All posts tagged: cannabinoids

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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Hope for Cannabis as a Future Treatment for Tourette’s Syndrome

Single center experience with medical cannabis in Gilles de la Tourette syndrome

A small study on adult Tourette’s patients demonstrated a reduction in tics after treatment with medical cannabis. Treatment with cannabis resulted in a global impression of efficacy score of 3.85 out of 5, signifying an improvement of symptoms. However, many patients reported undesirable effects that resulted in their withdrawal from the trial. Cannabis holds potential for Tourette’s syndrome treatment, however, more work is required to better understand what is causing the positive effects and to flush out reproducible benefits while minimizing the undesirables.

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Benjamin Caplan, MDHope for Cannabis as a Future Treatment for Tourette’s Syndrome
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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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Does Cannabis affect blood pressure, heart rate, brain blood flow?

Article title: Acute Cardiovascular Effects of Marijuana Use

The Review:

The authors of this systematic review combed through multiple previously published studies, looking at the short-term cardiovascular effects of THC on the body. The cardiovascular effects they covered included: changes in blood pressure, heart rate, and blood flow to the brain (cerebrovascular circulation).

This review showed that for blood pressure, the results were undecided, as some studied showed a drop in blood pressure, while others did not. For heart rate, the studies showed an increase after consuming marijuana, but quantity and duration were not mentioned. As for blood flow to the brain, only one study showed a potential decrease while the others found no change. The THC percentage of the products used (mainly inhaled ones) ranged from 1.2% to 17.5%.

Dr Caplan and the #MDTake:

This limited review aims to evaluate the effects of THC on blood pressure, heart rate and blood flow to the brain, but it has important limitations. In terms of how the changes were recorded in the studies and the relevant amounts (of what is changing) were not mentioned. For instance, while the study did show that THC may increase heart rate in the short term, it is not clear what the relevance is, what risk this may poses to consumers if any. Past literature has shown that heart muscle can respond to specific cannabinoids, both in the lab and in animals trails. Several case studies have reported individuals with grave reactions, although these concerns have yet to be replicated in a controlled manner, nor correlated with any specific circumstances or components of cannabis. Toward a goal of maximizing safety, caution is likely warranted for those consuming cannabis with known cardiac risk factors (including heart dysfunction, blood pressure concerns, rhythm abnormalities, and others) particularly with regard to the consumption of high THC products.

Clinical Impressions:

Clinically, there is a distinct trend of people who have found heart rate effects with their cannabis use, mostly increased heart rates at the beginning of use (both when first beginning to consume cannabis as well as early on during an episode of consumption.) There seems to be a tolerance to the heart rate effects because many report that this effect wanes over time. There are a clear group of patients for whom cannabis lowers blood pressure, but also groups for who it either has no effect or increases blood pressure. The long-term trend again seems that tolerance plays a role in bringing all extremes to the middle ground. Regarding blood flow, there seems to be a clear increase in local blood flow with topicals and, at least among CED Clinic patients, no observable relationship between cannabis use and blood flow, from a macroscopic perspective.

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Benjamin Caplan, MDDoes Cannabis affect blood pressure, heart rate, brain blood flow?
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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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Exciting New Cannabis Compound with Great Therapeutic Potential

Functionalized 6-(Piperidin-1-yl)-8,9-Diphenyl Purines as Peripherally Restricted Inverse Agonists of the CB1 Receptor

Summary information:

A recent study has developed a synthetic compound that can act as an inverse agonist (a reverse activator) of cannabinoid receptor 1 (CB1.) Considering how prevalent these receptors are in the body, this may serve as a useful treatment for a great many concerns that involve this receptor, and/or for altering the effects of other cannabinoid therapies. The developed compounds are orally bioavailable and peripherally selective for CB1, meaning they can be taken by mouth and can still have action in the periphery of the body, as opposed to simply at the brain’s receptors. The selectivity and therapeutic benefits of these novel compounds present a promising development for the potential treatment of metabolic syndrome, diabetes, liver diseases, and gastrointestinal disorders, to name but a few.

