CBD–The hype is real, but is the science?

When It comes to the topic of cannabidiol (CBD) there is no debating the fact it is everywhere and in everything from coffee to gummies to hand lotions and even in pet food. And the products containing it seem to claim it does everything, like a modern day “cure-all.” FDA has asked the industry for more safety data even while the agency continues hesitating on issuing any definitive regulations. At the same time, the media appears to be focusing on the negative consequences or impacts of vaping and somehow continues to confuse vaping with oral CBD. Nonetheless, vaping illnesses and deaths recently have been highly publicized. Together, the publicity and rapid fire introductions of new CBD-based products daily have alarm bells ringing.

If something sounds too good to be true, it probably is. It is estimated that by 2021, CBD sales alone will be just a tad under US$2 billion dollars per year, according to the Acosta report, “The CBD Effect: A Rapidly Emerging Consumer Trend.” The growth and sales increases year over year have been substantial. Of course, when there is a popular product and the sales growth is attractive, it will inevitably lead to more people joining the business side of the industry and, thus, trigger product expansion. It is wholly possible that not all products that come to market will be of high quality. All of this is creating an environment reminiscent of the historic gold rush−few rules, lots of hype and everyone rushing for the payoff. No doubt the hype is real, but the questions surrounding the hype are real, too.

Does CBD do everything that is claimed? Is there a difference in how CBD may work in a healthy person versus one with a disease such as diabetes or suffering from a pain condition? Are there only certain levels of anxiety or stress reduction that CBD may be good for and not for other forms? Does the dose of CBD matter? Is this effect the same in everyone? Perhaps above all, is it safe? One could easily see that there are many questions to answer and yet even more claims that are made. A look into the scientific literature reveals the evidence related to oral CBD in healthy people.

CBD’s benefit for a variety of clinical (medical or psychological, not nutritional) conditions has been recognized much longer than its recent public notoriety. In fact, CBD was first isolated and identified in 1940,¹ hence it is not a “Johnny come lately” phytochemical or potential dietary supplement. Simply stated, even though CBD has been known since 1940, the research is sparse and, more often than not, studies were done in animal models or on people who have medical or psychiatric conditions, not normal healthy people from the general population.

CBD’s widespread marketing and use in healthy people to self-treat a variety of ailments, from temporary sleeplessness to aches and pains from an extra hard workout, is relatively recent and raises a very important concern regarding the efficacy and safety of CBD in the healthy population. Most research has been conducted in clinical populations. This raises the question of why healthy people are being considered the same as, for example, someone with osteoporosis.

Much of the research on CBD was reported from the many studies done to attain FDA drug approval before marketing Epidiolex, a GW Pharmaceuticals CBD drug that is now FDA-approved for a specific use in treating certain types of epilepsy. The approval of this CBD drug shined the light on the potential for CBD as a therapeutic intervention. Positive findings opened up the idea box for those thinking that CBD, as a natural component of Cannabis sativa, should be on the market for a variety of self-care uses.

The media as well as public and private companies and the public ran with this drug research as a “valid” intervention to treat medical conditions both minor and more serious. In fact, a recent study reported that approximately 62% of CBD users reported using CBD to treat a medical condition.² The typical conditions that people utilize CBD for are pain, anxiety and depression. An alarming 75% of people taking CBD reported learning about CBD from sources other than a health professional.² In the marketing survey by Acosta, one-third of subjects report using CBD for “general wellness,” reporting no medical ailments. The results support that many people are using CBD to self-treat or self-manage their general health without medical supervision or knowledge as to its potential side effects.

To date, many of these questions concerning efficacy and safety are being addressed in the clinical population but much less is known about the efficacy of CBD for healthy people. As of Jan. 7, 2020, a search of the National Institutes of Health (NIH) ClinicalTrials.gov website listed a total of 215 registered trials using cannabidiol covering 192 different, though often overlapping, conditions; only 16 of the 215 studies were for healthy subjects (less than 8%). Brain health and psychological disorders are the most studied conditions with pain the second-most common.

Perhaps the most promising suggested benefits for CBD use in a non-clinical population (the normal healthy) are related to its effects on pain,^3,4,5 oxidation and inflammation.^6,7 It has been suggested that CBD is more effective than vitamins C and E as a neurological protective antioxidant and can help with many skin conditions such as acne.^8,9 In addition, there has been some promising evidence for improvements in anxiety-related sleep issues¹⁰ and sleep quality, decreased sleep disturbances and decreased time to fall asleep. Another study noted that CBD had utility for reducing social anxiety, such as when giving public talks.^11a There is talk of further examining CBD for aiding with different levels or intensities of anxiety. A recent systematic review identified a lack of well controlled trials examining the effects of CBD on sleep as well as the lack of studies exploring the potential negative effects of long term use.^9,12

Other suggested benefits have included cardiovascular, mood and focus. In one study of nine healthy men given 600 mg of CBD, resting blood pressure was lower, stroke volume was lower and heart rate was higher, and CBD blunted the blood pressure response to stress.¹³ In contrast, a systematic review of 25 studies in six different species concluded that acute and chronic administration of CBD had no effect on blood pressure (BP) or heart rate (HR) under controlled conditions, but did reduce BP and HR in stressful conditions.¹⁴ The implications of these findings are not clear, but surely more research is needed to determine the potential effects of CBD on the cardiovascular system in healthy subjects from the perspective of safety as well as in consideration of prevention of cardiovascular issues such as high BP. In addition, the impact of CBD on the cardiovascular response to exercise would be of great interest.

