Tag: Minor Cannabinoids

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ICRS 2023: Report from Toronto

Toronto skyline

I counted over 175 talks and posters at the 33rd annual gathering of the International Cannabinoid Research Society (ICRS), which convened in Toronto at the end of June. In accordance with longstanding ICRS policy, all speakers presented new findings and data that had not yet been published in a peer-reviewed journal. But this year’s 4-day ICRS conference was notable not only for its cutting-edge science. It was also the first ICRS meeting since the passing of its cofounder and guiding light Raphael Mechoulam.

Several colleagues paid homage to Mechoulam in a moving memorial session that honored his many contributions to the burgeoning field of cannabinoid science, which has grown to encompass numerous academic and clinical disciplines. The wide range of topics addressed at the conference is both a reflection of the endocannabinoid system’s ubiquitous role in health and disease and a testament to the enduring mysteries of plant medicine.

CBD & THC

Cannabidiol (CBD) figured prominently in several noteworthy oral presentations and posters that explored the therapeutic potential of plant cannabinoids from various angles. A few highlights:

CBD for breast cancer recovery. Researchers from McGill University in Montreal reported a case study of a 52-yr-old breast cancer survivor who experienced significant improvement in neuropathy symptoms and quality of life following self-administration of 300 mg/day of CBD isolate for six weeks.

CBD for post-concussion syndrome. John Patrick Neary and a team of scientists in Western Canada examined CBD’s impact on 3 female patients who suffered from post-concussion syndrome. They found that cannabidiol helped restore blood pressure dynamics and improve cardiac function in patients who consumed doses as low as 50 mg/day or as high as 400 mg/day.

CBD for psychosis.Dutch scientists from Utrecht University reported that impaired functioning of the brain’s default mode network “likely contributes to psychosis vulnerability.” They found that a CBD treatment regimen of 600 mg daily for four weeks attenuated dysfunctional default mode connectivity in a study of 31 recent-onset psychosis patients.

THC better than CBD for obesity. Israeli scientists assessed the impact of chronically administered CBD and THC on obesity and related metabolic disorders. Given the appetite-arousing qualities of cannabis (“the munchies”), it seems paradoxical that the “prevalence of obesity and metabolic diseases are lower in cannabis users compared to non-users,” the Israelis noted. Experiments on mice yielded biphasic results: 10 mg/kg of purified THC stimulated weight gain and impaired glucose-tolerance in mice, but 30 mg/kg of THC had the opposite effect, leading to a reduction in weight gain and improved glucose-tolerance. While CBD treatment enhanced glucose-tolerance regardless of weight gain, THC showed greater promise as an anti-obesity compound, according to this study. The researchers concluded that “chronic oral consumption of sufficient concentrations of THC, but not CBD, ameliorates diet-induced obesity and . . . metabolic disorders.”

Sufficient concentrations of THC, but not CBD, reduces diet-induced obesity and metabolic disorders.

CBD-rich cultivars for anxiety. University of Colorado researcher L. Cinnamon Bidwell examined the effects of three cannabis chemovars with different THC:CBD ratios. Not surprisingly, the CBD-dominant chemovar with little THC was associated with significant reductions in anxiety and tension among cannabis users as compared to the THC-dominant and the mixed THC:CBD chemovars.

Cannabis and cortisol. Washington State University researchers probed the chronic and acute effects of cannabis use on human cortisol rhythms. “Stress relief is the most cited reason for habitual cannabis use,” they noted in their assessment of how cannabis consumption impacts levels of cortisol, a stress-related hormone. “We found a significant decrease in cortisol concentrations following acute cannabis use,” they concluded. “These findings corroborate cannabis users’ self-reported experience of decreased stress following cannabis use.”

CBG and CBC. Preliminary results from a “double-blind, placebo-controlled, crossover, field trial” underscored the anxiolytic, stress-relieving, and memory-enhancing potential of cannabigerol (CBG), which produced greater reductions in anxiety than placebo. Cannabicromene (CBC), another minor phytocannabinoid, was reported to exert effects through various pathways, including the CB2 cannabinoid receptor, ion channels TRPA1 and TRPA4, and the nuclear receptor PPAR-gamma.

