What Studies Say about Hemp CBD
Is there a role for hemp's other cannabinoid in dietary supplement markets?
In the United States, hemp is often confused with marijuana. It’s a consumer misconception that has, for decades, slowed the market potential for hemp in the food, dietary supplement, textile, and even lumber industries. The dietary supplement industry, in particular, has a lot to gain from hemp, and not just with hemp oil and hemp protein. A substance called cannabidiol (CBD) has shown nutritional potential for years, yet the taboo around Cannabis has kept CBD off the radar. Now, with hemp gaining a better reputation, it looks as though its little compound is finally poised for big market growth. And much of that growth could be in stress and anxiety formulas.
What Is CBD?
CBD is a phytocannabinoid that is found in industrial hemp and marijuana, which are two different varieties of the Cannabis sativa plant. The current market for CBD as a dietary supplement is based on industrial hemp, not marijuana, because marijuana also contains significant amounts of tetrahydrocannabinol (THC), a phytocannabinoid that is psychoactive and, thus, capable of making a person high. Industrial hemp contains only negligible amounts of THC-no more than, say, poppy seeds contain opiates-and so it will not get you high. The plant is, thus, safe for human consumption and useful for components including CBD.
While CBD is not psychoactive like THC, it can still have a profound influence on the human brain, but first-is CBD legal?
Legal Status of CBD
In order to understand if CBD is legal for sale and consumption, one must look at the legality of hemp oil, which can be tailor-made for high concentrations of CBD.
Hemp oil is listed on the U.S. Harmonized Tariff Schedule (with no restrictions on CBD content) meaning that hemp oil is a legal U.S. import. This is important because federal law prohibits the farming of hemp in the United States. Hemp can only be purchased as an import. Some state laws override this federal law, but most of these, for now, just legalize hemp farming. At the time of this writing, Colorado and Kentucky are the only states that have laws permitting the farming and sale of hemp, and these are both very recent laws. The market for U.S.-grown hemp, thus, relies almost entirely on legal imports from established markets. Canada, Europe, and China are some of the world’s biggest hemp producers, so they control the U.S. market supply and will for at least a while longer.
As long as CBD-rich oils are imported, or farmed in states where cultivation and production is permitted by state law, CBD-rich hemp oils are legal. But they are not legal if their THC content is above 0.3%.1 This threshold keeps the distinction between hemp and marijuana in place.
Scientific Studies on CBD
As for how CBD works, CBD and other phytocannabinoids influence the brain by interacting with the brain’s very own cannabinoids, called endocannabinoids.
“Generally, phytocannabinoids like CBD can help to restore a more balanced ‘tone’ within the endocannabinoid system,” says Stuart Tomc, vice president of human nutrition for CBD oil supplier CannaVest Corp. (San Diego). “As such, CBD may positively, broadly affect various processes that control brain signaling, via neurotransmitter function, ion channel and membrane dynamics, inflammatory responses, and even gene expression.” It’s worth noting that Cannabis compounds aren’t the only ones capable of interacting with the brain’s endocannabinoid system. Compounds from flax and Brassica species, for instance, have shown potential to interact with the endocannabinoid system, too.2–3 With that said, why is this brain system so important?
The endocannabinoid system has broad influence over areas of the brain involved in sensations such as pain perception, movement, emotion, cognition, and sleep. For this reason, the endocannabinoid system likely has big sway over some brain health conditions. A blockage of cannabinoid receptors called CB1 receptors has been linked to behavioral effects consistent with antidepressant activity.4 Enhancement of anandamide, the first discovered endocannabinoid, may relieve chronic pain associated with neuropsychiatric disorders.5 Post-traumatic stress disorder appears to involve cannabinoid pathways, too.6
For all of the ways the endocannabinoid system can influence brain health, CBD’s own interaction with the endocannabinoid system could translate into some very significant health effects, and previously published studies so far offer positive indications. For extensive reading, a 2012 review of CBD studies provides a thorough overview of most of the existing human clinical trials (34 in total) on CBD for healthy and/or clinical patients.7 Here are some of the trials that stand out.
