Everyone is talking about CBD Oil. But what is it? Where does it come from? Find out more about this versatile medicine. Cannabidiol: Promise and Pitfalls Over the past few years, increasing public and political pressure has supported legalization of medical marijuana. One of the main thrusts in this effort has
CBD Oil: An Introduction
Medical patients swear by it. Researchers are intrigued by it. Government regulators are flustered by it. And investors are head over heels for it.
Medical patients swear by it. Researchers are intrigued by it. Government regulators are flustered by it. And investors are head over heels for it. CBD oil is the It-Medicine of the moment. A few years ago, hardly anyone knew about CBD oil. Today there’s a huge demand for it. Millions of people are taking CBD oil as a health supplement. But what exactly is it? Where does it come from? How is it made? And what should you know before you buy it?
Where Does CBD Oil Come From?
Cannabidiol ( CBD ) is one of more than 100 unique “cannabinoid” compounds that are found in the oily resin of the cannabis plant. The sticky, gooey resin is concentrated on the dense clusters of cannabis flowers, commonly called “buds,” which are covered by tiny, mushroom-shaped “trichomes.” This is where the magic happens.
Trichomes are specialized glandular structures that contain a treasure trove of oily, medicinal compounds, including CBD , tetrahydrocannabinol ( THC ), and various aromatic terpenes. Why does cannabis create these oily compounds? What does the resin do for the plant?
The oily trichomes protect the plant from heat and ultraviolet radiation. The oil also has antifungal, antibacterial and insecticidal properties that deter predators. The stickiness of the resin provides another defensive layer by trapping bugs.
As it happens, the same oily resin that protects the health of the plant includes components that are beneficial for human health. CBD , a non-intoxicating compound, has shown promise in treating and managing the symptoms of a broad range of diseases. Ditto for THC , CBD ’s intoxicating cousin.
CBD oil is extracted from the resinous trichomes of cannabis plants. There are many different cannabis “strains” or varietals. The amount of CBD present in the trichomes will depend on the particular variety of cannabis or hemp. Low resin industrial hemp, which is legally defined as cannabis with less than 0.3 percent THC by dry weight, has fewer trichomes – and therefore less oil – than high-resin cannabis varietals.
But most high resin cannabis strains these days are THC -dominant with little CBD . So choosing the appropriate CBD -rich cannabis chemovar, a variety of cannabis defined by its chemical constituents, is key for extracting CBD oil.
Trichomes are fragile structures that easily break off of the cannabis flower. Even rough handling is enough to shake off the trichomes. Making hashish or “kif” (hashish powder) involves manually removing the resinous trichomes by agitating the flower. Sometimes heat or pressure is applied to partially melt the trichomes together, turning the resin into a congealed slab, referred to as rosin, which can be smoked or ingested.
In addition to the resinous trichomes concentrated on the flowers and to a lesser extent on the leaves of the cannabis plant, there are the tiny sessile trichomes, which dot the stalk, but these contain hardly any oil or CBD . (Shaped like tiny inverted commas, non-glandular hairs without oil also cover the plant’s surface.) CBD is also absent in the roots or the seeds of cannabis and hemp. Companies that claim they derive CBD from hemp stalk or hemp seeds are making false claims.
How Is CBD Oil Made?
To make CBD oil, one must start with CBD -rich plant material. There are several ways to extract CBD oil from cannabis. Each method has its pros and cons. Some are safer and more effective than others.
After it is extracted from the plant and the solvent is removed, the CBD oil may be refined and formulated into a variety of consumable products – edibles, tinctures, gel caps, vape oil cartridges, topicals, beverages, and more.
The purpose of an extraction is to make CBD and other beneficial components of the plant (such as terpenes) available in a highly concentrated form. Because cannabinoids are oily by nature, separating CBD from the plant material will produce a thick, potent oil. The texture and purity of the oil depends largely on the method used to extract it.
CBD and the other plant cannabinoids are chemically classified as “terpenophenolic” compounds. To the non-scientists among us, this means that CBD is soluble in both oil and alcohol. Thus, the process of extracting CBD oil from cannabis often entails the use of a solvent that’s good at dissolving an oil or an alcohol-based compound. Solvents that are commonly used to extract CBD from cannabis include supercritical CO2 , ethanol, hydrocarbons (such as butane) and olive oil.
CO2 Extraction of CBD Oil
CO2 extraction is the most prevalent commercial method – as well as one of the safest ways – of separating CBD and other cannabinoids from cannabis biomass. At room temperature, carbon dioxide is a gas. But under high pressure and fluctuating temperature, CO2 liquifies while still maintaining the fluid dynamics of a gas. In this “supercritical” state, CO2 acts like a solvent, which flushes out the active ingredients from the plant matter.