Pain, Opioids & Addiction

Pain, opioids, and addiction comprised a major area of focus at ICRS 2023. Much of this research involved animal models and other preclinical experiments that shed light on the subtleties and inner workings of the endocannabinoid system. Medical scientists, for example, at Mount Sinai’s Department of Psychiatry and Neuroscience probed the neurobiological underpinnings of CBD’s ability to attenuate opioid relapse. Building on their previous work, which showed that CBD lessens cue-induced heroin-seeking in an animal model of relapse, the Mount Sinai lab identified “discrete biological pathways impacted by heroin” in the nucleus accumbens (NAc), the brain region that regulates motivation and reward: “Bioinformatic analysis revealed that CBD reversed a number of metabolic and cell signaling pathway alterations induced by heroin particularly in the NAc shell.”

Neuroscientists at Indiana University explored how allosteric modulation of the CB1 cannabinoid receptor affected opioid self-administration and relapse. Allosteric modulators can either enhance or weaken how a receptor signals. A negative allosteric modulator (NAM) — a synthetic research compound identified as GAT358 — reduced the reinforcing properties of morphine by altering the shape of the CB1 receptor and weakening its signal. This approach might “represent a viable therapeutic route to decrease opioid addictive behaviors and relapse,” the scientists surmised. The same lab reported that GAT358 suppressed “opioid-mediated unwanted side effects including tolerance and withdrawal” but did not block opioid analgesia.

The wide range of topics at ICRS is both a reflection of the endocannabinoid system’s ubiquitous role in health and disease and a testament to the enduring mysteries of plant medicine.

CBD, it should be noted, also acts as a negative allosteric modulator at the CB1 receptor, meaning that CBD doesn’t cause the CB1 receptor to signal (like THC does) but CBD influences how it signals. If the CB1 receptor is like a dimmer switch, then CBD turns it down a notch. It’s also possible for a positive allosteric modulator (PAM) to turn the dimmer switch up a notch and amplify CB1 signaling.

The Indiana University group led by Andrea G. Hohmann studied PAMs as well as NAMs, fine-tuning CB1 receptor signaling in both directions. They found that strengthening CB1 signaling via positive allosteric modulation “could suppress neuropathic pain without producing unwanted CNS side effects or tolerance.” Tweaking the CB1 receptor in such a manner avoided potential problems (intoxication, impairment) associated with direct activation of CB1 by THC or various synthetic cannabinoids. Mohammed Mustafa of Virginia Commonwealth University reported that positive allosteric modulation of the CB1 receptor also reduced somatic withdrawal signs of nicotine-dependent mice.

On the Shoulders of Giants

2023 saw the passing of two research pioneers who were giants in the field of cannabinoid science. Mary E. Abood, PhD, conducted groundbreaking studies on the structure and function of cannabinoid receptors. She also identified other receptor subtypes that bind to cannabinoids. A leading figure in the ICRS since its founding in the early 1990s, Abood was known for mentoring young women scientists. After her death on Feb. 19, 2023, the ICRS announced the creation of the “Mary E. Abood ICRS Women in Cannabinoid Research Fund” to support women trainees and investigators.

Mechoulam, 92, passed away three weeks after Abood died. For all his stunning achievements as a chemist, perhaps his greatest contribution was how he nurtured a robust noncompetitive spirit, an ethos of cooperation and collegiality that persists among scientists involved in cannabinoid research. This was evident at the dinner and awards ceremony at the end of conference — an ICRS tradition — as young scientists were acknowledged for their research accomplishments and recently elected ICRS officers were introduced. When ICRS president-elect Ziva Cooper, the director of UCLA’s Center for Cannabis and Cannabinoids, greeted the group, it felt like a generational hand-off had occurred, a passing-of-the-baton from the old guard to younger scientists who stand on the shoulders of giants.

Martin A. Lee is the director of Project CBD. He’s authored and edited several books, including Smoke Signals, Acid Dreams, and The Essential Guide to CBD. © Copyright, Project CBD. May not be reprinted without permission.

