Deep Dive: Cannabidiol Dosing

Cannabidiol (CBD) extracts—such as those derived from hemp or cannabis—are available to consumers in a variety of form factors for different consumption avenues. One of the most popular is the tincture, a liquid preparation based in alcohol or oil that is applied sublingually (under the tongue).

Because a tincture is absorbed sublingually, the onset of efficacy of cannabinoid- and terpene-based medicines delivered via this route is considerably faster than eating the same molecules (an ingestion route that requires about two hours for onset). The bioavailability onset of sublingual preparations like tinctures, on the contrary, is 10 to 20 minutes. For pain and anxiety patients, the difference between 20 minutes and two hours is significant.

Tinctures are a proven and valued method for storing and consuming herbal extractions and concentrates, including those from cannabis. The dosing of such sublingual tinctures, however, is not nearly as easy as their administration.

CBD molecular analogs (isomers)

In use in one form or another for millennia, tinctures first became common during the Victorian era, beginning in the early 19th century. Simple administration, long-term storage, rapid onset, and easy mobility made tinctures popular with consumers and medical doctors alike. Because they can also be easily added to drinks or food, tinctures are often the optimal route of administration for children, pets, and seniors.

One of the most important characteristics of a cannabis extract—beyond its formulation and the purity of its ingredients—is the correct dose. Research has revealed that the cliche American mantra "more is better" is not always true. The correct dosing of cannabis and hemp extracts depends to a large extent on the type of extract being considered.

Three primary categories of hemp extraction exist:

Full-spectrum products represent most or all of the cannabinoids and terpenes from the marijuana plant (some delicate terpenes, such as monoterpenes like pinene, may be lost during the extraction process). Full-spectrum is sometimes difficult to achieve and requires an expert focus on the preservation of these relatively delicate molecules.

Broad-spectrum represents the intentional filtering of the contents of the plant, typically with the intention of avoiding the inclusion of psychoactive tetrahydrocannabinol (delta-9 or delta-8 THC). However, technically speaking, a cannabis extract qualifies as broad-spectrum if anything has been filtered out, whether it is 1% or 99% of the original cannabinoid, terpene, and flavonoid profiles (the three major categories of wellness molecules from marijuana).

Isolates are the most strict category of extraction in terms of the purity and extreme filtering applied to achieve the end result. Isolates are a suspension of a single molecule. Popular isolates include CBD, THC, and sometimes CBG or CBN. Most isolates appear in the form of a powder or crystal and can be eaten, smoked, or vaporized.

Hemp is defined as cultivars (varieties) of the plant species cannabis sativa that feature <0.3% THC. Therefore, full-spectrum extractions of the herb introduce no intoxication or other potential negative effects of THC. It just so happens that full-spectrum extracts often require "much lower doses" to achieve the same efficacy.

Microdosing is a new term in the American vernacular. As its name implies, it is an approach to the consumption of herbal remedies involving very small doses, often administered throughout the day.

Sometimes called "precision dosing," microdosing is an effective approach for those beginning use of an hemp extract for overall wellness or in the treatment of a particular ailment or side effects of conventional pharmaceutical treatments (such as opioids or chemotherapy).

Microdosing involves a relatively small dose that ranges between one and five grams. It is an approach that sometimes involves consumption of smaller volumes of an extract, more times per day (with the goal of a sustained minimum efficacy). An effective microdose for one person may be inappropriate for another based on factors such as genetic predisposition, body weight, pharmaceutical drugs being consumed, existing conditions, and environmental factors and stressors.

Social media and online resources have allowed consumers from around the world to share the results of their dosing experimentation. This is especially true in particular patient communities where specific formulations and accurate dosing it critical to gain maximum efficacy. In many cases, efficacy can be objectively measured in terms of, for example, a reduction in number of seizures. In other use cases, efficacy is more obfuscated, such as in subjective reports of pain levels.

The CBD molecule

One user in New Zealand reported the greatest efficacy for a autism-related seizure disorder after a significant reduction in the dose of a full-spectrum hemp extract. Maximum seizure relief was found after reducing dosing from 240 mg per day to only 10 mg. While this evidence is purely anecdotal and should not be misinterpreted as clinical research findings, a reduction of 2,400 percent is significant. It allowed the user to gain the greatest relief while also dramatically reducing the cost of their wellness supplementation.

