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Bioavailability of different ways to use cannabis

Brain

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Different ways of consuming cannabis provide different amounts of cannabinoids to the body. There is a difference between smoking a joint, a bowl, a bong or a blunt and eating an edible or taking a small amount of tincture (or oil) that contains THC. There is also a difference when you consume cannabis concentrates, use transdermal patches, creams, lotions or other topicals.

What is bioavailability?
When you consume a cannabis product, whether it is Δ9-tetrahydrocannabinol (THC) or cannabidiol (CBD), how much does your body actually absorb? If the product says it contains 20 mg THC, and you take it all in, you assume you consumed 20 mg THC, right? Alas, that is not the case.

When trying to understand how cannabis is absorbed and metabolized in the body, understanding bioavailability is key. In essence, bioavailability determines the effectiveness of drugs by giving us an idea of how much and how quickly the medical cannabis taken becomes active at its intended site of physiological activity. The baseline level of bioavailability for any substance is intravenous injection. Any drug taken this way is 100% bioavailable, as the substance is immediately absorbed into the bloodstream. However, there is currently no dosage form of cannabis for intravenous administration, so instead, medical cannabis taken by patients must overcome various biological barriers depending on the route of administration used.

According to the Merriam Webster Dictionary, bioavailability is described as "the degree and speed with which a substance (e.g., a drug) is absorbed into a living system or becomes available at the site of physiological activity. This means that if a product has high bioavailability, you get more benefit from it compared to a product with low bioavailability. There are several complex metabolic factors that affect the bioavailability of different methods. Sometimes these factors differ depending on the metabolism and enzyme levels in a particular person compared to others.

When someone consumes THC with a certain level of bioavailability, they may only ingest 30% of the active ingredient they have just ingested. The rest is thought to be discarded by the body as waste, but some cannabinoids and their metabolites will bioaccumulate in the body depending on frequency and metabolic factors. This is why knowing the bioavailability of different methods of consumption can be very valuable to the recreational THC user trying to find the right regimen for their needs.

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Marijuana bioavailability and dosing methods
Cannabis contains hundreds of molecular compounds known as terpenes and cannabinoids. The most studied cannabinoids include THC, CBD and CBN. Research on cannabinoid content in marijuana remains limited, and there are data highlighting the effects of bioavailability depending on the mode of delivery.
When determining a substance’s bioavailability, it’s necessary to account for the following key factors:
  • Formulation
  • Interactions with other substances
  • Composition
  • Blood flow
  • Digestive health
The mode of delivery or consumption plays one of the most important roles in determining the bioavailability of marijuana.

The six main methods of consumption include inhalation, sublingual, oral, intravenous, transdermal, and with a suppository. Many people are known to have different preferences as to which delivery method they prefer. Some people may prefer smoking or vaporization, while others prefer faster methods of absorption, such as sublingual infusions (oil). With all of this in mind, let's take a look at these ways of consuming cannabis and see how bioavailability rates vary.

Oral administration of THC
According to a major review of cannabinoid pharmacokinetics, oral bioavailability was found to range from 4 to 20% with peak THC concentrations ranging from 4.4 to 11 ng/ml about 2 to 4 hours after ingestion of a cookie that contains 20 mg of THC. Dr. Huestis says that "different absorption, gastric breakdown of the drug, and significant first-pass metabolism to active 11-hydroxytetrahydrocannabinol and inactive metabolites in the liver" may be the main reason why this method of consumption offers such low bioavailability. When cannabis is taken orally and undergoes first-pass metabolism, 50% of the metabolizable THC is broken down to 11-OH-THC , before it circulates in the bloodstream, which is a major factor in the lower bioavailability. Also, some researchers believe that 11-OH-THC itself contributes four times more psychoactive effects than THC, which may explain why people tend to experience a stronger sense of "high" when taking cannabis orally.

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Despite the lower bioavailability of edibles, tinctures, and oral capsules, these products tend to persist longer in the body than other routes of administration. This is evident from the fact that cannabis concentrations in the blood reach peak levels in plasma from one to six hours, with a half-life of 20 to 30 hours. It is important to say that everyone digests food at a different rate and has different levels of digestive enzymes in the body. This means that the effects of oral cannabis use will vary from person to person. Because of this, one dose that works great for your friend may be too much or too little for you.

