Currently, the most talked about natural ingredient in the dietary supplement industry is probably CBD. It’s also the ingredient about which the most misinformation is being disseminated. One YouTube video may say it’s the cure for all ills, while another website may say that it’s not safe, and might even make you high. It really is a travesty that there is so much hype and unreliable personal opinion being expressed about CBD. In an effort to provide some clarity, this article will share science-based information about hemp, CBD and phytocannabinoids.

Defining CBD
Cannabidiol, or CBD, is a naturally-occurring compound found in plants. It belongs to a family of compounds called cannabinoids or, more specifically, phytocannabinoids — which means cannabinoids from plants (phyto = plant). Actually, there are over 100 different phytocannabinoids, and hemp provides a primary source. Other common plants, such as oregano and basil, also contain phytocannabinoids. It may be that, when you eat Italian foods, one of the reasons you may enjoy them so much (besides the delicious taste), is that the phytocannabinoids they contain help you feel good.

The most well-known of the phytocannabinoids, aside from CBD, is tetrahydrocannabinol, or THC. THC is the psychoactive compound found in marijuana that makes you high. To be clear, CBD and the other phytocannabinoids are not psychoactive, and will not make you high. They have other benefits, but they are not psychoactive.

Full-Spectrum Phytocannabinoids
While CBD is the most prevalent phytocannabinoid in hemp, it isn’t the only one. In fact, cannabinoids work together to create a greater overall synergistic activity. In scientific literature, the name for this is “the entourage effect.” This is similar to the way that various vitamins and minerals work together synergistically. If you’re just using isolated CBD, you’re not getting the benefits of the entourage effect.

A full-spectrum hemp extract, on the other hand, provides a full array of naturally-occurring phytocannabinoids, including a defined amount of CBD. That’s what you want: full-spectrum phytocannabinoids, not CBD isolate. It should also be noted that CBD isolate is less expensive than full-spectrum, as well as less effective.

The Endocannabinoid System
While most people can probably name a couple of body systems, like the immune and cardiovascular systems which consist of defined organs and other structures, the vast majority of people are unaware of the endocannabinoid system (ECS). The ECS is a different type of system, composed of a series of receptors which occur throughout the nervous system and, consequently, throughout every system in the body. The ECS plays a major role in regulating many physical and cognitive processes in the body.

In addition, the body produces endocannabinoids, which are its own internal cannabinoids. These activate the ECS receptors to initiate a cascade of powerful and important effects. Likewise, phytocannabinoids work with endocannabinoids to support and provide healthy functioning of the ECS. Just as every other system in the body needs nutritional support to stay healthy, the ECS needs such support as well. Supplementation with phytocannabinoids can help in the nourishment of the ECS.

Research On CBD/Phytocannabinoids
Regarding the benefits of cannabinoids let me start by saying that most CBD research is actually done on full-spectrum phytocannabinoids with a defined amount of CBD, not CBD isolate. So, that’s what I’m going to talk about. CBD/ phytocannabinoid research had been done on a broad range of health issues, with significant variations in dosage. In this article, we’ll focus on a few primary benefits associated with specific amounts of phytocannabinoids.

Relaxation And Sleep
Americans have a serious need to relax. Almost one-third of adults report that stress has a strong impact on their physical and mental health — and 42 percent of those report feeling nervous or anxious. In addition, about 46 percent of adults surveyed have reported lying awake at night due to stress. Essentially, stress just keeps their mind going and going, making it difficult to shut down for the night. Since the ECS plays an important role in the regulation and maintenance of all body systems, and phytocannabinoids support the ECS, it’s not surprising to learn that in human clinical research, 25 mg of phytocannabinoids daily have been shown to help calm stress and stress-induced anxiety, as well as help improve sleep.

