Tag Archives: THC

New Prospect for Cancer Cachexia: Medical Cannabinoid.

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“Cachexia is a common term for the wasting symptoms which may appear in almost every chronic illness, such as AIDS, tuberculosis, and cancer. Cancer cachexia (CCA) is a result of the interaction between the host and the tumor, mainly manifested in short-term wasting, malnutrition, and so on. Due to the chronic food shortages, absorption dysfunction and metabolic disorders, all of these eventually lead to hypoimmunity, organ failure, and higher susceptibility to pathogenic microorganisms. And then increased morbidity and mortality rates as well as reduced tolerance to anti-cancer treatments will be resulted in patients with CCA. Up to now, no standard guidelines have been established for cachexia treatment. Moreover, progestagens, the only drugs approved by FDA for cancer-related cachexia, can only increase adipose tissue and have not been confirmed to augment lean body mass. Cannabinoid, such as Δ-9-tetrahydrocannabinol (THC) and cannabidiol, is one of a class of diverse chemical compounds. Previous studies have showed that cannabinoid had considerable potential to improve the appetite, body weight, body fat level, caloric intake, mood, quality of life in kinds of diseases. This review will elaborate the anti-CCA role of cannabinoid and explore that whether cannabinoid is effective for CCA and provide a basis for guiding clinical drug use.”

https://www.ncbi.nlm.nih.gov/pubmed/30719170

http://www.jcancer.org/v10p0716.htm

Potential Use of Cannabinoids for the Treatment of Pancreatic Cancer.

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“Cannabinoid extracts may have anticancer properties, which can improve cancer treatment outcomes.

The aim of this review is to determine the potentially utility of cannabinoids in the treatment of pancreatic cancer.

Results: Cannabinol receptors have been identified in pancreatic cancer with several studies showing in vitroantiproliferative and proapoptotic effects. The main active substances found in cannabis plants are cannabidiol (CBD) and tetrahydrocannabinol (THC). There effects are predominately mediated through, but not limited to cannabinoid receptor-1, cannabinoid receptor-2, and G-protein-coupled receptor 55 pathways. In vitro studies consistently demonstrated tumor growth-inhibiting effects with CBD, THC, and synthetic derivatives. Synergistic treatment effects have been shown in two studies with the combination of CBD/synthetic cannabinoid receptor ligands and chemotherapy in xenograft and genetically modified spontaneous pancreatic cancer models. There are, however, no clinical studies to date showing treatment benefits in patients with pancreatic cancer.

Conclusions: Cannabinoids may be an effective adjunct for the treatment of pancreatic cancer. Data on the anticancer effectiveness of various cannabinoid formulations, treatment dosing, precise mode of action, and clinical studies are lacking.”

 https://www.ncbi.nlm.nih.gov/pubmed/30706048
“Endogenous cannabinoids, synthetic or cannabis extracted from plants, can reduce tumor invasion and growth, induce tumor cell death, and inhibit tumor angiogenesis via cannabinoid receptor or receptor-independent pathways. Cannabinoid receptors appear to be highly expressed in pancreatic cancer compared with normal pancreatic tissue. CBD and THC appear to have antiproliferative and proapoptotic effects.”
https://www.liebertpub.com/doi/10.1089/pancan.2018.0019

Dark Classics in Chemical Neuroscience: Δ9-Tetrahydrocannabinol.

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 ACS Chemical Neuroscience

“Cannabis (Cannabis sativa) is the most widely used illicit drug in the world, with an estimated 192 million users globally.

The main psychoactive component of cannabis is (-)-trans-Δ9-tetrahydrocannabinol (Δ9-THC), a molecule with a diverse range of pharmacological actions. The unique and distinctive intoxication caused by Δ9-THC primarily reflects partial agonist action at central cannabinoid type 1 (CB1) receptors.

Δ9-THC is an approved therapeutic treatment for a range of conditions, including chronic pain, chemotherapy-induced nausea and vomiting, and is being investigated in indications such as anorexia nervosa, agitation in dementia, and Tourette’s syndrome.

It is available as a regulated pharmaceutical in products such as Marinol®, Sativex®, and Namisol®, as well as in an ever-increasing range of unregistered medicinal and recreational cannabis products.

While cannabis is an ancient medicament, contemporary use is embroiled in legal, scientific, and social controversy, much of which relates to the potential hazards and benefits of Δ9-THC itself.

Robust contemporary debate surrounds the therapeutic value of Δ9-THC in different diseases, its capacity to produce psychosis and cognitive impairment, and the addictive and “gateway” potential of the drug.

