Perspectives on cannabis as a substitute for opioid analgesics.

Posted on January 27, 2019 by David

“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.

Posted on January 27, 2019 by David

“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!!

Posted on January 26, 2019 by David

“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

CB2R agonist prevents nicotine induced lung fibrosis.

Posted on January 26, 2019 by David

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

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

Posted on January 25, 2019 by David

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

Cannabis, cannabinoid receptors, and endocannabinoid system: yesterday, today, and tomorrow

Posted on January 24, 2019 by David

Related image

“Cannabis sativa, is also popularly known as marijuana, has been cultivated and used for recreational and medicinal purposes for many centuries.

The main psychoactive content in cannabis is Δ⁹-tetrahydrocannabinol (THC). In addition to plant cannabis sativa, there are two classes of cannabinoids—the synthetic cannabinoids (e.g., WIN55212–2) and the endogenous cannabinoids (eCB), anandamide (ANA) and 2-arachidonoylglycerol (2-AG).

The biological effects of cannabinoids are mainly mediated by two members of the G-protein-coupled receptor family, cannabinoid receptors 1 (CB₁R) and 2 (CB₂R). The endocannabinoids, cannabinoid receptors, and the enzymes/proteins responsible for their biosynthesis, degradation, and re-updating constitute the endocannabinoid system.

In recent decades, the endocannabinoid system has attracted considerable attention as a potential therapeutic target in numerous physiological conditions, such as in energy balance, appetite stimulation, blood pressure, pain modulation, embryogenesis, nausea and vomiting control, memory, learning and immune response, as well as in pathological conditions such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and multiple sclerosis.

The major goal of this Special Issue is to discuss and evaluate the current progress in cannabis and cannabinoid research in order to increase our understanding about cannabinoid action and the underlying biological mechanisms and promote the development cannabinoid-based pharmacotherapies.

Overall, the present special issue provides an overview and insight on pharmacological mechanisms and therapeutic potentials of cannabis, cannabinoid receptors, and eCB system. I believe that this special issue will promote further efforts to apply cannabinoid ligands as the therapeutic strategies for treating a variety of diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/30670816

https://www.nature.com/articles/s41401-019-0210-3

A survey of the attitudes, beliefs and knowledge about medical cannabis among primary care providers.

Posted on January 24, 2019 by David

Image result for bmc family practice “Healthcare providers play a critical role in facilitating patient access to medical cannabis. However, previous surveys suggest only a minority of providers believe that medical cannabis confers benefits to patients. Significant new knowledge about the potential benefits and harms of medical cannabis has recently emerged. Understanding current attitudes and beliefs of providers may provide insight into the ongoing challenges they face as states expand access to medical cannabis.

METHODS:

We conducted an electronic survey of primary care providers in a large Minnesota-based healthcare system between January 23 and February 5, 2018. We obtained information about provider characteristics, attitudes and beliefs about medical cannabis, provider comfort level in answering patient questions about medical cannabis, and whether providers were interested in receiving additional education.

RESULTS:

Sixty-two providers completed the survey (response rate 31%; 62/199). Seventy-six percent of respondents were physicians and the average age was 46.3 years. A majority of providers believed (“strongly agree” or “somewhat agree”) that medical cannabis was a legitimate medical therapy (58.1%) and 38.7% believed that providers should be offering to patients for managing medical conditions. A majority (> 50%) of providers believed that medical cannabis was helpful for treating the qualifying medical conditions of cancer, terminal illness, and intractable pain. A majority of providers did not know if medical cannabis was effective for managing nearly one-half of the other state designated qualifying medical conditions. Few believed that medical cannabis improved quality of life domains. Over one-third of providers believed that medical cannabis interacted with medical therapies. One-half of providers were not ready to or did not want to answer patient questions about medical cannabis, and the majority of providers wanted to learn more about it.

CONCLUSIONS:

Healthcare providers generally believe that medical cannabis is a legitimate medical therapy. Provider knowledge gaps about the effectiveness of medical cannabis for state designated qualifying conditions need to be addressed, and accurate information about the potential for drug interactions needs to be disseminated to address provider concerns. Clinical trial data about how medical cannabis improves patient quality of life domains is desperately needed as this information can impact clinical decision-making.”

https://www.ncbi.nlm.nih.gov/pubmed/30669979

https://bmcfampract.biomedcentral.com/articles/10.1186/s12875-019-0906-y

Cannabinoid Receptor as a potential therapeutic target for Parkinson’s Disease.

Posted on January 22, 2019 by David

Brain Research Bulletin

“Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, characterized by the loss of dopaminergic neurons from substantia nigra pars compacta of basal ganglia caused due to gene mutation, misfolded protein aggregation, reactive oxygen species generation and inflammatory stress. Degeneration of dopaminergic neurons results in muscle stiffness, uncoordinated body movements, sleep disturbance, fatigue, amnesia and impaired voice.

Currently, levodopa (L-DOPA) administration is the most widely used therapy for PD. But prolonged administration of L-DOPA is associated with the symptoms of dyskinesia.

However, emerging evidences suggest the role of cannabinoid receptors (CBRs) in curtailing the progression of PD by activating neuroprotective pathways. Hence, cannabinoid therapy could be a promising alternative to combat PD in future.

In the present review we have discussed the potential role of CBRs in attenuating the key mechanisms of PD and how the existing research gaps needs to be bridged in order to understand the molecular mechanism of CBRs in detail.”

https://www.ncbi.nlm.nih.gov/pubmed/30664919

https://www.sciencedirect.com/science/article/abs/pii/S0361923018306208?via%3Dihub

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

Posted on January 22, 2019 by David

“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

Oral cannabinoids in people living with HIV on effective antiretroviral therapy: CTN PT028-study protocol for a pilot randomised trial to assess safety, tolerability and effect on immune activation.

Posted on January 20, 2019 by David