Some cannabinoids demonstrate something called a biphasic response curve. This means that the chemical demonstrates a particular efficacy, or effect, at a low dose and a significantly different (and sometimes polar opposite) efficacy at a potent dose.

One example is the psychoactive cannabinoid tetrahydrocannabinol (THC). At relatively low doses, THC has been proven to reduce and sometimes alleviate anxiety. At higher doses, however—especially among novice users who feature little or no tolerance to this phytomolecule—THC can not only increase anxiety, but may also result in disorientation, confusion, discomfort, and even full-blown panic attacks.

The following interview between Curt Robbins and New Mexico-based physician and author Sunil Pai, MD helps explain the dynamics of CBD dosing:

Curt Robbins: "Some cannabinoids feature biphasic response curves involving one efficacy at a relatively low dose and another—and sometimes polar opposite—effect at stronger doses. As a practicing clinician, how does the issue of response curves affect your job?"

Sunil Pai, MD: "The dose response curve is an important element of using cannabinoids from cannabis or hemp. It is often misunderstood or ignored by those who lack a clinical comprehension of how it functions and how cannabinoids such as CBD should be titrated (dosed). For example, when treating pain with prescription medications, more medication is required as the pain level worsens. This is a simple model involving increases in dose that are proportional to pain or dysfunction level.

Dr. Sunil Pai, MD

"In this traditional model, greater pain obviously requires more medication to obtain an adequate response. For many prescription medications, this approach is correct. However, when it comes to the ECS and how CBD, THC, and other cannabinoids interact with receptors in the body, the dose response curve is completely different. It instead resembles a bell curve. When dosage is increased, an improved response is experienced—but only to a certain point. Improvement reaches a peak and then diminishes as dose is increased.

"When dosage is increased, an improved response is experienced—but only to a certain point. Improvement reaches a peak and then diminishes as dose is increased," said Dr. Pai.

"As a clinician treating patients daily, one of my greatest challenges is educating them about proper dosing. They are habituated to taking large doses at the beginning of their treatment and, if they do not experience an adequate response, increasing their dose. When I get new patients that exhibit no response who are currently taking strong doses, I have them restart with relatively low doses. We increase dosing slowly over time, but only until the patient feels the intended benefits. This is, without question, the best approach.

"Most companies that sell cannabis and hemp do not like this approach because they make more money selling greater volumes of their products. Many companies advertise that their customers should consume hundreds of milligrams or even multiple grams per day. This is incorrect and misleading!

"Products from companies and influencers that do not address the need to ‘start low and go slow,’ instead recommending unnecessarily huge doses, are a good example of ignorant marketers who lack a true understanding of the healing mechanisms of the human body. They seem to not possess the basic knowledge of how the products they sell actually work."

Much research has been conducted into the dosing characteristics of CBD. A brief review of this research is helpful to fully understand the dynamics of CBD titration and avoid the pitfalls of too weak—or too potent—a dose.

A 2020 research study entitled "Dosage, Efficacy and Safety of Cannabidiol Administration in Adults: A Systematic Review of Human Trials" that was published in the Journal of Clinical Medicine Research noted that "cannabidiol (CBD) seems to be a promising candidate for the treatment of both somatic and psychiatric disorders" and "collected dose(s), dosage schemes, efficacy and safety reports of CBD use in adults from clinical studies."

This literature review study included "25 studies: 22 controlled clinical trials and three non-controlled (single arm) trials." The researchers identified several potential benefits of CBD from the review, including anxiolytic (xx) benefits and that it can "improve psychotic symptoms in schizophrenia patients."

The study also found indications that CBD may be an effective treatment support for "Crohn’s disease, ulcerative colitis, dyslipidemia, and cannabis use disorders," but noted that additional research is necessary to fully understand the underlying mechanisms of such use, including dosing, potential negative side effects, tolerance building, and other important issues related to patient outcomes.

The researchers found that use of CBD among a variety of patient populations to be relatively safe. It reported "mild to moderate adverse effects with chronic administration."

View the original study.
 

A 2015 research study entitled "Overcoming the Bell‐Shaped Dose‐Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol" that was published in the journal Pharmacology & Pharmacy determined that a full-spectrum hemp extract to be more potent and feature enhanced efficacy compared to a CBD isolate.

Reported the researchers, "Our findings that CBD in the presence of other plant constituents improve the dose-response are supported by some recent reports showing that CBD in a standardized cannabis sativa extract is more potent or efficacious than pure CBD."

View the original study.