This review will provide a profile of the chemistry, pharmacology, toxicology, and recreational and therapeutic uses of Δ9-THC, as well as the historical and societal importance of this unique, distinctive, and ubiquitous psychoactive substance.”

https://www.ncbi.nlm.nih.gov/pubmed/30689342

https://pubs.acs.org/doi/10.1021/acschemneuro.8b00651

Cannabinoids (Marijuana) A Stem Cell Stimulator!!

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Institute of Regenerative Medicine®“Some time ago a wrote a blog about the use of certain components of the marijuana plant. It was a fairly short blog which I will include here. More and more states are proposing the legalization of marijuana. There are numerous health claims about hemp oil which is a derivative of Cannabis. There may be merit to these claims possibly by the action of the Cannabis on stem cells. Below is the blog and I will expand more on it:

“We use to think that marijuana was bad for one’s health. Now we are not so sure about it. We need to clarify things a bit.
Cannabinoids, the active components of cannabis (Cannabis sativa) extracts, have attracted the attention of human civilizations for centuries for a variety of uses. The use of Cannabis or Marijuana (scientific name is Cannabis sativa) came before we were able to discover the active portion or substrate. This substrate is called endocannabinoid system. The endocannabbinoid system has a number of components. The system consists of lipids, the receptors for the lipids and certain metabolic enzymes. The Cannabinoid signaling regulates cell proliferation, differentiation and it reduces cell aptosis or death. These receptors are found in the very early stages of life. The results of the Cannabinoid receptors depend upon molecular targets and cellular context involved. There are two main receptors which are called CB1 and CB2 receptors. These receptors seem to be involved in neural degeneration. They seem to be involved in all three germ layer formations. . CB1 and CB2 show opposite patterns of expression, the former increasing and the latter decreasing along neuronal differentiation. It is thought that the CB2 receptors may be most important. Recently, endocannabinoid (eCB) signaling has also been shown to regulate proliferation and differentiation of hematopoietic and mesenchymal stem cells, with a key role in determining the formation of several cell types in peripheral tissues, including blood cells, adipocytes, osteoblasts/osteoclasts and epithelial cells. The developmental regulation of cannabinoid receptor expression and cellular/sub-cellular localization, together with their role in progenitor/stem cell biology, may have important implications in human health and disease. Bone marrow and stem cells make endocannabinoids, these endocannabinoids interact with the cannabinoid receptors (Cannabinoid receptors have been found in nearly every cell in the human body). If cannabinoids can enhance stem cell migration and proliferation, this could be a powerful therapy. For instance, if you can increase the numbers and movement of stem cells to an injured tissue, you could vastly enhance the healing process. Lastly, the synthetic cannabinoid HU-210 is about 100-1000x times more potent than THC from Cannabis and this synthetic agent has been found to be neurogenic. Meaning that HU-210 can cause new neurons (brain cells) in the brain to form. However this study was done in rats…and humans are different from rats. Will I prescribe medical marijuana for my stem cell patients? At present I do not think I have enough information to make an intelligent decision about this. I suspect if some day I do prescribe this it will be some derivative of Cannabis. There are certainly some intriguing aspects of Cannabis but I feel the jury is still out. I suspect we will certainly hear more about this. Thanks Dr. P”

That was the blog I wrote some time ago. At this juncture I am getting closer to utilizing some component of Cannabis. I have further looked at the literature and there seems to be some very good science on the effect of Cannabis on stem cell workings. One of the intriguing aspects of the CB2 receptor is that it is found mostly in the immune system. At the University of South Carolina, a team discovered that THC could reduce the inflammation associated with autoimmune diseases by suppressing the activity of certain genes involved in the immune response. Its presence there interests scientists because the immune system triggers inflammation, and studies show marijuana can have an anti-inflammatory effect. When we start talking about the immune system we have a host of implications. We are aware that many diseases of aging may have some basis as an auto-immune disease. One of these that interests me is Osteoporosis. There may be both receptors at work. CB-2 works on the immune system while CB-1 is induced during osteogenic differentiation. As I have written in another blog, Very Small Embryonic Like Stem Cells may have a profound effect on the course of Osteoporosis. The next question is can we prime these cells additionally with Cannabis and take things to the next level. More to come I am sure. Dr. P.”

https://stcell.com/blogs/128/cannabinoids-marijuana-a-stem

Cannabinoid therapy in epilepsy.

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 Image result for curr opin neurol“To review the history, pharmacology, and clinical science of cannabidiol (CBD) in the treatment of epilepsy.