A large, retrospective series of case studies¹ was conducted in which the vast majority of 103 adult subjects with stress/anxiety and sleep complaints were given 25 mg phytocannabinoids per day in capsule form. If stress/anxiety complaints predominated the 25 mg dose was given in the morning after breakfast. If sleep complaints predominated, the dose was given in the evening after dinner. The results were that, on average, stress/anxiety and sleep improved for the majority of patients and these improvements were sustained over time. At the first monthly assessment following the start of phytocannabinoid supplementation, 79.2 percent and 66.7 percent of subjects experienced an improvement in stress/anxiety and sleep, respectively.

Other published case studies found similar results when phytocannabinoids were supplemented. In a case study² with a young girl with stress/anxiety, 25 mg of phytocannabinoids at bedtime resulted in a steady improvement in the quality and quantity of her sleep. Likewise, in a case study³ with a 27-year old man who had stress/anxiety and sleep issues, the subject reported that 24 mg of phytocannabinoids daily resulted in improvements in stress/anxiety as well as settling into a regular pattern of sleep.

There are other studies in a variety of populations^{4,5,6,7,8,9,10,11} in which phytocannabinoids have been successfully used at higher doses for stress/anxiety and sleep, but no studies in which phytocannabinoids have been used in lower doses.

Pain/Inflammation
An emerging area of phytocannabinoid research is inflammation and pain. Now before exploring the data, keep in mind that inflammation commonly occurs in a non-disease state. Inflammation occurs in everyone, every day. Higher intakes of red and processed meats, sweets, desserts, French fries, and refined grains are associated with experiencing more inflammation.¹² Colder temperatures are associated with experiencing more inflammation.¹³ Physical overexertion — like exercising extra hard at the gym — may result in temporary inflammation and pain.^14,15 So, when talking about pain and inflammation, these are the type of applications we're considering. Now, onto a review of phytocannabinoid research on inflammation and pain.

In research, there are various markers of inflammation. That is, there are inflammatory chemicals produced by our cells which contribute to the inflammatory process, and which can be measured. In one laboratory study,¹⁶ researchers sought to quantify the anti-inflammatory effects of cannabinoids, including phytocannabinoids, in cells that produced inflammatory markers. The results were that the cannabinoids successfully reduced inflammatory markers. Similar results were seen in other laboratory research with cannabinoids/phytocannabinoids and inflammation.^17,18,19 Other laboratory research suggests that phytocannabinoids may also have application for pain.^20,21

In addition to laboratory research, there is also human research in which various doses of phytocannabinoids have been used in different inflammation/pain situations. In double-blind, placebo-controlled research with 62 subjects, supplementation with 200 mg/day phytocannabinoids significantly reduced levels of resistin, a type of protein that promotes several proinflammatory cytokines.²² In other human research,²³ 50-100 mg/day of phytocannabinoids resulted in pain reduction in most subjects tested.

Furthermore, 2,409 phytocannabinoid users were recently surveyed regarding why they used phytocannabinoids. The results, published in a scientific journal,²⁴ were that almost 62 percent of the phytocannabinoid used reported using phytocannabinoids for specific health applications. The top three were pain, anxiety, and mood. Almost 36 percent of respondents reported that phytocannabinoids effectively addressed their issue(s) "very well by itself," while only 4.3 percent reported "not very well." Of course, this survey in and of itself does not constitute direct evidence of the effectiveness of phytocannabinoids of temporary pain applications, but when taken together with the other research cited it certainly provides interesting insights into the popular use of phytocannabinoids.

Conclusion
Much of the aforementioned research was conducted using a daily dose of 25 mg of phytocannabinoids. Nevertheless, you may find products on the market that contain 10 mg or even 5 mg of CBD/phytocannabinoids. Many people have asked me if these lower doses will do them any good. My answer is maybe, but since there's no research showing that doses lower than 25 mg have efficacy, I would recommend sticking with 25 mg dose for a greater likelihood of success.