Anxiety
To explore the impact of an ingredient on anxiety, scientists often first look at that ingredient’s impact on cortisol levels in the human blood after ingestion. Cortisol levels are heightened when animals are under extreme duress, and when Brazilian researchers investigated the effect of CBD doses on human cortisol levels in 11 volunteers in 1993, they found that CBD decreased cortisol levels significantly more than placebo. CBD subjects also reported a sedative effect from the treatment.8
Also in 1993, the same researchers compared the effects of CBD and two anxiety medications, ipsapirone and diazepam, on a group of 40 healthy individuals assigned to a simulated public speaking test. Using a Visual Analogue Mood Scale (VAMS) to assess personal anxiety before and after the public speaking test, the researchers determined that diazepam lowered anxiety before and after the test, while the ipsapirone and CBD only lowered anxiety after the test.9 Years later, in 2004, another team of Brazilian researchers analyzed CBD, but they upped the dosage by 100 mg (now 400 mg of CBD). Compared to placebo, subjects in this study reported significantly decreased anxiety and increased mental sedation. Brain imaging tests suggested that such effects were mediated in specific regions of the brain.10
Aside from a potential influence on healthy volunteers, CBD has shown some promise in subjects with established social anxiety disorders. Two studies in 2011 yielded favorable results for CBD supplementation in this type of population. In the first study, CBD use was associated with decreases in subjective anxiety and was accompanied by (presumably significant) changes in regional cerebral blood flow.11 The second study tied CBD to reduced anxiety and discomfort in response to a simulated public speaking test.12
Curiously, the presence of CBD alongside THC, in marijuana, has even shown potential to alleviate THC-induced anxiety and psychosis.13–14
Sleep
Early research suggests that CBD consumption can also affect sleep in a positive way-in particular, it may block rapid eye movement (REM) sleep-but such an effect may be more related to CBD’s anxiolytic (anxiety-inhibiting) properties than direct sleep regulation, per se.15 While the basis for this CBD-and-sleep theory is largely made in rodent studies, some research has been done on sleep-impaired but otherwise healthy humans.
In a 1981 Brazilian study, researchers at the Escola Paulista de Medicina in São Paulo assigned 15 insomniacs to a CBD dose (ranging between 40 mg and 160 mg), placebo, or nitrazepam, a hypnotic drug indicated for relief from anxiety and insomnia. With the highest CBD dose, sleep significantly increased, although dream recall was reduced, compared to placebo.16 The reduction of dream recall is presumably due to a reduction of REM sleep, wherein dreams are most active.
Also relating to sleep, somnolence, a state of feeling drowsy or sleepy, has been reported with CBD consumption. While the onset of somnolence may help humans sleep, such an effect should also be examined further for the sake of other CBD uses not related to sleep.
Schizophrenia
In light of the notion made earlier that CBD may attenuate the psychotic effect of THC, such anti-psychotic potential might conceivably help subjects with schizophrenia. This population can be burdened by acute psychosis, but also by anxiety.
Unfortunately, the outcomes from CBD studies on schizophrenia patients are a mixed bag. Where a 2009 German study found 600 mg of CBD to be as effective as amisulpride (an anti-psychotic drug) in reducing psychotic symptoms after four weeks,17 a Brazilian case series in 2006 found CBD well-tolerated but not necessarily effective for treatment-resistant schizophrenia.18 And of two studies conducted in 2010, one found CBD useful for managing schizophrenia, and the other did not.19–20
Market Outlook
The ongoing CBD research discussed herein provides broad market potential for the CBD supplements already in trade today. While concerns such as stress and poor sleep may provide avenues for selling CBD oils to the general population, manufacturers can also capitalize on some much more particular health concerns. Epilepsy, a health condition not discussed in detail here, provides one of the biggest opportunities for CBD today. In fact, the state of Missouri passed a bill earlier this year that legalizes the sale of “hemp extracts” containing CBD as prescribable medicine, but only for children with a rare form of epilepsy called intractable epilepsy.
Creating demand for CBD oil shouldn’t prove difficult, but creating a pro-hemp industry around the world is still a challenge.
“There are many international markets that are well ahead of the game when it comes to CBD,” says Andrew Hard, public relations director for CBD oil supplier HempMeds (Poway, CA). “Unfortunately, the United States is a huge influence on drug policies internationally, which has probably kept these [other] markets from growing as much as they could. We’re hopeful that as the attitudes and laws towards Cannabis in the United States change, the world will adjust accordingly.”
