Tag Archives: plant

The Endocannabinoid System and Cannabidiol’s Promise for the Treatment of Substance Use Disorder.

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 Related image“Substance use disorder is characterized by repeated use of a substance, leading to clinically significant distress, making it a serious public health concern. The endocannabinoid system plays an important role in common neurobiological processes underlying substance use disorder, in particular by mediating the rewarding and motivational effects of substances and substance-related cues. In turn, a number of cannabinoid drugs (e.g., rimonabant, nabiximols) have been suggested for potential pharmacological treatment for substance dependence. Recently, cannabidiol (CBD), a non-psychoactive phytocannabinoid found in the cannabis plant, has also been proposed as a potentially effective treatment for the management of substance use disorder. Animal and human studies suggest that these cannabinoids have the potential to reduce craving and relapse in abstinent substance users, by impairing reconsolidation of drug-reward memory, salience of drug cues, and inhibiting the reward-facilitating effect of drugs. Such functions likely arise through the targeting of the endocannabinoid and serotonergic systems, although the exact mechanism is yet to be elucidated. This article seeks to review the role of the endocannabinoid system in substance use disorder and the proposed pharmacological action supporting cannabinoid drugs’ therapeutic potential in addictions, with a focus on CBD. Subsequently, this article will evaluate the underlying evidence for CBD as a potential treatment for substance use disorder, across a range of substances including nicotine, alcohol, psychostimulants, opioids, and cannabis. While early research supports CBD’s promise, further investigation and validation of CBD’s efficacy, across preclinical and clinical trials will be necessary.”

https://www.ncbi.nlm.nih.gov/pubmed/30837904

https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00063/full

Plant-Based Modulators of Endocannabinoid Signaling.

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Journal of Natural Products

“Extracts from Cannabis species have aided the discovery of the endocannabinoid signaling system (ECSS) and phytocannabinoids that possess broad therapeutic potential. Whereas the reinforcing effects of C. sativa are largely attributed to CB1 receptor agonism by Δ9-tetrahydrocannabinol (Δ9-THC), the observed medicinal effects of Cannabis arise from the combined actions of various compounds. In addition to compounds bearing a classical cannabinoid structure, naturally occurring fatty acid amides and esters resembling anandamide and 2-arachidonoyl glycerol isolated from non- Cannabis species are also valuable tools for studying ECSS function. This review highlights the potential of plant-based secondary metabolites from Cannabis and unrelated species as ECSS modulators.”

https://www.ncbi.nlm.nih.gov/pubmed/30816712

https://pubs.acs.org/doi/10.1021/acs.jnatprod.8b00874

CBN: The cancer fighting Cannabinoid

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“CBN, cannabinol, is a mildly psychoactive cannabinoid found within the cannabis plant. We examine the very complex mechanisms that give allowance for this cannabinoids entrance into the cell membrane and its effect on cannabinoid receptors and the inhibition of the enzyme adenylate cyclase that is responsible for phosphate production. Prior study bears weight accordingly; we examine this phosphate as a potent energy source, the enzymes responsible for cell replication cycle and inhibition thereof. Moreover, how IL-2, (Interleukin-2), a type of cytokine signaling molecule in the immune system stops being produced when immune T cells are exposed to cannabinoids. How IL-2 stimulates the cell cycle via promotion of the c-Fos protein and is responsible for modulation of the immune response. This is shown by Faubert and Kaminski, that administration of CBN can slow cell replication and endure cell death (apoptosis).”

http://www.imedpub.com/proceedings/cbn-the-cancer-fighting-cannabinoid-5528.html

“Programmed Cell Death (Apoptosis)” http://www.ncbi.nlm.nih.gov/books/NBK26873/

Spontaneous, anecdotal, retrospective, open-label study on the efficacy, safety and tolerability of cannabis galenical preparation (Bedrocan).

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International Journal of Pharmacy Practice banner

“Our main aim was to investigate the short-term therapeutic effects, safety/tolerability and potential side effects of the cannabis galenical preparation (Bedrocan) in patients with a range of chronic conditions unresponsive to other treatments.

