Let's Talk About Cannabinoids - Let's Talk Terpenes

Delta 9 THC is probably one of the best documented cannabinoids besides CBD.

Delta 9 THC is the decarboxylated form of THC-A. Decarboxylation happens either rapidly through heating or over time naturally. You will notice that you can often tell when a plant was harvested in its growth cycle by the level of THC-A vs Delta 9 THC is in the plant. You may also notice that you can often tell if the plant was cured properly by this as well although there is much more nuance in the latter. There will always be a higher level of THC-A in flower cannabis, however the level of Delta 9 THC will rise as the plant matures and is cured.

Delta 9 THC is used across a massive spectrum of disorders from cancer, insomnia, anxiety, stress, depression and so much more. How it helps these different conditions is what we're here to approach in this article.

Simply speaking, Δ9-THC provides the psycho activity experienced from consuming Cannabis Sativa.

Now let's go a bit deeper and we will us THC to refer to Delta 9 THC from now own for conveniencec.

When you consume THC, the first thing that matters is the form of consumption.
1. Inhalation
2. Ingestion
3. Sublingual

For ingested THC, the bio availability of THC is 4%-12%. This means that overall, ingestion is the worst intake method based of efficiency. The first thing that happens when you intake THC is it travels to the liver where the majority of it is destroyed or metabolized. After that, the remaining THC is converted into 2 forms of 11-Hydroxy-THC (I mighta got the wording on that right :P). This form of THC is more potent than D9-THC and as such must be noted when giving recommendations on strength. Another important thing of note is that eating is extremely important when taking edibles. When THC is taken with edibles, there is fat molecules for it to bind to. This allows for a longer release and more effective delivery of ingested cannabis. When taken on an empty stomach, without fats to bind to, the THC is processed faster through your system.

This bio availability applies to terpenes as well and makes more ingested terpenes negligible in their effects. Through this, we can tell that the interest in gummies such as rosin infused stems from complex cannabinoid profiles and not terpene profiles. As such, with the right mix of cannabinoids, even distillate based edibles can take on the effects sought in "higher" end products.

Now to continue,

The next form we'll discuss is Sublingual.

Bio availability of THC when taken sublingually maxed at around 13%, though others have claimed high absorption I do not have references to these studies and as such will not quote them here. Now being a slightly more. Modern deliver methods may allow for high absorption rates. In the end, however they are processed in the liver similarly and therefore have similar bio availability. THC is often bound to MCT oil or other fats/alcohols to form the tincture.

The true benefit of sublingual THC is in patients with gastrointestinal issues as well is patients with issues with inhalation. Modern tinctures have very little flavor and thus are usually consumed quite easily. The downside to tinctures is the general higher pricing that comes with them.

The final form we'll discuss is inhalation. There are 2 forms of inhalation we'll discuss. First is combustion. This is currently the most common form of consumption, however the second form of inhalation we will discuss is quickly on the rise. The bio availability of THC when inhaled maxed at around 25%. This is due to THC being absorbed through the mucus membranes in the lungs and entering the blood stream more directly. As such, a much larger portion of THC is able to avoid metabolizing in the liver. This being the second most optimal method for THC and terpene delivery is hindered by one main thing, combustion. The fire used to combust and smoke the flower both destroys a portion of THC and terpenes as well as delivers more tar/toxins to the lungs. Though there is plenty of debate and research on the topic, the reality is that the heat and smoke delivered by smoking flower is not healthy and has the potential to cause damage over time. I've had too many people come to me with lung cancer having only smoked cannabis in their lifetime. And yes I am including anecdotal evidence in some of this.

Now the final and arguably optimum form of delivery. Vaporization. Vaporization can be done with both flower and concentrates. It allows for the heating of cannabinoids and terpenes to a point of volatility without destroying them in the process. As such the bio availability of vaporization maxed at around 35%. The absolute peak method is dry herb vaporization as it delivers only exactly what you need. The drawback is the high cost of entry, technology limitations and dishonesty by companies. We all would love a Volcano but unfortunately those puppies are expensive. The other methods are cartridges and inhalers. In cartridges are a concentrated form of THC is heated using a ceramic coil hot enough to vaporize the concentrate. It allows a cooler hit without the level of tar associated with smoking. The draw back is much high levels of THC being common with these products. Keeping terpene levels relative to THC levels is vastly important as the entourage effect represents the entire beauty of cannabis as a medication.

