Cannabinoids

The Therapeutic Potential of Indenopyrazoles

An overview of the synthetic and medicinal perspectives of indenopyrazoles

In Summary:

 Indenopyrazoles, molecules crucial to many biological signaling pathways, have been found to bind to cannabinoid receptors and seem to exhibit therapeutic properties in a variety of conditions. A review of studies on the molecule describes previously documented antimycobacterial, antipsychotic, anti-tumor, and anti-microbial properties, among others. The molecule has demonstrated moderate affinity for both cannabinoid-1 and cannabinoid-2 receptors, suggesting possible additional anti-inflammatory and anti-neurodegenerative capabilities related to the interactions with these receptors. Further research may uncover additional therapeutic applications and shed light on additional benefits of cannabinoid receptors.

Graphical abstract of actions of indenopyrazoles

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Benjamin Caplan, MDThe Therapeutic Potential of Indenopyrazoles
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Another Look Into Opioid and Cannabinoid Interactions

In Summary:

A recent study has revealed that the co-activation of mu-opioid receptors and cannabinoid receptor 1 (CB1) results in the attenuation of the response seen when each receptor type is activated on its own. The decreased response of the two receptor types during co-activation has been implicated in negatively modulating neuritogenesis (the process of generating new brain nerve cells). Neuritogenesis is important for the cells’ ability to receive and project signals leading the researchers to call for more research in order to elucidate the effect this may have on addiction.

The fact that there is co-interaction between opioid receptors and cannabinoid receptors is also interesting to inform the discussion of the place that cannabinoid actors may have in supporting the healing of those who are dependent or addicted to opiate medications.

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Benjamin Caplan, MDAnother Look Into Opioid and Cannabinoid Interactions
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Headache and Migraine Relief Using Cannabis

“Short- and Long-Term Effects of Cannabis on Headache and Migraine “

In Summary:

There are many headache and migraine medications on the market that advertise how they can make you feel better. But what happens when they make you feel worse? Medication overuse headaches occur in 15% of patients taking conventional migraine medication, so it’s no surprise that people are looking for alternatives that bring them relief without reduced risk.

A team of physicians from Washington University wanted to see if cannabis could be a contender. By reviewing data from about 2,000 patients who logged the details of their smoking sessions with the app StrainPrint, researchers were able to see if inhaling cannabis Flower or concentrate could be a solution for headache and migraine relief. They learned that there was, in fact, good reason to be hopeful for the herb.

While concentrates did have a larger reduction in severity rating, there haven’t been enough studies to say it is certainly better than Flower. Overall, inhaled cannabis reduced the severity of migraines and headaches by 50%. Some patients did report needing to use a larger dose for future sessions, indicating the development of tolerance, but the severity of the headaches or migraines wasn’t getting worse or more frequent like what can happen with conventional medications.

In a time when plant-based and all-natural medicines are becoming more sought out, it’s exciting to see medical cannabis is being considered more seriously as a contender. With the positive results from this study, and similar related work will hopefully encourage more physicians (and patients) to explore this centuries-old option.

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Benjamin Caplan, MDHeadache and Migraine Relief Using Cannabis
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Flavonoids Proven to be Safe and Effective Treatment for Chronic Venous Disease

Recommendations for the medical management of chronic venous disease- The role of Micronized Purified Flavonoid Fraction (MPFF)

In Summary:

A recent review has affirmed that treating chronic venous disease with Micronized Purified Flavonoid Fraction (MPFF) therapy is safe and effective. After reviewing 250 papers, the authors have found a large body of supportive evidence that the MPFF treatment, known as Diosmiplex, is effective for healing venous ulcers on its own or in combination with compression therapy. Diosmiplex, the only MPFF prescribed in the United States, as of 2017, is derived from orange rinds and favorable among patients due to its high safety rating. 

Dr. Caplan and the #MDTake:

Flavonoids are one of the categories of natural compounds produced in nature, including within the innate production system of the cannabis plant. Several patients have reported using strong cannabis topical agents to help venous insufficiency and disease, including conditions such as varicose veins, phlebitis, and post-surgical venous incompetence.

varicose veins picture

Process of leukocyte trapping to tissue degradation
contributing factors to  skin pathology and edema
Genetic and environmental risk factors for CVD
US and European Guideline Recommendations that include flavonoids  and MPFF
Cellular Molecular pathology of venous hypertension
CVI Symptom Assessment
WBC adhesion  with venous hypertension
Recommendations for the use of MPFF in the management of chronic venous disease

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Benjamin Caplan, MDFlavonoids Proven to be Safe and Effective Treatment for Chronic Venous Disease
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A Synthetic Flavonoid Derivative May Treat Triple-Negative Breast Cancer

