The cannabis plant contains many types of cannabinoids termed cannabinoid acids. These include CBDA, CBCA, CBGA, THCA and many other cannabinoids. These cannabinoid acids can interact with the cannabinoid receptors in the endocannabinoid system leading to the beneficial effects commonly reported.
While the acidic cannabinoids have not received as much attention as the decarboxylated forms, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), traditional cannabis tincture use prior to purification processes often contained these in higher amounts. The chemical structures of acidic cannabinoids in cannabis plant contains a carboxyl group that is typically lost during modern processing technologies. For example, these purification processes lead to the conversion of CBDA to CBD.
Known cannabinoids such as THC and CBD have been used to treat a number of health conditions that researchers are studying, but have only been approved by the FDA for a few conditions. These health conditions approved by the FDA are typically for epilepsy (CBD) and other pain relief management (THC) in some cancers, and are prescribed by physicians. Medical cannabis has been approved in some states, although not federally legal, and is commonly used as a treatment for pain relief in a variety of medical conditions.
THC and CBD are often associated with the nervous system and while they can have negative effects, such as risk of drug abuse for marijuana, they are not known to cause overdoses. Common side effects of cannabis plant use are typically associated with delta 9 THC from the marijuana plant and not CBD from the hemp plant which is not psychoactive. While both marijuana and hemp are from the same cannabis plant family, their main differences are in the concentration and amount of THC and CBD found in the flower.
People have been using the cannabis plant for a long time, dating back thousands of years, with many different benefits to the human body. Recently, with the ability to concentrate and isolate the cannabinoids from the cannabis plant, researchers have been able to produce and identify minor cannabinoids that may have important properties in addition to THC and CBD.
Some conditions that cannabinoids are used to treat:
While only a few conditions have been approved by the food and drug administration, many people turn to complementary and integrative health treatments to help boost their health.
The cannabis plant has been used for a long time to treat nausea and vomiting, and became a popular alternative for cancer patients who have trouble keeping their food down after chemotherapy. Often, the cannabinoids THC and CBD in combination with other minor cannabinoids, termed full spectrum, have been reported in the literature to show significant improvement in symptoms from patients looking for relief.
Multiple states have approved the use of cannabis for treatment of chronic pain, leading to medical marijuana becoming a popular option for patients with this health condition. While a number of studies have shown that CBD is able to provide relief, cannabis high in THC is the most popular product for treatment. Delta 9 THC has high affinity for cb1 receptors (cannabinoid receptor 1) which is more closely associated with pain alleviation than CB2 receptors.
CBD was first studied in epilepsy patients who did not respond well to conventional epileptic drugs. Currently, epilepsy is on of the few health conditions that the FDA has approved for cannabinoids, and has shown remarkable efficacy in helping patients control seizures. Epidiolex (cannabidiol) is an isolate, and used at very high concentrations for treatment, often ranging from 1000mg to 2000mg per day.
This highlights an interesting phenomena in the cannabis plant research community, often, many cannabinoids used in clinical trials have very high doses, above what consumers generally use.
Cannabinoids have been researched for their ability to reduce stress in a variety of models for anxiety and stress, both in animals and in people. Specifically, CBD alone and with other minor cannabinoids (full spectrum) have been shown to be effective at higher doses. Mateus B. et al found that 600mg of CBD was able to reduce the stress effects of social speaking in a group of individuals diagnosed with social anxiety disorder.
Almost a third of all adults in the US report using some sort of sleep aid. Using cannabinoids for sleep is one of the most common reports from consumers, and a number of major and minor cannabinoids have been reported to be beneficial. The most common minor cannabinoid for sleep aid is CBN (cannabinol), but CBD has also been well studied for its benefits for improving sleep in clinical studies.
The effects of smoking marijuana on cardiovascular health may be negative, since it is fairly well established that inhalation of organic matter can lead to significant complications of the vasculature. However, the use of CBD oil may be beneficial through its ability to bolster the endocannabinoid system system by elevated natural endocannabinoids that activate CB2 receptors. The data on cannabinoids and the cardiovascular system are still pre-clinical, and will need more studies to determine if the effects are relevent.
CBD has been tested by researchers in many models of addiction and response to drug cues to see if supplementation can help with getting people off of potentially harmful addictions. The most common targets have been opioid and tobacco, and have shown some modest effects in reducing cravings in individuals. While some of these studies have reported positive effects, there has not been widespread adoption yet since larger scale blinded studies are needed to better test the potential benefits.