Now what happens when you take THC? First your blood pressure spikes and heart rate increases. This must be noted with individuals with BP issues. On the flip side however, as cannabis takes effect in the system, it begins to lower BP and becomes a vaso-dilator. Depending on consumption method effects will be noticed anywhere from 6-15 minutes for sublingual, 30 minutes to 2 hours for ingestion and with inhalation instant to 5 minutes (to reach full effect).

THC has well documented and thoroughly proven anti emetic properties (anti-nausea). This makes it a fantastic option for chemo patients, chronic nausea, gastrointestinal issues and many other conditions what cause nausea. It must be noted however that dosing is important is too high of dosing can cause the opposite effect of nausea and vomiting. This most often occurs in edibles as users are often not instructed properly on their consumption.

THC also has a long proven history of anti-inflammatory properties as well. THC inhibits cytokine production by antagonizing the CB2 receptor. This is why THC is seen as a potential in cancer research as a synergistic treatment as it lowers the bodies immune response to chemo treatments and other inflammatory processes. Again as with everything, dosage is important, however it's true power lies in its synergy with cannabinoids and terpenes.

In patients with anxiety, THC can be a gift and a curse. If they are prone to anxiety, THC levels should be kept lower as most often users reporting anxiety either have not been properly dosed or have chronic anxiety need more relaxing cannabinoids to counter the intoxicating effects of THC. CBN and CBG can both be used in tandem with THC to lower anxiety and boost mood. CBD we must be careful with as more recent studies have show CBD helping raise bio availability of THC in users, increasing the intoxicating effects of cannabis. THC-V is another cannabinoid to be careful pairing with THC as it can be prone to causing or exacerbating anxiety.

CBD stands for Cannabidiol. This is probably the second if not first most well documented cannabinoid with it's proven vastly expanding list of uses.

Contrary to THC, CBD does not bind to CB1 and CB2 receptors. At high concentrations, CBD directly activates the 5-HT1A (hydroxytryptamine) serotonin receptor. This allows CBD to produce anti-anxiety effects.
CBD binds to TRPV1 receptors, which also function as ion channels. TRPV1 is known to mediate pain perception, inflammation and body temperature. Ion channels are integral membrane proteins that contain pathways through which ions can flow. CBD showed TRPV1 desensitization of up to 48%.

This shows us that CBD is highly effective at suppressing pain responses and inflammation responses in the human body. Chronic inflammation conditions as well as immune diseases and many many other conditions and have major benefits from the addition of CBD to their treatment plan. CBD should not necessarily replace a current treatment, but rather provide assistant and boost effectiveness of a patients current treatment plan.

CBD can increase the level of blood thinning and other medicines in your blood by competing for the liver enzymes that break down these drugs. Grapefruit has a similar effect with certain medicines. This interaction is particularly important if you are taking a blood thinner, an anti-epileptic, or an immunosuppressant medication, all of which need to have stable levels in your blood.

CBD can help lower cravings for tobacco and heroin under certain conditions, according to some research in humans. Animal models of addiction suggest it may also help lessen cravings for other addictive substances such as alcohol, opiates, and stimulants.

Interestingly, CBD has shown a paradoxical relationship with THC depending on the consumption method. When inhaled, CBD has shown to be more effective at lowering the levels of THC uptake at the CB1 receptor. This lowers the psychoative effects that THC provides. Alternatively, however when ingested CBD actually inhibits the livers ability to metabolize THC, allowing more THC to be released into the system. It's fascinating to see where the research is taking us.

Conditions CBD has been shown to be effective for are epilepsy, parkinsons, immuno compromised patients, chronic pain patients, chronic anxiety patients and many others. Dosage does make a difference and some barriers to entry can be price point as effective doses of CBD per condition can lead to higher costs. Hopefully higher concentration CBD products at lower cost can be produced in the future.

The intake methods related to CBD are primarily the same as THC so there is no need to dive into the same depth here.

CBG stands for Cannabigerol. CBG is the decarboxylated version of CBGA which is the mother cannabanoid to most other cannabinoids.

