Accurate Education – Marijuana (Cannabis): Dosing

General THC Dosing Guidelines

for the Initial Use:

• • Up to 2.5mg: One may feel the desired benefit, including nerve pain, side effects minimal to mild.
  • 6 – 15mg: Euphoria and impaired coordination may occur.
  • 16 –30mg: Extremely high dose for novice patient. Experienced patients may feel altered perception. This level may result in negative side effects for patients with low THC tolerance. 
  • 31 –50mg: Only for very experienced patients. Patients may experience side effects like paranoia, sweating, and increased heart rate.
  • 51+mg: Dangerous for novice patients and any patient with low to moderate THC tolerance. May lead to hallucinations.

Potential for Side Effects

Due to the greater potential for adverse side effects with THC compared with CBD, it is generally wise to also start with lower ratios of THC to CBD. That is, initiate use of cannabis products with greater amounts of CBD than THC. Due to expected side effects such as sedation, cannabis-based products  should be started at night prior to going to sleep. For those who feel activated by cannabis-based products, morning dosing should be initiated. Cannabis should be utilized with caution or avoided in unstable cardiac conditions, such as angina, due to potential for rapid heart rates and drop in blood pressure due to THC, but there are no QTc issues.

Route of Administration

Cannabis-based products can be placed under the tongue (subingual), in the buccal space adjacent to the gums and cheeks (buccal), inhaled, or taken orally as capsules or lozenges and swallowed. The onset and duration of action of a product will vary depending on which route is employed.

Bioavailability

The “bioavailability” of a medication is the measure of how effectively administration of that medicine achieves blood levels. As a standard of definition, the bioavailability of a medication given directly intravenously is 100%. Other forms of administration, such as smoking, eating and application to skin, will be associated with less bioavailability. Bioavailability is generally described in terms of maximum time in the blood (Cmax) and maximum overall absorption into the blood (AUC – Area under the Curve). Tmax is the time necessary to reach the maximum blood concentration after administration of a medication.

Bioavailability is the degree and rate at which a substance is absorbed into the blood where it can be delivered to the organ systems necessary for therapeutic effects. The greater the bioavailability, the less product needs to be consumed to achieve a therapeutic effect. Bioavailability of cannabis products varies somewhat from individual to individual and is determined mostly by how it is consumed, including if it is ingested with food. It is also affected by the individual’s age, general health and the presence of gastrointestinal disorders. As a general guide based on method of use, the bioavailability of cannabis is:

• • Smoking: 25-30% bioavailability (Reports vary from 2-56%)
  • Vaporization: 30-60% bioavailability
  • Tinctures (sublingual): 40-50% bioavailability
  • Edibles: 5-12% bioavailability (Reports vary from 4-20%)

Translating bioavailability to determine a dose:

Smoking

The amount of THC present in cannabis flower will depend on the potency of that flower. In general cannabis is considered low potency if the THC content is less than 15%, whereas it is considered high potency see if greater than 15% THC.  In studies evaluating the pain, benefit of inhaled cannabis for neuropathic pain, such as diabetic neuropathy, it was determined that low-potency cannabis (translated into a daily dose ranging from approximately 2mg to 10mg THC) provided significant pain belief with much less in the way of adverse effects compared with higher doses of THC. 

An average joint is reported to generally contain about 300 mg of flower.  If a flower contains 20% THC, then a joint would contain about 20% of 300 mg, or 60 mg of THC. With the reported bioavailability of smoking to be 25-30%, then smoking the entire joint would deliver 15-18 mg of THC to the blood. 

Vaping

A vaping device for flower holds up to 300 mg of flower in its chamber. If the flower contains 20% THC, then a chamber would contain about 20% of 300 mg, or 60 mg of THC. With the reported bioavailability of vaping to be 30-60%, then vaping the entire chamber would deliver 18-36 mg of THC to the blood. 