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Finding Rare Cannabinoids in Non-Cannabis Plants

Special glands protruding from cannabis flowers express a series of unique molecules. Cannabinoids, as they are known, exist in cannabis. But it turns out that identical molecules are present in non-cannabis plants, as well. Researchers from Israel’s Weizmann Institute recently reported that they found cannabigerolic acid (CBGA) and other rare cannabinoids in Helichrysum umbraculigerum, a perennial shrub informally known as the woolly umbrella.1

A South African Botanical

Ferdinand Bohlmann and Evelyn Hoffman first discussed the chemical irregularity of Helichrysum. In a 1979 paper published in Phytochemistry2, they analyzed the South African species H. umbraculigerum, native to the eastern part of the country, where it was used in traditional medicine and fumigation rituals.

Bohlmann and Hoffman asserted that the plant’s tops — both leaves and flowers — produce cannabis-specific compounds. But a follow-up study conducted by Italian researchers in 2017 failed to find CBG or its acidic precursor in H. umbraculigerum flowers. They did, however, identify an analog of CBG known as Heli-CBG (also present in some fiber hemp varietals), which binds to the CB2 cannabinoid receptor.3,4

In a May 2023 article in Nature Plants, Weissman Institute scientists confirmed that woolly umbrella produces CBGA in trichomes on its leaves, but hardly any CBGA was present on its flowers. That’s different from cannabis, where CBGA and other cannabinoids are concentrated in trichomes on flower tops.1

Trichomes found on cannabis inflorescence (flowers) have a special cellular build, according to a 2022 study by University of British Columbia researchers in Current Biology. The gland’s bulbous head holds large porous cells that let acidic cannabinoids (CBGA, CBDA, THCA, etc.) move through the trichome.5 The Weizmann Institute team reported that H. umbraculigerum produces a similar cannabinoid transport network on its leaves.1

Sourcing Rare Cannabinoids in Non-Cannabis Shrubs

How did the Israeli scientists figure this out? They fed woolly umbrella precursor compounds responsible for making cannabinoids in cannabis. When given two precursors (hexanoic acid and phenylalanine), the shrub produced more cannabinoids compared to plants fed regular nutrients. This means that the same biosynthetic pathway exists in both cannabis flowers and woolly umbrella leaves.

The woolly umbrella shrub naturally produces on its leaves over 4% cannabigerolic acid alongside other rare cannabinoids. The shrub also contains water-soluble cannabinoids, which are not found in cannabis.

The woolly umbrella shrub produces CBGA in trichomes on its leaves, but not on its flowers.

Essentially, two different plant species have developed the same machinery to produce CBGA. Yet, woolly umbrella is evolutionarily distinct from cannabis. And unlike the shrub, cannabis makes two unique enzymes that flip CBGA into either THCA and/or CBDA.

Exploring a New Phytocannabinoid Toolkit

Thus, there are two toolboxes for cannabinoid phyto-synthesis in the phylogenetic tree. Terpenes and a few flavonoids accompany lipophilic cannabis flowers, whereas a complex array of flavones and water-soluble cannabinoids develop in H. umbraculigerum. By understanding their similarities and differences, we can better assess the therapeutic potential of each plant.

Cannabinoid compounds found in woolly umbrella dissolve more easily in water and can target specific areas of the body, such as the deeper bowel. But greater bioavailability, an argument for water-soluble cannabinoids, is not necessarily equivalent to greater potency. That which is absorbed quickly and easily also leaves the body and loses efficacy faster. And cannabinoid receptors have more affinity for fat-loving compounds compared to water-soluble agonists.6,7

Travis Cesarone is a freelance writer and communicator focusing on medical cannabis sciences. © Copyright, Project CBD. May not be reprinted without permission.

