All posts tagged: cannabinoids

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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Veterans Using Cannabis Medicinally More Likely to have PTSD than Recreational Users

Title: Medicinal versus Recreational Cannabis Use among Returning Veterans

In Summary:

A recent study found significant mental and physical health differences between veterans who use cannabis that they label as “medicinal” use versus those who prefer to label their use as “recreational.” Veterans who feel that they are self-medicating with cannabis, in what they believe fits more closely with a “medical” label are five times more likely to suffer from post-traumatic stress disorder (PTSD), nearly four times more likely to suffer from Major Depressive Disorder, and are more likely to experience Insomnia, or trouble sleeping. Furthermore, a majority of veterans medicating with cannabis suffer from conditions that qualify them to receive a medical marijuana registration card. Even so, they tend to refrain from discussing their interest in access with their doctors, out of fear of losing their valuable VA benefits.

Dr. Caplan and the #MDTake:

Over the years, countless veterans have valiantly and courageously dedicated themselves to missions of support for their fellow men, women, and country. In preparation, training, service, battle, leadership, education, and so many other ways, veterans have given back to their culture in a way few others can. The understanding that they may be shunned by their culture for seeking help, related to the suffering they may have experienced while serving their country, is unconscionable. It is shameful that the government and military have not appreciated and supported the easy opportunity to give back to our veterans, and it is long overdue that the culture gives back to those who have given a piece of themselves so that others may share the liberties they have served to uphold.

group differences between medicinal and recreational cannabis users in diagnoses, cannabis-related problems, reasons for using marijuana, and other health-related and substance use outcomes

characteristics of medicinal cannabis users

characteristics of medicinal cannabis users

characteristics of medicinal cannabis users

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Benjamin Caplan, MDVeterans Using Cannabis Medicinally More Likely to have PTSD than Recreational Users
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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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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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Spinal Cord Injury and Severe Traumatic Brain Injury Patients Use Cannabis to Manage Symptoms

Cannabis Use in Individuals with Spinal Cord Injury or Moderate to Severe Traumatic Brain Injury in Colorado

In Summary:

Spinal cord injury patients report that medical cannabis helped them alleviate many symptoms of their injury including spasticity, pain, sleep disruptions, stress, and anxiety. Traumatic brain injury patients list their reason for use as reducing stress/anxiety and improving sleep. Both groups of patients reported recreational use prior to and following injury for a variety of reasons.

Dr. Caplan and the #MDTake:

Healing from traumatic injuries is never solely a matter of local tissue changes. The injured tissues, and the experience of being injured create ripple effects which can disrupt multiple other organ systems, and the entire experience of normalcy. A chemical stress response is one of the most common (and often adaptive) responses to an injury, but the burden of stress, adapting to a new illness, and associated loss of normalcy and sleep can be disastrous to the process of healing. As anxiety and sleeplessness snowball into daily problems themselves, a kernel of injury sometimes amplifies to become a life-altering change.

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Benjamin Caplan, MDSpinal Cord Injury and Severe Traumatic Brain Injury Patients Use Cannabis to Manage Symptoms
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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.

“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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Informing Doctors and Patients on Cannabis Use for Pain

Paper Title: Cannabis and Pain: A Clinical Review

Although results from many bench-scientific and preclinical animal trials support the use of medical cannabis for pain management, there is not yet an equal body of evidence in human clinical trials. However, this is, in part, due to the fact that, despite millennia of accounts supporting the use of cannabis to treat a large number of medical concerns, in the shorter history of cannabis research, the number of controlled, double-blind, placebo studies are limited, and to some points of view, may not even be possible. Additionally, in an era where increasingly more patients request cannabis therapy from their clinicians, health professionals are catastrophically undereducated on the topic. Furthermore, given the status of the modern opioid crisis, there is a growing need for alternative pain management strategies: states with medical marijuana laws experience significantly fewer opioid-related deaths than states lacking them. Additional research could reduce these deaths further and provide viable alternatives for patients seeking pain management when other therapies have failed. 

Below are interesting clippings from this article, points that are either described eloquently or bring a welcome addition to the ongoing discussion:

Benjamin Caplan, MDInforming Doctors and Patients on Cannabis Use for Pain
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Study Finds “Insufficient Evidence” to Support the Use of Medical Cannabis for Pain Management

In Summary:

In a recent review of systematic reviews and controlled studies, researchers were unable to find sufficient evidence to support the clinical use of medical cannabis or the pharmaceutical formulations for gastrointestinal, cancer, or rheumatic pain, or weight loss in cancer of AIDS. Many data from previous studies were either statistically insignificant or were of low quality. However, the authors did find that existing literature sufficiently supported the treatment of neuropathic pain with cannabis. Additional controlled studies may shed more light on the use of cannabis for general pain management. Interestingly, while the authors do raise two important limitations of the studies that they highlight in the article (inadequate size of some studies and generally limited supply of traditional scientific studies from which to draw conclusions) they do not address some of the more fundamental concerns with the reporting.

Dr. Caplan and the #MDTake:

The limitations of studies in cannabis are numerous and an important consideration for researchers as they study cannabis, and equally essentially to consider for those of us reading the study product. To my personal count, there are at least 40 different types of biases that can skew data in a way that delivers information other than a precise description of actual events. This study, as many like it, presumptuously assumes that, if data doesn’t show a trend that so-mocked “anecdotal” data shows, then surely the anecdote must be incorrect. What if the reviews are simply not yet accurately recording what human iteration has discovered repeatedly for millennia?

The conclusion the review draws follows:

Conclusion: The public perception of the efficacy, tolerability, and safety of cannabis-based medicines in pain management and palliative medicine con- flicts with the findings of systematic reviews and prospective observational studies conducted according to the standards of evidence-based medicine.

BUT…

Is the right question for science to question the validity of the stories that individuals are telling, against an imperfect science of information collection, as well as the limited scope of statistical validity for understanding data? Or is the right task for science to question its own methods of assumptions in discovery and understanding?

On the one hand, we have millions of people calling the color of the ocean “blue.” On the other hand, we have data that tells us that water, in fact, has no color. Similarly, the anecdotes from cannabis consumers are telling a story that is starkly different from the currently available data.

For those interested in combing through a close inspection of the many ways that data can be misrepresented and misunderstood, check out https://first10em.com/bias/

and/or watch the video below:

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Benjamin Caplan, MDStudy Finds “Insufficient Evidence” to Support the Use of Medical Cannabis for Pain Management
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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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