With countries worldwide slowly legalizing cannabis, research is finally growing and we’re constantly finding out more about the 120+ cannabinoids in the marijuana plant, namely CBDV, otherwise known as Cannabidivarin. 

People are looking beyond conventional THC or CBD and seeking out new cannabinoids like this one, and in this article, we will explain why CBDV is worth looking into. The laws have limited public access and therapeutic research on non-psychoactive cannabinoids. Fortunately, we’re discovering more and more cannabinoids that are non-psychoactive and still have the healing properties of cannabis.

So, what is CBDV?

Cannabidivarin (CBDV) is a Varin cannabinoid first reported in a benzene extract from a Thai cannabis variety referred to as “Meao” in 1977, and identified for the first time in 1969 Vollner et al. CBDV is a homolog of CBD and is a non-psychoactive cannabinoid. As you can see below, The slight difference here is the propyl chain that CBDV carries. 

Like CBD, cannabidivarin has 7 double bond isomers and 30 stereoisomers. There is a side-chain shortened by two methylene bridges. The biggest difference between CBD and CBDV is their concentrations in the cannabis plant. You can find trace amounts of CBDV in high-quality full-spectrum and broad-spectrum extracts that help to produce the entourage effect.

Varin cannabinoids (technically called varinolic cannabinoids) are a subfamily of cannabinoids that feature three carbons on their alkyl side chains. The most well-known examples are THCV, CBDV, CBGV, and CBCV. There are also acid forms of THCVA, CBDVA, CBGVA, and CBCVA.

CBDV exists in very small quantities. Recently, several African landrace strains (which are genetically pure and unimpacted by experimentation) of Cannabis indica were found to have CBDV and the related THCV in concentrations closer to 4%. There are also plant breeders creating high CBDV and THCV strains of hemp and marijuana — but the current record still sits below 7% CBDV. 

What are the medicinal effects?

Epilepsy

Due to the rise in popularity of CBDV, researchers are trying to discover its medical benefits. In 2014, GW Pharmaceuticals finished a Phase 1 clinical trial of its CBDV test product (known as GWP42006). The clinical trial explored the use of CBDV as an anti-epileptic drug. The company continues to research CBDV heavily. You won’t feel a psychoactive ‘high’ from CBDV. Instead, you can expect it similar effects to CBD. The lack of a ‘high’ means we can use CBDV similarly, which is still being researched.

GW were set to enter Phase III trials in late 2019 but had to terminate the study because of the pandemic. They’re currently recruiting for a new trial, and the CEO Justin Gover made the following statement;

“CBDV represents an additional product pipeline opportunity as a next-generation epilepsy therapy.”

This study follows the completion of a Phase 1 trial in 66 healthy subjects in 2014. In this trial, CBDV was well tolerated even at the highest tested dose and no significant side effects were observed. Most importantly, following this trial, There were no serious or severe adverse events, nor any withdrawals due to adverse events.

Rett Syndrome

As you may know, Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms with no cure available to date. A study was done on mice with CBDV being administered for 14 days. The study restored compromised general health status of the mice, the sociability, and the brain weight in RTT. While more studies are required, this shows great promise for the medical use of CBDV.

Autism

Some of the most interesting recent research into CBDV has been around the subject of autism. This condition, which affects more children and adults every year, is still being researched to find effective medications. The use of CBDV for autism has rapidly gained popularity over the last two years.

The study suggests that CBDV targets subcortical excitatory glutamate systems both in autistic and neurotypical adults. This study compared the effects of CBDV in neurodiverse patients and neurotypical patients. They noted a higher degree of difference in ASD patients with elevated glutamate. Very little benefit was reported on those with normal glutamate levels.

Some studies have even shown that people diagnosed with autism spectrum disorder (ASD) have below-average anandamide levels in the brain, one of the body’s endocannabinoids. 

Pain

In this study, patients underwent two successive treatment phases (4 weeks each) and were treated with CBDV. While the study wasn’t necessarily conclusive, it did explore the potential utility of CBDV for neuropathic pain. 

While CBDV research is increasing, so far there are no guarantees that cures or applications have been or will be found. The existing CBDV studies and research papers indicate grounds for medical optimism that previously may not have existed. With the growing interest in the industry, there’s endless potential. Fortunately, there should not be severe restrictions on CBDV, considering its lack of psycho-activity. 

