Neutral vs Acidic Cannabinoids: Know the Difference
Cannabinoid acids are the chemical precursors to the cannabinoids we all know and love. This might come as a shock to you, but cannabis doesn’t actually produce the neutral cannabinoids that most of us are familiar with. The plant possesses metabolic machinery that allows it to synthesize cannabinoid acids, but these pathways stop short of THC, CBD, CBG, and other neutral cannabinoids. THC and CBD exist only in trace quantities in raw flowers as products of degradation; the bulk of these molecules are created when their corresponding cannabinoid acids are exposed to heat in the form of lighters, vaporizers, and ovens. Drying and curing cannabis also results in the partial conversion of these molecules, albeit over a longer period. Before this transformation occurs (a process known as decarboxylation), cannabinoids feature an additional structural component known as a carboxylic acid group. The presence or absence of this extra bundle of carbon, oxygen, and hydrogen atoms determines what category the chemical belongs to: neutral or acidic. The principal psychoactive constituent in cannabis, THC, exists primarily as THCA in raw cannabis flowers. Chemical analysis shows that a cannabis cultivar with a THCA content of 24 percent, for example, possesses only about 0.5 percent THC before drying and heating commence.
Role of Cannabinoid Acids
Cannabis plants are often referred to as bio-factories, and for good reason. This versatile species contains more than 400 distinct compounds divided into numerous chemical groups. While neutral cannabinoids and terpenes occupy the limelight — largely due to their psychoactive effects and pleasant aromas — cannabinoid acids remain among the unsung heroes of these molecular entities. Cannabinoid acids are inherently valuable because they serve as the chemical predecessors to highly sought-after byproducts such as THC and CBD. However, because they feature different structures, they also fulfill different functions.
Much like neutral cannabinoids, cannabinoid acids also interface with the endocannabinoid system. Termed the universal regulator of the human body, this widespread signaling network helps to keep our physiological systems within their goldilocks zones of operation; it governs neurotransmitter firing, bone remodeling, and energy metabolism, among myriad other functions. The recreational and medicinal effects of neutral cannabinoids are largely dictated by how they interface with the receptors of this system. Because cannabinoid acids influence the endocannabinoid system differently than neutral cannabinoids, they’re also gaining traction among scientific researchers and lay users alike. However, these molecules aren’t easily tamed. Changing what we consume also requires that we change the way we consume. These fire-shy molecules are volatile and lend themselves to edibles, extracts, and tinctures as opposed to the higher temperatures of bong bowls and vape chambers.
Creating Cannabinoid Acids: Enzymes Determine Destiny
You’re probably familiar with trichomes. These glands are what give cannabis flowers their frosty appearance. You’ve probably also come across them up close as the centerpiece of countless magazine covers. These small structures might seem insignificant, but they underpin almost everything that makes cannabis a valuable crop. You can look at trichomes as tiny chemical factories. They’re kitted out with an arsenal of enzymes that enable them to convert precursor molecules into secondary metabolites — molecules that aren’t directly involved in growth and reproduction, but that play an important role in defense and survival. Cannabinoid acids and terpenes fall into this category.
The complete biosynthetic pathway of cannabinoid acids gets very complicated, so we’re going to deliver an abridged version. All cannabinoid acids start life in the same way in the form of two important chemicals: Olivetolic acid and geranyl pyrophosphate. The enzyme CBGA synthase acts on these molecules to create CBGA (cannabigerolic acid). You’ve likely come across articles labeling CBG (cannabigerol) as the “mother cannabinoid.” In truth, this prestigious title belongs to CBGA. Why? Because several major cannabinoids have their roots in this compound. THCA, CBDA, and CBCA all descend from CBGA when acted upon by the specialist enzymes THCA synthase, CBDA synthase, and CBCA synthase, respectively. These cannabinoid acids remain in this form until conversion takes place by way of heat and time. But what role do they fulfill in plants until then?
The Role of Cannabinoid Acids in Plants
Plants exist in highly competitive environments. Those that live in the wild are at the mercy of many predators. Even those that enjoy the shelter of growrooms and gardens face frequent assaults at the hands of bugs and diseases. For plants, it’s very much an insect-eat-leaf world. But insects aren’t the only adversaries your favorite cultivars have to contend with. All plants face two major forms of stress: biotic and abiotic. Biotic stress refers to all things living (think biology), including insects and pathogenic viruses and bacteria. Abiotic denotes anything non-living that causes stress in plants, including the UV rays of the sun, drought conditions, and extreme temperatures. As immobile and relatively unadvanced lifeforms, plants don’t get bundled into the back of an ambulance when sick, and they don’t have a vegetative police force to come to the rescue when they’re under attack. Instead, they take a different approach to defending themselves: chemical warfare.
