Sudden cardiac death associated to substances of abuse and psychotropic drugs consumed by young people- A population study based on forensic autopsies
A recent study out of Spain has revealed alarming trends among cases of sudden cardiac death associated with substances of abuse consumed by young people. Half of the 15-36-year-olds who suffered sudden cardiac death were found with illicit substances in their bodies, primarily cannabis, tobacco, and cocaine. Researchers found that although cannabis was the most common substance found in the deceased systems, cocaine and tobacco are known to have a stronger impact on the cardiovascular system and lead to ischemic heart disease, which is often the more acute causes of sudden death. It was also mentioned here that the duration of cannabis is far longer in the body than that of either tobacco or cocaine, and this duration may easily confuse people to associate it as a trigger for sudden death.
However, on the other hand, there are several tragic cases of young, otherwise heart-healthy individuals who have died with cannabis as the only substance discovered. Fortunately, these cases are extraordinarily rare, but unfortunately, no reproducible association has been established, so the mysterious concerns are not easily relieved or forgotten.
Dr. Caplan and the #MDTake:
While the return of medical cannabis to modern medical care seems to bring with it a return of appreciation for more naturalistic care, it is critical for us all to recognize that we still have much to learn. The tools and high standards of scientific evaluation have only recently been applied to cannabis, and there are reasonable arguments that the usual tools may not actually apply (for example, some are suggesting that the placebo effect, a cornerstone of randomized control trials may be a facet of effects related to the endocannabinoid system.)
For these, and a great many other unknowns, it is important for the discerning consumer to consult with trusted resources, including friends, family, scientists, and where possible, doctors, to ensure the appropriateness of use on an individual basis.
“Short- and Long-Term Effects of Cannabis on Headache and Migraine “
There are many headache and migraine medications on the market that advertise how they can make you feel better. But what happens when they make you feel worse? Medication overuse headaches occur in 15% of patients taking conventional migraine medication, so it’s no surprise that people are looking for alternatives that bring them relief without reduced risk.
A team of physicians from Washington University wanted to see if cannabis could be a contender. By reviewing data from about 2,000 patients who logged the details of their smoking sessions with the app StrainPrint, researchers were able to see if inhaling cannabis Flower or concentrate could be a solution for headache and migraine relief. They learned that there was, in fact, good reason to be hopeful for the herb.
While concentrates did have a larger reduction in severity rating, there haven’t been enough studies to say it is certainly better than Flower. Overall, inhaled cannabis reduced the severity of migraines and headaches by 50%. Some patients did report needing to use a larger dose for future sessions, indicating the development of tolerance, but the severity of the headaches or migraines wasn’t getting worse or more frequent like what can happen with conventional medications.
In a time when plant-based and all-natural medicines are becoming more sought out, it’s exciting to see medical cannabis is being considered more seriously as a contender. With the positive results from this study, and similar related work will hopefully encourage more physicians (and patients) to explore this centuries-old option.
Recommendations for the medical management of chronic venous disease- The role of Micronized Purified Flavonoid Fraction (MPFF)
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.
Oncologists Should Recommend Cannabis-Based Medicine for Palliative Care
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.
Cannabis-based medicines for chronic neuropathic pain in adults (Review)
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.
Cannabis Use in Individuals with Spinal Cord Injury or Moderate to Severe Traumatic Brain Injury in Colorado
Spinal cord injury patients report that medical cannabis helped them alleviate many symptoms of their injury including spasticity, pain, sleepdisruptions, 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.
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.“
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/
Cannabinoid receptor 2: Potential role in immunomodulation and neuroinflammation Review
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.
Crossing the Line: Care of a Pediatric Patient with Intractable Seizures and Severe Neuropathic Pain in Absence of Access to Medical Marijuana
A recent case report discussing a six-year-old patient suffering from a seizure disorder has exposed the difficulty is receiving treatment across state lines. The patient was prescribed medical marijuana that alleviated the severity and duration of her seizures but was weaned off of that medication when traveling to Nebraska for a therapeutic surgery, due to the legal status in the state. This case study exposes the difficulty of treating patients across the country due to the legal variability of cannabis across states.
