Blood-Levels

Acute THC Consumption Can Be Determined From Breath Concentration

Correlation of Breath and Blood Δ9 -Tetrahydrocannabinol Concentrations and Release Kinetics Following Controlled Administration of Smoked Cannabis

In Summary

A recent study has found a method to determine acute ∆-9-tetrahydrocannabinol (THC) intoxication by analyzing THC concentration in exhaled breath. The more common method of analyzing blood concentration of THC or urinalysis is unable to determine whether THC consumption is acute or chronic as concentrations in blood and urine matrices can remain high long after consumption. By standardizing a method to analyze acute intoxication researchers will be able to determine a legal limit of intoxication for driving or other activities, police officers will be able to better regulate driving under the influence, and hospitals will be able to better treat those who come in with intoxication symptoms. 

This research highlights the importance of standardizing cannabis-induced intoxication levels. People often drive under the influence of alcohol and are frequently the cause of accidents, but have been legally determined to drive as long as their blood-alcohol level is under 0.08. As cannabis is still under-researched and not recognized as a medically beneficial substance by the federal government the standardization of cannabis-intoxication levels has not been formed. As medical marijuana continues to be legalized at state levels local government should take care to implement methods to judge acute intoxication to better protect citizens and allow patients who need to consume cannabis to live their lives as normally as possible. 


The study is available for review or download here

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Benjamin Caplan, MDAcute THC Consumption Can Be Determined From Breath Concentration
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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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Should Oncologists Recommend Cannabis?

Oncologists Should Recommend Cannabis-Based Medicine for Palliative Care

Oncologists are encouraged to recommend cannabis: cannabis-based medicine for palliative care and more

In Summary:

Earlier this June, a review was published that encourages oncologists to recommend cannabis products to their patients as a safe and effective method of palliative care. The opinion piece highlights how cannabis is a useful treatment for a variety of illnesses (nausea, vomiting, sleep, mood, anxiety), and encourages practitioners to prescribe cannabis for their patients so that they can appreciate the safety and effectiveness of the product.  

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Benjamin Caplan, MDShould Oncologists Recommend Cannabis?
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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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Dr Caplan’s response to Surgeon General advisory statement

Last week’s statement by the US Surgeon General

https://www.hhs.gov/surgeongeneral/reports-and-publications/addiction-and-substance-misuse/advisory-on-marijuana-use-and-developing-brain/index.html

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Benjamin Caplan, MDDr Caplan’s response to Surgeon General advisory statement
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Cannabinoid Receptors Play Important Roles in Anti-inflammation, Anti-depression, Immune modulation, and HIV support

Cannabinoid receptor 2: Potential role in immunomodulation and neuroinflammation Review

Summary Info:

Previous research and characterization of cannabinoid receptors (CBs) have consistently demonstrated the therapeutic potential for many medical conditions. CB1, the receptor responsible for the intoxicating (and other psychoactive) effects of cannabis, has demonstrated the ability to modulate concentrations of certain other neurotransmitters, giving it the capability of acting as an antidepressant. Additionally, mice lacking CB1 receptors exhibited increased neurodegeneration, increased susceptibility for autoimmune encephalomyelitis, and inferior recovery to some traumatic nerve injuries. The CB2 receptor is generally attributed to support for modulating the immune system and calming some of the body’s natural, core inflammatory signaling systems. Activation of the receptor has been found to associate with neuroinflammatory conditions in the brain, and in appropriate circumstances, can result in the programming of cell death among some immune cells. This effect points toward a role in communication, inflammation and autoimmune diseases. Furthermore, evidence points to CB2 holding significant potential in HIV therapy. Binding partners of CB2 inhibit the HIV-1 infection and help to diminish HIV replication. Historically, these staggering findings have escaped traditional modern medical understanding. Further investigation into the therapeutic potential of cannabis, with respect to the treatment of inflammation, depression, autoimmune diseases, and HIV is at a minimum, clearly warranted for a more comprehensive understanding of effective medical therapy.

