Bioavailability of Cannabis Oils and Optimal Dosing

Most Cannabidiol (CBD) and Δ-9-Tetrahydrocannabinol (THC) oil goes to waste in the body. Amid the current frenzy in many North American jurisdictions surrounding legal Cannabis and its therapeutic benefits, it’s easy to gloss over the bioavailability of Cannabis products. Bioavailability refers to the degree and rate at which a substance is absorbed into the bloodstream to be used where needed. Physiological processes and consumption methods can affect Cannabis absorption, rendering its effects somewhat hit-and-miss. It’s critical to understand bioavailability in order to maximise the medicinal potency of Cannabis. The more bioavailable the Cannabis is, the lesser quantity of plant is required to reap all the benefits. The surge in Cannabis popularity in legal jurisdictions around the world can in part be attributed to the range of consumption methods available.

Edibles and tinctures can have less of the traditional stigma attached to them than the likes of joints, for example. However, when cannabinoids such as CBD and THC are ingested in oil form—oil is also used to make edibles—their bioavailability becomes compromised. CBD and THC oils resist absorption into the bloodstream because the human body is up to 60% water. Basic science dictates that oil and water do not mix and the same is true for Cannabis oil and the human body. “Cannabinoids are fat-loving molecules and have to traverse a cellular environment that is aqueous or watery”, explained Dr Patricia Frye, member of the Society of Cannabis Clinicians and current chief medical officer at Hello MD (US). When Cannabis is consumed as an oil, the onset of effects can become delayed and bioavailability limited.

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Another phenomenon that limits oil-based Cannabis extracts from reaching the bloodstream is the first-pass effect. When Cannabis is ingested orally, it is absorbed in the gastrointestinal tract and transported via the portal vein to the liver, where it is metabolised. As a result of this process, only a limited quantity reaches the circulatory system. Since Cannabis oil is often taken orally, its efficacy can be hindered. 
There has been some investigation into CBD, THC, and less into cannabinol, or CBN. Studies have shown the bioavailability of cannabinoids depends on the method of delivery. When applied as a topical ointment or transdermal patch, CBD can penetrate the tissue ten times more effectively than THC. The same is true of CBN. THC, however, is more bioavailable than CBD when administered orally or delivered via the lungs.

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clinical study found concentrations of THC in the bloodstream appeared 30-50% higher than CBD following oral delivery as a sublingual spray. However, bioavailability of THC is still limited and when consumed orally, averaged 4-12%. When smoked or vaped, the bioavailability of THC leaps to an average of 30%Some of the most common and convenient Cannabis products available across much of North America, such as capsules, soft gels, tinctures and edibles, limit bioavailability due to the first pass through the liver. “With edibles, absorption is slow, unpredictable and highly variable”, said Frye. “Only about 6% of the dose is absorbed. The onset of action can be as long as 6 hours; it’s very easy to take too much, and the effects can last as long as 20 hours”.

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Oral administration lasts longer than smoking, eliminating the need for frequent dosing and avoids irritation to the airways and risk of malignancies associated with smoking, for example. That said, inhaling Cannabis guarantees increased bioavailability because molecules are transported by vapour particles directly to the alveoli in the lungs. This allows cannabinoids to rapidly enter the bloodstream without being metabolised by the liver. Another lesser known method of administration is intranasal delivery, which enables cannabinoids to be easily absorbed with a rapid onset of ten minutes or less. “Intranasal methods are highly bioavailable at 34-46%”, said Frye. “It’s a particularly helpful mode of delivery for patients who are having a seizure or for patients trying to abort an impending seizure or migraine”.

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Transdermal patches can be super effective at targeting localised or systemic pain. They allow for a steady infusion of active ingredients to the delivery site, so the patient is unlikely to experience spikes of THC in the bloodstream. One method that boosts the absorption of edibles is to combine the Cannabis product with fats. Frye recommends combining edibles or tinctures with healthy fats such as guacamole, hummus, or dark chocolate. The same goes for alcohol-based tinctures. For those who smoke or vape, bioavailability can be enhanced by minimising sidestream loss and increasing the number of puffs. “Using a desktop or handheld vaporiser with flower will eliminate sidestream losses”, Frye advised. If you think you get more bang for your buck by holding your breath, think again. “There is no evidence supporting holding one’s breath for more than 10 seconds”, said Frye. 