Remember the secondary metabolites we touched upon? Well, plants use these molecules to protect themselves against both biotic and abiotic stress. They harness their trichomes to churn out a viscous resin packed with an armory of chemicals, including terpenes and cannabinoid acids. In reference to the latter, plants opt to expend energy on their creation because they yield a worthwhile return on metabolic investment. Trichomes rupture as herbivorous insects chow down on cannabis leaves. The gooey consistency of non-crystalizing cannabinoid acids glues the mandibles and appendages of grazing insects, preventing further feasting. Cannabinoid acid production also correlates positively with heat stress, reduced soil moisture, and low nutrient availability, suggesting an adaptive role to taxing conditions. These protective molecules also work as a natural sunscreen to filter out harmful UV-B radiation.
From Acidic to Neutral: A Tale of Decarboxylation
Decarboxylation refers to the ejection of the carboxylic acid group; a reaction that renders acidic cannabinoids neutral. Each cannabinoid acid transforms into its corresponding neutral cannabinoid when exposed to a specific temperature for a specific amount of time. Sufficient decarboxylation of THCA occurs at exposure to temperatures of 230°F for 30 minutes and 265°F for nine minutes. CBDA takes a little longer. Conversation occurs at 230°F for 45 minutes and 265°F for 20 minutes. Extracts of CBGA also undergo decarboxylation when subject to temperatures of 230°F. Knowledge of these parameters comes in useful for two primary reasons. Firstly, they serve as a target for those seeking decarboxylation. Lighter flames reach temperatures over 4,000°F, and most vaporizers feature precision temperature controls allowing users to target specific phytochemicals. Both methods of consumption guarantee decarboxylation. Secondly, these figures are important for both researchers and manufacturers aiming to preserve cannabinoid acids. These professionals cannot expose oils, edibles, and extracts that contain these molecules to temperatures that cause them to degrade. As well as heat, long-term storage also poses a problem. Cannabis scientists are looking for ways to solve this issue, including the legendary Dr. Raphael Mechoulam (the man who discovered THC). Using a process known as esterification,
Mechoulam has created a patented version of CBDA, known as EPM301, that demonstrates greater resistance to decarboxylation.
Now that you’re much more familiar with cannabinoid acids, how they’re made, and why plants produce them, it’s time to take a look at how they act in the body. Before we explore three of the most abundant cannabinoid acids, it’s important to keep in mind that most of the research remains in the early stages. While there are plenty of cell studies available, human trials are lacking. This means we need to take these results with a grain of salt before we see them replicated in humans.
THC vs THCA
THC underpins the psychoactive effects of cannabis by binding to an endocannabinoid receptor known as CB1. Aside from providing recreational enjoyment to millions of people each year, this molecule also demonstrates pain-killing, sleep-improving, anti-anxiety, and anti-cancer properties. The additional carboxylic acid group of THCA molecules prevents them from binding to CB1 in the same way, meaning the cannabinoid acid produces no psychoactive effect — a trait viewed as an advantage in certain clinical scenarios. To make things a tad more confusing, THCA exists in two different forms: THCA-A and THCA-B. However, THCA-A occurs in greater quantities in cannabis. Early studies have shown potential for this molecule in models of Parkinson’s disease and cancer and have found anti-inflammatory, immunomodulatory, and anti-inflammatory effects.
CBD vs CBDA
CBD has gained massive popularity in recent years as a supplement, cosmetic ingredient, and therapeutic agent. Its lack of psychoactive effects and widespread legal status makes it an appealing option for many cannabis users that don’t want to get high or break their county’s laws. Although CBD doesn’t have a strong affinity to the primary endocannabinoid receptors, it may help to elevate levels of endogenous cannabinoids such as anandamide, otherwise known as the “bliss molecule.” CBD also works in somewhat of a synergistic manner with THC by changing how it interacts with CB1 receptors. This action lends itself to curbing the cannabis high and balancing out the psychoactive effects of certain cultivars.
But what about CBDA? So far, scientists have figured out that it targets important sites, such as vanilloid receptors and so-called orphan cannabinoid receptors. The molecule also binds to serotonin receptors with far more potency than CBD itself, suggesting promise for mental health disorders such as depression and anxiety. Identified antiemetic effects also make CBDA a potential candidate as a nausea medication.
CBG vs CBGA
Cannabis users are becoming increasingly interested in CBG thanks to ongoing studies that have demonstrated therapeutic potential related to neuroprotection, gastrointestinal disease, and metabolic syndrome. While CBG only weakly binds to the CB1 receptor, it interacts with other endocannabinoid system sites, including vanilloid receptors. Although research on its corresponding cannabinoid acid remains sparse, studies show that CBGA might contribute to the anti-seizure effects of cannabis through activation of endocannabinoid system receptors and GABA receptors. A study performed on dogs also found CBGA to be absorbed around 40-fold better than CBG.
The Tip of the Acidic Iceberg
The cannabis plant produces more than 100 cannabinoids, and researchers have barely scratched the surface when it comes to their therapeutic effects and how they work in the body. Other examples of major cannabinoid acids include CBCA, CBGVA, THCVA, CBDVA, and CBCVA. Some cannabis users might feel frustrated at the fact we’re at such early stages in this game of detective. However, one thing can be said for sure: It’s certainly an interesting time in cannabis history. Prepare to see more cannabinoid acid products hit the shelves in the coming years.