This method is very effective because each compound can only be extracted by CO2 under specific conditions. Slight changes in temperature or pressure in a supercritical state allows for fine-tuning the extraction of CBD and other desirable plant components.
As the pressure drops, a crude, waxy, CBD -rich substance, golden in color, separates from the gas and deposits into a collection vessel. Afterwards, the golden oil undergoes a process known as “winterization,” which purifies and refines the extract to increase its quality and value. The plant waxes, which are not appropriate to include in certain kinds of products, are filtered out, resulting in a safe, clean, CBD -rich oil that is free of chlorophyll.
Supercritical CO2 extraction requires expensive equipment and a steep operational learning curve. But unlike combustible solvents, such as ethanol or butane, CO2 poses no danger of fire or explosion.
Ethanol Extraction of CBD Oil
The use of ethanol to extract medicinal compounds from cannabis and other plants has been a common practice in many cultures for centuries. In 1854, the U.S. Pharmacopeia recommended ethanol-based tinctures of “Indian hemp” to treat numerous ailments, including neuralgia, depression, hemorrhage, pain and muscle spasm.
These odiferous tinctures were a standard part of American health care prior to the passage of the Marihuana Tax Act of 1937, which prohibited all forms of cannabis consumption. But homemade cannabis tinctures persisted as an underground folk medicine, particularly in marginalized Latino communities, despite federal law.
In recent years, ethanol has re-emerged as a popular means of extracting cannabis oil, in general, and CBD oil, in particular. Whereas a tincture made from a cannabis extract could be equal in potency to the original flower, a concentrated version of the same tincture will be much more potent. Today, food-grade grain alcohol is a widely used solvent for creating very potent, high-quality CBD -rich oil, which is suitable for oral ingestion.
Ethanol extracts available in medical cannabis dispensaries are typically referred to as Rick Simpson Oil (aka RSO ) or Full-Extract Cannabis Oil ( FECO ). In order to make RSO or FECO , cannabis flower is soaked in ethanol, agitated, and strained; then the residual oil is gently heated until all that remains is a viscous, highly concentrated goo infused with cannabinoids, which can be difficult to dose accurately, given how thick it is.
Often sold in plastic, needleless syringes to make dosing and administration a little easier, RSO should contain the full spectrum of cannabinoids extracted from the plant. This means that a small amount THC will also be present in a CBD -rich ethanol extraction. Consumers are cautioned not to ingest a dose larger than a small grain of rice. With this type of cannabis oil, in particular, it’s always best to start low and go slow.
Hydrocarbon Extraction of CBD Oil
Using hydrocarbon solvents – such as butane, hexane and propane or mixtures thereof – to extract CBD from cannabis has major advantages as well as distinct disadvantages compared to other methods of manufacturing CBD oil. When properly implemented, this extraction technique is a very effective at separating cannabinoids and terpenes from unwanted cannabis components (e.g., chlorophyll), while preserving the unique scent and significant therapeutic attributes of the plant.
Potent cannabis concentrates made with hydrocarbons may resemble tree sap, ear wax, or brittle candy in texture. The product known as “shatter” (so named because of its glass-like appearance and the manner in which it breaks) is consumed via inhalation by using a “dab rig” or a high temperature vaporizer.
But butane and other hydrocarbons are highly flammable, neurotoxic solvents. If these solvents aren’t fully purged from the CBD oil extract, their consumption can be harmful – especially for someone with a compromised immune system. In addition to leaving toxic residues in the oil, unsafe manufacturing processes involving hydrocarbons have been known to cause deadly explosions.
Making Your Own CBD Oil
Project CBD strongly discourages home extraction using flammable solvents. There are much safer options for making a CBD oil extract in one’s own kitchen.
A 2013 study by Luigi L. Romano and Arno Hazekamp evaluated the efficacy and purity of five cannabis extraction solvents, including ethanol, naphtha (a harsh industrial poison that should be avoided), and olive oil. The authors found comparable efficiency between all the solvents but noted that olive oil, a nontoxic solvent, was better at extracting terpenes along with the cannabinoids. Moreover, according to Hazekamp, “You won’t blow yourself up making cannabis-infused olive oil.”
Olive oil extraction is safe, simple and straightforward. It’s also inexpensive. And you can do it yourself. Heating the plant matter in an oven will decarboxylate the cannabinoids, turning THCA into THC and CBDA into CBD . Steep the flower and leaves in the olive oil; then sift, strain, and separate the oil from what’s left of the herb. Cannabis-infused olive oil — whether CBD -rich or THC -dominant — is perishable and should be stored in a cool, dark place so it doesn’t turn rancid.
One can also extract CBD from cannabis by using other lipid solvents, including avocado, coconut or MCT [medium chain triglyceride] oil. Hemp seed oil is another effective extraction solvent and a carrier vehicle that mixes well with CBD .
