Update on MS Treatment: The P13K Pathway

We’re living in exciting times; human knowledge of cannabis, cannabinoids, and the endocannabinoid system is surging. If the sheer number of medical journal papers related to cannabis/cannabinoids is any indication, more researchers than ever are choosing to invest their lives and energy in exploring the subject. This, in turn, has allowed individual threads of research to unfold much more rapidly. As would be expected, the findings of one seemingly unrelated study often inform and develop the findings and questions of another. One such thread is that of MS (multiple sclerosis) treatment. We’ve written previously about the concept of using cannabinoids and the endocannabinoid system to treat MS (multiple sclerosis). For readers seeking a full recap, check out the links below: https://cornerstonecollective.com/real-life-cannabinoid-treatment-multiple-sclerosis/ https://cornerstonecollective.com/how-cannabinoids-can-beneficially-interact-with-neurodegenerative-disorder-treatment/ For readers that would rather a digested version, the basic idea is that the endocannabinoid system can control and alleviate inflammation by reducing the number of inflammatory molecules produced by the body. MS, in particular, is a disease in which the body’s immune system becomes confused and starts destroying healthy cells in the brain. If the brain can be pictured as a giant mass of neurons wired together in a network, MS destroys the outer lining of those wires, causing electrical signals to be released improperly or not at all. This process, at the time being, is not reversible or curable but is capable of being slowed. Patients with MS can live long lives, albeit with increasing disability and discomfort. Previous studies have shown that cannabinoids, in particular…

Is Inhaling Cannabis Bad for You?

As it stands, cannabis has proven beneficial to one's health in too many ways to list. The cannabinoids contained in cannabis exert their myriad of health effects in particularly gentle ways, and unlike most other pharmaceuticals, cannabis appears to have no toxic limit in healthy adults. Even so, frequent consumers of cannabis may wonder: is inhaling the smoke of anything, even cannabis, good for my lungs? Am I causing long-term damage similar to smoking cigarettes? The short answer: yes, you should avoid inhaling smoke or any burning material as much as possible. The lungs were not made to filter smoke continuously or really at all. For this reason, previous articles on the blog have discussed vaporizers and the importance of using non-combustive methods of consumption (edibles anyone?). Vaporizers not only improve taste of cannabis, but also virtually eliminate damage caused by smoking. Furthermore, vaporizers are generally able to glean a greater medicinal effect from a smaller amount of cannabis. Frequent users should find the financial investment a no-brainer. However, clever readers may also wonder: aside from the physical reality of inhaling burning material, what effects do cannabinoids actually have on the lungs? As it happens, cannabinoid research points to an overwhelmingly positive relationship between cannabinoids and lung health. In fact, while we are generally cautious of making strong statements, this is one area where we can be reasonably certain that the long-term effect of cannabis consumption is positive, at least from the properties inherent in cannabinoids themselves. A September article…

Teen IQ and Cannabis Use

As the U.S. continues the process of legalizing medicinal cannabis use, state by state, one of the biggest concerns from opponents remains the impact on adolescents. Although teenagers are not actually permitted to consume cannabis in most states, it’s logical enough that easier access and less cultural stigmatization of cannabis may increase rates of adolescent consumption. Factually, we haven’t seen definitive research either way on how cannabis affects adolescents, and lifetime cannabis users statistically have no cognitive impairment. However, as a society, it’s our responsibility to approach the issue carefully, for two reasons. First, as researchers often point out, the teenage brain is not fully formed, and medicines that may be safe for adults may not be safe for youth. The idea is that at the time regulatory patterns are being formed, cannabis use could theoretically alter the baseline balance permanently. Secondly, even a decreased cognitive performance during a temporary time period could hurt adolescents’ chances at higher education, which could be equally devastating. In other words, this topic deserves immediate attention from the scientific community. However, one familiar roadblock stands in the way; it’s difficult to control for conflated variables. Especially in the case of adolescents, those that currently choose to consume cannabis illegally are much more likely to exhibit high-risk behaviors that affect cognitive development (such as other drug use) or to already struggle in school. Performing a simple statistical regression may therefore falsely give the appearance of causation stemming from cannabis use. Thus, true understanding of the…