Dr Caplan and the #MDTake:

The main points here no longer seem to be investigational trends, but just pillars of Cannabis Medicine that are embarrassingly new, and poorly recognized by the modern medical establishment. While the bulk of consumers, including patients, may not engage with the science on a molecular basis, by iterative or intuitive science, individuals are diligently discovering what forms of cannabis serve their personal interests more effectively. This is, through a scientific lens, a trial-and-error adventure through products, which have various ratios of cannabinoid-receptor activation or inhibition, that ultimately achieves a similar result, which is a clinical relief for a particular ailment. Does the fact that the process does not begin with a clear understanding of the involved receptors and receptor modulators really matter? If one of the primary objectives of Medicine is to treat and/or ease suffering, and the products are built upon a bedrock of chemical safety (misuse, inappropriate, or misinformed production of products notwithstanding), it should not matter that people discover it by happy accident, or through more direct achievement.

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Benjamin Caplan, MDCannabinoid Receptors Play Important Roles in Anti-inflammation, Anti-depression, Immune modulation, and HIV support
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Vape-Gate 2019: Review of The Risks of vaping

Risks on the Production Side of the Market:

  • Bacteria: Within facilities that lack appropriate oversight, any bacteria present during the manufacturing of a vaped product can be a source of risk for the consumer.
  • Fungus: Similarly, fungus can be a normal part of ambient air and life on earth, particularly around plants and soil. If production facilities do not have state-of-the-science monitoring or control mechanisms to limit mold, fungus can accumulate during the manufacturing process and can be transmitted to consumers.
  • Particles: Nicotine- or cannabis-containing products that are not produced in regulated facilities (home-grown and/or street-sold real or counterfeit products) may contain dangerous solvents, including solutions that contain lipid content that does not belong inside human lungs. Equally concerning, even in states with strict regulatory oversight over cannabis, the regulations may not cover particulate matter which may come into the consumer’s body from the containers that store tested cannabis products. For example, labs across the US have identified particles of vapor cartridge construction materials that become airborne during the heating process of vaporization. There is currently no testing standard for such circumstances. More, the sheer volume of particles emitted by a tool producing vapor is unregulated. With respect to its effects on the lungs, it is likely that there are meaningful differences (and potential risk differences) between a vaporizer which produces a small cloud of particles compared with one that produces a large, dense cloud.
  • Nicotine/E-liquids: Many nicotine vaporizers contain flavoring, coloring, preservative liquids that can be irritating to the lungs and breathing architecture. Non-nicotine liquid mixers can include sugary substances which promote dangerous growth of bacteria, inside the lungs.
  • Supervision: Street or home-produced products lack quality control measures to ensure that they are made safely, and/or contain safe ingredients, and are being delivered inside safe devices. In contrast, most FDA-overseen nicotine products and state-overseen cannabis production facilities limit many risk factors for currently-known threats to health

Risks on the Consumer Side of the Market:

  • Bacteria: Once purchased, products exposed to everyday life can acquire potentially dangerous bacteria after they are produced and sold. When used with poor maintenance practices, or by a consumer with hygiene practices that may add additional risk, bacterial infections can arise.
  • Fungus: Like bacteria exposure and potential infections, mold/fungus can accumulate after a vaping product is purchased. Good maintenance/cleansing practices help to prevent this risk, and appropriate hygiene around the consumption of vaping products typically minimizes this concern.
  • Particulate Matter: When using and re-using vaporizer tools (pens, vaporizer ovens, edibles), foreign particulate matter may break-off from cartridges, or may accidentally enter into products that were previously free of these contaminants. Many of the popular vaporizer cartridges, for example, seem to come from three facilities in China and are sold, worldwide, because of the attractive low price-point. Across the US, lab evidence has discovered evidence of small particles of the cartridges themselves (plastics, metals, other materials.) These particles can cause irritation to, or have toxic local effects on, the lungs. These reactions can certainly stimulate an inflammatory response which is sometimes equally uncomfortable as the offending irritation.
  • Coughing: Vaporizing a product which causes the user to cough excessively can risk the accidental aspiration of bacteria or particles from the mouth. These particles, if small enough, can cause inflammation or infection in the lungs.
  • Nicotine: In addition to the well-documented increased risk of cancer from the consumption of nicotine, this chemical is an irritant to the tissues with which it interacts, causing arterial wall constriction and thickening. It increases blood pressure and heart rate, promotes increased inflammation and suppresses normal immune system function. More, it also artificially elevates dopamine, norepinephrine, and acetylcholine, with poorly understood consequences that are unlikely to be healthy for the lungs.
  • Maintenance: Vaporizing old or poorly-kept products may ignore the very real effects of deterioration of materials which may pose health concerns. A product which is not well-maintained or regularly cleaned may contain infectious particles, irritating particles, toxic elements which may also be found in a pocket or storage container (insecticides, animal poisons, other chemicals which may preserve or protect during production or travel)

Individual Differences:

Between the production and the consumer sides of the vaporization arena, individual differences and outside influences can have a tremendous impact on the experience of vapor. Someone with a history of lung disease may tolerate a very different product than someone without such a history. Similarly, someone with a weakened immune system may have a more difficult time healing from an average exposure (to an irritant or an infectious particle) than someone with different circumstances. These are not likely to explain a large incidence of illnesses, but in addition to the concerns above, they may help explain a smaller portion.


Some of the Medical Illnesses Potentially Associated with Vaping:

1. Pneumonia (bacterial)

2. Aspiration Pneumonia

3. Idiopathic Acute Eosinophilic Pneumonia

4. Hypersensitivity Pneumonitis (extrinsic allergic alveolitis)

Typically this is related to the components of e-cigarettes: nicotine, propylene glycol/glycerol, ethylene glycol, any of >7000 flavorings, metals including tin, lead, nickel, chromium, manganese, and arsenic (have all been found in e-cigarette liquids), also nitrosamines common to tobacco, carbonyl compounds, volatile organic compounds, and phenolic compounds.


General Recommendations for Safer Consumption:

  • Use state-supervised companies, including dispensaries for cannabis-related vaporizer materials, and reputable nicotine suppliers
  • Convection vaporizer ovens that involve safe heating materials (ceramic, glass, quartz) are preferable to vaporizer cartridges.
  • Any means of detaching product from direct contact with a heat source is preferable. For example, stainless-steel containers that hold product, and are then placed into a heating chamber, is likely to be safer than placing product directly against heat.
  • Safe heating elements: chamber-based convection/conduction heating
  • Avoid direct contact with coils, and avoid combustion
  • Use fresh products from state-sponsored dispensaries or stores
  • Avoid products that are repeatedly reused (including vaporizer pens and vaporizer heating tools that stay full of organic material for more than a brief period of time
  • Prefer systems that include the opportunity to easily clean and replace individual used components
  • Use rubbing alcohol to clean any heating tools regularly

In Infographic form :


Sample Reference News Articles:

All about Vitamin E Acetate:

1.

https://www.nytimes.com/2019/08/31/health/vaping-marijuana-ecigarettes-sickness.html?smid=nytcore-ios-share

2.

3.

https://www.washingtonpost.com/health/2019/09/05/contaminant-found-vaping-products-linked-deadly-lung-illnesses-state-federal-labs-show/

4.

https://www.foxbusiness.com/healthcare/electronic-cigarettes-vapes-scott-gottlieb

5.

https://www.cnbc.com/2019/08/26/fake-juul-pods-fill-shelves-after-vaping-giant-pulled-fruity-flavors.html

6.

https://www.latimes.com/california/story/2019-08-25/knockoff-cannabis-products-headache-for-california-legal-weed

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Benjamin Caplan, MDVape-Gate 2019: Review of The Risks of vaping
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A case of an abnormal heart rhythm. Is cannabis to blame?