Fortunately, the laws are already changing, and none have proved so significant for hemp as the 2014 U.S. Farm Bill. Signed by President Barack Obama at the beginning of the year, the Farm Bill contains a provision that legalizes hemp research pilot programs in states where cultivation is legal under state law. Through state and university agriculture departments, interested parties can now cultivate hemp and start to learn about its local harvest and local marketability. Since climate and soil conditions are far different in the United States than they are in, say, Canada, this research phase will help industry determine just what U.S.-grown hemp is made of. One thing about U.S. hemp is certain, though: it can be bred for high amounts of CBD.
Robby Gardner
Associate Editor
Nutritional Outlook magazine
robby.gardner@ubm.com
Photo © iStockphoto.com/AlenaPaulus
References
1. Agricultural Act of 2014, HR 2642, 113th Cong., section 7606, part B, subsection 2.
2. M Styrczewska et al., “Cannabinoid-like anti-inflammatory compounds from flax fiber,” Cellular & Molecular Biology Letters, vol. 17, no. 3 (September 2012): 479–499.
3. J Gertsch et al., “Phytocannabinoids beyond the Cannabis plant-Do they exist?” British Journal of Pharmacology, vol. 160, no. 3 (June 2010): 523–529.
4. JM Witkin et al., “A role for cannabinoid CB1 receptors in mood and anxiety disorders,” Behavioral Pharmacology, vol. 16, no. 5–6, (September 2005): 315–331.
5. E Lomazzo et al., “Therapeutic potential of inhibitors of endocannabinoid degradation for the treatment of stress-related hyperalgesia in an animal model of chronic pain,” Neuropsychopharmacology, published online on August 6, 2014.
6. RJ Ursano et al., “PTSD and traumatic stress from gene to community and bench to bedside,” Brain Research, vol. 1293 (October 1, 2009): 2–12.
7. S Zhornitsky et al., “Cannabidiol in humans-The Quest for Therapeutic Targets,” Pharmaceuticals, vol. 5, no. 5 (May 21, 2012): 529–552.
8. AW Zuardi et al., “Effect of cannabidiol on plasma prolactin, growth hormone, and cortisol in human volunteers,” Brazilian Journal of Medical and Biological Research, vol. 26, no. 2 (February 1993): 213–217.
9. AW Zuardi et al., “Effects of ipsapirone and cannabidiol on human experimental anxiety,” Journal of Psychopharmacology, vol. 7, supplement 1 (January 1993): 82–88.
10. JA Crippa et al., “Effects of cannabidiol (CBD) on regional cerebral blood flow,” Neuropsychopharmacology, vol. 29 (2004): 417–426.
11. JA Crippa et al., “Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: A preliminary report,” Journal of Psychopharmacology, vol. 25 (2011): 121–130.
12. MM Bergamaschi et al., “Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients,” Neuropsychopharmacology, vol. 36 (2011): 1219–1226.
13. IG Karniol et al., “Cannabidiol interferes with the effects of delta 9-tetrahydrocannabinol in man,” European Journal of Pharmacology, vol. 28 (1974): 172–177.
14. AB Ilan et al., “Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids,” Behavioral Pharmacology, vol. 16 (2005): 487–496.
15. Y-T Hsiao et al., “Effect of cannabidiol on sleep disruption induced by the repeated combination tests consisting of open field and elevated plus-maze in rats,” Neuropharmacology, vol. 62, no. 1 (January 2012): 373–384.
16. EA Carlini et al., “Hypnotic and antiepileptic effects of cannabidiol,” Journal of Clinical Pharmacology, vol. 21, no. S1 (August–September 1981): 417S–427S.
17. FM Leweke et al., “Antipsychotic effects of cannabidiol,” European Psychiatry, vol. 24 (2009): S207.
18. AW Zuardi et al., “Cannabidiol monotherapy for treatment-resistant schizophrenia,” Journal of Psychopharmacology, vol. 20, no. 5 (September 2006): 683–686.
19. AW Zuardi et al., “Cannabidiol was ineffective for manic episode of bipolar affective disorder,” Journal of Psychopharmacology, vol. 24, no. 1 (January 2010): 135–137.
20. JE Hallak et al., “Performance of schizophrenic patients in the Stroop Color Word Test and electrodermal responsiveness after acute administration of cannabidiol (CBD),” Revista Brasileira de Psiquiatria, vol. 32, no. 1 (March 2010): 56–61.
