All posts tagged: Anti-Inflammatory Properties

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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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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Extensive Cannabis Studies Underway Globally

Current Status and Prospects for Cannabidiol Preparations as New Therapeutic Agents

In Summary:

As of 2016, upwards of 60 clinical trials relating to the use of medical cannabis were in progress. The scope of clinical trials included conditions such as anxiety, cocaine dependence, infantile spasms, schizophrenia, solid tumor, and many more. The status of cannabis as a Schedule I drug, under the Controlled Substance Act, limits researchers’ ability to freely collect data if they require support from NIH funding. While there are opportunities for researchers to study cannabis and its derivatives with the support of private funds, this typically risks an appearance of sacrificed scientific integrity and independence. Very few private entities would condone research which might shed an unfavorable light on their products. On the other hand, current NIH-funded research requires the use of the national supply of cannabis, a crop well-known to be very limited in quality. Increasingly, more states have been legalizing the medical and recreational use of cannabis in recent years, allowing scientists with more opportunities for private funding in which to shed more light on the vast medicinal benefits of cannabis. Animal models and human trials have pointed toward clinical applications of medical cannabis including anxiety, nausea, seizures, and inflammation, although the array of competing and synergistic compounds within the plant seem to continually open new doors to relief from a large array of illnesses.

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Benjamin Caplan, MDExtensive Cannabis Studies Underway Globally
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Arthritis Sufferers Lead the Way for Advancing Cannabis as Pain Medicine

A Weedmaps News piece, looking earnestly at cannabis and arthritis. As the title suggests, arthritis sufferers are, indeed, leading the way for advancing cannabis as pain medicine.

https://news.weedmaps.com/2019/10/arthritis-sufferers-lead-the-way-for-advancing-cannabis-as-pain-medicine/

“We know cannabis is a powerful anti-inflammatory agent that functions differently from other drugs like Tylenol, Ibuprofen, steroids, or the biological options that work on the immune system and can present severe side-effects,” Caplan told Weedmaps News. “We don’t see that w/ cannabis”

“There is still not enough of what modern medicine calls the gold standard- randomized trials or review trials that collect multiple studies – but anecdote is not meaningless,” Caplan said.

“Stories we hear from individuals are very meaningful and worthwhile,” Caplan said. “We live in a scientific culture that thinks we should discount anecdotes and only pay attention to the highest quality data, which I think is misleading and not fair.”

Benjamin Caplan, MDArthritis Sufferers Lead the Way for Advancing Cannabis as Pain Medicine
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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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Psychiatric Disorders Reduce Survival Among Immune-Mediated Inflammatory Disease Patients

Psychiatric comorbidity increases mortality in immune-mediated inflammatory diseases

Summary Information:

A new study finds that a diagnosis of depression, anxiety, and/or bipolar disorder increases mortality rates for patients of one of three immune-mediated inflammatory diseases (IMID):

1) multiple sclerosis (MS), or

2) inflammatory bowel disease (IBD), or

3) rheumatoid arthritis (RA).

Depression and bipolar disorder can cause poor health behaviors in patients, as depression, bipolar disorder, and anxiety disorders are “associated with increased inflammation and immune dysregulation.” Suicide risk and attempts are increased among IMID patients with mental illness, compared with IMID patients who are not also suffering from one of these additional battles. Given that cannabis has shown promise in treating both inflammation and a range of psychiatric disorders, there is reason to be optimistic for further cannabis research to uncover multifunctional treatment options.  

Dr Caplan and the #MDTake:

Clinically, it’s rare to see medical patients who have only one concern. Sure, there are some who are hoping that cannabis will help them to treat seizures, headaches, anxiety, sleep troubles, or terrible back pain, but more often, it is a combination of several troubles that each add to a cumulative tipping point.

Naturally, very few individual systems act alone. When a body part is injured, sleeping (or not sleeping) effects the course of illness. Similarly, feeling less anxious, or improving sleep, may make symptoms of a struggle with consistent headaches seem more tolerable. Even when there aren’t direct connections between symptoms, a treatment which implements a systemic treatment can have multiplied benefits.

Many patients have found that cannabis offers them a way to attack more than one problem, with a single actor. Some with Diabetes are finding that some formulations are not only helping them reduce blood sugar levels, but also reducing appetite. Similarly, some patients with ADD are turning to cannabis options which may help them focus, without their ability to get to sleep at night.