But be forewarned about CBD product companies that claim they get their CBD from hemp seeds. While hemp seeds are an excellent source of protein-rich, omega 3 fatty acids, the seeds themselves don’t contain CBD , THC or any other cannabinoids. Trace amounts of cannabinoids may be present in oil pressed from hemp seeds if the seed covering, the bract (where resin can cling), isn’t thoroughly rinsed and removed prior to the extraction process.
Unregulated CBD Oil Products
To reiterate: CBD oil in not the same as “hemp oil” or “hemp seed oil.” Some companies are manufacturing inferior products by spiking hemp seed oil with a CBD isolate. Such products lack the synergistic array of beneficial components found in full-spectrum CBD -rich oil.
Unfortunately, there is little oversight for manufacturing hemp-derived CBD products, which can lead to confusion and deception. Many hemp-derived products are mislabeled as to CBD and THC content. And poorly processed CBD oil may be contaminated with dangerous solvent and pesticide residues, thinning agents, corn syrup, artificial flavors and colors, and other toxins.
If possible, it’s better to obtain CBD oil products from licensed dispensaries in states that have legalized cannabis for therapeutic or personal use. These states are likely to have stricter safety standards for CBD oil products than states or countries that refuse to regulate the booming CBD industry. Read the ingredients carefully before purchasing a CBD oil product, and look for evidence of laboratory tests and verification of CBD concentrations when buying a CBD remedy or supplement.
Zoe Sigman is Project CBD ’s Program Director and the Science Editor at Broccoli Magazine.
Copyright, Project CBD . May not be reprinted without permission.
Cannabidiol: Promise and Pitfalls
Over the past few years, increasing public and political pressure has supported legalization of medical marijuana. One of the main thrusts in this effort has related to the treatment of refractory epilepsy—especially in children with Dravet syndrome—using cannabidiol (CBD). Despite initiatives in numerous states to at least legalize possession of CBD oil for treating epilepsy, little published evidence is available to prove or disprove the efficacy and safety of CBD in patients with epilepsy. This review highlights some of the basic science theory behind the use of CBD, summarizes published data on clinical use of CBD for epilepsy, and highlights issues related to the use of currently available CBD products.
Cannabidiol is the major nonpsychoactive component of Cannabis sativa. Over the centuries, a number of medicinal preparations derived from C. sativa have been employed for a variety of disorders, including gout, rheumatism, malaria, pain, and fever. These preparations were widely employed as analgesics by Western medical practitioners in the 19 th century (1). More recently, there is clinical evidence suggesting efficacy in HIV-associated neuropathic pain, as well as spasms associated with multiple sclerosis (1).
Basic Pharmacological Mechanisms
Cannabidiol pharmacological effects are mediated through G protein coupled receptors, cannabinoid type I (CB1) and cannabinoid type II (CB2), which are highly expressed in the hippocampus and other parts of the central nervous system (2). When activated, CB1 receptors inhibit synaptic transmission through action on voltage-gated calcium and potassium channels, which are known to modulate epileptiform and seizure activity (3). CB2 receptors are primarily expressed in the immune system and have limited expression in the central nervous system. The effects of CBD are CB2 receptor independent (3).
Studies have demonstrated that CBD has a low affinity for the CB1 receptors, but even at low concentrations, CBD decreases G-protein activity (3). CB1 receptors are expressed on many glutamatergic synapses that have been implicated in seizure threshold modulation. CBD may act at CB1 receptors to inhibit glutamate release (4). Studies have shown changes in the expression of CB1 receptors during epileptogenesis and after recurrent seizures (5). CB1 receptor expression is upregulated at GABAergic synapses and shown to be downregulated at glutamatergic synapses in epilepsy, contributing to lowering seizure thresholds.
Other targets for CBD include transient receptor potential (TRP) channels that are involved with the modulation of intracellular calcium (1, 6). Cannabinoids are highly lipophilic, allowing access to intracellular sites of action, resulting in increases in calcium in a variety of cell types including hippocampal neurons. CBD actions on calcium homeostasis may provide a basis for CBD neuroprotective properties.
Evidence in Animal Models
When administered alone, CBD is an effective anticonvulsant in maximal electrical shock (MES), magnesium-free, 4-aminopyridine, and audiogenic models (7, 8). Co-administration with AEDs leads to various effects; anticonvulsant effects of CBD are enhanced with phenytoin or phenobarbital but decreased with chlordiazepoxide, clonazepam, trimethadione, and ethosuximide. In a recent study using an acute pilocarpine model, although CBD administration reduced the number of animals displaying seizure activity, CBD did not appear to have any significant effect on the number of seizures per animal (7).