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For those looking to optimise Cannabis bioavailability, Dr Fyre said: “The most cost-effective way to use Cannabis is not to use more than you need. Less is more”. Due to its biphasic nature, excessive dosing may exacerbate symptoms. Therapeutic Cannabis products consumed as oils or liquid capsules are more slowly absorbed with effects generally delayed for 30-90 minutes. Bioavailability of oral cannabinoids is low (10-20%) because of intestinal and first pass liver metabolism. Peak effects can occur two to four hours after consumption. Given the longer time frame, it is important to allow at least three hours between administration of single oral doses. Effects can last eight hours and as long as 24 hours. Given the slower onset and longer duration, taking therapeutic Cannabis products orally would be more useful for medical conditions or symptoms where control over longer periods of time is sought – similar to use of slow release medications.


Coconut Oil Canna Capsules

Cannabis oil capsules, infused/mixed with coconut oil, are an alternative way to therapeutically use Cannabis without having to inhale it via smoking or vaporising. Coconut oil is used due to its high amount of medium chain triglycerides (MCT) which makes it a good binding agent for the cannabinoids, not to mention its amazing health properties. Half the fat in coconut oil is comprised of lauric acid, a fat not frequently found in nature. Lauric acid has been called a ‘miracle’ ingredient due to its health promoting capabilities. Present in mother’s milk, it can be found in only three dietary sources – small amounts in butterfat and larger amounts in palm kernel and coconut oil. In the body, lauric acid is converted to monolaurin, a potent antiviral, antibacterial and anti-protozoal substance. Monolaurin, being a monoglyceride, can destroy lipid-coated viruses including measles, influenza, HIV, herpes and a number of pathogenic bacteria. Although it ‘targets’ the liver and gets processed there (metabolism), you can avoid this happening with your infusion/blend, and the ensuing metabolism of the cannabinoids (e.g. Δ-9-THC metabolises into Δ-11-THC in the liver), by a process commonly known as ‘pre-loading’. Consuming a large spoonful of coconut oil around half an hour before dosing with capsules occupies the metabolising enzymes and allows cannabinoids to enter the bloodstream and go about their business, as they are meant to, before going back to the liver.

Hempy Honeytongue,
Cannabis as Medicine and More – Its Your Life


 

According to Dr Dustin Sulak, dosage is the key factor in achieving the most benefits from Cannabis. After following thousands of patients using Cannabis therapeutically for eight years, he observed that dosing Cannabis is unlike any therapeutic agent to which he was exposed during medical training. A basic understanding of the key characteristics of Cannabis dosing can empower one to make the most of this incredibly versatile, safe and effective herb, Dr Sulak said. Some patients effectively use tiny amounts of Cannabis, while others use incredibly high doses. Dr Sulak has seen adult patients achieve therapeutic effects at 1 mg of total cannabinoids daily, while others consume over 2,000 mg daily. And while a 2000-fold dosing range is unusual for a medication, researchers have failed to kill monkeys at doses even 300 times higher than the highest dose Dr Sulak observed in the clinic.

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Within this unusually broad dosing range, Cannabis exhibits an unusual relationship between the dose and the expected response.  For most medications, a higher dose will result in a stronger therapeutic effect and a higher likelihood of adverse effects; this is described as a monophasic dose-response relationship. Cannabis simply does not follow this pattern. For most Cannabis consumers, gradually increasing their dose will at first result in stronger effects; but after a certain point (unique to each individual), subsequent dosage increases can result in weaker and weaker therapeutic effects.  Consumers who continue to increase their dosage to very high levels can often reclaim some or all of the previously lost benefit, and sometimes find additional therapeutic effects not achieved at the lower doses. Of course, ultra-high doses are much more expensive and can produce some unwanted side effects.

