TRP Channels
Maybe because most of us are still trying to organize our thinking about CB1 and CB2 receptors, we haven’t yet read the papers about Transient Receptor Potential (TRP) channels and how scientists are beginning to understand how cannabinoids activate them.TRP channels mediate a variety of neural signaling processes implicated in the sensation of temperature, pressure, and pH, as well as smell, taste, vision, and pain perception.Many diseases involve TRP channel dysfunction, including neuropathic pain, inflammation, and respiratory disorders.To date, six TRP channels from the three TRP subfamilies ( TRPV, TRPA and TRPM) have been reported to mediate cannabinoid activity: TRPV1, TRPV2, TRPV3, TRPV4, TRPA1, and TRPM8. The increasing set of data that has been reported regarding cannabinoid interactions with these receptors has prompted some researchers to consider these TRP channels to be “ionotropic cannabinoid receptors.”Move over CB1 and CB2 receptors! You will now need to share the limelight with TRP receptors. Scientific studies conducted over the last ten years demonstrate significant overlap between cannabinoids and ligands of TRP receptors.If you are a scientist, instead of reading our summary you may want to skip directly to the scientific paper published on January 15, 2019 in Frontiers in Molecular Neuroscience titled, “Cannabinoid Ligands Targeting TRP Channels” by Muller, Morales and Reggio at UNC-Greensboro. The paper cities over 60 other scientific papers. https://www.frontiersin.org/articles/10.3389/fnmol.2018.00487/full Chronic Pain
CBDV, CBD and other cannabinoids may soon be deployed to combat chronic pain in ways far beyond our current expectations for these naturally occurring molecules. Based on scientific evidence and hopefully soon clinical trials. As has been established from the physical evidence in ancient tombs in Egypt and archeological sites in China, cannabis sativa has been used by mankind for thousands of years to treat ailments including chronic pain. Extensive literature provides substantiation of various phytocannabinoids as pain modulators via different modes of action, now including TRP channels. Chronic pain is a heinously evil form of constant torture. It is a notoriously complex problem involving many different conditions, symptoms, and pathways. Unfortunately and regrettably in far too many cases, the most common as well as effective approach of treating chronic pain is with opioids. Addiction and many other negative long-term consequences have locked many innocent but unlucky people who have chronic pain into opioid addiction and ruined lives or worse. A total of six TRP channels have been discovered in the dorsal root ganglia (DRG) that can also be found in primary somatosensory neurons. They are participants in the complex system in our bodies that generate painful sensations from thermal, mechanical, or chemical stimuli. Researchers are targeting them in the development of treatments for chronic pain disorders. Of note because some may be familiar with them, capsaicin-based creams have been used for chronic pain. They desensitize TRP channels but their pungency can cause vascular and respiratory side effects from systemic administration thereby limiting their usefulness. And now the great news about how naturally occurring cannabinoids may be deployed to combat chronic pain, in the authors’ own words: “Targeting the endocannabinoid system has been shown to be a promising strategy for the modulation of pain (Woodhams et al., 2017). In fact, activation of the cannabinoid receptors CB1 and CB2, as well as inhibition of endocannabinoid deactivation (blockade of endocannabinoid uptake or degradation) has shown antinociceptive responses (Guindon and Hohmann, 2009). Pharmacological evidence suggests that cannabinoids and endocannabinoids target more than the canonical cannabinoid receptors (Morales and Reggio, 2017; Morales et al., 2017, 2018). There is evidence suggesting that some TRP channels (TRPV1-4, TRPA1, and TRPM8) can be modulated by cannabinoids, providing and promising multitarget approach for the treatment of pain. Interestingly, CB1 has been suggested to colocalize with TRP channels such as TRPV1 in sensory and brain neurons (Ahluwalia et al., 2003; Price et al., 2004; Cristino et al., 2006), while CB2 colocalizes with this channel in sensory neurons and osteoclasts (Anand et al., 2008; Rossi et al., 2009). This expression pattern makes concerted actions possible to modulate nociceptive responses, as well as a synergistic functional effect of cannabinoid ligands.” The scientific paper goes on and on in exquisite detail about TRP channels and concludes: “This information is the first step in understanding the importance of ionotropic channels to cannabinoid effects, such as analgesia for chronic pain. However, there is much more that needs to be discovered.” Andrea Holmes, PhD, PPM’s CGO and one of our research scientists, conducted a scientific literature survey with the following findings about cannabinoid molecules and specific
TRP channels: TRPA1 CBD, CBDA, CBG, CBC, and D9THC
TRPM8 CBG
TRPV1 CBD
TRPV2 CBD, CBN, D9THC
TRPV3 CBD, CBGV, CBGVA, THCV
TRPV4 CBDV, THCV, CBGV, CBGA, CBN, CBG Chronic pain and the associated over use and addiction to opioids is ghastly cost to individuals and their lives, to their families, and to society – this tragedy has finally been recognized in the last few years. It appears increasing number of patients will self-medicate with phytocannabinoids even without traditional clinical substantiation. In due course, chronic pain sufferers will be offered a plethora of phytocannabinoid-based remedies and products, possibly complemented by other naturally occurring bioactive molecules as well as traditional pharmaceutical drugs, that will provide better outcomes and higher qualities of life and far less negative consequences. Another recent paper that you may find enlightening if you are a scientist and inscrutable (other than its summary and conclusion) if you are a layman was published in January 2019, “Diverse TRPV1 Responses to Cannabinoids”: https://www.tandfonline.com/doi/full/10.1080/19336950.2019.1619436 What Makes PPM Unique: For several minor cannabinoids, including 100% hemp-derived CBN, we believe PPM is the only domestic producer of these naturally occurring minor cannabinoids selling kilos consistently and into highly demanding large company supply chains. PPM is led by a team of advanced-degreed scientists with pharmaceutical industry and university research backgrounds representing over 100 years of chemistry and plant medicine experience. PPM is committed to advancing the science and providing innovative true whole hemp plant extracts with fully customizable cannabinoid profiles, and minor and rare cannabinoid-based ingredients, both 100% hemp-derived and biosynthesized from hemp plant precursors versions including CBN, CBC, CBT, CBDA, THCV, CBDV, etc. to leading consumer product supply chains worldwide. Clean. Consistent. Compliant. Every day, every team member at PPM is inspired by the possibilities of plant-based medicine and remedies, and Mother Nature’s genius. Contact:
Krystle Jarrett
(303)319.6885
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