Cannabidiol (CBD)

kan-ə-bə-ˈdī-ˌȯl | Noun

Definition

A non-intoxicating cannabinoid found in cannabis. After tetrahydrocannabinol (THC), cannabidiol (CBD) is the second-most abundant cannabinoid in the plant, and has many potential therapeutic benefits, including anti-inflammatory, analgesic, anti-anxiety and seizure-suppressant properties. Cannabidiol can be sourced from both marijuana plants and hemp plants, which are legal in most countries as they contain less than 0.3% THC.  

 

“CBD is the yang to THC’s yin; it halts anxiety and elevates your level of chill without intoxication.”

 

“Combine THC and CBD to fully employ the entourage effect; THC and CBD work hand-in-hand to amplify each others’ effects.”

More about Cannabidiol (CBD)

The phytocannabinoid cannabidiol (CBD), is a non-intoxicating molecule that results from the heating, or decarboxylation, of cannabidiolic acid, or CBDA. As popular as CBD has become in both the cannabis community and mainstream consumerism, its natural precursor, CBDA, is one of 114 unique cannabinoids found in cannabis. In most cultivars, or cultivated varieties of cannabis, CBD ranks low on the expression chart; there often isn’t much. However, following a explosive discovery in 2009 — it was noted that a handful of strains are rich in CBD over THC. Droves of CBD-rich cultivars began cropping up all across the US, resulting in a marked uptick in CBD availability across the states.

How CBD works

CBD’s action within the brain and body is quite complicated. To date, scientists have discovered more than a dozen different mechanisms of action, or ways that CBD affect us. It’s very likely that the beneficial effects of CBD are a result of the total of its activation of all of these biological pathways, not a single one in particular. Much more research is needed to fully understand the mechanisms by which CBD relieves ailments such as anxiety and seizures.

 

CBD directly interacts with a number of proteins in the body and central nervous system, a few of which are components of the endogenous cannabinoid system. For instance, CBD binds to both the CB1 and CB2 cannabinoid receptors, but it binds in a way that sets off a reaction that is essentially the opposite of what THC does. CBD is an inverse agonist, while THC is an agonist at CB1. Simply put, CBD is not intoxicating; at the molecular level, it does the opposite of what THC does. Our bodies have several other receptor proteins that participate in the endogenous cannabinoid system (GPR3, GPR6, TRPV1 and TRPV2, for example). CBD binds to all of these, and many of its anti-inflammatory and pain-relieving effects may occur through these pathways.

 

CBD has some other very important jobs outside of the endocannabinoid system (ECS). For instance, CBD mildly activates one of the brain’s predominant serotonin receptors (5-HT1A), which may explain CBD’s effects on depression and anxiety. It also acts at the peroxisome proliferator activated receptors (PPARs), which halt the proliferation of cancer cells and convey neuro- and cardioprotection. By interacting with a particular PPAR (gamma), CBD could prove to be a promising new way to prevent alzheimer’s disease and other brain disorders.

 

CBD has powerful effects on the liver as well. Have you ever had a prescription that warns you not to take the medicine along with grapefruit? That’s because grapefruit inhibits certain drug-metabolizing enzymes in your liver, resulting in much higher levels of your medication in your bloodstream. CBD does the same thing, so it is wise to discuss your medication regimen with a doctor or pharmacist before engaging in CBD therapy.

The relationship between THC and CBD

The relationship between THC and CBD is complex, but in short, CBD appears to minimize some of THC’s undesirable effects, such as paranoia, heart palpitations, and impaired thinking. Compared with THC in isolation, or its synthetic cousins such as Marinol, the combination of THC and CBD has much greater therapeutic value to patients. This phenomenon of cannabis-derived molecules working better together than they do in isolation is commonly referred to as the entourage effect.

Medical Uses

Consumers report using CBD for a huge variety of health and wellness reasons, but a lot more research is needed to determine which symptoms and ailments it works best for. Currently, there are more than 40 clinical trials enrolling patients to examine the effectiveness of CBD for a variety of diseases, including substance use disorder, chronic pain, post-traumatic stress disorder (PTSD), depression, schizophrenia, and many others. Most importantly, CBD is incredibly safe, and not addictive. Even young children can tolerate daily doses of up to twenty milligrams (20 mg) per kilogram (1 kg) of body weight (for a 175 pound adult, that’s more than 1,500 mg). The most common side effect of high-dose CBD is sleepiness.

 

Some very good medical and scientific research has been conducted for the following conditions.  