RECENT FINDINGS:

Phase III randomized controlled trials and prospective open label trials have provided efficacy and safety data for the use of CBD in pediatric onset severe epilepsies. The product that was studied in the vast majority of these published trials, Epidiolex (>99% of CBD and <0.10% Δ9-tetrahydrocannabinol (THC); GW pharmaceuticals, Cambridge, UK), has now been FDA approved based on this published data.

SUMMARY:

Identification of CBD, Δ9-THC, and the endocannabinoid system in the mid-20th century has led to advancement of cannabis-based therapies for epilepsy. Based on clinical trial data, Epidiolex is the first CBD medication approved by a national regulatory agency (US Food and Drug Administration for Dravet and Lennox Gastaut syndrome; European Medicines Agency for Lennox Gastaut syndrome). Approval of CBD as a treatment for these rare and severe pediatric-onset epilepsy syndromes is an important milestone, but the complete spectrum of use of cannabis-derived products, and the use of CBD for other epilepsy syndromes remains to be determined.”

https://www.ncbi.nlm.nih.gov/pubmed/30676535

Delta-9-tetrahydrocannabinol inhibits the splenocyte proliferative response to herpes simplex virus type 2.

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“The present investigation was undertaken to determine the effect of in vivo Delta-9-tetrahydrocannabinol (Delta-9-THC) treatment on immune responsiveness to secondary exposure to herpes simplex virus type 2 (HSV2) antigens in vitro.

Administration of 50 mg/kg or 100 mg/kg Delta-9-THC to B6C3F1 mice in concert with HSV2 infection resulted in suppression of the proliferative response to HSV2 cell-surface antigens expressed on virus-infected mouse embryo fibroblasts. Similarly, in vitro treatment of HSV2-infected cells with Delta-9-THC (10(-7) M to 10(-5) M) resulted in a dose-dependent suppression of proliferative responsiveness of splenocytes of non-drug-treated HSV2-sensitized mice.

These results suggest that Delta-9-THC inhibits immune responsiveness of B6C3F1 mice to homotypic challenge with HSV2. This inhibition may be resultant of drug action on both effector immunocytes and target HSV2 antigen-bearing cells.”

https://www.ncbi.nlm.nih.gov/pubmed/2830329

https://www.tandfonline.com/doi/abs/10.3109/08923978709035219

“Inhibition of cell-associated herpes simplex virus type 2 glycoproteins by delta 9-tetrahydrocannabinol. These results indicate that delta 9-THC inhibits the synthesis, maturation, and cellular transport of HSV2-specified glycoproteins.” https://www.ncbi.nlm.nih.gov/pubmed/3033681

A randomised controlled trial of vaporised Δ9-tetrahydrocannabinol and cannabidiol alone and in combination in frequent and infrequent cannabis users: acute intoxication effects.

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“Access to cannabis and cannabinoid products is increasing worldwide for recreational and medicinal use. Two primary compounds within cannabis plant matter, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are both psychoactive, but only THC is considered intoxicating. There is significant interest in potential therapeutic properties of these cannabinoids and of CBD in particular.

Some research has suggested that CBD may ameliorate adverse effects of THC, but this may be dose dependent as other evidence suggests possible potentiating effects of THC by low doses of CBD. We conducted a randomised placebo controlled trial to examine the acute effects of these compounds alone and in combination when administered by vaporisation to frequent and infrequent cannabis users.

Participants (n = 36; 31 male) completed 5 drug conditions spaced one week apart, with the following planned contrasts: placebo vs CBD alone (400 mg); THC alone (8 mg) vs THC combined with low (4 mg) or high (400 mg) doses of CBD. Objective (blind observer ratings) and subjective (self-rated) measures of intoxication were the primary outcomes, with additional indices of intoxication examined.

CBD showed some intoxicating properties relative to placebo.

Low doses of CBD when combined with THC enhanced, while high doses of CBD reduced the intoxicating effects of THC.

The enhancement of intoxication by low-dose CBD was particularly prominent in infrequent cannabis users and was consistent across objective and subjective measures. Most effects were significant at p < .0001.