References

1. Shannon S, Lewis N, Lee H, Hughes S. Cannabidiol (CBD) in Anxiety and Sleep: A large case series. Unpublished. n.d. 10 pgs.
2. Shannon S, Opila-Lehman J. Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report. Perm J. 2016 Fall;20(4):108-11.
3. Shannon S, Opila-Lehman J. Cannabidiol Oil for Decreasing Addictive Use of Marijuana: A Case Report. Integrative Medicine. 2015;14(6):31-5.
4. Fusar-Poli P, Allen P, Bhattacharyya S, Crippa JA, Mechelli A, Borgwardt S, Martin-Santos R, Seal ML, O'Carrol C, Atakan Z, Zuardi AW, McGuire P. Modulation of effective connectivity during emotional processing by Delta 9-tetrahydrocannabinol and cannabidiol. Int J Neuropsychopharmacol. 2010 May;13(4):421-32.
5. Crippa JA, Derenusson GN, Ferrari TB, Wichert-Ana L, Duran FL, Martin-Santos R, Simoes MV, Bhattacharyya S, Fusar-Poli P, Atakan Z, Santos Filho A, Freitas-Ferrari MC, McGuire PK, Zuardi AW, Busatto GF, Hallak JE. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. J Psychopharmacol. 2011 Jan;25(1):121-30.
6. Bergamaschi MM, Queiroz RH, Chagas MH, de Oliveira DC, De Martinis BS, Kapczinski F, Quevedo J, Roesler R, Schroder N, Nardi AE, Martin-Santos R, Hallak JE, Zuardi AW, Crippa JA. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology. 2011 May;36(6):1219-26.
7. Das RK, Kamboj SK, Ramadas M, Yogan K, Gupta V, Redman E, Curran HV, Morgan CJ. Cannabidiol enhances consolidation of explicit fear extinction in humans. Psychopharmacology (Berl). 2013 Apr;226(4):781-92.
8. Carlini EA, Cunha JM. Hypnotic and antiepileptic effects of cannabidiol. J Clin Pharmacol. 1981 Aug-Sep;21(S1):417S-27S.
9. Zuardi AW, Crippa JA, Hallak JE et al. Cannabidiol for the treatment of psychosis in Parkinson's disease. J Psychopharmacol, 2009;23(8):979.83.
10. Chagas MH, Eckeli AL, Zuardi AW, Pena-Pereira MA, Sobreira-Neto MA, Sobreira ET, Camilo MR, Bergamaschi MM, Schenck CH, Hallak JE, Tumas V, Crippa JA. Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson's disease patients: a case series. J Clin Pharm Ther. 2014 Oct;39(5):564.6.
11. Pesantez-Rios G, Armijos-Acurio L, Jimbo-Sotomayor R, Pascual-Pascual SI, Pesantez-Cuesta G. [Cannabidiol: its use in refractory epilepsies]. Rev Neurol. 2017 Aug 16;65(4):157.60. [Article in Spanish]
12. Lopez-Garcia E, Schulze MB, Fung TT, Meigs JB, Rifai N, Manson JE, Hu FB. Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction. Am J Clin Nutr. 2004 Oct;80(4):1029.35.
13. Halonen JI, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J. Associations between outdoor temperature and markers of inflammation: a cohort study. Environ Health.2010 Jul 23;9:42.
14. Suzuki K, Peake J, Nosaka K, et al. Changes in markers of muscle damage, inflammation and HSP70 after an Ironman Triathlon race. Eur J Appl Physiol. 2006 Dec;98(6):525.34.
15. Rowlands DS, Pearce E, Aboud A, et al. Oxidative stress, inflammation, and muscle soreness in an 894-km relay trail run. Eur J Appl Physiol. 2012 May;112(5):1839.48.
16. Couch DG, Tasker C, Theophilidou E, Lund JN, O'Sullivan SE. Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon. Clin Sci(Lond). 2017 Oct 25;131(21):2611.26.
17. Koay LC, Rigby RJ, Wright KL. Cannabinoid-induced autophagy regulates suppressor of cytokine signaling-3 in intestinal epithelium. Am J Physiol Gastrointest Liver Physiol. 2014 Jul 15;307(2):G140.8.
18. Kozela E, Juknat A, Kaushansky N, Rimmerman N, Ben-Nun A, Vogel Z. Cannabinoids decrease the th17 inflammatory autoimmune phenotype. J Neuroimmune Pharmacol. 2013 Dec;8(5):1265.76.
19. De Filippis D, Esposito G, Cirillo C, Cipriano M, De Winter BY, Scuderi C, Sarnelli G, Cuomo R, Steardo L, De Man JG, Iuvone T. Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis. PLoS One. 2011;6(12):e28159.
20. Booz GW. Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Free Radic Biol Med. 2011 Sep 1;51(5):1054.61.
21. Xiong W, Cui T, Cheng K, Yang F, Chen SR, Willenbring D, Guan Y, Pan HL, Ren K, Xu Y, Zhang L. Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors. J Exp Med. 2012 Jun 4;209(6):1121.34.
22. Jadoon KA, Ratcliffe SH, Barrett DA, Thomas EL, Stott C, Bell JD, O'Sullivan SE, Tan GD. Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study. Diabetes Care. 2016 Oct;39(10):1777.86.
23. Cunetti L, Manzo L, Peyraube R, Arnaiz J, Curi L, Orihuela S. Chronic Pain Treatment With Cannabidiol in Kidney Transplant Patients in Uruguay. Transplant Proc. 2018 Mar;50(2):461.4.
24. Corroon J, Phillips JA. A Cross-Sectional Study of Cannabidiol Users. Cannabis Cannabinoid Res. 2018 Jul 1;3(1):152.61.