Let's just go down the list of potential benefits of CBG

Neuro-protective agent. I mouse studies CBG showed effective ability to increate motor funtion control in mice with Huntingston disease. On top of this, CBG has high anti-oxidant properties and as oxidative stress is a significant factor in neurological diseases, has shown to have high potential benefits.
CBG protects against AB Toxicity though the exact mechanism as to which it provides this protection has not been further researched as far as I am aware.
CBG also lowered MS-induced cytokines, adding the ability to help slow symptom progression along with other treatments.

Recent studies showed that cannabinoids downregulate cytokine and chemokine production and, in some models, upregulate T-regulatory cells (Tregs) as a mechanism to suppress inflammatory responses. This can help with controlling tumours from becoming Metastatic. It is important to remember to that these Cannabinoids should be used in tandem with current treatments, NOT AS A SUBSTITUTE!

One of the biggest benefits of CBG is its high level of anti-inflammatory as well as immuno-regulatory processes. It was shown to help heavily in patients with IDB, allergic asthma and other chronic inflammatory conditions. Specifically its binding with CB2 was the main contributor to this anti-inflammatory response. Remember, CB2 is most active when inflammation is present in the body.

From an anti-bacterial stand point, CBG has shown to be fairly wider ranged in its anti-bacterial effects than CBD or other cannabinoids. The exact mechanism as to why it effects these more is theorized to be due to weakening the bacterial cell membrane and allowing cellular collapse of the bacteria. CBG has also been show to inhibit activities like biofilm formation and virulence.

CBG has shown an affinity to a2AR Activation of α2AR inhibits the release of norepinephrine causing vasodilation (relaxation of blood vessels), bradycardia (slower heart rate), and decreased contractility (weaker heart contractions), ultimately resulting in lower blood pressure. It seems like this effect was greatly increased with chronic use of CBG, not short term use.

For this part I am now going to quote a study so know that none of these words are my own and I have linked the study at the bottom of the page.

"Accumulating evidence has substantiated the anti-tumorigenic properties of CBG, showcasing its efficacy in reducing cell proliferation, migration, and survival in various tumor types, including prostate cancer, glioblastoma, colorectal carcinoma, pancreatic cancer, and breast cancer.Cannabinoids have been well-researched in cancer, with the bulk of the research focused on THC and CBD, both of which increase the survival of glioblastoma patients . These two agents have progressed to clinical trials, coupling chemotherapy with phytocannabinoids to assess breast and colon cancer patient recovery. CBG, whilst not at the clinical trial stage as of yet, has shown much promise with regard to treating glioblastoma. CBG, like many other cannabinoids, is lipid-soluble. This property allows it to easily pass through the lipid bilayer of cell membranes, including the blood–brain barrier, and it was found to reduce C6-rat glioma cell proliferation.

A study in 2021 found that CBG alone and in combination with CBD effectively promoted apoptosis in glioblastoma stem cells. CBG inhibited the invasive behavior of glioblastoma cells, in a similar way as CBD combined with temozolomide, a chemotherapeutic. The CBG plus CBD combination was found to be more effective than CBD with THC in inducing cytotoxicity and reducing invasion in a 3D spheroid assay.

The inhibitory effects of CBG and CBD on glioblastoma stem cells are likely primarily involved in the modulation of GPR55 and TRPV1 signaling. As solid tumors progress, the tumor microenvironment (TME) undergoes changes that transform into a highly immunosuppressive milieu. Regulatory myeloid cells play key roles in the immunosuppressive environment and activate tumor-secreted cytokines. It was found that CBG decreased the CSF-1 secretion by melanoma cells. CBG significantly reduces the expansion and macrophage transition of the monocytic-myeloid-derived suppressor cells (MDSCs) subpopulation. It is a promising treatment for tumors with elevated CSF-1 expression.

In a study of minor phytocannabinoids on Multiple myeloma (MM), CBG was found to inhibit MM cell growth in a dose-dependent manner and reduce the invasion of MM cells toward osteoblasts cells.During tumor progression, genetic and epigenetic alterations can enable tumors to evade immune detection, a phenomenon known as immune escape. The adaptive immune system’s ability to detect and eliminate emerging tumors relies on immune surveillance by cytotoxic T lymphocytes (CTLs). CTLs recognize tumor cells by binding to major histocompatibility complex class I (MHC-I) molecules, which present fragments of tumor-derived proteins. Dada et al. demonstrated that CBG can reverse this immune escape phenotype in vitro by upregulating MHC-I expression on various metastatic tumor cells, thereby rendering them susceptible to T cell recognition.The mechanism of anti-tumor effects of CBG involved the Hippo-YAP, TRP channels, EGFR-RAS pathways, and targeted tumor-secreted cytokines. The Hippo-YAP pathway is a crucial cellular signaling pathway that regulates organ size, cell proliferation, and apoptosis. When this pathway is dysregulated, it can contribute to tumorigenesis.

