Neuropathy

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-clinical Evidence for Analgesic Effects of Cannabis Doesn’t Match Human Trial Results

Current evidence of cannabinoid-based analgesia obtained in preclinical and human experimental settings

In Summary:

Pre-clinical animal models of pain provide a wealth of data supporting the pain-relief capabilities of cannabis; however, reproducing this data in human clinical trials has proved difficult. Data from the animal pre-clinical trials point to cannabinoids reducing stress responses and pain-evoked stress, desensitizing pain receptors, and increased pain sensitivity in animals that lack cannabinoid receptors. However, human trials present conflicting results: several studies have shown dose-dependent relationships, and in the current review this was experienced by many participants, wherein lower and medium doses provided pain relief, but higher doses triggered increased sensitivity to pain. Controlled studies may show a lack of impressive pain relief effects, personal reports of pain relief associated with cannabis use are nearly universal in retrospective reports. This suggests that there may be an important effect on well-being or mood, rather merely sensory pain. Furthermore, the relieving effects of cannabis appear to impact men and women differently.

Dr. Caplan and the #MDTake:

Additionally, much of pain relief is subjective, in both sensation, description, and inside the study environment. The description of pain varies from person to person, and researchers may be asking the wrong questions to the right people or the right questions to the wrong people. In fact, a growing perspective is that this mismatch may be more common and more pronounced than previously recognized. The makeup of pain is also quite complicated. For instance, a limb might hurt, but if there is swelling or tenderness nearby, those may amplify the discomfort. How can we take the full picture into account in the form of helpful data points? What of the emotional or psychological impacts of pain? Is it even possible that such things can be fully understood, let alone measured reliably? Assuming that emotional phenomenon or stress/suffering can be conveyed to research scientists, how can we ever hope to compare one person’s experience to another’s? For example, one would imagine that frustration associated with the pain experienced by a venerable world war veteran, who has previously endured tremendous and complex pains and associated psychological trauma may be quite different from someone who has never experienced a particular pain before.

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Benjamin Caplan, MDPre-clinical Evidence for Analgesic Effects of Cannabis Doesn’t Match Human Trial Results
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Many Chronic Pain-Related Cannabis Studies Lack “High-Quality” Evidence

Cannabis-based medicines for chronic neuropathic pain in adults (Review)

In Summary:

In a recent Cochrane meta-analysis of studies investigating the use of medical cannabis for chronic neuropathic pain management, the authors determined that no results were what they could consider “high quality.” All data which related to degrees of pain relief, adverse events, and “Patient Global Impression of Change” were largely of very low or low quality, with some outcomes being of moderate quality. The meta-analysis concluded that no existing evidence backs up the use of cannabis for chronic neuropathic pain; however, the quality of evidence examined highlights the need for more controlled studies.  

Dr. Caplan and the #MDTake:

Depending on the system of organization one prefers, pain can be divided up into different subtypes. For one system, it’s three subtypes: neuropathic, nociceptive, and “other.” For another system, pain can be organized by timing (sharp, acute, chronic, breakthrough), location (bone, soft tissue, nerve, referred, phantom), or by the relative system (emotional, cancer, body.) This review discusses the subtype category of “neuropathic pain” as a means of grouping pain to study. The measures used to assess the pain are as subjective as the categories themselves. Clearly, compounding the two subjective divisions is unlikely to produce “high quality” data, but it is a misleading interpretation to take away that there is no good quality information to glean from the observations this review organizes, and also a misinterpretation to jump to an idea that cannabis is not helpful. Rather, given the statistical tools we currently use, and the subjective systems of understanding pain are not well-matched to translating the effects of cannabis on pain into this type of data.

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Benjamin Caplan, MDMany Chronic Pain-Related Cannabis Studies Lack “High-Quality” Evidence
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Medical Marijuana Offers Benefits Comparable to Prescription Medication, Without the Side Effects

Title: Preferences for Medical Marijuana over Prescription Medications Among Persons Living with Chronic Conditions: Alternative, Complementary, and Tapering Uses

In a survey of 30 patients using medical cannabis for a range of diseases including rheumatoid arthritis, cancer, hepatitis C, PTSD, among others, patients reported an array of benefits they have reaped from cannabis use. Patients successfully used cannabis in several ways: as an alternative to prescription medication, complementarily with prescription medicine, and to gradually replace use of prescription medication.

Benefits described by participants included the effects of cannabis lasting longer than that of opioids, lower risk of addiction, fewer side-effects. Patients also saw their sleep, anxiety, appetite, and adverse reactions improve with the use of medical cannabis. Larger, more controlled studies may suggest cannabis more affirmatively as an alternative or complementary therapy with prescription medications.

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Benjamin Caplan, MDMedical Marijuana Offers Benefits Comparable to Prescription Medication, Without the Side Effects
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New Developments of Cannabinoid-Based Drugs

Title: Novel approaches in clinical development of cannabinoid drugs

A pamphlet has recently been published that highlights new approaches in the clinical development of cannabinoid-based therapies. The pamphlet begins with a look into how current cannabinoids affect patients based on gender, stress, physiological variations, and also delves into how cannabis works on the body in general.

A novel therapy that features an oral version of tetrahydrocannabinol (THC) and a synthetic activator of cannabinoid-receptor-1 (CB1) is explored in this piece and frames it to be a promising future therapy. The pharmacological properties of these two novel therapies were optimized during development after various analysis techniques, forming medications that the authors hope to see in future clinical trials. 

Although the authors remain hopeful that their cannabis-based therapies will reach clinical trials soon, trials featuring cannabinoids are difficult to test in a formal setting because of a dire lack of funding. The federal government still lists cannabis as a Schedule I substance, under the Controlled Substances Act, meaning that the federal government does not support the idea that cannabis has any medical use. Considering the legal status of cannabis, only privately-funded studies are able to take place, and unfortunately, that leaves cannabis research in an area of complete bias and prohibitively underfunded. Considering the massive literature supporting a myriad of novel therapeutic benefits, this is a costly reality to the health and well-being of millions.


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Benjamin Caplan, MDNew Developments of Cannabinoid-Based Drugs
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CB1 and CB2 receptors play differential roles in early zebrafish locomotor development

Scientists found that blocking CB1 receptors and CB2-receptors in young zebrafish resulted in morphological deficits, reductions in heart rate, and non-inflated swim bladders. These findings indicate that the endocannabinoid system is pivotal to the development of the locomotor system in zebrafish, and that disturbances to the endocannabinoid system in early life may have detrimental effects.

The translation of these effects to humans is obviously not direct, but it is important for science to learn about safety and expected effects, to examine how chemistry interacts in petri dishes, how basic organic/animal functions are impacted in a living thing, and when the time is appropriate, to then assess any effects in humans

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Benjamin Caplan, MDCB1 and CB2 receptors play differential roles in early zebrafish locomotor development
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Video: Do-It-Yourself Cannabis Tinctures

One of the terrific realities of modern Cannabis is that it is possible, and often quite simple, to make effective products at home. With suitable education and access to testing facilities, the soil, nutrients, and plant growth can be supported at home, lab-tested for make-up and potency, as well as safety-checked for potential microscopic contaminants, and ultimately, individualized medicine can be created right at home!

Here is a sample instructional for just one way that cannabis tincture can be made at home. There are countless others and hopefully, many that are yet to be discovered!

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Benjamin Caplan, MDVideo: Do-It-Yourself Cannabis Tinctures
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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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