CBDV and the endocannabinoid system:

CBDV interacts with the endocannabinoid system (ECS) the same way as CBD. However, it’s thought to have about 25% of CBD potency. CBDV does not stimulate the ECS as CBD and THC do; it has a modulating action instead. According to the British Pharmacological Society;

“CBDV and all the acids inhibited DAGLα.”

DAGLα is an enzyme responsible for the synthesis of the endocannabinoid 2-AG.

Is CBDV Legal? 

CBDV is legal in the United States, as long as it is produced from Hemp rather than marijuana. This is because CBDV derived from marijuana is illegal on a federal level and is considered a schedule 1 drug by the Drug Enforcement Agency (DEA). Some states have legalized marijuana for medicinal or recreational use. The states that have legalized marijuana have also legalized its derivatives, including CBDV. 

CBDV derived from hemp containing no more than 0.3 percent THC is considered legal on a federal level due to the 2018 Farm Bill. This Bill gave states the power to further regulate hemp products, which some states have by restricting any traces of THC. Although hemp-derived CBDV is difficult to find, it’s legal in all states as long as it abides by the state THC regulations. 

What is the difference between CBDV and CBD?

As previously mentioned, the molecular structures between CBD and CBDV are different, which impacts their chemical responses. Furthermore, CBDV can be used to develop THCV (tetrahydrocannabivarin) when it’s exposed to an acidic environment. CBD doesn’t have this same ability to transform into THC. When dealing with CBDV vs CBD, both cannabinoids share huge similarities that could be a massive hit in the medical industry because of the therapeutic effects offered. Above all, CBD and CBDV both interact with the endocannabinoid system, but CBDV binds with the cannabinoid receptors and CBD simply interacts or blocks the receptors.

Based on all the information provided, it’s clear why Cannabidivarin might be the next significant cannabinoid the world will witness, and we can only hope that research increases to increase the use of CBDV globally.

If you’re a cannabis user, you’re probably familiar with the sugary, crystal-like appearance that appears on the flower, leaves, or bract - known as trichomes. Trichomes are produced across the cannabis plant, which holds the plant's cannabinoids and terpenes. Most people recognize trichomes as the ‘tiny hairs’ on the plant, so it’s likely that you’ve already seen them.

So, what are trichomes?

The word trichome originates from the Greek word “Tríchōma,” which means growth of hair. The actual definition is “appendages on plants, algae, lichens, and certain protists.” - These tiny outgrowths, or sources of resin, allow the production of cannabis concentrates like; shatter, cannabis oil, hash, and wax. Each trichome has a unique size, shape, and biochemical function.

Trichomes are minuscule biological cannabinoid factories found predominantly on the flowers and sugar leaves of weed, providing a variety of functions and benefits to the plant. Scientists have said that trichomes could affect leaf temperature and photosynthesis, or more complicated functions, such as pest-deterrence via their physical structures or production of compounds, as studied by George J Wagner, stating that trichomes;

“Guide the path of pollinators or affect photosynthesis, leaf temperature, or water loss through increased light reflectance as in desert species.”

What are the different trichomes?

Scientists have identified three categories of trichomes found on cannabis plants:

1. Bulbous trichomes
2. Capitate-stalked trichomes
3. Capitate sessile trichomes

It is believed that trichomes function as a form of survival for the cannabis plant. The sticky resin that coats the plant provides a frontline defense against fungus, insects, and herbivores. Trichomes also play an essential role in helping cannabis grow in difficult climatic conditions.

1. Bulbous trichomes
2. These are the smallest type of trichomes, sometimes being as little as 10 microns wide - which is actually a fraction of the largest size. These can be found across the surface of the plant - but are too difficult to see.

2. Capitate sessile trichomes

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These trichomes are larger than bulbous trichomes, with enough cell    numbers to form a trichome head and a very short base. These trichomes have a width of around 20-30 microns, which are not as large as the final category of trichomes, nor as easy to see.

3. Capitate-stalked trichomes

These are much larger and can be seen by the naked eye. These range from 50-100 micrometers wide typically. Capitate stalked trichomes have a stalk that is made from cells known as epidermal and hypodermic cells. On top of the stalk is the head of the resin gland, the ‘capitate.’ The ball-shaped head of the resin gland has a waxy outer cuticle layer which acts as a ‘skin.’ Inside the resin head are the cannabinoids and terpenes. These are produced by specialized cells in-between the top of the trichome stalk and the spherical resin head.