Recently, a paper evaluated the cytotoxic and cytostatic effects of CBG alone or in combination with curcumin and piperine in colon carcinoma cell lines HCT116 and HT29. Both mono and combination treatments demonstrated a notable reduction in the expression of the YAP oncogene in cell lines. Cannabinoid compounds, along with curcumin/piperine, effectively inhibit the proliferation of HCT116 cells by activating the Hippo signaling pathway. In contrast, the suppression of proliferation in the HT29 cell line appears to be mediated by a decrease in YAP expression independent of Hippo signaling. These findings underscore CBG’s multifaceted potential in modulating critical pathways, presenting it as a noteworthy candidate for therapeutic interventions in various cancers.

In a study conducted by Lamtha and coworkers, the kinase-inhibition activity of CBG to tyrosine-kinase of EGFR, which is involved in over 70% of all cancers, was evaluated. The binding kinetics information indicated that CBG had a high binding affinity and kinase inhibitory activity against EGFR-TK. In addition, CBG significantly induced cell apoptosis in the EGFR-positive cancer A431 line. Zeppa et al. investigated the effects of CBG on pancreatic ductal adenocarcinoma (PDAC) cell lines PANC-1 and MIAPaCa-1. Their findings demonstrated that CBG reduced mTOR protein expression and suppressed EGFR expression in both of the two cell lines. Moreover, the data supported that CBG reduces downstream RAS signaling.

The combination of CBG and conventional chemotherapy agents holds promise for enhancing treatment efficacy. Potentiation of chemotherapy and reduction of chemotherapy side effects are the potential ways by combining CBG with chemotherapy. CBG alone was found to suppress hormone-refractory prostate cancer (HRPC) development in a mouse model of prostate cancer (TRAMP mice) via reprogramming metabolic and oncogenic signaling, although this effect was less pronounced than CBD. However, the two in combination exhibited potent anti-cancer effects even in mice unresponsive to enzalutamide (androgen receptor antagonist) treatment. As such, combination therapy may be an attractive adjuvant therapeutic option for prostate cancer patients.

Further studies in pre-clinical in vivo models on CBG are necessary to better understand its role in cancer progression and immune escape. In vivo studies would be particularly useful to more deeply investigate its anticancer effects More research is needed to fully understand the interactions between CBG and chemotherapy drugs. However, the potential benefits of this combination warrant further investigation." -https://pmc.ncbi.nlm.nih.gov/articles/PMC11597810/#sec2-molecules-29-05471

Coming Soon

CBC stands for Cannabichromene. Though lesser studied, has shown great therapeutic and analgesic potential when combined with CBD and THC.

Going through a few studies linked at the bottom of this tab lead me to a few tid bits.

First and foremost, CBC does not interact with the CB1 receptor however is a proven CB2 receptor. It acts as an surface inhibitor to CB2 receptors, lowering the reactivity and uptake in CB2 binding compounds.
Now we know CB2 receptors are primarily activated when inflammation is present.

So how does this apply to us as humans?
As best I can tell (and reading another study linked below) since research is still younger with CBC, CBC is a potential down regulator of inflammatory responses in humans. When applied to diseases and conditions with chronic pain due to over reaction of our immune response. Conditions where the problem stems from someones immune system over reacting to a bodies pain and inflammation response. Lupus, rheumatoid arthritis (RA), psoriasis to name a few potentials.

The other benefit to CBC is it contains basically no psycho activity. Since cannabis has begun to grow and expand in the mainstream, we as users must understand the absolute necessity for non-psychoactive treatments for patients. A "high" is not necessary for many conditions and especially in a therapeutic environment. There are a large number of people who do not tolerate the effects of THC well and need routes and pathways to achieve the help they need without displacing their own comfort.

At this time this is about the limit of my knowledge on CBC.