Article title: Atrioventricular Nodal Reentrant Tachycardia Triggered by Marijuana Use: A case report and review of the literature

Summary:

The effect of cannabis on the heart is not yet well-understood. This report highlights a case of one 40-year-old patient who had, an hour after smoking cannabis, a specific type of cardiac rhythm abnormality (arrhythmia) called atrioventricular nodal reentrant tachycardia (AVNRT).  There is a physical component of this abnormality, an errant track where aberrant rhythms re-enter the heart and can cause rapid heartbeats (tachycardia.) In the discussion, the authors suggest that cannabis use, at higher doses, may stimulate the parasympathetic system, which happens to be involved in electrical current tracks in our heart. The authors further hypothesize that in susceptible people, as in this case, cannabis may affect this electrical pathway in the heart, and may disrupt a stable rhythm.

Dr Caplan and the #MDTake:

Abnormal heart rhythm disorders can be life-concerning conditions, however, there have only been 17 or so reported cases (see Table 1) of life-threatening cases in the medical literature. As it is exceedingly rare, it can be difficult to determine if cannabis is implicated or not.

Clinical Impressions:

Including rare, serious heart conditions, relatively benign circumstances, and conditions related to structural heart disease, arrhythmias are a relatively uncommon condition. Nevertheless, CED Clinic has seen many patients who have atrial fibrillation, a smaller but significant number of patients who have stable low or elevated heart rates, and a rare few with irregularly irregular abnormalities. Some patients have embraced cannabis while anticoagulated (helpful to reduce the risks of potentially dangerous clots), and some who are engaging with cannabis have been treated surgically. The approach to cannabis that most seem to prefer is a slow, gradually increasing dosage routine, where one can become accustomed to low doses, prior to advancing to something which may be more therapeutic, while minimizing the potential cardiac impact. Fortunately, to date, we have observed no grave repercussions that seemed caused, correlated or attributable to cannabis.

ECG showing AVNRT at the time of presentation.

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Benjamin Caplan, MDA case of an abnormal heart rhythm. Is cannabis to blame?
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Is Sativex absorbed in the mouth or gut? To eat or not to eat beforehand?

Article Title: A meta-opinion: cannabinoids delivered to oral mucosa by a spray for systemic absorption are rather ingested into gastro-intestinal tract: the influences of fed/fasting states.

Sativex® spray is made of a 1:1 ratio of THC and CBD. It is marketed for use in the treatment of spasticity in patients with Multiple Sclerosis and is absorbed into the bloodstream through the oral mucosa. This absorption has the benefit of rapid absorption, as it avoids the slow process of digestion which is the typical path of absorption for edibles. This meta-opinion (expert opinion) review argues that Sativex is actually washed down by our saliva and digested through our gastrointestinal tract very much like edibles, and NOT merely absorbed in the mouth via oral mucosa, as the producers suggest. The authors reviewed several research studies which have found that the concentrations of THC and CBD in the body, following administration of Sativex differed if a patient had a meal or not beforehand. This would suggest that Sativex is indeed absorbed in the gastrointestinal tract, rather than merely through the oral mucosa.

How this matters to consumers:

Toward a goal of reproducible dosing and effects, consumers would do well to understand the effects of various methods of absorption. Specifically, it is helpful to know that the effect of Sativex may be delayed if it follows a meal.

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Benjamin Caplan, MDIs Sativex absorbed in the mouth or gut? To eat or not to eat beforehand?
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Flavonoids as Pain Relief

Forget CBD; flavonoids found in cannabis have been found to be 30 times more effective painkillers than aspirin, targeting inflammation at the source and making them great alternatives for pain killers. If produced on a larger scale, they could help get away from the opioid crisis.

http://bit.ly/2TbAxoG

Here, a folder w/ hundreds more specific reviews of the medical benefits of flavonoids: http://bit.ly/2XugfvI

Benjamin Caplan, MDFlavonoids as Pain Relief
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