References

  1. Berman, P., de Haro, L.A., Jozwiak, A. et al. Parallel evolution of cannabinoid biosynthesis. Nat. Plants (2023).
  2. Cannabigerol-ähnliche verbindungen aus Helichrysum umbraculigerum. Phytochemistry. 1979;18(8):1371-1374.
  3. Pollastro, F., De Petrocellis, L., Schiano-Moriello, A., Chianese, G., Heyman, H., Appendino, G., & Taglialatela-Scafati, O. (2017). Amorfrutin-type phytocannabinoids from Helichrysum umbraculigerum. Fitoterapia, 123, 13–17.
  4. Pollastro F, Taglialatela-Scafati O, Allarà M, Muñoz E, Di Marzo V, De Petrocellis L, Appendino G. Bioactive prenylogous cannabinoid from fiber hemp (Cannabis sativa). J Nat Prod. 2011 Sep 23;74(9):2019-22. doi: 10.1021/np200500p. Epub 2011 Sep 8. PMID: 21902175.
  5. Livingston, S. J., Rensing, K. H., Page, J. E., & Samuels, A. L. (2022). A polarized supercell produces specialized metabolites in cannabis trichomes. Current biology : CB, 32(18), 4040–4047.e4. https://doi.org/10.1016/j.cub.2022.07.014
  6. Li, X., Chang, H., Bouma, J. et al. Structural basis of selective cannabinoid CB2 receptor activation. Nat Commun 14, 1447 (2023).
  7. Stadel, R., Ahn, K. H., & Kendall, D. A. (2011). The cannabinoid type-1 receptor carboxyl-terminus, more than just a tail. Journal of neurochemistry, 117(1), 1–18. https://doi.org/10.1111/j.1471-4159.2011.07186.x

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Getting to Know Cannabigerol with Bonni Goldstein, MD

This transcript is adapted from CannMed’s weekly podcast, hosted by Ben Amirault, who recently interviewed Bonni Goldstein, MD, one of the country’s most respected and experienced medical cannabis physicians. Dr. Goldstein has treated thousands of patients with medical cannabis. She is the medical director of Canna-Centers Wellness & Education and the clinical advisor to Cannformatics. She is also the author of Cannabis is Medicine: How Medical Cannabis and CBD are Healing Everything from Anxiety to Chronic Pain. Dr. Goldstein will be leading the Medical Practicum at CannMed 2023 (May 15-17), where she will also be speaking about CBG and other minor cannabinoids during the main session.

Ben Amirault, CannMed: I wanted to discuss one of the so-called minor compounds that you’ll be covering during your talk at CannMed this month. You have said that cannabigerol, or CBG, is one of your favorite cannabinoids. Why?

Dr. Goldstein: It appears that CBG does a lot of things that THC does and a lot of things that CBD does — but maybe even a little bit better. It’s kind of a bridge between THC and CBD. CBG is not intoxicating or impairing. It seems to be effective at lower doses compared to CBD. And it does appear to address some of the main issues that people turn to cannabis for — inflammation, pain, anxiety, sleep problems, depression, and cancer. So, like it checks all the boxes, especially for people who don’t want to get high and who don’t have the ability to pay for very high doses of CBD.

CannMed: It’s interesting that you say CBG is a bridge between THC and CBD. Is that because CBG is a precursor for the other plant cannabinoids?

Dr. Goldstein: CBG’s parent compound, cannabigerolic acid (CBGA), is kind of known as the mother of all the cannabinoids in that it’s the compound that’s found in immature cannabis flower. And then, based on the genetics of the plant and the enzymes that it’s exposed to, CBGA changes into CBDA and/or THCA, which turn into CBD and THCA when heated. CBGA hasn’t really been studied very much. I would say it is highly understudied. But I suspect that we will eventually find out that CBGA has some very interesting anti-inflammatory and anti-cancer properties. We don’t know really know yet. But at least CBG is being studied. I constantly look at the scientific literature, and just this year there’s a study published from Israel on how CBG may be helpful for multiple sclerosis. And there’s another study that looked at CBG’s mechanism of action in terms of how it works for pain and inflammation. So, there’s a lot of interest in CBG, which is really exciting.

CannMed: For what conditions do you think CBG has the most promise? What are you most interested in?

Dr. Goldstein: I think CBG holds a lot of promise for people who struggle with inflammation, pain, and mood disorders, like anxiety or depression. Ethan Russo, along with other researchers, recently did a survey of CBG users. About 70 percent of people said CBG was superior to their conventional medication. It was highly rated for anxiety, pain, depression, and sleep problems. I don’t know that it’s a direct sleep agent, but when you are having less anxiety and less pain you likely will fall asleep a little bit easier and maybe sleep better. It’s noteworthy that much of this anecdotal data is supported by findings from preclinical research.