Tincture (Oromucosal/Sublingual)

Tinctures are sold as containing 150 mg, 300 mg, 600 mg or 900 mg of liquid tincture in a 30 ml bottle. A 30 ml bottle containing 300 mg of THC would contain 10 mg/ml. Each full dropper contains about 1 ml, or 10 mg of THC. If 1 ml (or 10 mg of THC) is held under the tongue for 1-10 minutes, based on the reported bioavailability of 40-50%, then 4-5 mg of THC would be delivered  to the blood.

Edibles

The bioavailability of ingested THC will vary widely based on whether it is ingested with food which, although it slows absorption of THC somewhat, enhances total absorption. Ingesting cannabinoids with a moderate to high-fat meal can enhance intestinal lymphatic transport and markedly increase systemic bioavailability.

THC and CBD are both rapidly absorbed in the fasting condition, reaching their peak plasma concentrations at about 1.5 hours, compared to fed conditions, about 4 hours after dosing. However, the presence of food enhances absorption, so more cannabinoids are absorbed. Absorption is 2.8-fold higher for THC and 4.1-fold higher for CBD after a meal.

Given the reported bioavailability of edible THC of 5-12%, ingesting 10 mg of THC would deliver 0.5 t0 1.2 mg of THC to the blood, depending of fasting or fed condition.

To determine actual dosing of THC and/or CBD, it will depend on the product and route of administration – see specific product for dosing particulars.

(1) Sublingual and buccal products are fast-acting (10-30 minutes to onset of maximum effect) and will sustain their activity to a moderate degree. Because sublingual and buccal preparations will also be swallowed with saliva, they do share limited properties of oral, swallowed products. The consensus of opinion is that one should hold the tincture under the tongue for 1-2 minutes to provide optimal absorption. While sublingual/buccal (oromucosal) administration circumvents some of the problems associated with the oral route, and provides a more rapid onset of action, research suggests that a substantial proportion of the oromucosal delivered dose is actually absorbed by the GI tract.

(2) Inhaled, or vaped, products provided by metered-dose inhalers (MDIs) have the fastest onset of action (5-10 minutes to onset of maximum effect) but the shortest time of activity. The safety of vaped products has recently come under scrutiny due to users developing serious pulmonary complications including death. The circumstances appear to suggest the problem may come from additives to the products but definitive answers to the underlying cause remain elusive. Caution is advised, particularly to avoid vaping products with Propylene Glycol.

See: Marijuana – Inhaled (Smoked and Vaporized) & Dosing: Flower vs Pharmaceutical

(3) Orally swallowed products have the slowest onset of action (1-3 hours to onset of maximum effect) but the longest time of activity. Both THC and CBD are lipophilic molecules meaning they dissolve well in fat but not water. This characteristic slows and limits their absorption from the gut. However, absorption will be increased substantially overall if they are ingested with or after eating foods containing fats or oils. The presence of fats or oils in the gut stimulate the release of bile salts into the gut that facilitate absorption of fatty compounds, including THC and CBD. Therefore, although total absorption will be enhanced in the presence of food in the gut by as much as 25%, the absorption and therapeutic response will be slower.

While being absorbed from the gut, THC and CBD are initially metabolized by CYP enzymes in the intestine and then  will pass through the liver before reaching the blood stream to achieve their effects. Passing through the liver allows THC and CBD to be further metabolized and these breakdown products, or metabolites, provide their own therapeutic effects and side effects. 

THC will be partially metabolized into 11-hydroxy THC, a metabolite that shares at least some of the effects of THC including the psychoactive effects of feeling high and euphoric. Research suggests that 11-hydroxy THC may also have a stronger impact than THC relative to the “high” (and also other therapeutic benefits of THC?). Thus oral products may offer different therapeutic effects as well as different side effects than the same product used sublingually (oromucosal) or inhaled.

See: Marijuana (Cannabis) – Oral Use (Edibles)

Tolerance to Cannabinoids

As with opioids, the degree of a patient’s tolerance to cannabinoids will be an important variable in establishing the optimal dose. For those patients with a long established history of marijuana use there may be significant tolerance to the therapeutic effects of cannabinoids which may require higher doses to achieve benefit. Those individuals without previous exposure to marijuana or cannabinoids will be expected to have minimal tolerance and should be started at lower doses.