There are many naturally occurring plant cannabinoids, also known as phytocannabinoids (i.e. phyto = plant). The two most well-known of these are CBD and THC, which are derived from hemp or marijuana, both varietal plants of the Cannabis sativa species. In past years, cannabinoids were defined as “terpene phenolic constituents” of Cannabis known to directly interact with cannabinoid receptors in the body, which are part of the endocannabinoid system (eCBs). However, in more recent years the scientific community has recognized there are several plant compounds that are not from Cannabis but are capable of either directly interacting with cannabinoid receptors or sharing chemical similarity with cannabinoids or both. Consequently, the term phytocannabinoids is now inclusive of these other plant compounds as well as those from Cannabis.¹

The first part of this article will review the phytocannabinoid properties of resveratrol, a natural antioxidant compound found in grapes, peanuts² and Japanese Knotweed (Polygonum cuspidatum),³ providing antioxidant protection to the plants— as well as to humans that consume them.⁴ The second part of the article will compare resveratrol to CBD in terms of human health benefits.

Resveratrol 101
Resveratrol originally made its introduction splash into the dietary supplement marketplace based upon the consideration that intake of it and other polyphenol compounds from red wine may contribute to the “French paradox”—the unexpectedly low rate of death from cardiovascular disease in the Mediterranean population despite the relatively higher intake of saturated fats.⁵ Then, the excitement increased with the understanding that resveratrol helped activate the SIRT 1 gene, associated with longevity.⁶ Since that time, interest in resveratrol has continued to expand due to human research demonstrating its effectiveness for reducing inflammation and other health benefits.

Resveratrol and the eCBs
As research continued, it became evident that resveratrol also affects signaling with endocannabinoid receptors. In turn, this exerts modulatory effects in the survival signaling pathways, neural plasticity (i.e. the ability of the brain to change continuously throughout an individual’s life), as well as a variety of neuroinflammatory and neurodegenerative processes. The therapeutic effects of this ubiquitous signaling system in Alzheimer’s disease, epilepsy, multiple sclerosis, mood and movement disorders, spinal cord injury, and stroke have been well-documented,⁷ and helps to explain why it is that resveratrol has a broad range of activities.