Most patients do much better at the lowest effective dose. For many Cannabis users, this means that less can be more. In a study of 263 opioid-treated cancer patients with poorly controlled pain, the group receiving 21 mg of combined THC and CBD each day experienced significant improvements in pain levels, more so than the group that received 52 mg daily. The group that received 83 mg daily reduced their pain no better than placebo, but experienced more adverse effects. How is this possible? The Endocannabinoid System (ECS) is a sensitive, highly tuned physiologic infrastructure designed to maintain balance at a cellular level. When the cannabinoid receptors become overstimulated by high doses of Cannabis, the cells pull the receptors inside, where they are either recycled or degraded. As cannabinoid receptor levels diminish, the effects of Cannabis will diminish as well, even (or especially) in the face of dose escalation.

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This is known as tolerance-building, something that many regular Cannabis users have experienced. The term therapeutic window describes the range between the lowest effective dose and the dose that produces unwanted or intolerable side effects. People who have little or no experience using Cannabis typically have a very narrow therapeutic window, while regular users develop a wider therapeutic window. This is due to the fact that individuals build tolerance to the various effects of Cannabis at different rates and most build tolerance to unwanted effects faster than desired effects. Cannabis also has the ability to produce opposite (or bidirectional) effects in different people, with different strains, and at different dosages. For example, anxious people who take Cannabis may relax while non-anxious people who take the same dose can become anxious.

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The same dose of two different varieties of Cannabis can cause opposite effects – one might be an awakening strain and the other might put you to sleep. CBD and THC have many overlapping therapeutic qualities, including relief of pain, anxiety, seizures and nausea, although they work via different mechanisms of action. When combined, CBD and THC can enhance each other’s benefits while reducing unwanted effects. By adding CBD to THC, the therapeutic window becomes even wider. Consumers should know, however, that the total dose of cannabinoids needed to treat a symptom or condition will also likely increase. For example, in a study of 177 patients with cancer pain, one group received an oral spray of THC, while another group received an oral spray of combined THC and CBD at an approximate 1:1 ratio. Both groups were allowed to gradually increase their dose until they experienced satisfactory relief.

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The THC group ended up using an average of 27 mg daily, while the CBD+THC group used close to 60 total mg daily, but the CBD+THC group had a superior reduction in pain. Some patients do well with ultra-high doses (hundreds or thousands of milligrams daily). THC consumers have to slowly work up to these high doses, but many patients can quickly reach high doses of CBD without adverse effects. On the other hand, ultra-low doses can be extremely effective, sometimes even more so than the other extreme. Most people are surprised to learn that the therapeutic effects of THC-dominant Cannabis can be achieved at dosages lower than those required to produce euphoria. Cannabis microdosing, taking a dose for the purpose of improving heath and productivity, has been gaining popularity across many legal jurisdictions.

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People report better mood, reduced anxiety, improved focus, enhanced resilience to stress, less pain (and/or less bothersome pain) and other benefits without any adverse effects. Most consumers find 1-5 mg works well. Some emerging evidence even suggests a practice like this could be protective against damage of a heart attack or brain injury. For new Cannabis users, Dr Sulak abides by an old adage: “Start low, go slow, and don’t be afraid to go all the way”. Dr Sulak has  developed an easy- to-follow program to help find the optimal dose, along with other useful resources available on Healer.com. If you’ve not tried non-inhaled delivery methods such as tinctures or sprays, and haven’t experimented with the combination of CBD and THC, Dr Sulak suggests both endeavours will help you continue to unlock the full power of this incredible herb.

Adapted from Most THC and CBD oil goes to waste in your body—here’s whyA Physician’s Perspective on Optimal Cannabis Dosing with Guidance for the use of medicinal cannabis in Australia: Overview and Granny Storm Crow’s List Phytocannabinoids 2015-2019 

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