These findings are important to consider in terms of recommended proportions of THC and CBD in cannabis plant matter whether used medicinally or recreationally and have implications for novice or less experienced cannabis users.”

https://www.ncbi.nlm.nih.gov/pubmed/30661105

https://link.springer.com/article/10.1007%2Fs00406-019-00978-2

Tetrahydrocannabinol: cannabidiol oromucosal spray for treating symptoms of multiple sclerosis spasticity: newest evidence

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“Proceedings of an Almirall-sponsored satellite symposium held at the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin, Germany, 10 October 2018.” https://www.futuremedicine.com/doi/10.2217/nmt-2018-0048

“Newest evidence for tetrahydrocannabinol:cannabidiol oromucosal spray from postapproval pragmatic studies. Postapproval studies have an essential role in demonstrating that an intervention is effective and well tolerated during use in daily clinical practice. Numerous large observational and registry studies of tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray have been conducted subsequent to its approval in Europe in 2011. Collectively, these studies provide valuable insight into various aspects of THC:CBD spray during real-world use in patients with multiple sclerosis spasticity, including its long-term effectiveness and tolerability. The Italian Medicines Agency’s web-based registry is the largest observational study of THC:CBD oromucosal spray conducted to date, reporting on more than 1600 patients prescribed THC:CBD spray since it was introduced in Italy in 2013, and further supporting its effectiveness and tolerability profile.” https://www.futuremedicine.com/doi/10.2217/nmt-2018-0049

“Newest evidence for tetrahydrocannabinol:cannabidiol oromucosal spray from randomized clinical trials. Subsequent to EMA approval of tetrahydrocannabinol (THC): cannabidiol (CBD) oromucosal spray based on results of various studies, including an enriched-design clinical trial, two newer postapproval randomized trials have confirmed its efficacy and safety for treating resistant multiple sclerosis spasticity, while simultaneously addressing specific authorities’ concerns. A double-blind, placebo-controlled, Phase IV trial, conducted as part of the EMA’s risk management plan, found no effect of THC:CBD spray on cognition and mood after 50 weeks of treatment. In the Sativex® as add-on therapy versus further optimized first-line ANTispastics (SAVANT)  study, add-on THC:CBD spray was significantly more effective than readjusting standard antispasticity therapy and provided new evidence of efficacy as requested by German authorities. SAVANT results support practical recommendations for treating resistant multiple sclerosis spasticity in daily practice.”  https://www.futuremedicine.com/doi/10.2217/nmt-2018-0050

Real life Experience of Medical Cannabis Treatment in Autism: Analysis of Safety and Efficacy.

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Scientific Reports

“There has been a dramatic increase in the number of children diagnosed with autism spectrum disorders (ASD) worldwide. Recently anecdotal evidence of possible therapeutic effects of cannabis products has emerged.

The aim of this study is to characterize the epidemiology of ASD patients receiving medical cannabis treatment and to describe its safety and efficacy.

We analysed the data prospectively collected as part of the treatment program of 188 ASD patients treated with medical cannabis between 2015 and 2017. The treatment in majority of the patients was based on cannabis oil containing 30% CBD and 1.5% THC. Symptoms inventory, patient global assessment and side effects at 6 months were primary outcomes of interest and were assessed by structured questionnaires.

After six months of treatment 82.4% of patients (155) were in active treatment and 60.0% (93) have been assessed; 28 patients (30.1%) reported a significant improvement, 50 (53.7%) moderate, 6 (6.4%) slight and 8 (8.6%) had no change in their condition. Twenty-three patients (25.2%) experienced at least one side effect; the most common was restlessness (6.6%).

Cannabis in ASD patients appears to be well tolerated, safe and effective option to relieve symptoms associated with ASD.”

https://www.ncbi.nlm.nih.gov/pubmed/30655581

https://www.nature.com/articles/s41598-018-37570-y

“Medical cannabis is an effective, well-tolerated, and most importantly, a safe treatment for autism in children, helping to reduce a range of symptoms in those with the condition, a new study finds.” https://www.studyfinds.org/cannabis-safe-effective-treatment-autism-young-children/

Self-management strategies amongst Australian women with endometriosis: a national online survey.

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“Endometriosis has a significant negative impact on the lives of women, and current medical treatments often do not give sufficient pain relief or have intolerable side effects for many women. The majority of women with primary dysmenorrhea use self-management strategies (including self-care techniques or lifestyle choices) to help manage period related symptoms, but little is known about self-management in women with endometriosis.

The aim of this survey was to determine the prevalence of use, safety, and self-rated effectiveness of common forms of self-management.

Cannabis, heat, hemp/CBD oil, and dietary changes were the most highly rated in terms of self-reported effectiveness in pain reduction. Physical interventions such as yoga/Pilates, stretching, and exercise were rated as being less effective.

Self-management was very commonly used by women with endometriosis and form an important part of self-management.

Women using cannabis reported the highest self-rated effectiveness.”

https://www.ncbi.nlm.nih.gov/pubmed/30646891

https://bmccomplementalternmed.biomedcentral.com/articles/10.1186/s12906-019-2431-x