Resveratrol, eCBs, cognition and mood
Recently, resveratrol is implicated in the biology of nerve growth factor (NGF), a critical player in the maintenance of neuronal growth and function. Likewise, resveratrol has also shown antidepressant-like effects in behavioral studies. The interaction between the nerve growth factor (NGF) and eCBs and their contribution to the antidepressant/emotional activity prompted researchers to further evaluate the mechanism of action of resveratrol. Results were that four-week treatment with resveratrol led to significant and sustained enhancement of NGF and eCB contents in dose-dependent and brain region-specific manner. Essentially, resveratrol like the classical antidepressant, amitriptyline, affects brain NGF and eCB signaling under the regulatory drive of CB1 receptors in the eCBs.⁸

A practical application of resveratrol effects in this regard were demonstrated in a study⁹ in which 80 post-menopausal women aged 45–85 years received resveratrol (75 mg, twice daily) or placebo for 14 weeks to examine the effect on cognitive performance and other parameters. Results were that, compared to placebo, significant improvements were observed in the performance of cognitive tasks in the domain of verbal memory (p = 0.041) and in overall cognitive performance (p = 0.020). Mood also tended to improve in multiple measures. In another study, 200 mg of resveratrol daily improved memory performance in association with improved glucose metabolism in older adults.¹⁰

Resveratrol, eCBs and inflammation
Resveratrol has been shown to have anti-inflammatory effects with as little as 40 mg/day in normal human subjects.¹¹ This included the reduction of inflammatory markers such as TNFalpha, IL-6, and C-reactive protein, with no changes in the placebo group. Similarly, in postmenopausal women with osteoarthritis pain, 75 mg of resveratrol twice daily significantly reduced pain and improved total well-being.¹² Other research has also shown similar results, including research^13,14 in patients with ulcerative colitis (a chronic inflammatory bowel disease) receiving 500 mg/day of resveratrol, and research¹⁵ in receiving 100 mg/day resveratrol.

But what is resveratrol’s mechanism of action for these anti-inflammatory effects? This was examined in a 6-week resveratrol study¹⁶ on rats who were fed a high-fat diet (HFD), which in turn resulted in non-alcoholic steatohepatitis (NASH)—a condition of liver inflammation and damage caused by a buildup of fat in the liver. The HFD caused an increase in body weight, liver index, hepatic lipid accumulation, and inflammation, which was inhibited by resveratrol. Resveratrol also attenuated gut microbial dysbiosis (i.e. imbalance of microorganisms in the gut). Moreover, resveratrol led to a reduction in metabolic endotoxemia and colon inflammation. These benefits appear to have been mediated by resveratrol’s effect on the CB1 and CB2 receptors in the gut eCBs. In short, these data indicate that the eCBs, particularly the expressions of CB1 and CB2, appears to play a crucial role in the resveratrol induced anti-NASH effect by maintaining the gut barrier integrity and inhibiting gut inflammation. Other research¹⁷ has also suggested that resveratrol induces peripheral blocking of pain through ì-opioid receptor and CB1 receptor activation by endogenous opioid and endocannabinoid releasing.

CBD 101
Much has been written about CBD elsewhere, so I won’t spend much time in a lengthy reiteration. Rather, here is a short overview. As previously mentioned, cannabidiol, or CBD, is a naturally-occurring phytocannabinoid from hemp. Human clinical research on CBD has revealed that it is effective in helping to reduce stress/anxiety and sleep complaints with daily doses of 25 mg.^18,19,20 In a more recent study,²¹ 15 mg of hemp-derived CBD for six weeks led to significant decreases in appetite, along with improvements in sleep quality and duration, and enhancements in “quality of life” scores in healthy humans. An emerging area of CBD research is inflammation and pain. However, considerably higher doses of CBD were used in these studies,^22,23 ranging between 100–300 mg/day. Other research on CBD also exists, but those studies center around more serious health issues and require medical intervention.