While there have been serious questions regarding the safety of CBD, especially over the long term and from multiple sources, there is limited research on the toxicology of CBD in humans. However, use is generally considered safe and adverse events considered dose dependent.^15,16 Doses of as high as 1500 mg/day for four weeks have been well tolerated.^15,17 Single doses of up to 6,000 mg (6 g) and multiple doses of up to 1,500 mg twice daily (less than 3 g) for seven days were reported to be well tolerated in healthy subjects, with mild diarrhea, nausea and headache being the only reported adverse events.¹⁸ In addition, doses of up to 50 mg/kg/day for three months have been reported in clinical population as well.^19,20 It should be noted that the CBD used in these studies also contained less than 3% THC and were from different formulations.

Furthermore, data related to dosing and absorption varies significantly depending on whether the CBD is inhaled, or ingested by some other means²¹ and there are greater individual differences particularly between users and non-users.²² There has been a call in the literature as well as by major health agencies and government organizations for more long term studies with a larger number of participants.¹⁶

Typically, it would be the goal of the writer to provide a definitive answer to the questions posed in the beginning of an article. However, in this case, we can only say that the research is evolving and, because of the widespread use of CBD, there is an urgent need for studies to include healthy individuals, mirror the use as it exists in “real life” and, most certainly, focus on collecting human safety data. That said, the research does suggest promise for the use of CBD in the treatment and management of several clinical ailments. Whether or not this translates to the general healthy population remains to be scientifically supported.

To read related content, check out the “Hemp/CBD: Market evolution” digital magazine.

Susan Hewlings, PhD, RD, is director of scientific affairs at Nutrasource. Douglas Kalman, PhD, RD, is vice president of scientific affairs at Nutrasource. Both are co-founders of Substantiation Sciences.

References

1 Russo EB. “History of cannabis and its preparations in saga, science and sobriquet.” Chem Biodivers. 2007;4:2624-2648.

2 Corroon J, Phillips JA. “A Cross-Sectional Study of Cannabidiol Users.” Cannabis and cannabinoid research. 2018;3(1):152-161.

3 Banerjee S, McCormack S. “Medical Cannabis for the Treatment of Chronic Pain: A Review of Clinical Effectiveness and Guidelines.” Ottawa (ON): Canadian Agency for Drugs and Technologies in Health. 2019.

4 Mucke M et al. “Cannabis-based medicines for chronic neuropathic pain in adults.” The Cochrane database of systematic reviews. 2018;3:Cd012182.

5 Lynch ME, Ware MA. “Cannabinoids for the Treatment of Chronic Non-Cancer Pain: An Updated Systematic Review of Randomized Controlled Trials.” J Neuroimmune Pharmacol. 2015;10(2):293-301.

6 Atalay S, Jarocka-Karpowicz I, Skrzydlewska E. “Antioxidative and Anti-Inflammatory Properties of Cannabidiol.” Antioxidants (Basel). 2019;9(1).

7 Burstein S. “Cannabidiol (CBD) and its analogs: a review of their effects on inflammation.” Bioorg Med Chem. 2015;23(7):1377-1385.

8 Hampson AJ  et al. “Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants.” Proc Natl Acad Sci U S A. 1998;95(14):8268-8273.

9 Olah A et al. “Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes.” JCI Insight. 2014;124(9):3713-3724.

10 Shannon S et al. “Cannabidiol in Anxiety and Sleep: A Large Case Series.” Perm J. 2019;23:18-41.

11 Linare IM 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.

12 Kuhathasan N et al. “The use of cannabinoids for sleep: A critical review on clinical trials.” Exp Clin Psychopharmacol. 2019;27(4):383-401.

13 Jadoon KA, Tan GD, O'Sullivan SE. A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study. JCI insight. 2017;2(12).

14 Sultan SR et al. “A Systematic Review and Meta-Analysis of the Haemodynamic Effects of Cannabidiol.” Front Pharmacol. 2017;8:81.

15 Bergamaschi MM et al. “Safety and side effects of cannabidiol, a Cannabis sativa constituent.” Curr Drug Saf. 2011;6(4):237-249.

16 Iffland K, Grotenhermen F. “An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies.” Cannabis Cannabinoid Res. 2017;2(1):139-154.

17 Stout SM, Cimino NM. “Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review.” Drug Metab Rev. 2014;46(1):86-95.

18 Taylor L et al. “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.

19 Hess EJ et al. “Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis complex.” Epilepsia. 2016;57(10):1617-1624.

20 Devinsky O et al. “Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial.” Lancet Neurol. 2016;15(3):270-278.

21 Grotenhermen F. “Pharmacokinetics and pharmacodynamics of cannabinoids.” Clin Pharmacokinet. 2003;42(4):327-360.

22 Millar SA et al. “A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans.” Front Pharmacol. 2018;9:1365.