Author’s summary reflections:
“The current state-specific approach to medical marijuana notably burdens patients, families, and health care systems with a fragmented approach to symptom management based on local context. The stigmatization or legal implications of medical marijuana in certain settings may lead well-meaning providers to avoid asking about use or to struggle with appropriate response. Provider response to parents reporting medical marijuana use in Schedule I settings notably varies from direct inquiry, feigned ignorance, or informed ignoring. Ideally, providers would compassionately and competently inquire about pharmaceutical and nonpharmaceutical interventions (to include medical marijuana use) as part of comprehensive palliative care symptom assessments.”
“Pancreatic cancer is particularly refractory to modern therapies, with a 5-year survival rate for patients at a dismal 8%. One of the significant barriers to effective treatment is the immunosuppressive pancreatic tumor microenvironment and development of resistance to treatment. New treatment options to increase both the survival and quality of life of patients are urgently needed. This study reports on a new non-cannabinoid, non-psychoactive derivative of cannabis, termed FBL-03G, with the potential to treat pancreatic cancer. In vitro results show major increase in apoptosis and consequential decrease in survival for two pancreatic cancer models- Panc-02 and KPC pancreatic cancer cells treated with varying concentrations of FBL-03G and radiotherapy. Meanwhile, in vivo results demonstrate therapeutic efficacy in delaying both local and metastatic tumor progression in animal models with pancreatic cancer when using FBL-03G sustainably delivered from smart radiotherapy biomaterials. Repeated experiments also showed significant (P < 0.0001) increase in survival for animals with pancreatic cancer compared to control cohorts. The findings demonstrate the potential for this new cannabis derivative in the treatment of both localized and advanced pancreatic cancer, providing impetus for further studies toward clinical translation.
“From the results of this study, the key findings include, observation that a non-cannabinoid derivative of cannabis can enhance radiotherapy treatment outcomes in-vitro and in-vivo as highlighted in Figures 2, 4. Secondly, the sustained delivery of the cannabis derivative FBL-03G from smart radiotherapy biomaterials (SRBs) results in tumor growth inhibition of both locally treated and distant untreated tumors, with and without radiotherapy. The use of smart radiotherapy biomaterials (SRBs) (8, 23) was recently proposed as a novel approach to deliver cannabinoids, allowing for prolonged exposure of tumor cells to these cannabis derivatives, which is expected to be more effective (10). The FBL-03G payload used in this study is a flavonoid non- cannabinoid derivative of cannabis, and the potential to inhibit both local and metastatic tumor progression is remarkable, especially for pancreatic cancer, with a dismal 5-year survival rate of 8% (1).”
“While the results indicate that sustained exposure of tumor cells to FBL-03G can boost both local and metastatic tumor cell kill, the mechanism of such action needs to be further investigated. One hypothesis is that, FBL-03G can serve as an immunotherapy agent, inhibiting growth of locally treated and untreated tumors, representing metastasis. Metastasis accounts for most of all cancer-associated suffering and death, and questionably presents the most daunting challenge in cancer management. Henceforth, the observed significant increase in survival is promising, especially for pancreatic cancer which is often recalcitrant to treatments. Another hypothesis is that sustained delivery allows FBL-03G to reach the untreated tumor over a prolonged period as well. Either way, the FBL-03G results reveal a new potential non-cannabinoid cannabis derivative with major potential for consideration in further investigations in the treatment of pancreatic cancer, where new therapy options are urgently needed.”
Dr Caplan’s Take:
This article is one in a growing collection of impressive data that highlights a critical area of Medicine that has hidden from the scientific community for decades. The goal of the review is NOT to hail praise on cannabis as a panacea, nor even a sole treatment option, for pancreatic cancer. Rather, it highlights that it seems to be working effectively, both in living tumor cells in the lab and in animal models with live tumor cells. For a devastating illness that currently carries a grim prognosis, the proposition here is to learn more.
The milestones between pioneering scientific study and effective medication are many and there is much work to be done. Studies must be reviewed, criticized, replicated, integrated, before pioneering products can be developed, produced, tested, scaled, brought to market, marketed, sold, and consumed. The process is long, but at least there is a seed of hope at the beginning!