Anti inflammatory properties of cannabis plants is widely reported in a number of pre-clinical models for many of the minor cannabinoids as well as CBD and its acidic cannabinoid counterpart CBDA. Systematic review of anti inflammatory properties shows that targeting the endocannabinoid system can reduce some markers of inflammation, CBDA has recently been shown to decrease COX-2 enzyme and activity, a key protein involved in driving inflammation in many pathologies.
Sometimes people interchange between cannabis and marijuana, and this causes a lot of confusion. They are different things. Cannabis is typically referred to as any product that consists of the cultivated plant, whether that is hemp or marijuana which are defined from a federal level based on their THC content. Throughout this article, we will use “Cannabis” to describe the sativa plant, and any hemp or marijuana plant that cannabinoids come from.
While there are many known cannabinoids in the cannabis plant, most of them termed minor cannabinoids, only a smaller subset have been under investigation for potential medical use. Below is a list of the more well known cannabinoids and their acidic counterparts:
The cannabinoids produced by the hemp plant originate with the “mother” cannabinoid CBGA. From this, a complex series of enzymes can turn this cannabinoid into the main cannabinoids typically associated with hemp or marijuana (THC and CBD), but also the other minor cannabinoids.
Cannabis plants are often bred to produce various amounts of specific cannabinoids. Most strains will produce a variety of cannabinoids, with a preference based on their genes and the environment that they are grown in.
Synthetic cannabinoids are not typically found in the cannabis plant, but are derived from a starting cannabinoid, like CBD, and created in a lab. In addition, some cannabinoids that are naturally found in the cannabis plant, can also be synthesized from a starting cannabinoid, such as converting CBD to THC, or THC to CBN. In the past, black market synthetic cannabinoids (aka Spice) were found to have serious side effects and the national institute on drug abuse issued a warning on their use.
While most of the research and reports from the alternative health community revolve around the benefits of THC or CBD, uses for minor cannabinoids are starting to gain traction. Recently, there has been a lot of focus on CBDA and its benefits as a new cannabinoid product, and while it is not a minor cannabinoid, new purification technologies have allowed it to be purified without decarboxylation.
The scientists at Natural Dos have recently developed a new technology that isolates out only the acidic cannabinoids, which means a high concentration of CBDA in their full spectrum product. Only recently has CBDA been discovered for it very high absorption properties, which conservatively has over 450% higher absorption than CBD. As this acidic cannabinoid is further researched, it is found to provide significant help with nausea and vomiting in pre-clinical trials. Additionally, it also appears to be a significant affinity for the 5HT1A receptor in the brain, an important target for serotonin function.
The acidic cannabinoid CBGA is another recent minor cannabinoid on the market, and like CBDA, has been shown to have 10-fold higher absorption compared to its decarboxylated form CBG. New studies on hemp oil high in CBGA or CBDA have found that they can inhibit the enzyme aldose reductase, a critical enzyme in driving disease in patients with high blood glucose. For both CBGA and CBDA, this study found a 50% reduction in aldose reductase enzyme activity. Aldose reductase inhibitors are widely studied for their ability to decrease complications in models of diabetes, which are thought to be partially caused by a buildup of side products in the polyol pathway.
Research on CBG is not as extensive as CBD, but a lot of consumers report that it helps with concentration and focus. Pre-clinical research has found that CBG may also be beneficial in inflammatory bowel disease, Huntington’s disease, cancer, and bacterial infections. Importantly, while pre-clinical studies are a necessary step in understanding potential mechanisms of action, clinical trials are needed for determining if CBG may be beneficial for these conditions.
Cannabichromene (CBC) has been reported to reduce inflammation in both in vivo and in vitro studies. This appears to work through the TRPV1 receptor, which are partially responsible for pain stimulation in the neurons, and play a role in inflammatory processes. The use of CBC for inflammation still needs further studies, but has shown limited side effects and toxicity compared to other anti inflammatory compounds.
A common pattern of minor cannabinoids is their ability to activate TRPV1, and CBDV is no exception. This cannabinoid has been found to activate both TRPV1 & TRPV2 transmembrane proteins involved in pain and inflammation. When a CBDV rich hempoil was used in an in vivo model of epilepsy, it was found to decrease seizures independent of CB1 receptor activation, suggesting that there are multiple mechanisms of activation for CBDV that are not related to the classical endocannabinoid system receptors.
THCV has been reported to help relieve stress, anxiety, and panic attacks, a pattern similar to CBD and CBDA. Mechanistic studies show that THCV can be both and agonist (activate) and antagonist (inhibit) the CB1 receptor depending on the concentration. It was also shown to be a potent CB2 agonist, which may explain some of the similar benefits it has with THC and CBD.