The Hunt to Establish New Cannabinoid Receptors: G Protein Pathways

For readers of the blog, we’ve always broken the endocannabinoid system down as follows: cannabinoids (from plants, labs, or produced in the human body) cannabinoid receptors (two kinds, CB1 and CB2) enzymes that break down cannabinoids Readers will therefore be surprised to learn that beyond CB1 and CB2, there are likely two other receptors in the human body that are capable of receiving cannabinoids. The scientific community is now informally calling these CB3 and CB4, although since these receptors are active in multiple signaling systems, the naming seems irrelevant. Today, we will focus on the receptor known as “GPR55”. “GPR” and “GPCR” stand for “G protein receptor” and “G protein-coupled receptor” respectively. Both terms mean receptors that are bonding sites for G proteins. G protein receptors are the largest family of signal transducers, with roughly 1000 kinds. These receive hormones, neurotransmitters, odors, light-sensitive compounds, etc. and can be located all throughout the brain and body. In fact, GPCR-creating DNA accounts for almost 3% of our human genome! Readers may not be surprised that GPCRs, with all these applications, therefore account for the target sites of 40-60% of modern pharmaceuticals. However, not all GPCRs are characterized. Researchers have identified around 150 GPCRs with unknown ligands (signaling molecules). Finding a signaling molecule for a new receptor might be akin to finding a needle in a haystack. Imagine sitting in front of a padlock with thousands and thousands of keys and painstakingly trying each one. For this reason, these receptors are referred to…

Medical Marijuana Laws and Adolescent Marijuana Use

One of the biggest hurdles with medical cannabis legislation is convincing the public that new laws will do more good than harm. In California, the rate of adults who have used medical cannabis is reportedly one in 20, which leaves 19 in 20 uninterested (or dishonest on surveys). Assuming the proportion of adults is roughly equal in other states, this means a large majority of voters are not voting with the mindset, “this enables me to use medical cannabis,” but instead voting with the mindset, “this enables others to use medical cannabis.” While those voters may realize the societal benefits of medical cannabis (such as decriminalization and reducing healthcare costs), their primary concerns will still be, “will this negatively affect me or my loved ones?”.  At the forefront of this discussion is the impact of medical cannabis laws on the opinions of teenagers toward cannabis. As reported in a recent study by Columbia University, almost 20% of high school seniors reported they’d be more likely to use cannabis if it were legalized for medical use, with 55% of adolescents believing cannabis would be easier to acquire. As a lawmaker, this is cause for alarm. To determine the best course for society, we must weigh the advantages of medical cannabis against possible disadvantages. However, just because teens believe themselves more likely to use cannabis because of medical cannabis laws does not necessarily make that true. Thus, researchers at Columbia set out to conduct a survey to establish the rate of adolescent…

Better Bladder Health with Cannabis?

The endocannabinoid system might be one of the most fascinating and most complex regulatory systems of the human body. Unlike many other areas of medicine, where basic domains of influence are well established, the endocannabinoid system represents an open, unsettled territory for bold researchers. New effects mediated by the system are being discovered constantly and in some of the most unlikely places. Effects are not limited to activation or deactivation of cannabinoid receptors alone. The system has shown itself capable of affecting the body through other side routes, as exhibited by CBD, which has numerous therapeutic qualities yet a surprisingly low affinity for either type of cannabinoid receptor. As is the case with most scientific research, new questions often arise from unexpected results from other experiments (think post-it notes arising from super glue research). In the case of bladder research, the first studies to indicate that cannabis might be helpful in relieving overactive bladder stemmed from studies of multiple sclerosis (MS) patients. MS can frequently lead to bladder spasms and other incontinence issues as muscles deteriorate. Patients using Sativex (a popular extract of cannabis) noted reduced urinary urgency and number of incontinence episodes. This observation lead to a multi-center study involving over 600 patients who self-reported reduction of bladder issues while taking Sativex. While results of the survey indicated a reduction in problems, self-reported studies are only meant as initial inquiries because they are subject to bias, differing standards, poorly-defined language in questionnaires, etc. However, this study none-the-less encouraged researchers…

THC May Help Break Down Harmful Memories

Lately cannabidiol (CBD) has been hogging the therapeutic limelight; it’s an anti-inflammatory, an anti-tumor, and it helps inhibit psychotic behavior. THC, the psychoactive chemical most prized in the recreational community, has been deemed to have less potential for therapeutic use, in part due to the side effects that accompany dosage. For this reason, much clinical research has shifted toward CBD and away from THC. However, THC’s psychedelic, mindset-altering activity is exactly what lends it therapeutic benefits in situations involving memory and fear consolidation. Fear memory consolidation occurs after a painful memory is acquired, and is the process through which that memory is stabilized in the brain. Although not all aspects are understood, we know that the consolidation process involves strengthening synapses the brain deems useful and paring down synapses the brain deems less useful. Aside from this process, memories are also converted from being dependent on the short-term memory region of the brain to being independent of this region and placed in a longer-term storage area. However, memories are also capable of being re-consolidated and forming new associations. To put all of this into practical terms, someone suffering from Post-Traumatic Stress Disorder (PTSD) stemming from military service may initially suffer injury while hearing an unrelated stimulus, such as a warning siren. The brain may then associate the pain and injury with that sound. Unfortunately, as the individual returns to normal society and hears similar sounds, such as ambulance sirens, those memories and fears may resurface, causing additional pain, aggression, and…

Better Metabolism with Cannabis?

