Perspectives on cannabis as a substitute for opioid analgesics.

 Future Medicine Logo“With the opioid epidemic reaching new heights in the USA, it has become critical to find suitable alternatives to opioids.

Cannabis, an antinociceptive, is a strong contender to help patients reduce their opioid usage.

A growing literature has been examining the complex effects cannabis has on pain relief and on opioid usage; whether it is a substitute for opioids or increases their use. This review explores the studies that compare cannabis-opioid interactions and presents some challenges of cannabis research and usage.

The practical clinical pharmacology of cannabis as an analgesic, including the route of administration, safety and pharmacokinetics, are discussed to address the concerns, as well as possible solutions, of cannabis as a pain reliever.”

https://www.ncbi.nlm.nih.gov/pubmed/30681029

https://www.futuremedicine.com/doi/10.2217/pmt-2018-0051

Prospects for the Use of Cannabinoids in Oncology and Palliative Care Practice: A Review of the Evidence.

 cancers-logo“There is an increased interest in the use of cannabinoids in the treatment of symptoms in cancer and palliative care patients. Their multimodal action, in spite of limited efficacy, may make them an attractive alternative, particularly in patients with multiple concomitant symptoms of mild and moderate intensity. There is evidence to indicate cannabis in the treatment of pain, spasticity, seizures, sleep disorders, nausea and vomiting, and Tourette syndrome. Although the effectiveness of cannabinoids is limited, it was confirmed in neuropathic pain management and combination with opioids. A relatively favorable adverse effects profile, including no depressive effect on the respiratory system, may make cannabis complement a rather narrow armamentarium that is in the disposition of a palliative care professional.”

https://www.ncbi.nlm.nih.gov/pubmed/30678303

https://www.mdpi.com/2072-6694/11/2/129

Cannabinoids (Marijuana) A Stem Cell Stimulator!!

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

Attitudes toward and knowledge of medical cannabis among individuals with spinal cord injury.

Image result for spinal cord series and cases

“An observational study based on an online survey addressing attitudes toward and knowledge of cannabis among people living with spinal cord injury (SCI).

Participants largely believed that cannabis use is safe, has potential therapeutic benefits, and ought to be legal.

This study is the first to assess beliefs about and attitudes toward cannabis use among a nationwide sample of people with SCI. While limited, it provides a roadmap for future research. It also offers medical providers an initial understanding of which factors may encourage or dissuade their patients with SCI from seeking medical cannabis treatment.”

https://www.ncbi.nlm.nih.gov/pubmed/30675390

https://www.nature.com/articles/s41394-019-0151-6 

“Cannabis cures the spine.” https://www.ncbi.nlm.nih.gov/pubmed/30172587

Cannabinoid therapy in epilepsy.

 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

CB2R agonist prevents nicotine induced lung fibrosis.

 Publication Cover“Nicotine stimulates fibroblast proliferation while increasing inflammation and fibrosis of tissues.

The cannabinoid receptor 1 (CB1R) is mainly located in the CNS, while cannabinoid receptor 2 (CB2R) is located in the immune cells within the body. CB2R regulates inflammatory processes and fibroblast function.

Nicotine induces interstitial lung fibrosis that is enhanced by the CB2R antagonist and diminished by the CB2R agonist. Therefore, the CB2R agonist may offer a protection against fibrosis.”

https://www.ncbi.nlm.nih.gov/pubmed/30675824

https://www.tandfonline.com/doi/abs/10.1080/01902148.2018.1543368?journalCode=ielu20

Reduction of Benzodiazepine Use in Patients Prescribed Medical Cannabis

View details for Cannabis and Cannabinoid Research cover image

Benzodiazepines are a class of medication with sedative properties, commonly used for anxiety and other neurological conditions. These medications are associated with several well-known adverse effects.

This observational study aims to investigate the reduction of benzodiazepine use in patients using prescribed medical cannabis.

Within a cohort of 146 patients initiated on medical cannabis therapy, 45.2% patients successfully discontinued their pre-existing benzodiazepine therapy.

Medical cannabis remains a controversial but potentially effective treatment for patients suffering from a variety of medical conditions. Within a cohort of patients initiated on medical cannabis therapy, a large proportion successfully discontinued their pre-existing benzodiazepine therapy.

This study therefore supports the continued research of medical cannabis and urges further exploration into its therapeutic value.”

https://www.liebertpub.com/doi/10.1089/can.2018.0020

“A significant number of cannabis patients discontinue use of benzodiazepines”  https://www.psypost.org/2019/05/a-significant-number-of-cannabis-patients-discontinue-use-of-benzodiazepines-53636

Some Prospective Alternatives for Treating Pain: The Endocannabinoid System and Its Putative Receptors GPR18 and GPR55.

Image result for frontiers in pharmacology“Marijuana extracts (cannabinoids) have been used for several millennia for pain treatment.

Regarding the site of action, cannabinoids are highly promiscuous molecules, but only two cannabinoid receptors (CB1 and CB2) have been deeply studied and classified.

Thus, therapeutic actions, side effects and pharmacological targets for cannabinoids have been explained based on the pharmacology of cannabinoid CB1/CB2 receptors. However, the accumulation of confusing and sometimes contradictory results suggests the existence of other cannabinoid receptors.

Different orphan proteins (e.g., GPR18, GPR55, GPR119, etc.) have been proposed as putative cannabinoid receptors.

According to their expression, GPR18 and GPR55 could be involved in sensory transmission and pain integration.

This work summarized novel data supporting that, besides cannabinoid CB1 and CB2receptors, GPR18 and GPR55 may be useful for pain treatment.

Conclusion: There is evidence to support an antinociceptive role for GPR18 and GPR55.”

https://www.ncbi.nlm.nih.gov/pubmed/30670965

https://www.frontiersin.org/articles/10.3389/fphar.2018.01496/full

Cannabinoid receptor 2 activation mitigates lipopolysaccharide-induced neuroinflammation and sickness behavior in mice.

 Image result for psychopharmacology journal“Cannabinoid receptor 2 (CB2R) signaling in the brain is associated with the pathophysiology of depression.

Sickness behavior, characterized by lessened mobility, social interaction, and depressive behavior, is linked with neuroinflammation, oxidative stress, and immune system.

The present study was aimed at evaluating 1-phenylisatin (PI), a CB2R agonist, in sickness behavior.

Our data propose that acute and long-term activation of CB2R might prevent neuroinflammation and oxidative stress-associated sickness behavior.”

https://www.ncbi.nlm.nih.gov/pubmed/30666359

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

Publication Cover

“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