Cannabis trichomes typically appear early in the flowering stage on healthy plants. As trichome heads age, they go from being completely clear to opaque, milky white, and, eventually, amber. See below for reference;

What do the different trichome colors mean?

Clear Trichomes:

As a plant transitions into the flowering phase, noticeably the first trichomes appear. Young and immature trichomes feature a clear, translucent appearance. They maintain this appearance for the first part of this phase before their chemical composition changes significantly for the first time. This color indicates that THC and terpene production is at their peak, while CBD levels are still low. This means harvesting at this color will have a more cerebral psychoactive effect. However, it is still not ideal to harvest at this stage and should be harvested at the next.

Cloudy Trichomes:

Cloudy trichomes occur prior to harvest and indicate that cannabinoid levels have reached their maximum. This does not necessarily mean that it is an extremely potent THC strain, however, as that depends on other factors. While it doesn’t guarantee potency, it is a good indicator of when the strain has reached its production peak.

This is when most growers harvest their flowers, and it is generally considered the right time to harvest. You can also use the pistils as an indicator when more than 50% of the hairs have turned orange it means you’re at this stage.

Trichomes remain cloudy for approximately two weeks. Towards the end of this stage, they start to change appearance once again, indicating more developments in their phytochemical composition - which is why they start turning amber in color.

Amber Trichomes:

If trichomes have turned a visible amber hue, the cannabis plant has probably aged past peak potency. This trait makes trichomes a good indicator of when a plant is ready for harvest. Most growers pay close attention to the state of the plant's trichomes and try to harvest buds right when the trichomes are milky white before they have degraded to amber.

Trichomes turning amber indicate deteriorating THC levels, so it is a fine balance of checking on them several times a day to ensure that harvest happens at the peak moment for both high THC levels and the desired couchlock effects.

What impacts trichome production?

1. Stress training
   
2. Stress training can significantly increase yields when performed correctly. Higher yields tend to mean more trichomes. The process typically involves manipulating the plant's shape to distribute hormones more evenly across the top buds, allowing the plant to make better use of the light.
   
   However, the process of stress training can have negative consequences, like bud discoloration, re-vegging, or hermies, so it’s an ambiguous process to say the least. However, it is usually safe as long as you save any major stress for the last week or two before harvest.

1. Lighting
   
2. The light spectrum is one of the most fundamental parts of a cannabis plant’s ability to increase trichome production. The trichomes protect the plant from UV rays, which means that the more light the plant gets - the more resin it will produce.
   
   Some believe that exposing cannabis buds to UV-B light for the last 2-3 weeks before harvest can increase trichome production and overall potency. The most common source of UV-B light is Metal Halide grow lights.  

1. Temperature and humidity
   
2. Temperature and humidity have a massive effect on the growth of cannabis flowers. When temperature and humidity are adjusted to induce stress, the plant may increase trichome production as a defense mechanism.

1. Adjusting the environment
   
2. Each stage of cannabis plant growth influences the production of trichomes. The glands are highly fragile and volatile, which is why ensuring that the plant is growing in the right environment should be a priority - especially in the flowering stage. The purpose of adjusting heat periodically is to avoid the trichomes and terpenes from getting damaged by heat.
   
   This is the general rule of thumb when altering the environment:
   Humidity below 30% – Drop the humidity of the growth space below 30% RH for the last 2-3 weeks before harvest to increase trichome production.

Temperature between 70-80°F – Make sure your temperature stays under 80°F (26°C) to ensure the potency is not being baked right off your buds.

1. Supplements
2. It is essential to give your plants plenty of phosphorus and potassium during their flowering stage. Boosting trichome production requires that a cannabis plant is fed the correct amount of nutrients. If a plant is deficient in nutrients, it slows down all its functions.

Genetics plays the most significant role when it comes to getting the most trichomes out of your cannabis. Genetics are crucial If you want to achieve the best and most trichomes you can, so choosing genetics that produce an abundance of trichomes is essential.