Fact #1: Cannabis use increases caloric intake. Fact #2: Cannabis users on average have lower BMI’s (body mass index) and smaller waistlines than non-cannabis users. Initially, these statements appear to conflict on a basic logical level. With “the munchies” being frequently referenced in popular culture, and with some of the first medical cannabis approvals hinging around appetite stimulation, it’s no secret that cannabis can cause users to eat more than intended. Increased caloric intake should mean increased weight gain. So in what world are these two facts compatible? The answer is…our world. Although weight does relate to caloric intake, ultimately the calories stored in the body depend on how completely the body has turned incoming food into usable energy, a process referred to as metabolization. In large data-based studies, researchers have noticed that cannabis users on average have lower BMI’s and smaller waistlines, which means they are less likely to be obese than non-cannabis users. Until recently, this fact has been viewed as a quirky, unexplained observation. Although data-based studies are wonderful for checking the validity of general correlations, once the data is exhausted, the track is dead. Without more data concerning metabolism specifically, researchers were not sure where to go next. However, in 2013, one research group, from the Harvard School of Public Health, focused on this research target and added another variable to the mix: blood samples. Blood samples allow blood sugar and insulin levels to be measured, which then allows a live read of how bodies are…

Prenatal Exposure and Adolescent Cannabis Use

Today we have a more sobering topic to discuss: the issue of early-onset cannabis use and pre-natal cannabis exposure. Before beginning, we’d like to clarify that the following information applies specifically to cannabis containing primarily THC. The jury is out as to whether CBD-heavy strains, which are not nearly as psychoactive, are harmful for adolescent brain development. In many such situations, treating children with CBD cannabis is the last resort for serious, debilitating conditions that have not responded to pharmaceuticals and pose greater detriment to the child’s health than the possible ramifications of cannabis use. In these cases, the isolation of CBD from THC to avoid any psychoactive byproduct is typically seen. Hence administering cannabis to children might be the best option available to avoid heavy narcotic-based drugs. This article, on the contrary, is about pre-natal exposure and unregulated use of  THC dominant cannabis by adolescents. While research has indicated some limited neural-protective effects of cannabis for adults, the picture seems very different for adolescents, particularly children. Until the age of around 16, major brain structure developments continue to occur, often brought about by hormonal changes in the body. The endocannabinoid system is linked to the endocrine system that controls those hormones, which means that cannabis is capable of affecting brain development during adolescence. The degree and in what way that effect occurs is still being investigated and has not been elucidated as clearly as early-onset alcohol use has. Thus far, we have yet to come across a study that…

How far we’ve come: A History of Endocannabinoid Research

Like many scientific developments, the elucidation of the endocannabinoid system required development in several fields at once. The first developments naturally came in the field of chemistry since in the early 1900’s very little was understood about the actual function of various parts of the brain. Scientists were aware that cannabis must contain a principal active ingredient that creates the psychoactive effects observed. As a result, researchers experimented with ways of isolating that ingredient with manual and chemical methods. Unfortunately, many of these efforts failed and the structure of the chemical now known as THC remained elusive. We now know why this was so complicated for early researchers. Imagine sorting through a box of small, nearly identical objects from twenty feet away. Many of the cannabinoids found in cannabis are almost identical in structure, making it difficult to find a method that only extracts the particular cannabinoid being sought after. This difficulty was compounded by not knowing which, of the over 80 cannabinoids, was responsible for the observed psychoactivity. As a result, for the first half of the 1900’s, separation techniques were too rudimentary to allow progress. This period ended in 1964 upon Raphael Mechoulam’s identification and isolation of THC, which led to a process of manufacturing it synthetically. Just prior, Mechoulam’s research group had also identified the specific structure of cannabidiol (CBD). Mechoulam, like any other scientist prior to his research, had been forced to obtain cannabis and hash samples from police through non-standard and semi-established protocols. This not…

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