Dr Caplan’s Input:

We have CB1 receptors from head-to-toe, through every organ, and just about everywhere in the body. This article highlights a few interesting points. While we have compounds which can activate a target cannabinoid receptor, the action in this review is actually stimulating an opposite impact (activating the opposite action, or an “inverse agonist” effect.) Also, the concept of targeting central (at the brain) vs peripheral (everywhere else) has not been well-addressed yet in Cannabis Medicine. If we can separate the two targets easily, the options for applications of cannabinoid therapies multiplies, as does the opportunity to eliminate undesirable effects.

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Benjamin Caplan, MDExciting New Cannabis Compound with Great Therapeutic Potential
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The Cannabinoid System Provides Target for Novel Alzheimer’s Treatment

Discovery of novel benzofuran-based compounds with neuroprotective and immunomodulatory properties for Alzheimer’s disease treatment

A recent study has revealed that novel therapeutic methods that modulate the endocannabinoid system may help to treat Alzheimer’s disease. Researchers have isolated two compounds that provide neuroprotective benefits regulated by the endocannabinoid system. This treatment is specifically thought to slow the progression of the disease as it provides anti-inflammatory and neuroprotective effects that would prevent the aggressive degradation of the cholinergic system.  Further research will hopefully continue to expand on findings such as these, toward the development of much-needed medications. 

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Benjamin Caplan, MDThe Cannabinoid System Provides Target for Novel Alzheimer’s Treatment
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Cannabinoid Receptors Regulating the Function of Opioid Receptors

Constitutive Activity of the Cannabinoid CB1 Receptor Regulates the Function of Co-expressed Mu Opioid Receptors

Summary info:

Cannabinoid receptors have been found to regulate the function of co-expressed mu-opioid receptors. Researchers have found data that indicates the constitutive activity within the cannabinoid system reduced the capacity of expressed mu-opioid receptor functions. This research brings to light the possible benefits of modulating opioid consumption with  cannabis-based medicines. 

Dr Caplan Discussion Points:

One of the interesting discussion points in this paper is a close look at the effects of the CB1 receptor and its capacity to reduce the function of some mu-opioid receptors, through a mechanism different than naloxone. This suggests some appropriate optimism for cannabinoid-based tools in the battle against the worldwide opioid epidemic.

Learn more at http://bit.ly/2wRsbbt 

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Benjamin Caplan, MDCannabinoid Receptors Regulating the Function of Opioid Receptors
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Natural & Cannabinoid Changes in Dopamine: A key to the psychosis question?

Comparing dopaminergic dynamics in the dorsolateral striatum between adolescent and adult rats- Effect of an acute dose of WIN55212-2

Brief summary:

A recent study has exposed an age-dependent mechanism within the dopaminergic system that relies on cannabinoid receptor 1 (CB1). Adult and adolescent dopamine levels were examined in the presence of a CB1 agonist and increased levels of extracellular dopamine were found in adolescents. This study reveals the different effects cannabis-based medicine has depended on the age of the patient and warrants future research to ensure cannabis has the desired therapeutic effect on patients.   

Dr Caplan Discussion Points:

This adds a helpful layer of insight to the way an animal model of dopamine changes over time, as well as its interaction with exogenous cannabinoids. This sheds light on the natural evolution of the dopamine control system (irrespective of how it interacts with endocannabinoids), and it also points to how cannabinoids may be involved.

This helps to educate the discussion about how psychosis and cannabis use may interact. There is a long-held understanding that dopamine abnormalities in the specific parts of the brain (mesolimbic and prefrontal brain regions) exist in schizophrenia. More recently, research has also strongly suggested that other neurotransmitters, including glutamate, GABA, acetylcholine, and serotonin are also involved in schizophrenia (and, coincidentally, there is also interaction with these other neurotransmitters from various components of cannabis). Nonetheless, this study simply suggests that, by nature, basal dopamine levels increase during adolescence. Also, the study points out that some cannabinoids boost basal levels too. It seems logical to suggest that excessive dopamine may create a problematic force of additional tipping toward illness, within individuals for whom a congenital predisposition toward illness exists.

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Benjamin Caplan, MDNatural & Cannabinoid Changes in Dopamine: A key to the psychosis question?
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