VESIsorb® Cutting Edge Technology Used to Enhance Therapeutic CBD Bioavailability  

The statements mentioned in this content have not been evaluated by the FDA, and are not intended to prevent, diagnosis, or treat any disease. Always work with your personal healthcare provider.

By Chris D. Meletis, N.D.

There are many reasons to employ CBD oil in clinical practice, as it has been found to be beneficial for a diverse array of conditions. Yet, CBD is not always well-absorbed and used by the body. That’s why one of the most interesting recent developments in the CBD space is the invention of technologies to make it more bioavailable. Dosing is only effective if our patients are actually absorbing the CBD in the first place. In this article, I’ll briefly review some of the clinical applications of CBD and then discuss factors that interfere with CBD’s bioavailability, as well as a recently developed technology that improves the effectiveness of CBD.  

CBD and the Pain Response

CBD works through the endocannabinoid system, a pathway that includes endogenous endocannabinoids produced in the body such as anandamide (AEA) and 2-arachidonylglycerol (2-AG). CBD can activate the same receptors as AEA and 2-AG. It is interesting to note that pain relievers such as NSAIDs and acetaminophen work by slowing the breakdown of natural endocannabinoids, illustrating the link between the endocannabinoid system and pain reduction.1 These endocannabinoid-enhancing effects of NSAIDs and acetaminophen indicate their use together with CBD may increase their pain-relieving effects. CBD-rich hemp oil is of clinical use in various types of pain including osteoarthritis, fibromyalgia, migraines, irritable bowel syndrome, and musculoskeletal inflammation.2-4

CBD indirectly acts on one of the primary receptors in the endocannabinoid system, cannabinoid receptor 1 (CB1). Opioids act on receptors in the brain that govern respiration, which is the reason they are associated with often fatal respiratory depression.5 However, CB1 expression is weak in these brain areas, which is why phytocannabinoids like CBD can be safely used as painkillers.5 Furthermore, CBD can interact with the CB2 receptor, which indirectly activates opioid receptors to suppress pain.1       

Calming Effects for Stress, Anxiety, and Sleep 

People who have a difficult time coping with stress, such as individuals with post-traumatic stress disorder, often have an imbalanced endocannabinoid system6,7 that can benefit by CBD supplementation. CBD’s ability to reduce stress and anxiety has been well documented in several studies of humans giving a simulated public speech. For example, in a double-blind study of 57 healthy male participants given one of three doses of CBD (150 mg, 300 mg, or 600 mg) or a placebo 300 mg of CBD markedly lowered anxiety during the public speech.8 The other CBD doses had no effect. However, in another study of patients with Generalized Social Anxiety Disorder, a higher dose of CBD (600 mg) was needed to reduce anxiety, cognitive impairment, and discomfort in speech performance.9 One of the mechanism of actions of CBD’s calming effects is regulating blood flow in brain regions involved in stress and sustaining endocannabinoid levels in the limbic and paralimbic brain areas.10

The endocannabinoid system also plays a role in the circadian sleep-wake cycle.11 This may explain CBD’s ability to promote restful sleep.12 Patients with insomnia given 160 mg CBD could sleep longer and more deeply during the night compared to a placebo.12 CBD may also be beneficial in REM sleep behavior disorder and excessive daytime sleepiness.13

CBD’s Possible Role in Immunity

The endocannabinoid system plays a role in a healthy immune response. It assists with the regulation of bacteria, viruses, and some protozoa and their elimination from the body.14 Additionally, the endocannabinoid AEA and the CB2 receptor regulate gut immunity.15 In fact, CB2 is found primarily in immune cells.16  Working through the endocannabinoid system, CBD may suppress viral hepatitis, according to an in vitro study.17 In animals, CBD has demonstrated antibacterial effects.18,19 CBD also reduces inflammation in the lungs of mice20 and enhances natural killer cell activity.21 Its stress-relieving properties, discussed earlier in this article, are also beneficial to the immune system, given the well-known ability of stress to impair immunity.22