Pain Relief / Anti-inflammation

Understanding CBD’s analgesic, or pain-relieving, interactions with the ECS can shed light on CBD’s other interactions and effects. Importantly, the ECS participates in our bodies’ pain processing, but when CBD is introduced to our ECS, it stops the body from absorbing a pain-regulating compound known as anandamide — one of our body’s’ own natural cannabinoid molecules. Inhibiting the absorption of this compound shunts excess quantities into the bloodstream that in turn reduces pain. One study has revealed that CBD targets alpha-3 (α3) glycine receptors to suppress chronic pain and inflammation associated with dysfunctional glycine receptors, which are an important target for pain processing in the spine. In both humans and animal models, CBD has been shown to have a variety of anti-inflammatory properties.

Epilepsy and seizures

One of CBD’s chief properties is its anticonvulsant nature. Clinical trials have shown that CBD is effective at reducing seizures in children, and the FDA is likely to approve Epidiolex, a pharmaceutical-grade version of CBD for this use, in summer 2018. Although CBD has been documented as an antiepileptic since 1881, CBD’s anticonvulsant mechanisms still remain unclear. Not enough studies have been conducted to understand this relationship fully. One possible explanation for CBD’s neuroprotective effects is its interaction with NMDA receptors, which play a key role in the overly active neuron activity that is a hallmark of epilepsy.

Addiction treatment

In 2015, researchers conducted a comprehensive review to get at the heart of CBD and its intervention of addictive behaviors. These researchers gathered 14 studies, nine (9) of which involved animals, while the remaining five (5) involved humans, to find that CBD may indeed have therapeutic properties on opioid, cocaine, and psychostimulant addiction. Further, studies heavily suggest that CBD may also be beneficial in the treatment of marijuana and tobacco addiction. One reason that CBD may be effective as treatment for addictive disorders is its ability to ease the anxiety that leads people to crave drugs like heroin.

Other conditions

At sufficient doses (400-600 mg), CBD can alleviate situational anxiety, such as public speaking. Interestingly, cannabis cultivars, or strains, that are high in CBD and low in THC are better than other cultivars for alleviating depression. But when used over a long period of time, any kind of cannabis could make depression worse.  Although clinical trials in people haven’t yet been completed, there is very compelling “petri dish” evidence that CBD can reduce inflammation, for painful conditions such as Crohn’s disease, and fight some cancerous tumors. There is a massive amount of scientific research being done on CBD right now, and we are likely to see many medical breakthroughs in the next decade.

Single compound vs. whole plant

In 2015, The Hebrew University of Israel published a study that documented the potency of single-molecule CBD extract versus the potency of whole-plant CBD-rich extract. It found that extract taken from whole plant CBD-rich cannabis is therapeutically superior to single-molecule extract. The scientists behind this study noticed that science had been utilizing pure, single-molecule CBD, which resulted in a bell-shaped dose-response curve. This means that CBD’s efficacy plummets at very high and very low doses.

 

The 2015 study from Israel essentially documented the synergistic effects of whole plant cannabinoid profiles; as noted above, this is the entourage effect. The difference here, however, is that this most recent study dove into what extent whole-plant CBD can be more therapeutic than single-molecule CBD extract.

Industrial hemp and whole-plant marijuana

Although both hemp and marijuana are cannabis, hemp produces less than 0.3% THC, while marijuana produces more than 0.3% THC and is considered a “drug-type” product.

 

The age-old question: What’s better, CBD derived from industrial hemp or CBD derived from whole-plant marijuana? The answer is whole plant marijuana, but perhaps not for the reasons you’d assume.

 

Industrial hemp contains, by weight, far less CBD than CBD-rich cultivars such as Harlequin or Sour Tsunami. This means that producing a single 10 mL dose of CBD would require the cultivation and extraction of far more hemp than it would from whole-plant marijuana; thus raising the risk of exposing users to more contaminants. Hemp is classified as a “bioaccumulator,” or a plant that naturally absorbs toxicants from the soil.

 

Also, CBD derived from industrial hemp lacks the the incredibly diverse profile of different cannabinoids and terpenes found in whole-plant marijuana. CBD derived from hemp boasts a greatly weaker entourage effect.

 

And the final nail in industrial hemp’s proverbial coffin: Federal law in the United States prohibits the use of hemp leaves and flowers to make drug products. That said, isolating CBD nullifies these distinctions, rendering its source irrelevant as CBD isolate contains nothing but CBD. In this case, the differences between industrial hemp and whole-plant marijuana are far less significant.

How should patients choose CBD products?