CBG holds a lot of promise for people who struggle with inflammation, pain, and mood disorders, like anxiety or depression.

CannMed: In the survey you mentioned, was that CBG being taken by itself or in combination with other cannabinoids?

Dr. Goldstein: In the survey, I think they tried to sort that out, and it was people taking plant CBG that they buy in the hemp market because most CBG products that are on the market do not contain a significant amount of THC. They are coming from hemp plants, so they are readily available on the hemp market. I’ve seen it as flower, I’ve seen it as topical, which has anti-bacterial and anti-psoriatic effects. Psoriasis is a well-known condition where people get not only joint pain but they also get these thick red patches and scales on their skin. It can be a very difficult condition. And CBG has been found to have anti-psoriatic properties. It acts on the skin cells themselves and inhibits the build-up of those scaly patches. I think this just goes to show that the applications of cannabinoids are truly wide-ranging. People often ask: How is it possible that these compounds can do so many things? Well, they have multiple targets in the brain and body and that’s what makes them so amazing. Remember, the pharmaceutical model is “this medicine addresses this specific target.” Whereas cannabinoids are what we call promiscuous – they go to a lot of targets.

CannMed: How does CBG differ in its targets from other plant cannabinoids? Does it work on the same receptors with similar mechanisms of action?

Dr. Goldstein: There’s overlap with some of the actions of THC and CBD, for example. But then there are also some opposite reactions. CBD and CBG have opposite reactions at a specific serotonin receptor — 5HT1A — where CBD binds to it and CBG blocks it. They both act at that receptor, but in different ways. CBG also overlaps with CBD by binding to what we call PPAR receptors [on the surface of the cell’s nucleus]. And both of these plant cannabinoids interact with TRP [ion] channels to help with inflammation and pain.

CBG is the only cannabinoid that has been found to work at the alpha-adrenergic receptor, which mediates pain perception and inflammation. There are pharmaceuticals for ADHD or behavioral issues, for example, which target this receptor. CBG is always a compound I consider when treating children who have either behavior or other types of difficulties. I have used it in some of my patients with autism. Some families report their child is calmer, has better focus, even speech is improving in some of the children with autism who are non-verbal. But other parents report that CBG makes their child way too hyper. That may be a dosing issue. Why not try it? We know that it’s safe. And it’s under medical supervision. We start with very low doses so that we can control what’s going on and of course there’s a lot of oversight. The parents are watching, I’m watching. We’re just trying to make sure that we do no harm. Thus far, I’d say about 60 percent of kids that try CBG seem to get some benefit from it.

CannMed: I’m glad you brought up ADHD. Full disclosure: my son has been diagnosed with ADHD. I was surprised to learn that CBG might be helpful for that.

Dr. Goldstein: We don’t have clinical trials to say, yes this is definitively beneficial or detrimental for children. But we may be on the cusp of having those trials, which would be very exciting. In my practice, which is in California, I am allowed to work with parents to try different cannabinoids to see what might help. We do it very methodically. As I discuss in my book, we have a saying, ‘Rule it in or rule it out’. We start low dose, and we titrate up. We focus on one compound to see if there are benefits. And remember, too, that sometimes when we’re seeing a benefit it may be because the child is also on CBD — and maybe that combination is working well. If you add a compound and see enhanced benefits, you don’t know if it’s working because of that particular compound or the combination of the two if they’re already on something else. There’s a lot of trial and error involved, and it takes time to sort it out. I always tell families when I first meet them that we’re going to be working together for quite some time. It’s not like we just pick something and it immediately works great. We might get lucky. That happens, but that’s not the usual case.

CannMed: Another thing that stood out to me was this idea of CBG enhancing the body’s function. I was wondering if you could speak a bit to that.