Relieving Seizures

One of the most promising uses for CBD is its application in epilepsy. A number of human studies have pointed to its clinical usefulness in this respect.23-25 One randomized, double-blind, placebo-controlled 14-week study of Dravet syndrome patients found that CBD combined with anti-epileptic medications led to more notable reductions in the frequency of convulsive seizures compared to the subjects on the placebo.23 In another randomized, double-blind trial, 16 people who had achieved no benefit from antiepileptic medications were administered 200-300 mg daily of  CBD plus conventional medications or placebo.26 Four of the eight patients on CBD were nearly free of seizures throughout the trial. Three other participants experienced some improvement after taking CBD. Only one patient in the CBD group did not experience any benefits. In the placebo group, seven participants experienced no benefits and only one patient noted any improvement.  

Autism and Schizophrenia

In addition to promoting calm and relaxation and encouraging restful sleep, CBD may improve social interactions. It inhibited social withdrawal and improved social interaction and cognition in two rat models of schizophrenia.27,28 In another rodent model of Dravet Syndrome, CBD reduced seizures and behaviors similar to those seen in autism.29

How Bioavailable is CBD?

Clearly, CBD has many potential applications in clinical practice. However, CBD’s usefulness is limited if it is not being absorbed effectively. There are several factors that can affect CBD bioavailability. Body size and composition of patients can determine how well CBD is absorbed. People who have a larger fat free mass experience a faster time to maximum concentration (Tmax) after oral ingestion of some CBD formulas.30 This may be due to an increased rate of clearance by metabolically active tissues such as skeletal muscle that are well-perfused as a result of larger fat free mass being associated with increased blood volume. 30 For some CBD formulations, body mass index is also positively correlated with the time to maximum concentration (Tmax) of CBD levels in the blood.30 Fat mass may modulate CBD absorption due to the lipid-soluble nature of CBD, which may build up in fat tissue.30 

Another factor that affects CBD bioavailability is the lipid-soluble nature of CBD. CBD has poor water solubility and plasma concentrations are higher when taken together with a high-fat meal.31,32  Additionally, whether CBD is administered as a food or beverage, additional ingredients in the formula, and method of delivery can affect its absorption.30 Inside the body, gut absorption and breakdown during first pass metabolism also will play a significant role in circulating CBD levels.30 

Factors That Effect CBD Bioavailability
• Its lipid-soluble properties • Patients’ body composition • Ingestion on an empty stomach or with a high-fat meal • Delivery system of the CBD product • Gut absorption • First-pass metabolism

Recent Developments in Enhancing CBD Bioavailability

On account of CBD’s inconsistent bioavailability, research has revolved around improving the absorption of CBD through the use of various technologies. One of the most promising of these technologies is self-emulsifying drug delivery systems (SEDDS) using VESIsorb® technology, a lipophilic delivery system which self-assembles on contact with an aqueous phase into a colloidal delivery system, enhancing diffusion, absorption, and consequently bioavailability.33 This type of delivery system was previously used to successfully increase the oral bioavailability of coenzyme Q10 (ubiquinone) and is therefore considered as a promising means to improve the bioavailability of CBD.34   

SEDDS are mixtures of oils, surfactants, and may contain hydrophilic solvents. Upon contact with aqueous fluids such as those found in the gastrointestinal tract, SEDDS-CBD spontaneously emulsifies under conditions such as those encountered in the gastrointestinal tract.33 This leads to the formation of droplets that are transported across the aqueous lumen of the gastrointestinal tract to the surface of the enterocyte. Here, single molecules of CBD separate from the droplets and are transferred to the enterocyte membrane and subsequently to the blood or lymphatic vessels.33 