To a related note, many elderly patients are treated with too many medications. Modern Western medical treatment often compels patients into silos of treatments by isolated specialists, who are not always monitoring the patient as a being beyond individual organ systems. Medications, such as cannabis, which have the opportunity to treat more than one system, without multiplying the risk of potential drug-drug interactions presents a much safer approach to care

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Benjamin Caplan, MDPsychiatric Disorders Reduce Survival Among Immune-Mediated Inflammatory Disease Patients
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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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Student-Athletes are at an Increased Risk for Binge Drinking and Substance Use

Title: Psychological correlates and binge drinking behaviours among Canadian youth- a cross-sectional analysis of the mental health pilot data from the COMPASS study

A recent study has examined data from the COMPASS program and found that student-athletes in Canada were more likely to engage in binge-drinking and illicit substance use. Researchers focussed on the measure of flourishing, defined as an overall healthy mental state and emotional connectedness, and how flourishing related to concerning drinking and substance use behavior. Student-athletes were found to be the most at risk for binge-drinking, defined as consuming 5 or more drinks in a single session, and those more likely to binge-drink were also more likely to co-use illicit substances. This research provides evidence for the formation of targeted prevention programs.

Cannabis use is banned among athletes by most sports organizations. Cannabis appeals to athletes considering the many different consumption methods, allowing discreet consumption and personalization with variable potential opportunities for relief. Cannabinoids are generally naturally occurring substances unless clearly manufactured, and have been shown to be beneficial for post-workout recovery, muscle soreness, anxiety, sleep, and relaxation. All of those symptoms, including the emotionally driven ones, are common among student-athletes who often feel an immense amount of pressure to perform in competition. As in most other areas of modern culture, Cannabidiol (CBD) finds itself in a grey area for most sports organizations’ substance regulations given that it is not intoxicating and readily available with a notable safety profile. Even if cannabis is not federally legal, CBD is so widely available that many athletes are embracing it, in lieu of more dangerous, or potentially addictive, medications.

Tweet: A recent study has examined data from the #COMPASS program and found that #studentathletes in Canada were more likely to engage in #binge-drinking and illicit substance use. Read this and other linked studies:

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Benjamin Caplan, MDStudent-Athletes are at an Increased Risk for Binge Drinking and Substance Use
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Genes in the Endocannabinoid and Opioid Systems may Provide Biomarkers of Obesity

Title: Preclinical and Clinical Evidence for a Distinct Regulation of Mu Opioid and Type 1 Cannabinoid Receptor Genes Expression in Obesity

Researchers have recently found that alterations of the type 1 cannabinoid receptor gene (CNR1) and mu opioid receptor gene (OPRM1)  contribute to the development of obesity. This phenomenon was shown in rat models who were given a high-fat diet and humans currently dealing with obesity. Due to the possibility of the up-regulation of CNR1 and OPRM1 providing a mechanism for developing the obesity phenotype, those two genes could serve as biomarkers for obesity. Fortunately, the up-regulation of CNR1 and OPRM1 is reversible and may also provide a target for combatting obesity and encouraging weight loss in obese individuals. 

Highlighted here are the interactions of the endocannabinoid and opioid systems. Contradictory evidence concerning the interaction of the two systems has come out in recent years making it difficult to come to any conclusions. The endocannabinoid system has been thought to provide a safe and effective method for combatting the opioid crisis. Opioids are highly addictive and dangerous, but they are an efficient way to minimize pain which has kept them in mainstream medicine. Opioids have led to countless overdoses in recent decades causing researchers to search for a more ethical option for pain relief. Cannabis has a much better safety profile, poses no risk of overdose, and offers a welcome change of pace to traditional choices. Conclusive research is still needed to confirm, and reconfirm the details.

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Benjamin Caplan, MDGenes in the Endocannabinoid and Opioid Systems may Provide Biomarkers of Obesity
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Cannabinoids Treat Chronic Gastrointestinal Disorders

Title: Nabilone administration in refractory chronic diarrhea- a case series

A new study reveals the efficacy of treating chronic gastrointestinal disorders with cannabinoids, such as Nabilone. Researchers followed case studies in which patients were given nabilone which greatly reduced symptoms of chronic diarrhea and weight gain, over a period of three months.

The cannabinoid treatment also reduced the abdominal pain felt by patients and improved their overall quality of life. Considering the favorable safety profile of cannabinoids and the effectiveness demonstrated in the patients, cannabinoids were deemed an appropriate and clinically beneficial method for the treatment of chronic gastrointestinal disorders, such as chronic diarrhea. 

Highlighted by this article are the many symptoms cannabis used to treat before the prohibition of cannabis and the scheduling of the medication under the Controlled Substances Act. Cannabis has been used in eastern medicine, for thousands of years, and used to be a prevalent medication in the late 19th and early 20th centuries, and has just recently been re-recognized as an option to treat anorexia associated with human immunodeficiency virus (HIV), nausea and vomiting due to chemotherapy, and various sleep disorders. Cannabis was once a well-recognized medication, but it has been mercilessly slandered by politicians. The rise and fall of cannabis have largely been politically driven pushes, and the plant and its effects deserve further study to examine the scope and efficacy of its therapeutic benefits. 

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Benjamin Caplan, MDCannabinoids Treat Chronic Gastrointestinal Disorders
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