Dr. Goldstein: A number of endocannabinoids, including CBD and CBG, delay the breakdown of our endocannabinoids. Remember, our endocannabinoids are our inner cannabis-like compounds, which our body releases on demand in response to a trigger, usually something that is stressing us, whether it be an illness or a traumatic insult or an infection of some sort. Your body cranks out these endocannabinoids to help maintain balance among all the various messages that our cells are constantly sending and receiving. The endocannabinoid system is a physiological regulator, and it’s helping you stay in balance. We can enhance our own natural endocannabinoid system with plant cannabinoids, which delay the breakdown of endogenous cannabinoids so that they last longer. It’s kind of like the way some anti-depressants work by increasing how long serotonin is hanging around.

We can enhance our own natural endocannabinoid system with plant cannabinoids.

CannMed: Now correct me if I’m wrong, but physical exercise is another way to spur your body into creating endocannabinoids?

Dr. Goldstein: Yes.

CannMed: Would supplementing with CBD or CBG be an effective way to keep anandamide in the system and get more benefits from our natural cannabinoids?

Dr. Goldstein: Theoretically you could look at it that way. I don’t know that there’s a direct correlation, as in take a dose and now you have extra anandamide. But I do think the literature supports this whole idea of cannabinoids being anti-inflammatory, antioxidant, neuroprotective — and one dose is not going to do the trick. It’s helpful to think in terms of a wellness regimen that includes cannabinoids, of course, in addition to other healthy things that you should be doing to enhance your endocannabinoid system – healthy diet, exercise, good sleep, really trying to control your stress.

CannMed: Could you speak to how CBG might enhance the effects of other cannabinoids or situations where you think the combination is useful?

Dr. Goldstein: There’s a 2019 animal study that showed the combination of CBD and CBG decreased neuroinflammation. They were looking specifically at neurodegenerative disorders with dementia, what we call Lou Gehrig’s Disease or ALS. And it showed in this preclinical study that CBD and CBG worked together and gave better results for protecting against neuroinflammation. This ties into the concept of the entourage effect, whereby combinations of cannabinoids and terpenes appear to enhance the benefits, the positive results. Another recent study showed that CBG in addition to THC and/or CBD has anti-cancer effects in test tube experiment looking at certain brain tumor cells. When some of my cancer patients come to me with advanced cancer, very poor prognosis — and I’ve been doing this now for a number of years — I add CBG into the mix. To me there is no harm in doing so. It doesn’t cause the impairment that anti-cancer doses of THC can sometimes cause.

CannMed: What other scenarios or situations do you encounter where you think CBG is either the right tool or might be a good companion if you have already started a cannabis regimen and you’re not getting the right results?

Dr. Goldstein: I think that if you’re trying to treat anxiety, pain, inflammation, and you are not getting great results with either THC and/or CBD, which, of course, are the two most common cannabinoids being used right now, then certainly the addition of CBG is worth a try. Remember too, that when you combine cannabinoids sometimes you can get away with a lower dose of either or both, while getting an enhanced effect from that entourage. Because there are studies that show sub-therapeutic doses of cannabinoids — meaning doses not expected to do anything clinically — when combined will work better. For a lot of people high, high doses are just not financially feasible. And sometimes that combination of small amounts of two compounds actually is more effective. As for what I would recommend CBG for — anxiety, pain, psoriasis, I use it in my patients with autism, I use it in my patients with cancer. Because it’s safe, and if somebody’s struggling and conventional medicine is not helping them or it is only helping to a point, I don’t see any reason, especially under medical supervision, not to try CBG and other cannabinoids when there’s compelling preclinical research that begs for clinical trials.

CBG is always a compound I consider when treating children who have behavior or other types of difficulties.

CannMed: It seems like CBG is very well tolerated by patients, but are there adverse reactions that you’ve run into?