Choosing CBD products isn’t as simple as picking something off the dispensary shelf and then walking out the door. Consumers should be aware that a handful of hemp products on the market pay lip service to governmental regulations by labeling themselves as hemp, despite containing cannabinoids and terpenoids. Some CBD products are completely devoid of cannabinoids including CBD, despite package labeling. The FDA purchased a number of CBD products online in 2015 and 2016 to test them for the presence of CBD and other cannabinoids. They found that the amount of CBD these products claimed on their labels was markedly inaccurate; some didn’t even contain CBD.

 

In states with medical cannabis laws, consumers should try to purchase cannabis from licensed suppliers who share their test results, which hopefully validate their products’ robust cannabinoid and terpenoid profiles. If you’re looking to purchase hemp through an online outlet, research your purchase beforehand to ensure that you aren’t being duped.

Cultivars Marketed as CBD-rich

AC/DC: A Sativa-dominant phenotype of Cannatonic, this cultivar boasts one of the highest ratios of CBD to THC, clocking in at 20:1. AC/DC is claimed to help reduce pain, anxiety, depression and migraines while reducing symptoms in patients with epilepsy, some forms of cancer, and multiple sclerosis. This cultivar’s pinene-rich terpene profile offers potent clear-headed pain relief.

 

Cannatonic: A potent pain-reliever, Cannatonic hails from Spain and stands as one of the earliest cultivars to be bred for its high CBD content. This cultivar is a cross between MK Ultra and G13 Haze, and it helps relieves anxiety, muscle spasms, pain, and migraines while providing uplifting energy. Cannatonic tends to relax and loosen muscles without locking users to their couches.

 

Harlequin: This cultivar was bred by crossing classic landraces from Nepal, Switzerland, and Thailand. Its consistent 5:2 CBD to THC ratio ranks it among the CBD-rich staple cultivars. It smells of a fresh pine forest dotted with hints of cherry. Harlequin helps mute pain and stress without fogging the mind.

 

Sour Tsunami: One of the first strains bred for its CBD content, Sour Tsunami washes pain away. This cultivar typically sports a 1:1 ratio of CBD to THC, making full use of the “entourage effect” to deliver potent relief without an overwhelming high. This Sativa-dominant Hybrid smells of musky diesel but refreshes the soul like a warm cup of tea.

 

Ringo’s Gift: This cultivar is named after the cannabidiol pioneer, Lawrence Ringo. Ringo’s Gift is a cross between two other CBD-rich strains, AC/DC and Harle-tsu. Its CBD to THC ratio varies from 1:1 to 22:1, but it consistently favors CBD. Ringo’s Gift smells of earthy pine and promises full-bodied relaxation in tandem with calming cerebral effects which, together, silence pain and anxiety.

The Pharmacological History of CBD

CBD was first discovered in 1940 by Roger Adams, a prominent organic chemist at the University of Illinois. Shortly thereafter, other scientists began testing isolated cannabinoids on lab animals; notably, Walter S. Loewe ran trials on mice and rabbits with the cannabinoids THC, CBD and CBN. He found that CBD produced no observable effects in the animals’ behavior while THC caused, what he called, a “central excitant action” in rabbits. Despite science’s movement forward, scientists were completely unaware of the cannabinoids’ chemical structure, so no one could tell which specific compound resulted in which effect.

Dr. Raphael Mechoulam

Cannabis made another leap forward in 1964 when Israeli scientist Dr. Raphael Mechoulam identified the structure of delta-9-tetrahydrocannabinol, or THC. This discovery earned him godfather status of modern cannabis. This particular discovery allowed science to understand THC’s nature as a psychoactive compound in cannabis as well as CBD’s non-intoxicating but vastly therapeutic benefits.

 

But he wasn’t finished. In February of 1980, Dr. Mechoulam teamed up with South American researchers to publish a study regarding cannabis and epilepsy. This study is seen as one of the earliest double-blind studies of CBD on clinical subjects. The study Dr. Mechoulam and his team conducted included 16 people, many of whom were children, who all suffered from severe epilepsy. The results were startling: Every subject who received CBD experienced improvement in their condition with little to no side effects. This anticonvulsant study has since proven to be an integral milestone in the world of clinical marijuana research, but largely went unnoticed at the time.

 

Dr. Mechoulam’s study wouldn’t remain alone for long. In 1993, a group of scientists researched and studied the effects of CBD on anxiety and found that it has potent anxiolytic, or anti-anxiety, properties as well.