Clinical Evidence in Epilepsy
While animal experimental data clearly suggest a potential benefit, supportive clinical data are quite sparse. In a case-control study of 308 cases of new onset seizures, Brust and colleagues found that marijuana use was significantly less prevalent among men who had unprovoked seizures compared to case controls (9). This difference was not significant in women. The authors suggest a potential protective effect against seizures with marijuana use; however, this should be considered speculative.
A survey of patients seen in a tertiary epilepsy center found that 21% of patients admitted to using marijuana in the last year, and 24% of patients believed marijuana to be effective for their seizures (10). While interesting, this anecdotal observation does not rise to the level of evidence needed to evaluate a potential new therapeutic modality.
Gloss and Vickrey conducted a Cochrane systematic review of the use of CBD in the treatment of epilepsy (11). Their methodology included only those trials that were randomized and controlled and excluded case series, case reports, and expert opinion. They were able to identify only 4 randomized controlled studies reported in the literature, and they included a letter to the editor and an abstract. The total number of subjects enrolled in these studies was 48 (11–14). While only four studies and a letter to the editor were in the actual analysis, the authors included a complete reference listing of all articles reviewed for inclusion.
These reports suffered from a number of design flaws, including incomplete baseline quantification of baseline seizure frequency, indeterminate time periods for outcome determination and, in some cases, inadequate (or missing) statistical analysis—in general, a lack of sufficient detail to adequately evaluate and interpret the findings. Limitations aside, several studies did report that administration of adjunctive CBD did not result in meaningful changes in seizure frequency (11–13).
Cunha et al. reported a 2-phase pilot study of CBD versus placebo in normal volunteers and patients with refractory secondarily generalized epilepsy (14). In the first phase, 8 normal volunteers received CBD or placebo in a doubled-blind fashion, at a dose of 3 mg/kg for 30 days. The second phase was also double-blinded in 15 patients with epilepsy receiving 200 to 300 mg daily of CBD or placebo for 135 days. Patients continued baseline AED. All subjects tolerated CBD well, with no serious adverse events. Four of the epilepsy patients receiving CBD were “almost free of convulsive crisis” for the duration of the study. Three other patients receiving CBD had a partial reduction in seizures, and 1 subject had no response. Of the 7 patients receiving placebo, seizure frequency was unchanged in 6, and 1 had clear improvement in seizure control.
Using rigorous review methodology, Gloss and Vickery conclude that based on the low quality of the reports available, there is insufficient data available to draw any conclusions regarding the efficacy and or long-term safety of CBD in treating epilepsy (11). From the data available, it does appear that daily doses of 200 to 300 mg were safe in this small group of patients for a short period of time (14).
Tolerability and Drug Interactions
CBD is well tolerated in humans with doses up to 600 mg not resulting in psychotic symptoms (15). In the few small placebo-controlled studies performed, no significant CNS effects were noted. Oral CBD undergoes extensive first-pass metabolism via CYP3A4, with a bioavailability of 6%. Following single doses in humans, the half-life of CBD when taken orally is about 1 to 2 days.1 In vitro studies have shown that CBD is a potent inhibitor of multiple CYP isozymes, including CYP 2C and CYP3A (16, 17). Whether these in vitro observations are relevant at plasma concentrations likely to be seen in patients is unclear. In addition, given its metabolism via CYP3A4, clinical trials of CBD in patients receiving enzyme-inducing AEDs, such as carbamazepine or phenytoin, will require detailed pharmacokinetic studies.
A number of difficulties exist in evaluating published data on CBD or marijuana use for epilepsy. The extremely limited published studies were small, poorly described, and not well designed. Contributing to the difficulty of interpreting published studies, CBD products are not produced under the guidance of good manufacturing practices (GMP) and are not subject to regulations governing labeling, purity, and reliability. In other words, currently, there is no guarantee of consistency between products, or even differing lots produced by the same manufacturer. Without independent testing (e.g. USP certification) of CBD products for content and purity, as well as bioavailability testing of specific products, uncertainty surrounds the use of available CBD products in routine clinical settings.
At this time, there does seem to be a growing body of basic pharmacologic data suggesting there may be a role for CBD, especially in the treatment of refractory epilepsy. However, given the lack of well-controlled trials, we must also ask if we are getting ahead of ourselves. Clearly, this is an emotionally and politically charged issue. If this were any other uninvestigated pharmaceutical compound, would we feel as compelled to make the agent widely available before statistically valid class 1 evidence was available for review? Until data from well-designed clinical trials are available and reliable, and standardized CBD products that are produced using GMP are available, caution must be exercised in any consideration of using CBD for the treatment of epilepsy. In the meantime, based upon promising preliminary data, further clinical research should be wholeheartedly pursued.