Conclusion
Comparing resveratrol to CBD (See table above) Although they are both phytocannabinoids, resveratrol and CBD’s applications are not precisely the same. This table demonstrating the specific applications of each, including daily doses used in human research:

In reviewing the areas in which resveratrol and CBD offer benefits, it is clear that there are some distinct differences as well as some overlap. Both offer benefits for pain/inflammation. That being said, there are significant differences in cost. The minimum effective dose of CBD shown to have efficacy for this purpose is exponentially higher than that of the highest dose of resveratrol shown to have efficacy. So for purposes of pain/inflammation, resveratrol is the better choice—although it could certainly be combined with lower, more affordable doses of CBD.

Resveratrol is also the clear winner with regard to cognition/mood, while CBD has the advantage for stress/anxiety. In addition, resveratrol also offers benefits for arterial function and exercise-related muscle fatigue that CBD does not have. Conversely, CBD offers benefits for promoting sleep, while resveratrol does not.

Both resveratrol and CBD have different but complementary effects with regard to weight management. CBD appears to help reduce appetite, while resveratrol has a more direct effect on fat metabolism/weight loss. Hence, both phytocannabinoids could be used together to help achieve a greater overall effect.

References

1. Gertsch J, Pertwee RG, Di Marzo V. Phytocannabinoids beyond the Cannabis plant—do they exist? Br J Pharmacol. 2010; 160:523–29.
2. Soleas GJ, Diamandis EP, Goldberg DM. Resveratrol: A molecule whose time has come? And gone? Clin Biochem 1997;30:91–113.
3. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nature reviews. Drug discovery 2006; 5(6):493–506.
4. Bradamante S, Barenghi L, Villa A. Cardiovascular protective effects of resveratrol. Cardiovasc Drug Rev 2004; 22(3):169–88.
5. Labinskyy N, Csiszar A, Veress G, Stef G, Pacher P, Oroszi G, Wu J, Ungvari Z. Vascular dysfunction in aging: potential effects of resveratrol, an anti-inflammatory phytoestrogen. Current Medicinal Chemistry 2006; 13(9):989–96.
6. Borra MT, Smith BC, Denu JM.Mechanism of human SIRT1 activation by resveratrol. J Biol Chem.2005 Apr 29;280(17):17187–95.
7. Hassanzadeh P, Atyabi F, Dinarvand R. Resveratrol: More than a phytochemical. Biomed Rev 2015; 26: 13–21.
8. Hassanzadeh P, Arbabi E, Atyabi F, Dinarvand R. The endocannabinoid system and NGF are involved in the mechanism of action of resveratrol: a multi-target nutraceutical with therapeutic potential in neuropsychiatric disorders. Psychopharmacology (Berl). 2016 Mar;233(6):1087–96.
9. Evans HM, Howe PR, Wong RH. Effects of Resveratrol on Cognitive Performance, Mood and Cerebrovascular Function in Post-Menopausal Women; A 14-Week Randomised Placebo-Controlled Intervention Trial. Nutrients. 2017 Jan 3;9(1). pii: E27.
10. Witte AV, Kerti L, Margulies DS, Flöel A. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. J Neurosci. 2014 Jun 4;34(23):7862–70.
11. Ghanim H, Sia CL, Abuaysheh S, Korzeniewski K, Patnaik P, Marumganti A, Chaudhuri A, Dandona P. An antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol. J Clin Endocrinol Metab. 2010 Sep;95(9):E1–8.
12. Wong RHX, Evans HM, Howe PRC. Resveratrol supplementation reduces pain experience by postmenopausal women. Menopause. 2017 Aug;24(8):916–22.