Inhaling
In inhalation methods, such as smoking a joint or vaping, the bioavailability of THC averages about 30% according to a 2018 systematic review. In addition, plasma bioavailability and THC levels are thought to vary depending on how large a puff is inhaled and how deeply cannabis smoke is inhaled into the lungs.

When it comes to joints, they typically contain 0.5 to 0.8 grams of cannabis, which is usually about 8% THC. Experts believe that 20 to 70% of the THC enters your lungs, with about 30% of it becoming bioavailable once it enters the bloodstream. THC peaks in the bloodstream after 3-10 minutes and is no longer bioavailable after about 3 hours due to smoking.

In earlier studies with cigarettes containing 3.55% THC, the participant reached peak plasma levels of 152±86.3 ng/mL approximately 10 minutes after inhalation. However, this study concluded that "post-smoking bioavailability was 2-56%, in part because of intra- and inter-subject variability in smoking dynamics, which contributes to uncertainty in dose delivery.

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Smoking cannabis with a bong is said to remove higher levels of tar, but one study found that it also actually removes higher levels of THC from cannabis. However, the bong does remove gaseous intoxicants from marijuana smoke, including carbon dioxide, ammonia and nitrosamines. Many people assume that inhaling cannabis, whether smoking or vaporizing, gives your body the same amount of THC, but this is not true. Vaporizing cannabis actually delivers cannabis to your lungs more efficiently, while inhaling less resin. Typically, the ratio of cannabinoids to resin is 1:10, as opposed to 1:27 for smoking cigarettes and an average of 1:27 for smoking cannabis through a pipe. It is important to note that the concentration of CBD and THC in different strains of cannabis has increased over the years, and cannabis can now contain equal parts CBD and THC. Depending on the level of CBD compared to THC, the feeling of "getting high" as well as the therapeutic effects of cannabis can change.

Transdermal application of THC
Topical and transdermal preparations containing THC help relieve pain and inflammation through the skin. This is because they are easily repelled by water, which allows them to move easily through the water layer of the skin. Although there are very few studies on the bioavailability of cannabinoids when administered topically or transdermally, preclinical animal studies are promising. These methods of administration avoid first-pass metabolic effects and, because of their slow release, provide dosing over a longer period of time than other delivery methods. They are also likely to be poorly absorbed into the rest of the body beyond the site of application, meaning that systemic absorption is extremely low. It is unlikely that you will feel the psychoactive effects of cannabis when it is applied to the skin. More research is needed to determine the true bioavailability of topical products.

The topical and transdermal application of cannabinoid products has shown higher bioavailability rates in the presence of enhancers and has also prolonged steady plasma concentration compared to other routes of delivery. Additionally, the acidic degradation of CBD to THC, with the consequent psychotropic effects, is effectively mediated via its transdermal application due to the exclusion of digestive processes and a neutral skin environment. Transdermal patches imbued with ∆8-THC induced a steady-state plasma concentration within 1.4 h post-administration, which was preserved in subjects for at least 48 h.

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When it comes to the use of transdermal patches, researchers hope it may reduce the negative side effects of cannabis use seen with smoking. They also believe that transdermal patches bypass first-pass cannabinoid metabolism, which may help increase the effectiveness of the transdermal patches used. Ironically, many users experience greater and longer lasting relief from joint and muscle pain when using transdermal patches compared to topical products, but this may also depend on the amount of THC and CBD in each product.

Sublingual mode of use
Many people consider sublingual consumption of cannabinoids to be very comparable to inhalation in terms of bioavailability simply because they use similar mucosal membranes for absorption into the bloodstream, but this is not true. In fact, sublingual or oral-mucosal cannabinoids are a mixed method of delivery, mostly involving absorption through the oral mucous membranes, and some are even digested. The effects are faster and usually reach higher concentrations than with edible (oral) marijuana.

According to studies of Sativex, a 1:1 CBD:THC prescription oral mucosal spray, bioavailability was estimated at 92-98%. Nabiximols is a prescription-only oral spray that is currently in trials for FDA approval, but it is available in Canada, the United Kingdom and some European countries. It is designed to relieve symptoms of neuropathy , spasticity and bladder hyperactivity in patients with multiple sclerosis. However, various bioavailability studies of tetrahydrocannabinol have found that the actual sublingual bioavailability for THC averages 10% (rates range from 9 to 15%).