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Cannabis lovers have watched highly anticipated, high-inducing cannabinoids divide the hemp industry for the last few months. With an ever-growing marketplace, hemp companies are looking for an edge, and some are turning to controversial, synthetic cannabinoids such as HHC and THC-O. Marketing the artificial compounds as "new,” "rare," or "extremely potent" without disclosing the facts - these compounds are neither legal nor safe. However, the bold claims presented by some companies are driving tremendous interest.

The cause for attraction is due to the higher potency of their therapeutic and psychoactive properties. The consequence of this is that sales of extracts are snowballing, which is why the unnatural, synthetic cannabinoid known as THC-O acetate is one of the substances gaining attention. The continuation of prohibition has been a catalyst to this kind of development of products that people would like to think are legal but are not. Not only are people being drawn to the higher potency, but there is a misbelief that higher potency substances bear higher benefits.

However, in this study, you can see that higher potency does NOT equal higher efficacy or improved benefits.

“Both A and B achieve the same maximum effect, i.e., they have equal efficacy.”

THC-O acetate, or THC-O, is a synthetic analog of THC. That means that THC-O is not naturally occurring and can only be manufactured via modern cannabis tech. The main reason it’s gaining rapid popularity and becoming the topic of conversation is that it is said to produce effects three times stronger than conventional THC. This might seem exciting to the regular cannabis user, but on the contrary, it’s anything but exciting. THC-O’s potency and chemical composition suggest an uncertain future.

So, what is THC-O acetate, and how is it derived?

According to the United States Patent for THC-O;

“Tetrahydrocannabinol (THC) in cannabis oil reacts with acetic anhydride under reflux to produce THC-O-acetate and acetic acid.”

The process requires material high in THC (typically includes 75-90% THC and 5% other cannabinoids). Specifically, the material that is needed to produce THC-O is THC Delta-9 Distillate. The method of making THC-O acetate is inherently dangerous. The acetic anhydride that's part of the process is highly flammable and potentially explosive. This has to be done in a technical lab, which adds additional layers of complication to an already toxic outcome.

The patent explicitly states the definition of THC as;

“A phytocannabinoid molecule that is found in the cannabis plant mostly in its acidic form, tetrahydrocannabinolic acid (THCA)...THC is known for its psychoactive effect when consumed or inhaled. It is more correctly known as delta-9-tetrahydrocannabinol.”

It then clarifies that THC levels in cannabis plants are typically very low, e.g., <2%. THC is known for its psychoactive effect when consumed or inhaled, and It is more correctly known as delta-9-tetrahydrocannabinol, not to be confused with other forms of THC such as Delta-8.

The patented process requires a reflux reaction between decarboxylated cannabis oil, which has a presence of THC, and acetic anhydride occurs, resulting in a crude product of THC-O-acetate. It then states that you can, in fact, utilize the process using other cannabinoids; however, the result is an entirely different variant and is not THC-O as some companies may be claiming it to be.

“As an alternative, the whole process may be applied for the acetylation of cannabinoids other than THC such as CBD, CBG, and CBN.”

What are its effects?

In the book ‘Marijuana Potency’ by Michael Starks, he classifies THC-O-acetate as 300% stronger than the THC we all know, which explains why many liken its effects to that of the psychedelic realm. Although few people have tried it, and little research has been done, it is spiritual and introspective. in the 1974 book Cannabis Alchemy: Art of Modern Hashmaking by Author D. Gold; he stated the following;

"The effect of the acetate is more spiritual and psychedelic than that of the ordinary product.”

While the exact effects aren’t widely known, we do know that it takes far longer for the user to feel its effects. The effects only activate and become noticeable once enzymes deacetylate the THC-O-acetate in the body, which is highly unusual compared to regular THC. After administration, the substance is metabolized, and only then are the effects felt - which makes it prodrug.

What is the history behind THC-O-acetate?

THC-O-acetate was first investigated between 1949 and 1975. It was being tested as a non-lethal incapacitating agent on dogs but was soon after found to be almost twice as strong as regular THC.

THC-O-acetate’s first encounter with the U.S. DEA was in 1978; the DEA expressed concerns that THC-O-acetate was being made analogously, similar to how heroin is made from morphine, but that was classified as an isolated incident, so the suggestion of making it a controlled substance was dropped. Similarly, in 1995, the United Kingdom ruled THC-O-acetate as a class A drug. It has only been until recently, around 2018 when the USA’s legal changes erased restrictions on the cultivation of industrial hemp.

So what exactly is the issue with THC-O-acetate?