Regulators and mechanisms of anoikis in triple-negative breast cancer (TNBC)- a review

In Summary:

Researchers are always exploring new methods to treat highly aggressive forms of breast cancer. As the scientific culture opens up to cannabis as a natural pharmaceutical factory, eyes have been drawn to the individual chemical components born inside cannabis, namely cannabinoids, terpenoids, and flavonoid compounds. Recently, a group stumbled upon a promising synthetic flavonoid derivative. This derivative, named GL-V9, has been found to have an inhibitory effect on the growth of triple-negative breast cancer (TNBC) tumors and has shown other anti-metastatic properties. The growth-stopping and anti-spreading effects would address two of the central aspects of TNBC that have thus far made it difficult to treat. The growing understanding of flavonoids and their potential therapeutic benefits seem all but sure to enshrine its place among future research regarding cancer treatments. 

Dr. Caplan and the #MDTake:

In scientific and medical circles, it’s not uncommon to hear the phrase, “everything causes cancer.” It’s often repeated contemptuously, a tongue-in-cheek expression that calls attention to unknowns associated with the spawning and growth of cancers but also bends to the hurricane force of nature’s impact on living organisms. As living biology, cancers are born and thrive while provided sustenance by particular inputs and supports. Because of this fact, there are also innumerable opportunities to stifle or prevent the birth of tumors and many avenues to interrupt its growth or end the life of cancer cells.

The human cultural history has taught all cultures that sleep, exercise, fruits, vegetables, fiber, and water are all required ingredients for sustained, healthy growth. What is it about fruits and veggies that is healthy? They have fiber that is healthy for the human digestive tract, but they also have natural components, terpenes and flavonoids, which support wellness, healing, and the normal cycling (features of both living and dying) of our cells. Cancer represents the inappropriate over-replication of cells. In a sense, the body’s natural ability to end the cells which are not responding to normal signals is lost. If we know that the cannabis factory happens to produce many of the same compounds that are found elsewhere in vegetation and fruits, is it so surprising that we would see cancer-fighting effects?

Breast cancer & flavonoids: current research and treatments
Graphical Abstract: anolkis resistance; breast cancer-related chemsitry

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Benjamin Caplan, MDA Synthetic Flavonoid Derivative May Treat Triple-Negative Breast Cancer
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Recent Study Reveals Natural Method for Improved Crop Growth (Microbiome!)

Plant-derived coumarins shape the composition of an Arabidopsis synthetic root microbiome

In Summary:

While investigating plant molecules that inhibit parasitic growth, researchers have uncovered a new method for improving crop growth and overall yield. Small molecules, such as flavonoids and coumarins, improve the microbiome of plant roots in order to help them grow and maintain their health. While investigating how the absence of coumarins and flavonoids affect the growth of a common weed the authors stumbled upon a molecular mechanism that will facilitate efforts to grow crops in iron-deficient soils.

Dr. Caplan and the #MDTake:

The natural machinery of Cannabis supports the production of tremendous numbers of flavonoids, coumarins, and microbiome-supporting compounds. Over millennia, cannabis has evolved fastidious attention to detail, and an integral role in the animal ecosystem. Although this natural role has historically been disagreeable to many oppressive movements (religious and cultural), it is nonetheless, self-evident as modern society returns to embrace the science of cannabis. The scientific, medical, textile, farming, nutrition, recreational, and materials construction industries are all wishing only that they had come back to cannabis sooner.

plant microbiome image

the gnotobiotic platform used to investigate the effect of plant metabolism on root microbiome composition
root coumarins shiting the microbial community of plants
root-excluded purified coumarins shiting the microbial community of plants
purified coumarins shiting the microbial community of plants

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Benjamin Caplan, MDRecent Study Reveals Natural Method for Improved Crop Growth (Microbiome!)
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CBD sold not quite as advertised

Here’s an argument for the need for accountability in #cannabisindustry. What is sold ought to be closer to what is advertised. Is government regulation the solution? 3rd party transparency? Individual accountability? Court of public opinion?

https://www.leafly.com/news/strains-products/cbd-oil-test-results

What this study found for CBD truth to advertising
tested products that delivered CBD as advertised within a 20% margin
visual of what is advertised vs tested with CBD
Benjamin Caplan, MDCBD sold not quite as advertised
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Participants in Cannabis for Chronic Pain Study Describe Life-Changing Results

Restored Self: A Phenomenological Study of Pain Relief by Cannabis

In Summary:

In an Israeli qualitative study investigating the impact of cannabis use on chronic pain patients, all but one of the nineteen study participants experienced pain relief after cannabis use. Participants explained how cannabis allowed them to not just discontinue medications treating their pain, but also medications treating secondary outcomes of their pain, such as poor sleep and anxiety. Patients described feeling “a sigh of relief,” being “reborn” or being saved by cannabis use after years of debilitating pain and medication side effects.

