Food effects on the formulation, dosing, and administration of cannabidiol (CBD) in humans: A systematic review of clinical studies

Silmore, Lucy H.; Willmer, Andrew R.; Capparelli, Edmund V.; Rosania, Gus R.

doi:10.1002/phar.2512

Cited by 29 publications

(15 citation statements)

References 21 publications

(212 reference statements)

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“…We observed a 22-fold increase in CBD recovery in the micellar fraction in the fed digestion compared to the fasted state digestion. Moreover, human studies on oral bioavailability of CBD in vivo using different CBD formulations showed greater CBD bioavailability in fed patients [19]. However, the difference in the micellarization efficiency between starved digestion and fed digestion may not reflect the same extent of difference in oral bioavailability in vivo.…”

Section: Bioaccessibilitymentioning

confidence: 99%

“…Many of the psychoactive analgesic effects of THC are due to its interaction with the CB 1 receptor, while the non-psychoactive cannabinoids, like CBD, have a lower affinity for both CB 1 and CB 2 receptors [3]. Previous studies have focused on the oral and intraperitoneal pharmacokinetics of THC and CBD together in human plasma and also on CBD in humans, dogs, rats and pigs [15][16][17][18][19]. However, despite many publications on cannabinoid metabolism and distribution in human and animal studies, there is a lack of information regarding the absorption and bioavailability of cannabinoids.…”

Section: Introductionmentioning

confidence: 99%

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The Effects of Food on Cannabidiol Bioaccessibility

Mozaffari

Willette²,

Lucker³

et al. 2021

Molecules

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Cannabidiol (CBD) is a hydrophobic non-psychoactive compound with therapeutic characteristics. Animal and human studies have shown its poor oral bioavailability in vivo, and the impact of consuming lipid-soluble CBD with and without food on gut bioaccessibility has not been explored. The purpose of this research was to study the bioaccessibility of CBD after a three-phase upper digestion experiment with and without food, and to test lipase activity with different substrate concentrations. Our results showed that lipase enzyme activity and fatty acid absorption increased in the presence of bile salts, which may also contribute to an increase in CBD bioaccessibility. The food matrix used was a mixture of olive oil and baby food. Overall, the fed-state digestion revealed significantly higher micellarization efficiency for CBD (14.15 ± 0.6% for 10 mg and 22.67 ± 2.1% for 100 mg CBD ingested) than the fasted state digestion of CBD (0.65 ± 0.7% for 10 mg and 0.14 ± 0.1% for 100 mg CBD ingested). The increase in bioaccessibility of CBD with food could be explained by the fact that micelle formation from hydrolyzed lipids aid in bioaccessibility of hydrophobic molecules. In conclusion, the bioaccessibility of CBD depends on the food matrix and the presence of lipase and bile salts.

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Section: Bioaccessibilitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Effects of Food on Cannabidiol Bioaccessibility

Mozaffari

Willette²,

Lucker³

et al. 2021

Molecules

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“…Common administration methods for THC and/or CBD include oral (ingestion), oro-buccal mucous membrane absorption or inhalation (Britch et al 2021 ; Millar et al 2018 ; Silmore et al 2021 ; Taylor et al 2018 ; Vitetta et al 2021 ; Moltke and Hindocha 2021 ). Because THC and CBD have poor aqueous solubility, ingestion delivers poor and erratic absorption, and most of the THC and CBD that is absorbed is modified by first-pass metabolism, which reduces systemic bioavailability to only 6% (Fasinu et al 2016 ; Millar et al 2018 ; Lucas et al 2018 ).…”

Section: Pharmacokinetics Of Thc and Cbdmentioning

confidence: 99%

“…THC and CBD bind to blood cells and proteins and have a high apparent volume of distribution of 6.4 L/kg and 32 L/kg, respectively (Fasinu et al 2016 ; Ohlsson et al 1986 ). Administration of oral, sublingual and oro-buccal THC and/or CBD at therapeutic doses for chronic pain, stress, anxiety, and insomnia provide plasma THC and CBD levels in the order of 1–10 ng/ml for THC, and 1–30 ng/mL for CBD (Britch et al 2021 ; Crippa et al 2021 ; Guy and Flint 2004 ; Henson et al 2021 ; Millar et al 2018 ; Prieto González and Vila Silván 2021 ; Silmore et al 2021 ; Stott et al 2013 ; Torres-Moreno et al 2018 ; Vitetta et al 2021 ).…”