CBN products that help with sleep often contain CBN as a minor cannabinoid that has considerable side effects of drowsiness. While there is limited studies on CBN and sleep, a lot of consumers report beneficial effects from using this minor cannabinoids. Some studies have tested the effects of CBN in combination with CBD on muscle pain. This study reported improved sensitization in vivo, suggesting that combination treatment of CBD and CBN may affect pain receptors and could be beneficial for sore muscles.
The body naturally makes endocannabinoids, which are small molecules that are produced as part of the regulation of the endocannabinoid system. There are two main endocannabinoids, N-arachidonoylethanolamine (AEA; anandamide) and 2-Arachidonoylglycerol (2-AG). Both AEA and 2-AG are critical signaling molecules, that can interact with a number of cellular receptors in the endocannabinoid system, such as cannabinoid receptors 1 & 2 (CB1 and CB2 receptors).
The functional difference between endocannabinoids and cannabinoids from the cannabis plant are the different targets and specificities for receptors in the endocannabinoid system. While it is commonly thought that the main targets of THC, CBD and other minor cannabinoids are the CB1 and CB2 receptors, there are other critical receptor proteins such as 5HT1A that are important.
The endocannabinoid system is present in all mammals, and includes a wide range of cellular proteins and functions. It is responsible for modulating mood, immune function, inflammation, and many others, studies are continually showing that the endocannabinoid system is highly integrated in many physiological processes. The classical receptors involved in the endocannabinoid system are the CB1 and CB2 receptors, and are found on most cells including neurons and immune lymphocytes. However, other important protein receptors are also part of the endocannabinoid system, and these include TRPV1 and 5HT1A, both important neuromodulator targets. The scope of this article does not focus on this important physiological system as it would be too long, see our article on some of the basics of the endocannabinoid system.
Many CBD products, such as CBD tinctures and CBD gummies are sold at low doses, such as 10mg to 50mg. However, much of the research indicates that higher doses are necessary to achieve therapeutic results. These can range from 100mg to 600mg per day, and even epilepsy patients can be up to 2000mg per day with medical supervision. Because CBDA and acidic cannabinoids have enhanced absorption, much less, around 30mg to 50mg, is needed to get the same absorption properties as CBD. See our CBDA dosing guide.
With Natural Spectrum CBDA products, you can get all the benefits of enhanced absorption without needing to buy a new bottle every week.
Any supplement or drug taken at high enough doses can cause some side effects. The most significant reports for CBD side effects was potential liver toxicity at higher doses in patients already on medication. This was found in the clinical trials of patients with epilepsy using the CBD drug Epidiolex. Patients were taking 1000mg to 2000mg per day, and there were indications of drug-drug interactions in the CYP450 liver metabolism pathway. These results appear to indicate that multiple medications on top of high doses of daily CBD were able to increase markers of liver damage.
The FDA has not approved minor cannabinoids for treatment, and much of the research is still ongoing. At this time, only THC and CBD have been approved for limited use in some conditions. It should be noted that there may be drug-drug interactions with THC and CBD with some medications, so it is important to speak with your physician before adding cannabis plant based oils to your daily regiment.
Endocannabinoids are considered among the most important therapeutic fields in psychopharmacology over the last decade, opening up a range of new medicines and therapies. The distribution of endocannabinoids in the brain is interesting as reports find effects that are can affect mood, inflammation, and stress. Complexity found in the integration with other neurotransmitting systems like dopamine, GABA and glutamatergic could influence the development of therapies and potential side effects that are still unknown with cannabis use. Searching the national library of medicine for cannabis and cannabinoids will help you stay up to date on all the current studies.
This can vary a lot depending on the hemp strain and how it is grown. For hemp grown outdoors and used for extraction of CBD, CBDA, CBG etc, you typically see a range of 5% to 12% in the hemp flower. However, for hemp grown indoors for the purposes of being smoke, you can see ranges from 15% up to 25%.
Hemp oil can mean a number of different things depending on the stage of extraction and purification.
For crude hemp extracts, which is simply an extraction without purification, you can see around 40% to 70% cannabinoids.
For purified hemp oil, typically called distillate, it can have between 80% to 95% cannabinoids.
We should note that hemp oil typically has 3 to 10 different kinds of cannabinoids in them depending on the strain and processor. This can include CBD, CBDA, CBG, CBGA, THCV, THCVA, THC, THCA, CBC and CBCA among other.
Hemp cannabinoids are known for containing a high amount of CBD, although technically hemp contains CBDA, the precursor to CBD prior to heated purification. However, similar to marijuana, hemp also contains over 100 other cannabinoids in much lower amounts.
The most common other minor cannabinoids are typically CBGA, CBG, CBC, CBCA, THC, THCA, THCVA, THCV, CBN, CBDVA and CBDV. The amounts of individual cannabinoid kinds will depend on the strain.
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