer, as well as characterizing and highlighting the pharmacotherapeutic considerations of the newest formulation of dronabinol.”

https://www.ncbi.nlm.nih.gov/pubmed/29670357

https://www.dovepress.com/dronabinol-oral-solution-in-the-management-of-anorexia-and-weight-loss-peer-reviewed-article-TCRM

The use of cannabis in supportive care and treatment of brain tumor

Posted on April 15, 2018 by David

Issue Cover

“Anticancer Effects of Cannabinoids may be able to Prolong Life.

Cannabinoids are multitarget substances. Currently available are dronabinol (synthetic delta-9-tetrahydrocannabinol, THC), synthetic cannabidiol (CBD) the respective substances isolated and purified from cannabis, a refined extract, nabiximols (THC:CBD = 1.08:1.00); and nabilone, which is also synthetic and has properties that are very similar to those of THC.

Cannabinoids have a role in the treatment of cancer as palliative interventions against nausea, vomiting, pain, anxiety, and sleep disturbances. THC and nabilone are also used for anorexia and weight loss, whereas CBD has no orexigenic effect. The psychotropic effects of THC and nabilone, although often undesirable, can improve mood when administered in low doses. CBD has no psychotropic effects; it is anxiolytic and antidepressive.

Of particular interest are glioma studies in animals where relatively high doses of CBD and THC demonstrated significant regression of tumor volumes (approximately 50% to 95% and even complete eradication in rare cases). Concomitant treatment with X-rays or temozolomide enhanced activity further. Similarly, a combination of THC with CBD showed synergistic effects. Although many questions, such as on optimized treatment schedules, are still unresolved, today’s scientific results suggest that cannabinoids could play an important role in palliative care of brain tumor patients.

THC, a partial CB1, CB2 agonist, has the stigma of psychotropic effects that are mediated by CB1 stimulation. However, CB1 stimulation is necessary for improving mood and appetite and many other effects. At present, it is hard to imagine a better approach than adjusting THC doses individually to balance wanted versus unwanted effects. Generally, higher doses are needed to achieve analgesic and antiemetic effects. Even much higher, supraphysiologic oral doses would be needed to combat tumors.

Combinations were synergistic under many circumstances such as in pain and antitumor studies. Cannabinoids differ in their antitumor activities and probably in their mechanisms and targets, which is a rationale for combinations. However, for many pharmacological effects (except against tumors) roughly 10-times higher daily doses are needed for CBD compared to THC.

In summary, the endocannabinoid system is likely playing a crucial role in palliative care. The future will show whether an optimized treatment strategy with cannabinoids can also prolong life of brain tumor patients by their virtue to combat cancer cells.”

https://academic.oup.com/nop/article/4/3/151/2918616

“Cannabinoid Drug Prolongs the Life of Brain Tumor Patients in Phase II Trials” https://labiotech.eu/gw-pharmaceuticals-brain-tumor/

Cannabinoid Type 1 Receptors are Upregulated During Acute Activation of Brown Adipose Tissue.

Posted on April 14, 2018 by David

Diabetes

“Activating brown adipose tissue (BAT) could provide a potential approach for the treatment of obesity and metabolic disease in humans.

Obesity is associated with up-regulation of the endocannabinoid system, and blocking the cannabinoid type 1 receptor (CB1R) has been shown to cause weight loss and decrease cardiometabolic risk factors. These effects may partly be mediated via increased BAT metabolism, since there is evidence that CB1R antagonism activates BAT in rodents.

To investigate the significance of CB1R in BAT function, we quantified the density of CB1R in human and rodent BAT using the positron emission tomography (PET) radioligand [¹⁸F]FMPEP-d₂ , and in parallel measured BAT activation with the glucose analogue [¹⁸F]FDG. Activation by cold exposure markedly increased CB1R density and glucose uptake in BAT of lean men. Similarly, β3-receptor agonism increased CB1R density in BAT of rats.

In contrast, overweight men with reduced BAT activity exhibited decreased CB1R in BAT, reflecting impaired endocannabinoid regulation. Image-guided biopsies confirmed CB1R mRNA expression in human BAT. Furthermore, CB1R blockade increased glucose uptake and lipolysis of brown adipocytes.

Our results highlight that CB1Rs are significant for human BAT activity, and the CB1R provide a novel therapeutic target for BAT activation in humans.”

https://www.ncbi.nlm.nih.gov/pubmed/29650773

http://diabetes.diabetesjournals.org/content/early/2018/04/06/db17-1366

www.thctotalhealthcare.com

Tag Archives: treatment