Section: Pharmacokinetics Of Thc and Cbdmentioning

confidence: 99%

Tetrahydrocannabinol and cannabidiol medicines for chronic pain and mental health conditions

Henson¹,

Vitetta

Hall³

2022

Inflammopharmacol

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Combination tetrahydrocannabinol (THC)/cannabidiol (CBD) medicines or CBD-only medicines are prospective treatments for chronic pain, stress, anxiety, depression, and insomnia. THC and CBD increase signaling from cannabinoid receptors, which reduces synaptic transmission in parts of the central and peripheral nervous systems and reduces the secretion of inflammatory factors from immune and glial cells. The overall effect of adding CBD to THC medicines is to enhance the analgesic effect but counteract some of the adverse effects. There is substantial evidence for the effectiveness of THC/CBD combination medicines for chronic pain, especially neuropathic and nociplastic pain or pain with an inflammatory component. For CBD-only medication, there is substantial evidence for stress, moderate evidence for anxiety and insomnia, and minimal evidence for depression and pain. THC/CBD combination medicines have a good tolerability and safety profile relative to opioid analgesics and have negligible dependence and abuse potential; however, should be avoided in patients predisposed to depression, psychosis and suicide as these conditions appear to be exacerbated. Non-serious adverse events are usually dose-proportional, subject to tachyphylaxis and are rarely dose limiting when patients are commenced on a low dose with gradual up-titration. THC and CBD inhibit several Phase I and II metabolism enzymes, which increases the exposure to a wide range of drugs and appropriate care needs to be taken. Low-dose CBD that appears effective for chronic pain and mental health has good tolerability and safety, with few adverse effects and is appropriate as an initial treatment.

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“…CBD is also binds to proteins and blood cells and has a high apparent volume of distribution of 32 L/kg [88,92]. Low-dose CBD administration provides serum CBD levels in the order of 1-10 ng/mL [83][84][85]87,91]. CBD is mainly metabolized in the liver by CYP3A-and CYP2C-dependent phase I metabolism to its active metabolite 7-OH-CBD, which is then metabolized and excreted in feces and urine after phase II metabolism by uridine 5 -diphospho-glucuronosyltransferase (UGT) enzymes [84,88].…”

Section: Safety Tolerability and Pharmacokineticsmentioning

confidence: 99%

Enhancing Endocannabinoid Control of Stress with Cannabidiol

Henson

Vitetta

Quezada

et al. 2021

JCM

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The stress response is a well-defined physiological function activated frequently by life events. However, sometimes the stress response can be inappropriate, excessive, or prolonged; in which case, it can hinder rather than help in coping with the stressor, impair normal functioning, and increase the risk of somatic and mental health disorders. There is a need for a more effective and safe pharmacological treatment that can dampen maladaptive stress responses. The endocannabinoid system is one of the main regulators of the stress response. A basal endocannabinoid tone inhibits the stress response, modulation of this tone permits/curtails an active stress response, and chronic deficiency in the endocannabinoid tone is associated with the pathological complications of chronic stress. Cannabidiol is a safe exogenous cannabinoid enhancer of the endocannabinoid system that could be a useful treatment for stress. There have been seven double-blind placebo controlled clinical trials of CBD for stress on a combined total of 232 participants and one partially controlled study on 120 participants. All showed that CBD was effective in significantly reducing the stress response and was non-inferior to pharmaceutical comparators, when included. The clinical trial results are supported by the established mechanisms of action of CBD (including increased N-arachidonylethanolamine levels) and extensive real-world and preclinical evidence of the effectiveness of CBD for treating stress.

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Food effects on the formulation, dosing, and administration of cannabidiol (CBD) in humans: A systematic review of clinical studies

Cited by 29 publications

References 21 publications

The Effects of Food on Cannabidiol Bioaccessibility

The Effects of Food on Cannabidiol Bioaccessibility

Tetrahydrocannabinol and cannabidiol medicines for chronic pain and mental health conditions

Enhancing Endocannabinoid Control of Stress with Cannabidiol

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