A 2019 study demonstrated that the VESIsorb® SEDDS delivery system technology increased the bioavailability of a CBD-rich hemp extract (SEDDS-CBD).33 In this randomized, double-blind, cross-over study, 16 healthy volunteers under fasted conditions received either SEDDS-CBD or the same hemp extract diluted with medium-chain triglycerides (MCT-CBD) at a standardized dose of 25 mg. Single oral administration of SEDDS-CBD led to 4.4-fold higher concentrations compared to the MCT-CBD, as well as 2.85-fold higher area under the curve (AUC) at 8 hours and 1.70-fold AUC at 24 hours. Faster absorption was also achieved during SEDDS-CBD administration (1 hour) compared to 3 hours with MCT-CBD. During administration of MCT-CBD there was higher bioavailability in women compared with men. However, during SEDDS-CBD ingestion there were no significant differences in CBD concentrations in women compared with men. Only a slightly faster time to maximum concentration was observed in men compared to women during the SEDDS-CBD intervention.    


CBD is useful in a variety of applications including pain, stress, insomnia, immune support, and mental health. However, a number of factors can interfere with its bioavailability, including its water-soluble properties and patients’ body compositions. New technologies are being invented to improve CBD’s bioavailability. A self-emulsifying drug delivery system (SEDDS) using VESIsorb® technology is one of the most promising of these technologies. This type of technology leads to 4.4 fold higher concentrations of CBD compared to an MCT-CBD delivery system. When treating patients with such a potentially useful modality as CBD, ensuring they are receiving meaningful quantities of this phytocannabinoid is critical to achieving successful therapeutic outcomes.  


1. Vanegas H, Vazquez E, Tortorici V. NSAIDs, Opioids, Cannabinoids and the Control of Pain by the Central Nervous System. Pharmaceuticals (Basel). 2010;3(5):1335-1347.

2. Russo EB. Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes. Cannabis Cannabinoid Res. 2016;1(1):154-165.

3. Philpott HT, OʼBrien M, McDougall JJ. Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis. Pain. 2017;158(12):2442-2451.

4. Sumariwalla PF, Gallily R, Tchilibon S, Fride E, Mechoulam R, Feldmann M. A novel synthetic, nonpsychoactive cannabinoid acid (HU-320) with antiinflammatory properties in murine collagen-induced arthritis. Arthritis Rheum. 2004;50(3):985-998.

5. Shaladi AM, Crestani F, Tartari S, Piva B. [Cannabinoids in the control of pain]. Recenti Prog Med. 2008;99(12):616-624.

6. Patel S, Roelke CT, Rademacher DJ, Cullinan WE, Hillard CJ. Endocannabinoid signaling negatively modulates stress-induced activation of the hypothalamic-pituitary-adrenal axis. Endocrinology. 2004;145(12):5431-5438.

7. Hill MN, McLaughlin RJ, Morrish AC, et al. Suppression of amygdalar endocannabinoid signaling by stress contributes to activation of the hypothalamic-pituitary-adrenal axis. Neuropsychopharmacology. 2009;34(13):2733-2745.

8. Linares IM, Zuardi AW, Pereira LC, et al. Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test. Braz J Psychiatry. 2019;41(1):9-14.

9. Bergamaschi MM, Queiroz RH, Chagas MH, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology. 2011;36(6):1219-1226.

10. Crippa JA, Derenusson GN, Ferrari TB, et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. J Psychopharmacol. 2011;25(1):121-130.

11. Sanford AE, Castillo E, Gannon RL. Cannabinoids and hamster circadian activity rhythms. Brain Res. 2008;1222:141-148.

12. Carlini EA, Cunha JM. Hypnotic and antiepileptic effects of cannabidiol. J Clin Pharmacol. 1981;21(S1):417s-427s.

13. Babson KA, Sottile J, Morabito D. Cannabis, Cannabinoids, and Sleep: a Review of the Literature. Curr Psychiatry Rep. 2017;19(4):23.