13. Samsamikor M, Daryani NE, Asl PR, Hekmatdoost A. Resveratrol Supplementation and Oxidative/Anti-Oxidative Status in Patients with Ulcerative Colitis: A Randomized, Double-Blind, Placebo-controlled Pilot Study. Arch Med Res. 2016 May;47(4):304–9.
14. Samsami-Kor M, Daryani NE, Asl PR, Hekmatdoost A. Anti-Inflammatory Effects of Resveratrol in Patients with Ulcerative Colitis: A Randomized, Double-Blind, Placebo-controlled Pilot Study. Arch Med Res. 2015 May;46(4):280–5.
15. Macedo RC, Vieira A1, Marin DP2, Otton R3. Effects of chronic resveratrol supplementation in military firefighters undergo a physical fitness test--a placebocontrolled, double blind study. Chem Biol Interact. 2015 Feb 5;227:89–95.
16. Chen M, Hou P, Zhou M, Ren Q, Wang X, Huang L, Hui S, Yi L, Mi M. Resveratrol attenuates high-fat diet-induced non-alcoholic steatohepatitis by maintaining gut barrier integrity and inhibiting gut inflammation through regulation of the endocannabinoid system. Clin Nutr. 2019 May 30. pii: S0261-5614(19)30231–6.
17. Oliveira CDC, Castor MGME, Castor CGME, Costa ÁF, Ferreira RCM, Silva JFD, Pelaez JMN, Capettini LDSA, Lemos VS, Duarte IDG, Perez AC, Santos SHS, Romero TRL. Evidence for the involvement of opioid and cannabinoid systems in the peripheral antinociception mediated by resveratrol. Toxicol Appl Pharmacol. 2019 Apr 15;369:30–8.
18. Shannon S, Lewis N, Lee H, Hughes S. Cannabidiol (CBD) in Anxiety and Sleep: A large case series. Unpublished. n.d. 10 pgs.
19. Shannon S, Opila-Lehman J. Cannabidiol Oil for Decreasing Addictive Use of Marijuana: A Case Report. Integrative Medicine. 2015;14(6):31-5.
20. Shannon S, Opila-Lehman J. Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report. Perm J. 2016 Fall;20(4):108–111.
21. Lopez HL, Ziegenfuss TN, Cesar KR, et al. Effects of a CBD-containing Supercritical Fluid Extract of Hemp on Markers of Optimal Wellness, Stress Resilience, and Recovery in Healthy Subjects. Poster presentation. 16th Annual Conference of the International Society of Sports Nutrition (ISSN), Las Vegas, June 13–15, 2019.
22. Jadoon KA, Ratcliffe SH, Barrett DA, Thomas EL, Stott C, Bell JD, O’Sullivan SE, Tan GD. Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study. Diabetes Care. 2016 Oct;39(10):1777–86.
23. Cuñetti L, Manzo L, Peyraube R, Arnaiz J, Curi L, Orihuela S. Chronic Pain Treatment With Cannabidiol in Kidney Transplant Patients in Uruguay. Transplant Proc. 2018 Mar;50(2):461–4.
24. Imamura H, Yamaguchi T, Nagayama D, Saiki A, Shirai K, Tatsuno I. Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus. Int Heart J. 2017 Aug 3;58(4):577–83.
25. Pollack RM, Barzilai N, Anghel V, Kulkarni AS, Golden A, O’Broin P, Sinclair DA, Bonkowski MS, Coleville AJ, Powell D, Kim S, Moaddel R, Stein D, Zhang K, Hawkins M, Crandall JP. Resveratrol Improves Vascular Function and Mitochondrial Number but Not Glucose Metabolism in Older Adults. J Gerontol A Biol Sci Med Sci. 2017 Nov 9;72(12):1703–9.
26. Alway SE, McCrory JL, Kearcher K, Vickers A, Frear B, Gilleland DL, Bonner DE, Thomas JM, Donley DA, Lively MW, Mohamed JS.Resveratrol Enhances Exercise-Induced Cellular and Functional Adaptations of Skeletal Muscle in Older Men and Women. J Gerontol A Biol Sci Med Sci. 2017 Nov 9;72(12):1595–606.
27. Konings E, Timmers S, Boekschoten MV, Goossens GH, Jocken JW, Afman LA, Müller M, Schrauwen P, Mariman EC, Blaak EE. The effects of 30 days resveratrol supplementation on adipose tissue morphology and gene expression patterns in obese men. Int J Obes (Lond). 2014 Mar;38(3):470–3.