All posts tagged: Adult

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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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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Cannabis Use for Medicinal Purposes is No New Phenomenon

Article Title:

Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history

In Summary:

Although medical cannabis has only lately become more popularized, its use dates back to as early as 3,000-10,000 B.C. According to evidence in ancient texts and glyphs, Cannabis sativa was used to treat fatigue, rheumatism, and malaria, as well as numerous other common maladies. Around 60 B.C., Assyrian clay tablets and Egyptian Ebers Papyrus document ancient Egyptian women using C. sativa for pain management and to improve their mood. More recently, nineteenth-century English doctors prescribed cannabis to reduce pain, inflammation, nausea, and seizures, and to soothe difficulties of menstruation. In a shock to the human historical trend, both England and the United States moved to prohibit its use in the 1930s, creating steep barriers for its therapeutic use, and an enduring smokescreen for the memory of its historical continuity.

Dr. Caplan and the #MDTake:

The history of cannabis use is often shocking to modern consumers, who have grown up hearing the biased views of the 20th-century leaders. A testament to the powerful reach of political propaganda, even medical schools adopted the rhetoric of the age, without second-guessing. Fortunately, the march of oral history and social spread of cannabis use perpetuated a very different, much less menacing tale. Now, it is time for the sophistication of modern medicine to catch up and lift cannabis understanding and consumption to modern medical standards.

History of Cannabis YouTube playlist: bit.ly/CEDCannabisHistory

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Benjamin Caplan, MDCannabis Use for Medicinal Purposes is No New Phenomenon
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Could Inhaled Cannabis Be More Effective to Relieve Pain than Oral Cannabinoids?

Cannabis for Chronic Pain: Challenges and Considerations

In Summary:

Comparisons between the use of inhaled cannabis plant versus pharmaceutical-grade oral cannabinoids demonstrate an advantage of inhalation over oral delivery. Conditions for which inhalation has provided superior over oral consumption include:

HIV, diabetic neuropathy, post-herpetic neuralgia, complex regional pain syndrome, spinal cord injury, traumatic neuropathic pain, multiple sclerosis, and cervical disk disease.

An important note: patients consuming cannabinoids orally are more likely to withdraw from studies due to negative side effects and lack of efficacy. Also, edible cannabis may compete, amplify, or have effects delayed, when interacting with other ingested foods and drinks, A major advantage of inhalation is the opportunity for patients to titrate, or easily test varying dosages at home, with reasonably rapid feedback. On the other hand, dosage adjustments for oral food-borne cannabinoids are much more complex, and cannabis in the form of oral pharmaceutical-products may require a doctor visit and a new prescription.

Dr. Caplan and the #MDTake:

In the clinic, there seems to be a great divide in the population, a group of patients who simply adore the edibles (often in low-dose candies, low-dose chocolate, or titrated tinctures), and a group who use inhalation, almost exclusively. There are also some who are discovering topicals (salves, patches, lotions). There is a growing number of patients who use each of these methods with intention, related to their timing of onset and their duration of action, but this requires education, practice, and a degree of sophistication in use that is relatively new to the industry.

As with most consumption, medicinal or not, it seems common for individuals to find a method that they enjoy and stick to it. Interestingly, in recent years, the US cannabis industry has evolved in a wild growth phase. As it has embraced a dynamic landscape, with increasing competition from all sides, including new stores and product offerings popping up all the time, there seems to be a growing openness, in consumers, to trying new products and exploring new offerings. Coincidentally, this openness to change and the unfamiliar happens to mirror one of the core neurobiological functions of cannabis in the brain, as seen across the neuropsychiatric and neuroimaging cannabis literature.

How exciting to imagine a future medicine that may help consumers to be more open to change?

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Benjamin Caplan, MDCould Inhaled Cannabis Be More Effective to Relieve Pain than Oral Cannabinoids?
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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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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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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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