14. Hernández-Cervantes R, Méndez-Díaz M, Prospéro-García Ó, Morales-Montor J. Immunoregulatory Role of Cannabinoids during Infectious Disease. Neuroimmunomodulation. 2017;24(4-5):183-199.

15. Acharya N, Penukonda S, Shcheglova T, Hagymasi AT, Basu S, Srivastava PK. Endocannabinoid system acts as a regulator of immune homeostasis in the gut. Proc Natl Acad Sci U S A. 2017;114(19):5005-5010.

16. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153(2):199-215.

17. Lowe HI, Toyang NJ, McLaughlin W. Potential of Cannabidiol for the Treatment of Viral Hepatitis. Pharmacognosy Res. 2017;9(1):116-118.

18. Barichello T, Ceretta RA, Generoso JS, et al. Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis. Eur J Pharmacol. 2012;697(1-3):158-164.

19. Appendino G, Gibbons S, Giana A, et al. Antibacterial cannabinoids from Cannabis sativa: a structure-activity study. J Nat Prod. 2008;71(8):1427-1430.

20. Ribeiro A, Almeida VI, Costola-de-Souza C, et al. Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury. Immunopharmacol Immunotoxicol. 2015;37(1):35-41.

21. Ignatowska-Jankowska B, Jankowski M, Glac W, Swiergel AH. Cannabidiol-induced lymphopenia does not involve NKT and NK cells. J Physiol Pharmacol. 2009;60 Suppl 3:99-103.

22. Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull. 2004;130(4):601-630.

23. Devinsky O, Cross JH, Laux L, et al. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017;376(21):2011-2020.

24. Devinsky O, Patel AD, Cross JH, et al. Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome. N Engl J Med. 2018;378(20):1888-1897.

25. Thiele EA, Marsh ED, French JA, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10125):1085-1096.

26. Cunha JM, Carlini EA, Pereira AE, et al. Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology. 1980;21(3):175-185.

27. Gururajan A, Taylor DA, Malone DT. Effect of cannabidiol in a MK-801-rodent model of aspects of schizophrenia. Behav Brain Res. 2011;222(2):299-308.

28. Osborne AL, Solowij N, Babic I, Huang XF, Weston-Green K. Improved Social Interaction, Recognition and Working Memory with Cannabidiol Treatment in a Prenatal Infection (poly I:C) Rat Model. Neuropsychopharmacology. 2017;42(7):1447-1457.

29. Kaplan JS, Stella N, Catterall WA, Westenbroek RE. Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome. Proc Natl Acad Sci U S A. 2017;114(42):11229-11234.

30. Williams NNB, Ewell TR, Abbotts KSS, et al. Comparison of Five Oral Cannabidiol Preparations in Adult Humans: Pharmacokinetics, Body Composition, and Heart Rate Variability. Pharmaceuticals (Basel). 2021;14(1).

31. Birnbaum AK, Karanam A, Marino SE, et al. Food effect on pharmacokinetics of cannabidiol oral capsules in adult patients with refractory epilepsy. Epilepsia. 2019;60(8):1586-1592.

32. Taylor L, Gidal B, Blakey G, Tayo B, Morrison G. A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Multiple Dose, and Food Effect Trial of the Safety, Tolerability and Pharmacokinetics of Highly Purified Cannabidiol in Healthy Subjects. CNS Drugs. 2018;32(11):1053-1067.

33. Knaub K, Sartorius T, Dharsono T, Wacker R, Wilhelm M, Schön C. A Novel Self-Emulsifying Drug Delivery System (SEDDS) Based on VESIsorb(®) Formulation Technology Improving the Oral Bioavailability of Cannabidiol in Healthy Subjects. Molecules. 2019;24(16).

34. Liu ZX, Artmann C. Relative bioavailability comparison of different coenzyme Q10 formulations with a novel delivery system. Altern Ther Health Med. 2009;15(2):42-46.