Suppositories
There are several different CBD and THC suppositories on the market. One may wonder what they are used for. Studies show that rectal administration can be very valuable for those suffering from gastrointestinal problems, severe nausea, cachexia, altered mental status, speech/swallowing disorders and the elderly. Also, the use of suppositories gives a person local pain relief, unlike other delivery methods in which THC enters the bloodstream. Thus, the overall bioavailability of THC used in the form of suppositories has an average of 15%. However, there are some studies (e.g., from 1985 on the rectal administration of THC in rhesus macaques) that demonstrated that THC was not bioavailable after rectal administration. The study also compared the rectal route of THC administration with oral, intravenous, and intramuscular modes of cannabis delivery.

One study focused on the rectal administration of marinol. Marinol, a synthetic THC drug, has been approved by the FDA and is mainly used for uncontrolled nausea during chemotherapy in cancer patients. This study of marinol for spasticity concluded that rectal administration of 2.5-5 mg of THC resulted in a maximum plasma concentration of 1.1-4.1 ng/ml within 2-8 hours. The researchers found that the rectal bioavailability of marinol was about twice that of oral administration. Rectal administration was shown to absorb the drug faster and the bioavailability was higher because the drug is rectally absorbed in larger amounts and has a lower "first-pass metabolism." It is possible that these results may be due to the fact that Marinol is not real THC, but a synthetic THC.

Additional studies show that, like marinol, a chemically modified version of THC, called THC-hemisuccinate (THC-HS), has good bioavailability in the rectum. Rectal use of THC-HS can lead to decreased spasticity, stiffness, and pain. A 2018 study published in the journal Medical Cannabis and Cannabinoids showed that after rectal administration of THC-HS, Δ9-THC levels were about 70-80% bioavailable. This bioavailability measurement was two and a half times higher than levels after oral THC capsule administration.

Thus, there are currently few data on the bioavailability of THC with rectal use, but based on the available studies, this could range from 13% to 23% if THC is synthetic or structurally altered. Also, there is no information on the bioavailability of THC or CBD when used vaginally in suppositories, although studies are underway. Despite this, many women choose to use cannabis-based suppositories for a variety of female health problems, including vulvodynia, endometriosis, pelvic floor dysfunction, and painful intercourse.

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Is it possible to increase the bioavailability of THC?
Researchers have conducted numerous studies highlighting how saturated fat improves intracellular transport of cannabinoids, primarily CBD and THC. Both of these molecules are fat soluble and are better absorbed by the liver when combined with fatty acids. Thus, fatty foods accelerate the delivery and enhance the effects of marijuana cannabinoids on the user.

This brings us to the first of several ways to increase the bioavailability of cannabis by replacing cooking oils with oils that are rich in THC or CBD when cooking. Bioavailability is also increased when cannabis is consumed with certain dairy products, meats, seafood, fruits, vegetables, spices and herbs. It is important to note that the opposite effect - lower bioavailability - is common when certain foods, drinks or substances are consumed with marijuana. Alcohol-based tinctures infused with cannabis can also be used to provide bioavailability.

Those who want to enhance the psychoactive effects of THC but are not too enamored with edibles and topicals and prefer to smoke cannabis should consider vaping. Conventional smoking methods are wasteful; a significant amount of cannabis flower burns to the ground and is of no value to the user. The amount of cannabis heated to the right temperature to release cannabinoids into the smoke the user inhales becomes a collateral loss. Smokers can use vape pens or vaporizers to increase the bioavailability of THC.

For those interested in convenient and readily available cannabis products with optimal bioavailability, soft and capsule pills, tinctures, and nutritional products are ideal. However, when using cannabis, it is important to remember that the onset time is longer and the effects are erratic and often unpredictable.

The art of responsible cannabis dosing means trying different products and methods of consumption to find out which treats are best for your needs. For more information on different THC dosing methods, as well as any information related to the pharmacology of psychoactive substances - feel free to private message @Brain.
 
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