Dr. Caplan and the #MDTake:

The pathway through which cannabis works to combat pain is different from the usual pathways doctors have used for the last 90 years. Prior to the 1930s, cannabis was used routinely, just about everywhere, but political and social agendas kidnapped the medicine and hid it away from most of the mainstream and from routine medical education.

Patients often describe typical pain relievers as adjusting the impact of the pain. Reducing or quieting the pain, softening discomfort, allowing the sufferer to perform previously typical tasks without debilitation or dysfunction. Cannabis, on the other hand, is sometimes described as “taking the sufferer away from the pain,” rather than the other way around. The effects that cannabis can have on the reduction of inflammation, attention, memory, and relaxation, provide a new type of opportunity for relief.

Still, other patients describe the effects of cannabis through a lens of mental focus. Whereas in daily use we typically open a standard set of drawers, some have said, the use of cannabis allows the consumer to open up a different set of draws, and through this adjusted lens, to see discomfort from a different perspective.

For those suffering with chronic pain, years upon years of discomfort, suffering that, when paired with modern medicines, has only met frustration and further discomfort, cannabis is frequently seen as a welcome “sigh of relief.”

different types of  pain
Discussion  from text of research  doc
Sample of text discussing lack of adverse  side effects of cannabis

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Benjamin Caplan, MDParticipants in Cannabis for Chronic Pain Study Describe Life-Changing Results
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Cannabinoids Further Demonstrate Therapeutic Potential in Interactions with Adrenaline and Serotonin Systems

Regulation of noradrenergic and serotonergic systems by cannabinoids: relevance to cannabinoid-induced effects

In Summary:

Among many system-wide interactive effects, the noradrenergic and serotonergic hormone/signaling systems are responsible for pain, mood, arousal, wakefulness, learning, anxiety, and feelings of reward. A recent review dives deeper into the interactions between cannabinoids and these two systems: cannabinoids play roles in exciting, inhibiting, and regulating the nerve activity and feedback of both the noradrenergic and serotonergic systems. This data further underscores the therapeutic potential of cannabis for conditions such as depression, chronic pain, and insomnia, all of which are mediated, at least in part, by these systems. Further research may uncover more specific therapies targeted toward the noradrenergic and serotonergic systems and their interactions with cannabinoids.

Dr. Caplan and the #MDTake:

It would be shocking to imagine that, in addition to the usual fruits and vegetables on display at supermarkets, all of a sudden, there was a new category of healthy food. Similarly, the recognition that cannabinoids play a central role in animal physiology is embarrassingly recent. Surveying a sea of illnesses that have become increasingly common, over the last hundred years, before which cannabis was a common household product, also begs the question about a relationship between the circumstances. Might some of the common maladies of modern medicine be attributable to a cannabinoid deficiency syndrome?

A Schematic overview for regulation of NA/LC and 5-HT/DRN cells by the CB1 receptor
Neurochemical Evidence for cannabinoid-induced effects
Electrophysiological evidence for acute effects of cannabinoids on neuronal activity
Neurochemical evidence for cannabinoid-induced effects in the locus coeruleus
Functional evidence fo cannabinoid-induced effects
Electrophysiological evidence for acute effects of cannabinoids

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Benjamin Caplan, MDCannabinoids Further Demonstrate Therapeutic Potential in Interactions with Adrenaline and Serotonin Systems
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Pre- and Post-natal Tobacco and Cannabis Exposure Impacts Children in a Sex-Specific Manner

Pre- and postnatal tobacco and cannabis exposure and child behavior problems: Bidirectional associations, joint effects, and sex differences

Summary Info:

Prenatal maternal cannabis and tobacco use is predictive of behavioral problems among toddlers. Resulting differences from control groups include anxiety, depression, and attention problems. Female children of mom’s consuming substances, in particular, seem to be more susceptible to problems relating to internalization, attention, and sleep. Additionally, the behavioral problems induced by prenatal cannabis and tobacco consumption often lead to further maternal substance consumption, which frequently exacerbates existing behavioral problems. 

Highlights of study of mother's prenatal and postnatal consumption of  cannabis
Highlights of interplay of mother's prenatal and postnatal consumption of  cannabis with children
Highlights of interplay of mother's prenatal and postnatal consumption of  cannabis with toddlers

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Benjamin Caplan, MDPre- and Post-natal Tobacco and Cannabis Exposure Impacts Children in a Sex-Specific Manner
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