Dr. Goldstein: I haven’t really seen a lot of adverse reactions, except for a few specific ones related to the population of children that I take care of. In some kids with autism, it’s just too overstimulating. It makes behavior go off the charts. So, I warn the families about this before we get started. It may be a dosage thing. Dosing is very, very important. Lower doses may be overstimulating. If that’s the case, we might try higher doses. But that’s specifically related to a certain population. I have not observed or heard of too many side effects from adults taking CBG. Some patients say that CBG is somewhat alerting, meaning it feels a little up. So, you would not want to take CBG right before bedtime. You figure out how you respond to it, and then don’t use it at night if that’s the effect you get. On the other hand, some people say it helps with sleep. Maybe it’s helping with sleep because it’s calming and decreases anxiety. When a doctor hands you an antidepressant or an opioid, nobody knows how you’re going to respond if you’ve not taken that before. It’s the same thing with CBG. There is always a chance when you take a new medication that you may be the person who doesn’t respond very well. Or you might be the person who gets a great result.

CannMed: CBG is still one of the lesser-known cannabinoids. How easy is it to access CBG products?

Dr. Goldstein: In the video that I put up on YouTube, there’s a slide that shows some of the CBG products. You can get it as flower if you want to vaporize it. You can get it as a topical, as I’ve mentioned. Mostly I’ve seen it in tincture form, which means an extract in a bottle where you have a little eyedropper or syringe and you measure out your dose and squirt it under the tongue. I don’t endorse any company, but certainly a quick Google search will lead you to where you can find CBG. And of course, always, always before you purchase anything, you want to make sure you get a Certificate of Analysis (CoA) so you see what is supposed to be in that bottle before you buy it. And if a CoA isn’t available or not readily transparent, move on to the next product.

CannMed: We actually did a podcast with a laboratory professional who was talking about how some manufacturers will even falsify their CoA’s. She had some good tips for being able to spot the real ones and the less scrupulous ones. So, Bonni, before I let you go, I want to thank you so much for talking about CBG with us. I look forward to hearing your talk on some of the other cannabinoids at CannMed 2023, where you’re also going to be leading our Medical Practicum, along with Dustin Sulak, Kevin Spelman, and Eloise Thiessen. Could you give us a sneak quick preview of what people can expect at the Practicum and why you believe it’s important to have events like this to educate clinicians and laypersons about cannabis medicine.

Dr. Goldstein: It’s important because for health care professionals there is no full board training program, no residency or internship that focuses on cannabis therapeutics. The feedback we’ve gotten is it’s very helpful to hear directly from clinicians who are actually practicing this type of specialty and who are exploring the nuances of cannabis medicine. The practicum is a full day of education. We start off with endocannabinoid system physiology, the physiology of the cannabinoids and other constituents of the plant. Dr Kevin Spelman, who’s a brilliant botanist and herbalist with many years of experience, is one of the teachers. His lectures are amazing. Especially coming from my world as an MD, an allopathic world, it was a big change for me to understand botanical medicine. Having him on board really helps bridge that gap for those of us who are coming from the allopathic field. During the practicum, we also go through clinical applications for cannabis, special considerations for geriatric patients, chronic pain treatment. I’ll be talking about pediatrics, my area of specialty. And then there will be practical panels where we’ll be giving case reports and advice on how to help your patients pick the right medicine. It’s really a full day with lots of information for anyone who wants to advance their knowledge. I really enjoy it. It’s great to be around like-minded people, and it’s great to hear about other people’s experiences. I always learn something from my colleagues at CannMed, from people in the audience, and from the other speakers.

For more information on Dr. Goldstein, visit her YouTube channel Bonni Goldstein MD. She occasionally posts on Instagram, and she is also on LinkedIn. To hear the full CannMed podcast with Dr. Bonni Goldstein, go here.

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Cannabichromene, a Minor Cannabinoid with Major Upside

In 2013, Noriko Shinjyo, Ph.D., a Research Associate at Chiba University in Japan, coauthored a study with Italian scientist Vincenzo Di Marzo on cannabichromene (CBC), a phytocannabinoid that exerts profound effects on the nervous system.1

Published in Neurochemistry International, their paper probed how CBC influences the fate of adult neural stem progenitor cells, which are described as “an essential component of brain function in health as well as in pathology.” As stem cells mature, they change and differentiate into new neurons and other cells. CBC was shown to have a positive effect on neural stem progenitor cells during their maturation phase, according to in vitro research.

