CBD Science Update

The 29th annual International Cannabinoid Research Society (ICRS) symposium, which convened last month in Bethesda, Maryland, featured new developments in CBD science that have far-reaching implications for many areas of medicine.

Over 200 scientists from around the world attended the four-day conference, which included 65 oral presentations and nearly 200 posters covering a wide range of topics – with the caveat that researchers had to present new, unpiblished data.

Harvard University scientist Staci Gruber shared encouraging results from “the first open-label to double-blind clinical trial” assessing the impact of a high-CBD, low-THC sublingual tincture in patients who experience moderate anxiety. None of the participants had been using any cannabinoid-based products prior to this study.

Preliminary data “suggests significant improvement following four weeks of treatment when compared to baseline,” Gruber noted. “Specifically, findings suggest that the use of a custom-formulated, whole plant-derived high CBD sublingual tincture results in less severe anxiety and fewer anxiety-related symptoms.”

After the completion of this open-label trial, Gruber intends to undertake a double-blind, placebo-controlled experiment that will generate “empirically sound data regarding the efficacy of sublingual CBD for anxiety.”

CBD for hypertension

Human subjects were also recruited for a CBD study at the University of Nottingham in the United Kingdom, where Saoirse E. O’Sullivan and her team examined the acute and chronic effects of cannabidiol on cardiovascular function.

Previously, the Nottingham scientists had shown that “acute oral administration of CBD (600 mg) causes a reduction in blood pressure at rest and in response to stress.” But would tolerance develop with repeated dosing, thereby mitigating CBD’s hypotensive effect?

To find out, twenty-six healthy males were given 600 mg CBD or a placebo orally for seven days in a randomized, placebo-controlled, double-blind, parallel study. The results were mixed. Measurements of resting blood pressure revealed that tolerance developed in response to chronic CBD administration, but CBD’s ability to lower blood pressure persisted during stress.

“The reduction of arterial stiffness, and improvements in internal carotid artery blood flow and endothelial function after chronic CBD treatment, indicate a positive effect in vascular function that warrants further investigation in relevant patient populations,” O’Sullivan reported.

Preclinical promise

ICRS 2019 included several talks devoted to clinical studies, but most of the CBD presentations showcased cutting-edge data based on preclinical research. The astonishing depth and range of this research underscored CBD’s versatile therapeutic potential.

• CBD for stroke. A meta-analysis by scientists at the University of Nottingham surveyed the effects of CBD in animal models of focal ischemic stroke. The study found that CBD limited the damage caused by induced brain injury: “CBD significantly reduces infarct volume and improved early functional outcome in experimental stroke in rodents.” University of Nottingham researchers also conducted hands-on, preclinical research that examined the anti-inflammatory and neuroprotective effects of cannabidiolic acid (CBDA), the raw, unheated version of CBD found in the cannabis plant. “Like CBD,” the researchers concluded, “CBDA is effective in reducing blood brain permeability and inflammation in a cellular model of stroke.” A compromised blood-brain barrier is a key factor in the secondary injury cascade that wreaks havoc on the brain during ischemia-reperfusion. CBD and CBDA restore BBB integrity by activating the 5-HT1a serotonin receptor, which also mediates CBD’s and CBDA’s anti-inflammatory effects. In Spain, neonatal animal experiments have paved the way for clinical testing of CBD on brain-damaged babies.
• CBD for substance abuse. There are no FDA-approved medications to treat cocaine addiction. So, researchers at the National Institute on Drug Abuse (NIDA) set out to assess the CBD’s as an anti-cocaine remedy. The NIDA team gave CBD to cocaine-addicted rats and observed that systemic CBD treatment “shifted cocaine self-administration dose-response curve downward,” meaning that CBD tempered the rats’ craving for cocaine. “These findings suggest that CBD may have therapeutic utility to blunt rewarding effects of cocaine,” the NIDA researchers surmised. They also identified several molecular pathways whereby CBD conferred an anti-addictive effect on lab animals. These included the 5-HT1a serotonin receptor, the CB2 cannabinoid receptor, and an ion channel receptor known as “TRPV1” (pronounced trip-vee-one). When chemical “antagonists” were administered to block the signaling of these receptors, it negated CBD’s anti-addictive effects.
• CBD for prostate cancer. Italian scientists conducted follow-up research into the combined effect of two plant cannabinoids – CBD and cannabigerol (CBG) – on aggressive prostate cancer. A previous study had shown that 1:1 combination of CBD:CBG “significantly reduced tumor relapse in animals with hormone refractory status, and, in vitro, inhibited cell proliferation and induced apoptosis.” Their latest findings, as reported at ICRS, disclosed “how purified plant cannabinoids (CBD and CBG) affect the metabolic system of malignant tumors,” leading to “notable shifts of specific oncogenic related signaling pathways” in prostate cancer cells. This proves “the efficacy of phytocanabinoids as metabolic reprogramming agents,” which could form the basis of a breakthrough therapy for “highly malignant hormone refractory prostate cancer,” according to the Italian researchers. Scientists at Auburn University reached a similar conclusion regarding the antitumoral properties of CBD and THC, which inhibited prostate cell proliferation in a dose-dependent manner. This is encouraging news for the one out of nine men who will develop prostate cancer, the second leading cause of cancer death among American males. The preclinical experiment at Auburn suggests “that cannabinoids could be developed as novel therapeutic agents for the treatment of prostate cancer.”
• CBD for arthritis and gum disease. A team of Israeli, British, and American scientists analyzed the anti-inflammatory and painkilling effects of synthetic CBD in an animal model of arthritis. “CBD was shown to exert a potent analgesic effect” in preclinical research, which shed new light on CBD’s “anti-inflammatory mechanisms of action.” Another preclinical probe, conducted at the University of Leeds School of Dentistry in the UK, documented the potent anti-inflammatory effects of CBD on gum disease. The ability of CBD to modulate immune function “could provide possible therapeutic applications in the field of periodontal research,” the Leeds study concluded.

CBD oil products

There’s good reason to be excited about CBD’s potential health benefits, but a word of caution is necessary. Administering pure CBD to animals in a controlled laboratory setting is not the same as human consumption of a CBD oil product purchased from an unregulated internet storefront.

The Prague-based International Cannabis and Cannabinoids Institute (ICCI) analyzed the quality of 70 hemp-derived CBD oil samples available in the European Union, and the results reported at the ICRS symposium were sobering, to say the least. Twenty percent of the samples contained less CBD than indicated on the label. THC was present in 89 percent of the samples, but in most cases no amount of THC was provided. And traces of highly toxic polycyclic aromatic hydrocarbons were found in all the oils tested, underscoring the strong need for better extraction and processing practices by CBD product-makers.

Similar problems plague the CBD market in the United States. Inaccurate or incomplete CBD product labels undermine a consumer’s ability to make well-informed decisions. According to researchers at Thomas Jefferson University in Philadelphia and Washington University in St. Louis: “Recent studies have demonstrated that hemp-derived CBD products purchased over the internet are frequently mislabeled, contaminated, or are outright fraudulent (contain no cannabinoids whatsoever). Therefore, patients are more likely to receive medical benefit from products that are routed through state-licensed cannabis markets, where lab testing for CBD content is required.”

Licensed cannabis dispensaries and delivery services also need to up their game and improve their product offerings. “Despite the obvious medical benefits, the availability of CBD-containing products in state-licensed retail stores is highly variable and surprisingly sparse. In one Pennsylvania store only 20 of products (39 or 196) contained CBD,” the U.S. researchers noted. “Results highlight the need for expanded patient access to CBD products.”