California sets a CBD precedent

Outside of the aforementioned studies, CBD’s progress toward its place in society today suffered from intermittent spurts and starts until 1996 when California became the first US state to legalize medical cannabis. This groundbreaking moment paved the way for public support and lucrative research opportunities. Other states including Oregon, Alaska, Washington, Maine, Hawaii, Nevada, and Colorado would follow suit before the close of 2000.

 

California’s legalization spurred Dr. Geoffrey Guy and Dr. Brian Whittle to found GW Pharmaceuticals, a company that would utilize clinical trials to unpack various cannabinoid formulations as potential therapies with the overriding focus of developing what would later be known as Sativex (Nabiximols). This oral mucosal spray was made up of CBD and THC in a 1:1 ratio and successfully combated neuropathic pain, spasticity, overactive bladder, and symptoms of multiple sclerosis.

Problems with intelligent selection

These mounting developments in the elicited a problem amongst cannabis cultivators across the US: decades of selectively breeding cannabis to achieve the maximum amount of THC for a strong high reduced the overall preponderance of CBD in cultivars across the country to trace lows. Essentially, CBD had been selectively bred out of existence across the country.

 

Years passed, and more studies rolled out with medically beneficial findings regarding cannabis until 2009 when Steep Hill Laboratory in Oakland, California, tested cannabis samples provided by Harborside Health Center to discover that a handful of cultivars contained more CBD than THC. This discovery kicked other labs into gear. They wanted to study medical cannabis to understand and potentially calibrate their cannabinoid ratios. Soon thereafter, laboratories uncovered CBD-dominant strains boasting 20:1 CBD to THC ratios, which opened up the cannabis market for a panoply of CBD products.

CBD Products

Cannabidiol is as versatile as THC — perhaps even more so. Through science and determination, CBD has worked its way into an entire host of products.

 

Flower: As expanded above, CBD-rich cultivars can be located all across the globe due to the boom in interest in the late 2000’s. Combusting or vaporizing flower allows users to almost immediately feel the therapeutic effects of CBD. This method also allows for “topping up,” should pain resurface without going overboard.

 

Isolate: CBD isolate is cannabidiol in its purest form: a fine white powder. This form of CBD is incredibly distinct as it resembles other substances looking suspiciously like confectioner’s sugar. However, this Crystalline form of CBD is versatile and allows users to measure exactly how much CBD they’re consuming.

 

Concentrates: CBD can also be purchased in concentrate form, including cartridges, vape pens, syringes and more. Concentrates bridge the gap between CBD flower and CBD isolate. They range in purity and often come combined with other native cannabinoids, including THC, in specific ratios to utilize the “entourage effect.”

 

Infusions: Research and opportunity have driven chefs and chemists to infuse CBD into all sorts of readily usable products, such as edibles to elixirs, sublingual sprays, capsules and even topicals. Much like concentrates, each infusion sports specific combinations or isolations of CBD, THC, and other cannabinoids, allowing users to pick and choose products that suit their exact needs. CBD topicals, for example, are incredibly effective when applied to surface-level problems like bruises, joint aches, and headaches, and have been scientifically proven to successfully combat skin-based issues including pruritus with far broader implications.

Legality

In the United States

The legality of CBD in the US varies from state to state, but at the federal level, CBD is mysteriously classified as a Schedule I drug despite its sourcing. According to the federal government, Schedule I drugs are substances or chemicals with no currently accepted medical use and a high potential for abuse. Other Schedule I drugs include heroin, LSD, marijuana, and ecstasy. However, CBD can be purchased as a dietary supplement throughout the country despite the FDA’s official stance that CBD isn’t a supplement. The landscape of CBD legality in the US is exactly as confusing as it reads; that squirrely, perplexing itch at the back of your brain is cognitive dissonance, and it’s an entirely normal reaction.

Some states only allow for products infused with CBD, some only allow for high-CBD and low-THC products, while others allow both THC and CBD. To further confuse the American citizenry, some states permit patients the use of CBD, but require that they travel to another state to purchase it. To make sense of this confounding patchwork and to learn about each individual state’s CBD laws, read the Weedmaps Laws and Regulations page.

Internationally

The mosaic of laws that govern CBD legality across the globe varies just as much as the legislation across the US. Generally, CBD extract is legal in most countries, but what makes it illegal is where and what it’s extracted from. Most Group of 20 (G20) countries allow CBD extracted from industrial hemp, but not CBD extracted from whole-plant marijuana. Note, however, the differences between the two. Legislation regarding international travel with CBD also varies among countries. For the foreseeable future, the best practice would be to search online, or contact the respective embassies or consulates, before traveling to determine whether your CBD is safe and legal.