Recently a different group of scientists has followed up on this decade-old discovery by delineating seven mechanisms through which CBC is able to protect and regenerate the nervous system. They reported their findings in Life, a Swiss scientific journal, noting that CBC, a “neurogenesis enhancer,” enables stem cells “to sustain their viability and differentiation.”2

What Are Neural Stem Cells?

Scientists have identified specific areas of the brain — the hippocampus and the lateral ventricles — where neural stem cells are created. These cells undergo a maturation process, known as differentiation, which is an important stage for young cells located in the spinal cord, brainstem, and brain regions programmed for muscle control. Young stem cells evolve into new neurons, but they can also form cells that comprise the protective sheath surrounding nerves.

Some neural stem cells differentiate into astroglial cells, also known as astrocytes. These abundant star-shaped cells populate the grey and white matter of the brain, where they regulate cerebral blood flow and the transmission of electrical impulses. They also play a crucial role in maintaining the blood-brain barrier and repairing the brain and spinal cord following an infection or a traumatic injury.

CBC is a “neurogenesis enhancer” that enables stem cells “to sustain their viability and differentiation.”

But a subpopulation of these mature cells remains dormant. That’s fortunate, given that active astrocytes can stunt the brain’s natural ability to regenerate after an injury. This means that a regulated maturation of neural stem cells, located in the brain and spinal cord, helps to protect and regenerate the nervous system. And this process is augmented by CBC, a cannabis compound, which regulates the production of new neurons, while also reducing the formation of active mature cells that may impede regeneration after a brain injury.

Can CBC Regenerate Embryonic Cells?

In 2023, a team of six Italian scientists published new details that explain how CBC protects and regenerates damaged neurons and nervous system components. They used a special type of spinal cord cell derived from an embryonic mouse, combined with neuroblastoma cells, to make their discovery. The team assessed changes in the genetic landscape of the cells after exposing them to CBC and a control media.

By further refining their analysis, the team elucidated newly discovered mechanisms behind cannabichromene. The plant cannabinoid helps to facilitate proper dopamine neuron and glutamate receptor maturation. And while various cannabinoids regulate the formation of the nerve’s protective sheath, their neuronal regeneration depends on other functions of CBC.

A Balancing Act with Choline

It seems that one newly found mechanism of CBC might work synergistically with tetrahydrocannabinol (THC), while also counteracting the effects of alpha-pinene, a terpene found in various cannabis chemovars and other botanicals.3

Alpha-pinene appears to act directly against CBC at a specific neurotransmitter that sends signals from muscle to neuron. That transmitter is in the choline family, which is protected by pinene but is broken down more rapidly under CBC exposure. Choline is important for cognition, brain development, neural stem cell maturation, muscle movement, and other basic functions.

THC downregulates the choline transmitter, while CBC boosts a gene that codes for a special choline-destroying enzyme; thus, both CBC and THC are implicated in the reduction of choline, and this can protect the nervous system and regenerate neurons. Alpha-pinene, on the other hand, keeps cognition taut by protecting choline. It’s a balancing act. The use of CBC, the scientists conclude, “could represent an important addition to the regeneration of the nervous system, but further experiments need to clarify and optimize how CBC could be effectively used for this purpose.”

Travis Cesarone is a freelance writer and communicator focusing on medical cannabis sciences. © Copyright, Project CBD. May not be reprinted without permission.

Footnotes

  1. Shinjyo, N., & Di Marzo, V. (2013). The effect of cannabichromene on adult neural stem/progenitor cells. Neurochemistry international, 63(5), 432–437. https://doi.org/10.1016/j.neuint.2013.08.002
  2. Valeri A, Chiricosta L, D’Angiolini S, Pollastro F, Salamone S, Mazzon E. Cannabichromene Induces Neuronal Differentiation in NSC-34 Cells: Insights from Transcriptomic Analysis. Life (Basel). 2023 Mar 9;13(3):742. doi: 10.3390/life13030742. PMID: 36983897; PMCID: PMC10051538.
  3. Russo, E. B., & Marcu, J. (2017). Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads. Advances in pharmacology (San Diego, Calif.), 80, 67–134. https://doi.org/10.1016/bs.apha.2017.03.004

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