Constitutive Activity of the Cannabinoid CB1 Receptor Regulates the Function of Co-expressed Mu Opioid Receptors
Summary info:
Cannabinoid receptors have been found to regulate the function of co-expressed mu-opioid receptors. Researchers have found data that indicates the constitutive activity within the cannabinoid system reduced the capacity of expressed mu-opioid receptor functions. This research brings to light the possible benefits of modulating opioid consumption with cannabis-based medicines.
Dr Caplan Discussion Points:
One of the interesting discussion points in this paper is a close look at the effects of the CB1 receptor and its capacity to reduce the function of some mu-opioid receptors, through a mechanism different than naloxone. This suggests some appropriate optimism for cannabinoid-based tools in the battle against the worldwide opioid epidemic.
Title: Monoacylglycerol lipase blockade impairs fine motor coordination and triggers cerebellar neuroinflammation through cyclooxygenase-2
Researchers are constantly considering how cannabis may impact the human brain, for better or worse. A recently published work points out a negative effect on the cerebellum, caused by the inhibition of the main enzyme that is used to break down the endocannabinoid “2- arachidonoylglycerol” (2-AG). By inhibiting the degradation of 2-AG, more of the endocannabinoid is allowed to remain in, and act upon, the human nervous system. This abundance of 2-AG results in reduced synthesis of prostaglandins, which produces an anti-inflammatory effect.
Unfortunately, the abundance of 2-AG also results in motor coordination deficits related to the effect on the cerebellum, but the addition of a cyclooxygenase-2 (COX-2) inhibitor (commonly found in many over-the-counter anti-inflammatory medications) reverses these cerebellar deficits.
This highlights the far-reaching capabilities of the endocannabinoid system and at least one powerful angle where researchers could develop medications to indirectly impact the endocannabinoid system. Cannabinoids are still a politically hot topic, but synthesizing drugs that alter the level of endogenous cannabinoids available in the body is an ideal way to study the endocannabinoid system and its therapeutic benefits, without engaging with the red tape that surrounds cannabis. The receptors mechanisms for the endocannabinoid system certainly warrants further investigation.
Tweet: Researchers have recently revealed the negative effects on the #cerebellum caused by the inhibition of the main enzyme utilized for the degradation of the #endocannabinoid 2- arachidonoylglycerol (#2-AG). Learn more at
A Forbes article shedding light on #CBD and its effects on the livers of mice. Dr Peter Grinspoon and Devitt-Lee wisely talk some sense around the lousy methods and insensible dosage used on mice to command sensational headlines. http://bit.ly/2XMP36W
Title: Cyclic vomiting syndrome- Pathophysiology, comorbidities, and future research directions
A recent article has called for the establishment of a multicenter registry in order to learn more about cyclic vomiting syndrome and related disorders. Creating such a registry would provide a database of patients for clinical trial recruitment, research on patient outcomes across different treatment methods, the underlying mechanism for the disorder, and the ability to identify potential biomarkers for the disorder. The registry would expand our understanding of the disorder, on all fronts, and hopefully, reveal the most effective treatment method.
Could such a registry be created while still safeguarding patient privacy?
Highlighted in this article is the similarity of cyclic vomiting syndrome and cannabinoid hyperemesis syndrome (CHS). CHS is often misdiagnosed or goes undiagnosed for an exorbitant amount of time. By creating this registry for cyclic vomiting syndrome and related disorders, including CHS, the same information about genetics, underlying mechanisms, and effective treatments could also be determined.
Finding a genetic basis for cannabinoid hyperemesis syndrome would support patients looking into cannabis-based medicine to decide if cannabis would even be an effective treatment, by allowing them to discover possible side effects to which they might be more susceptible.
A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain ECS
The cannabinoid system provides momentum to develop cannabinoid-based medications to treat inflammatory and neuropathic pain as researchers continue to find promising therapeutic targets. These new targets may lead to the formation of novel pain-relief medications that may serve well to alleviate pain for those suffering from cancer, multiple sclerosis, and fibromyalgia. Cannabis-based pain medicine is also being researched for opioid-sparing effects and effectiveness in reducing the necessary dose of opioids.
Here, an excellent example of how valuable it is for scientific literature to be read critically and thoughtfully. When reporters read, or extract, or convey only partial conclusions, it is all-too-easy for consumers to absorb an incomplete, undigested message. As consumers of journalism, the public deserves a more knowledgeable understanding. Here (http://bit.ly/2KV0jeG), Forbes (Mike Adams) conveys an unfortunate lack of deep consideration in the reporting. Thankfully, a brief quote is conveyed by Dr. Koturbash, who “was quick to point out that the CBD products coming to market may not pose this particular risk” – but this stone-throw of even-handedness falls short to appropriately balance an article already dripping with misgivings and incomplete evaluation of the material at hand.
For a more layered view of the science, the word “gavage,” as was applied to the mice in the study, describes force-feeding animals with a tube down their throats, often taped to mouths which are then kept gaping open. This is meant to simulate the biological processes of eating (different from giving meds IV, for example.) There is no regard to the stress that this process causes the animals, as they are treated as though they are biological CBD-processing machines. In the days where many people are taking 10mg pills of CBD per day, the amounts of CBD that were force-fed to these animals in this study, if translated to humans, would be 4,305mg, 12,915mg, and 43,050mg over 10 days, or 17,220mg, 51,660mg, and 172,200mg in one-shot doses.) For reference, these days, most dispensaries sell CBD in doses of 10mg, 20mg, up to 2-300mg.)
In the study, the authors suggest that they allow animals to eat “ad libitum,” as if to convey that they are treated with a buffet. And yet, the animals being stuffed with 43,050mg (human equivalent) of CBD still lost weight, while others (given 172,200mg (human equivalent) had uneven weight distribution.) To any reader considering these values critically, it must seem absurd to make conclusions about the actions of CBD as what is causing these effects, as if the fact of over-stuffing itself has no impact at all.
An analogy to this study: If you add 17,000 cars (or 172,000!) to a tunnel on the way to the airport, and stuff each car full of way too many people, there might be problematic levels of concern inside that tunnel.
Let’s hope to see more even-handed consideration and reporting from Forbes, in the future.
Here, another study that shows very different results. Instead of overstuffing mice w/ unrealistic amounts, if one administers CBD at sensible doses in the same population of mice, it turns out that CBD could directly reduce alcohol drinking, improve healthy processes in the liver, and alcohol-related brain damage…
“CBD reduces alcohol-related steatosis & fibrosis in the liver by reducing lipid accumulation, stimulating autophagy, modulating inflammation, reducing oxidative stress, & by inducing death of activated hepatic stellate cells” This new study:
Misleading headlines make it seem like this woman may have died of THC overdose, however, we know that it would be nearly impossible to consume lethal amounts of THC, and the coroner clearly made vague, and incomplete assumptions. This, likely feeding into a comfortable, though quite false stigma around cannabis. http://bit.ly/31iwwlK
Benjamin Caplan, MDMisleading Headlines of THC “overdose”
