The Anxiety Economy

Tens of millions of fidget spinners, fidget cubes and weighted blankets haven’t been sufficient to reduce the need for THC and CBD in the emerging anxiety economy. 

THC (Tetrahydrocannabinol) works as an analgesic but also produces a psychoactive side effect known affectionately as a “high.” CBD (cannabidiol) possesses anti-anxiety properties but only induces calm, not euphoria.

In the last few years, millions of Americans suffering from anxiety, depression, insomnia and joint pain have embraced CBD. According to Brightfield Group, 41% of CBD users partake of it daily and an astounding 43% of CBD users choose cannabis instead of over-the-counter or physician-prescribed pharmaceuticals.

Despite the enthusiastic adoption of CBD, serious questions remain unanswered with respect to regulatory oversight, consumer protection, dosage and efficacy. To help sort the variables, luckbox called on physicians, consumer advocates, manufacturers and retailers. At stake for investors is a CBD market estimated at $5 billion this year and expected to reach $24 billion by 2023.

Cannabidiol (CBD) is finding a home these days in everything from skin creams and ingestibles to craft cocktails and pet products. CBD stores are popping up on street corners and in malls, and independent pharmacies and major drugstore chains are
selling products laced with CBD. But what’s the underlying story?
Does science back up the hype or is this another here-today-gone-
tomorrow health fad? luckbox enlisted pharmacologist Mike James, Ph.D., to separate fact from fiction.

High or not?
Cannabidiol (CBD) and tetrahydrocannabinol (THC) are both components of hemp and marijuana. THC gets users high, while most consider CBD merely relaxing. To say the least, CBD has recently attracted the attention of the popular press and the scientific community.

Marijuana and hemp come from different strains of the plant Cannabis sativa. Growers have bred marijuana strains for higher levels of THC, ranging from 25% to 40%. Hemp strains have been selected for higher levels of CBD and very low levels of THC, less than 0.3 % by federal law.

CBD’s uncertain potential
Users and entrepreneurs are touting CBD as a cure-all for a lengthy list of complaints and ailments. In two recent surveys, 38% to 55% of CBD users reported they use it for relaxation or to promote good health. CBD users in the studies cited at 15 medical conditions they attempt to treat with CBD.

The most common health problems cited in the surveys were pain, anxiety, depression and insomnia. As with many dietary supplements, advocates of using CBD to treat those conditions generally base their assumptions on animal studies, case reports or small clinical studies. Let’s look at what’s known about the usefulness of CBD for treating the top conditions.

A prescription-only, oral form of CBD called Epidiolex  has earned the approval of the U.S. Food and Drug Administration (FDA) for two rare types of epilepsy (Lennox-Gastaut syndrome and Dravet syndrome). FDA approval requires proof of effectiveness in well-designed clinical trials. Hardly anyone disputes this use of CBD.

Its effectiveness is not so certain with anxiety. The positive effects of CBD in animal models of anxiety make a strong case for studying CBD in clinical trials, but the results in human trials have been mixed. Whether animal models truly represent human anxiety remains questionable. It’s also unclear from animal studies if long-term dosing maintains the positive effects of CBD on anxiety.

Clinical studies provide directly applicable data but researchers conduct many of the CBD clinical trials on anxiety disorders with only small numbers of patients. Results from small studies are more difficult to apply to the general population because of a lack of statistical power. In other words, a small study may exaggerate or underestimate the effects of CBD.

In addition, several clinical studies on the effectiveness of CBD for anxiety used THC as the anxiety-inducing stimulus. THC-induced anxiety may not provide a good representation of anxiety produced under other conditions. Most of the studies were single-dose studies and would be of limited value in assessing long-term effectiveness.

CBD and the combination of CBD and THC reduce pain in studies of animals, but evidence of the effectiveness of CBD alone on pain in humans is lacking. However, a study of a combination of THC and CBD for treatment of pain caused by nerve damage induced by cancer chemotherapy yielded positive results.

But combining CBD and THC without a comparison to each agent alone makes it difficult to interpret those results. A comparison with the individual components would have made it possible to determine whether the effects were due to THC or CBD or unique to the combination of the two.

Evidence that CBD’s useful for treating depression seems to come solely from pre-clinical (animal) data. A 2017 review of using CBD in psychiatry found no clinical evidence that it alleviated depression.

A single small study of 15 subjects on the effects of CBD on insomnia showed that at the highest dose tested,160 mg, subjects reported that they slept longer but did not find it easier to go to sleep.

Acne and inflammatory skin conditions
Some evidence in human skin cells suggests CBD may be useful in treating acne. But the effectiveness of CBD against acne hasn’t been determined in clinical trials. A small retrospective study showed a subjective improvement in acne and psoriasis scarring.