Most labs cannot provide a potency analysis for THC-O. This poses a massive issue for the industry as a number of companies are selling ‘THC-O’ that is clearly not THC-O, and have no reference of standard from a credible 3rd party. ChemHistory, a credible lab used by many, explained that while they have the THC-O standard, they couldn’t quantify the exact target analyte of the analyzed sample because no CRM for this material currently exists.

“We do not have a certified reference for it. For reference, the THC-O-Acetate standard was provided by Cerilliant, who just developed this standard a few months ago.

ChemHistory is familiar with the standard for testing THC-O but cannot identify the exact analyte submitted (on-hand) because it’s not THC-O. On pg. 13 of the report, the tech analysis explains that the submitted isomer is similar in appearance but not THC-O and was likely created using something other than Delta-9 Distillate (required for producing THC-O). They state that if THC-O-acetate were the goal of this production, using THC Delta-9 distillate would have yielded higher and more accurate results.

“As you can see, this peak also has a very THC-O-Acetate spectral profile. However, its retention time is remarkably different. We suspect that this is either a THC-O-Acetate isomer or perhaps a different acetylated cannabinoid. Perhaps CBD-O-Acetate?”

As previously mentioned, the material that is needed to produce THC-O is THC Delta-9 Distillate. You can make similar isomers using other sources such as THC Delta-8 as opposed to D-9, but as mentioned in the tech notes (lab analysis above), the result is not the same. If THC Delta-8 is used as the source material, the result is CBD-O-Acetate, NOT THC-O-Acetate.

The main problem is that hemp companies do not have the licensing to possess Delta-9 distillate as this is a marijuana extract. Furthermore, if they attempt to create THC-O with a different base, such as THC-Delta 8, the result is CBD-O and not THC-O. Thus some may be using a "hemp-derived product," but in using the incorrect source material, They're mislabeling the product as THC-O when in-fact, it’s not.

What are some concerns about how THC-O-acetate may be used?

The fear of the fraud and illegality behind the substance is a top concern.

1. As stated above in the tech notes, no standard currently exists for the material these companies are submitting - which means that hemp Companies cannot reliably report the potency of the CBD-O that they’re claiming to be THC-O.
2. Hemp companies are marketing a THC-O isomer, or perhaps a completely different acetylate cannabinoid (as mentioned in the lab report) as THC-O, which is a blatantly false claim, and borderline fraud.

Our concern lies in the fact that companies are taking advantage of an uneducated marketplace for monetary gain. Pursuing higher potency has been an ongoing goal of the industry for years, but illegally creating a product and falsely marketing it as such is not accelerating the industry’s growth.

How are companies contributing to the problem?

For one, companies are exploiting "new" and "rare" cannabinoids at an alarming rate, using processes that are not standardized, dangerous, and toxic. A lack of research and regulation based on actual data means that mysteries about THC-O acetate are prevalent. A company should not be selling anything that is not backed by enough research or data. This means that companies are creating products with wide variations of quality due to the lack of data. As we saw from the lab report above, companies are likely getting far less pure of a product than what they’re marketing.

Companies exploit the miseducation in the industry and purposefully find loopholes in the legislation to pursue a dangerous, toxic, and illegal product. Companies should be well aware of the Federal Analogue Act, which states;

“any chemical "substantially similar" to a controlled substance listed in Schedule I or II to be treated as if it were listed in Schedule I.”

Products with THC-O exist in the marginal legal space between hemp, which is legal, and cannabis - which is not federally legal and is highly regulated in the states that allow it. THC-O needs to come under a state-regulated system before consumer consumption to ensure they can weigh the benefits themselves. With companies falsely advertising the end product - the consumer can’t understand and consider the risks and benefits. Companies should follow safe practices and perform their due diligence before offering the latest, but certainly not the greatest, cannabinoids.

The industry is complicated, but unlicensed hemp-derived products are undercutting the market and tarnishing the reputation of an industry that has spent decades building a focus around health and wellness. As a consumer, you should have complete confidence that what you’re buying is what you’re getting - and you should have comfort in the fact that your chosen company puts your health first. It’s up to you to educate yourself and stand against companies advocating for substances like this.

The daunting reality is; when companies are calling a substance something that it isn't, can you imagine what else they're not telling you?

Sources for further reading:

Lab report

Patent

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