METHODS:

In this retrospective, ‘compassionate use’, observational, open-label study, 20 patients (age 18-80 years) who had appealed to our ‘Second Opinion Medical Consulting Network’ (Modena, Italy), were instructed to take sublingually the galenical oil twice a day for 3 months of treatment. The usual starting dose was low (0.5 ml/day) and gradually titrated upward to the highest recommended dose (1 ml/day). Tolerability and adverse effects were assessed at baseline and monthly thereafter during the treatment period through direct contact (email or telephone) or visit if required. Patients’ quality of life was evaluated at baseline and 3 months using the medical outcome short-form health survey questionnaire (SF-36).

KEY FINDINGS:

From baseline to 6 months post-treatment, SF-36 scores showed: reductions in total pain (P < 0.03); improvements in the physical component (P < 0.02); vitality (P < 0.03); social role functioning (P < 0.02); and general health state (P < 0.02). No changes in role limitations (P = 0.02) due to emotional state (e.g. panic, depression, mood alteration) were reported. Monthly reports of psychoactive adverse effects showed significant insomnia reduction (P < 0.03) and improvement in mood (P < 0.03) and concentration (P < 0.01).

CONCLUSIONS:

These data suggest that a cannabis galenical preparation may be therapeutically effective and safe for the symptomatic treatment of some chronic diseases. Further studies on the efficacy of cannabis as well as cannabinoid system involvement in the pathophysiology are warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/30768819

https://onlinelibrary.wiley.com/doi/full/10.1111/ijpp.12514

An Update of Current Cannabis-Based Pharmaceuticals in Pain Medicine.

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“Cannabis users have long reported therapeutic properties of the plant for a variety of conditions, some of which include nausea, emesis, seizures, cancer, neurogenic diseases and pain control. Research has elucidated many cannabinoid pharmacodynamic and pharmacokinetic properties, expanding the potential use of cannabinoids as a medical therapy.

Due to the inconsistent delivery and control of the active components involved with smoking, pharmaceutical companies are investigating and prioritizing routes other than smoke inhalation for therapeutic use of cannabinoids. In this relatively new field of pharmaceutical development, ongoing drug development promises great benefit from targeted endocannabinoid receptor agonism.

Available in Canada and Europe, nabiximols, a specific extract from the Cannabis plant, has demonstrated great benefit in the treatment of pain related to spasticity in multiple sclerosis, cancer and otherwise chronic pain conditions.

The cannabidiol oral solution Epidiolex®, which is available in the USA, is indicated for management of refractory epilepsy but may offer therapeutic relief to chronic pain conditions as well.

Current investigative drugs, such as those developed by Cara Therapeutics and Zynerba Pharmaceuticals, are synthetic cannabinoids which show promise to specifically target neuropsychiatric conditions and chronic pain symptoms such as neuropathy and allodynia.

The objective of this review is to provide clinicians with an update of currently available and promising developmental cannabis pharmaceutical derivatives which may stand to greatly benefit patients with otherwise difficult-to-treat chronic conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/30721403

https://link.springer.com/article/10.1007%2Fs40122-019-0114-4

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

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

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

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“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 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

Cannabidiol-induced apoptosis is mediated by activation of Noxa in human colorectal cancer cells.

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Cancer Letters

“Cannabidiol (CBD), one of the compounds present in the marijuana plant, has anti-tumor properties, but its mechanism is not well known.

This study aimed to evaluate the apoptotic action of CBD in colorectal cancer (CRC) cells, and focused on its effects on the novel pro-apoptotic Noxa-reactive oxygen species (ROS) signaling pathway.

CBD experiments were performed using the CRC cell lines HCT116 and DLD-1. CBD induced apoptosis by regulating many pro- and anti-apoptotic proteins, of which Noxa showed significantly higher expression. To understand the relationship between Noxa and CBD-induced apoptosis, Noxa levels were downregulated using siRNA, and the expression of apoptosis markers decreased.

After ROS production was blocked, the level of Noxa also decreased, suggesting that ROS is involved in the regulation of Noxa, which along with ROS is a well-known pro-apoptotic signaling agents. As a result, CBD induced apoptosis in a Noxa-and-ROS-dependent manner.

Taken together, the results obtained in this study re-demonstrated the effects of CBD treatment in vivo, thus confirming its role as a novel, reliable anticancer drug.”

https://www.ncbi.nlm.nih.gov/pubmed/30660647

“Our results using cells, mice, and patient-derived cells strongly suggest, for the first time, that that CBD can cause Noxa-induced cell death. These results suggest that that CBD has important implications for the potential treatment of human CRC.”