But the topical ointment in that study included several natural ingredients besides CBD and did not include a control group using ointment without CBD. Those factors make it difficult to attribute the observed effects to CBD.

Other uses
A small clinical trial suggested CBD may be useful in treatment of opioid-seeking behavior in heroin addicts. Other studies have suggested CBD may ease nicotine and marijuana dependence. Clinical trials in larger populations may confirm those preliminary studies.

Also, a small, single-dose study showed a decrease in resting blood pressure and decreases in the elevation of blood pressure in response to exercise and cold stress. Further studies may determine the significance of this effect.

CBD’s downside
For the prescription form of oral CBD, the most common side effects include drowsiness, decreased appetite, diarrhea and an increase in transaminase levels in the blood. Transaminases are liver enzymes normally found only in low levels. Elevated transaminase can indicate liver damage. So anyone with liver disease should consult a physician before using CBD.

Other side effects have included general weakness, trouble sleeping and infections. Because of the effects of CBD on alertness, caution should be used when driving or performing other tasks requiring concentration.

In addition, the way oral CBD is broken down in the liver can cause it to interact with a number of drugs. So check with a pharmacist before taking CBD. Another note of caution: CBD may harm a developing fetus. No data is available regarding the effects in pregnant women, so see a physician before using CBD during pregnancy or lactation.

CBD abuse?
The Drug Enforcement Administration (DEA) ranks drugs according to their potential for abuse and places them on Schedules I-V. Schedule I controlled substances have high potential for abuse and no recognized medical use. Schedule II have high potential for abuse but have a recognized medical use. Schedules III, IV and V have recognized medical uses with less potential abuse as the designation increases.

So where does CBD fall in the DEA rankings? The oral prescription-only form of CBD (Epidiolex) is a Schedule V controlled substance. Still, in tests, CBD did not produce drug-seeking behavior in animals or subjective effects similar to THC in humans. Tests also produced no evidence of dependence in humans who took CBD for 28 days.

Taking CBD
CBD comes as an oil, in capsules, as a sublingual tincture (an alcohol-based solution dropped under the tongue), cartridges for vaping pens, edibles and topical creams. Making definitive statements about dosing is difficult for two reasons: The amount of CBD in these products varies greatly, and clinical data for most of the proposed uses of CBD remains scarce.

In addition, data is derived from studies of only one- or two-dose levels, so complete dosing information isn’t available. When it comes to dietary supplements and medications, more doesn’t equal better. Users should choose the lowest effective dose to decrease the chances of unwanted side effects. 

Deciding on CBD
Except for treating two specific, rare forms of epilepsy in children, the clinical evidence for using CBD remains sketchy. Given the potential side effects and drug interactions, it’s difficult to justify using it.

Pharmacokinetic studies have shown people can absorb a significant amount of CBD into the bloodstream after application to the skin, so even topical application of CBD products may have adverse effects.

CBD products also have uncertain legal status. The Hemp Farming Act of 2018 legalized the growing of hemp in the United States. The Hemp Farming Act was passed as part of the larger farm bill The Agricultural Improvement Act of 2018.

However, in April 2018, The Ninth District Court of Appeals ruled that CBD is a Schedule I controlled substance under federal law (meaning it has abuse potential and no recognized medical use). Schedule I substances are regulated by the DEA and the FDA.

CBD is legal in states that have legalized medicinal or recreational marijuana. However, the Health Department of the State of Hawaii issued a statement in May that says selling CBD products to anyone without a medical marijuana card is illegal. The FDA and some states are working to develop regulations governing sales and safety monitoring for CBD products.

CBD in urine tests
Urine tests for marijuana detect a metabolite (breakdown product) of THC. The most commonly used tests should not detect CBD. In addition, all CBD products must contain less than 0.1% THC, so CBD products that comply with regulations should not produce positive results on urine drug tests for marijuana.

CBD hype?
Is the clamor over CBD overblown? The short answer is “no.” CBD is popping up everywhere in almost anything. But the hype for CBD for uses other than epilepsy seems premature.

Other claims need more supporting data. Wider acceptance and use should come only after more studies with larger numbers of subjects demonstrate that CBD works.

Unless researchers pick up the pace and begin producing more test data, or CBD develops into a true cultural phenomenon, expect to see a “For Lease” sign on that little CBD shop on the corner. 

Portions of this story were previously published in The AGEIST

Mike James, Ph.D., a pharmacologist who’s published more than 20 peer-reviewed articles, has researched neuropharmacology, endocrinology, metabolic, oncology and cardiovascular diseases.