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A Cross-Sectional Study of Cannabidiol Users 1 The Center for Medical Cannabis Education, Del Mar, California. 2 Helfgott Research Institute, National University of Natural Medicine (NUNM), CBD has been touted to help with sleep, anxiety, pain, and more, and there are myriad ways to take it. But does CBD work? Is it safe? We’ve got answers.

A Cross-Sectional Study of Cannabidiol Users

1 The Center for Medical Cannabis Education, Del Mar, California.

2 Helfgott Research Institute, National University of Natural Medicine (NUNM), Portland, Oregon.

Joy A. Phillips

3 Donald P. Shiley BioScience Center, San Diego State University, San Diego, California.

* Address correspondence to: Jamie Corroon, ND, MPH, The Center for Medical Cannabis Education, 1155 Camino Del Mar, #187, Del Mar, CA 92014, E-mail: [email protected]

This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Introduction: Preclinical and clinical studies suggest that cannabidiol (CBD) found in Cannabis spp. has broad therapeutic value. CBD products can currently be purchased online, over the counter and at Cannabis-specific dispensaries throughout most of the country, despite the fact that CBD is generally deemed a Schedule I controlled substance by the U.S. Drug Enforcement Administration and renounced as a dietary supplement ingredient by the U.S. Food and Drug Administration. Consumer demand for CBD is high and growing, but few studies have examined the reasons for increasing CBD use.

Materials and Methods: A self-selected convenience sample (n = 2409) was recruited via an online survey designed to characterize whom, how, and why individuals are currently using CBD. The anonymous questionnaire was accessed from October 25, 2017 to January 25, 2018. Participants were recruited through social media.

Results: Almost 62% of CBD users reported using CBD to treat a medical condition. The top three medical conditions were pain, anxiety, and depression. Almost 36% of respondents reported that CBD treats their medical condition(s) “very well by itself,” while only 4.3% reported “not very well.” One out of every three users reported a nonserious adverse effect. The odds of using CBD to treat a medical condition were 1.44 (95% confidence interval, 1.16–1.79) times greater among nonregular users of Cannabis than among regular users.

Conclusion: Consumers are using CBD as a specific therapy for multiple diverse medical conditions—particularly pain, anxiety, depression, and sleep disorders. These data provide a compelling rationale for further research to better understand the therapeutic potential of CBD.

Introduction

Cannabidiol (CBD) is one of more than a hundred cannabinoids found in Cannabis sativa L (Cannabis spp. or Cannabis), a plant more well known colloquially as marijuana and hemp. CBD is typically the second most abundant cannabinoid found in Cannabis after tetrahydrocannabinol (THC). 1 CBD was first isolated in 1940 and characterized structurally in 1963. 2,3

CBD is well tolerated in humans and maintains a good safety profile. 4,5 Neither abuse nor dependence has been demonstrated. 5 In preclinical studies, CBD shows potential therapeutic efficacy against a diverse assortment of medical conditions. These include seizure disorders, psychotic symptoms, anxiety, depression, inflammation, cancer, cardiovascular diseases, neurodegeneration, symptoms of multiple sclerosis, and chronic pain, either used alone or when coadministered with THC. 5–20

In October of 2017, a New Drug Application was submitted to the U.S. Food and Drug Administration (FDA) to seek approval of CBD isolated from marijuana for the treatment of two pediatric seizure disorders. Approval was granted in June, 2018, making Epidiolex (cannabidiol) the first plant-derived Cannabis compound approved as a drug by the FDA. Availability of Epidiolex is pending Drug Enforcement Administration (DEA) rescheduling of cannabidiol, which is expected to occur within 90 days. 21–23 Sativex (nabiximols), a combination drug with equal parts CBD and THC extracted from marijuana, is currently approved to treat spasticity due to multiple sclerosis in >30 countries worldwide but is not approved in the United States. 17,21

The worldwide regulatory status of CBD is complex and constantly changing. 5 While CBD is legal in many countries as a component of prescription Sativex (nabiximols), it may be simultaneously illegal as a component of a nonapproved Cannabis extract containing >0.2% (particularly in European countries) or 0.3% THC. In Europe, individual European Union Member States currently determine the legality of CBD within their borders. Most allow prescription CBD products, as do Australia and New Zealand. 5,24 Canada became the second nation in the world to legalize Cannabis for recreational use in June 2018. 25 The World Health Organization’s Expert Committee on Drug Dependence recommended that CBD should not be controlled by Schedule I of the 1961 UN Single Convention on Narcotic Drugs. 5 Their comprehensive report is expected this year.

In the United States, until such time as it is rescheduled, CBD from marijuana is deemed by the DEA to fall within the purview of the “marihuana extract rule” (Rule). A dispute over the scope of the Rule was litigated in federal court. The Court found that the Rule applies to extracts of marijuana but that the industrial hemp provisions of the 2014 Farm Act (i.e., “The 2014 Farm Bill”) preempt the Controlled Substances Act (CSA), which the DEA enforces. 26 Thus, hemp cultivated in compliance with the Farm Bill is not a controlled substance. The Court did not address the issue of CBD directly, however, and left open the issue of the legal status of CBD derived from industrial hemp, from imported “nonpsychoactive hemp” or from parts of the Cannabis sativa plant excluded from the legal definition of marijuana in the Controlled Substances Act of 1970. 27–35 Despite conflicting legal interpretations, and DEA prohibition, hemp-derived CBD products can currently be purchased as dietary supplements both online and over the counter throughout most of the country. To complicate matters further, the FDA does not recognize CBD as a dietary supplement ingredient because of its status as an Investigational New Drug. 36

This regulatory confusion has not deterred consumers from exploring the purported benefits of CBD. Retail sales of hemp-derived CBD products in the United States reached $170 million in 2016, and are projected to grow at a 55% compound annual growth rate over the next 5 years to reach >$1 billion. These estimates do not include marijuana-derived CBD. 37 Although Cannabis users have been extensively studied data characterizing the individual use of CBD are scarce. The goal of this study was to collect survey data to elucidate how, and why, individuals are using CBD.

Methods

Survey

The study protocol was submitted electronically to the Institutional Review Board (IRB) of San Diego State University. Given the voluntary nature of the survey, and the lack of identifying information, the electronic approval process determined that no IRB approval was necessary.

We developed a novel questionnaire to assess broad characteristics of self-described CBD users and underlying reasons for, and methods of, CBD use. The survey consisted of structured questions answered by either yes/no or multiple-choice responses. Questions focused on several key domains: sociodemographics; reasons for use; duration and frequency of use; method of administration; perceived clinical efficacy; and adverse effects. Study data were collected and managed using Qualtrics ® Survey Software, a secure tool allowing participants to directly enter responses anonymously.

Subjects were a self-selected convenience sample who accessed the online survey from October 25, 2017 to January 25, 2018. Recruitment strategies included promotion on survey-specific Web pages on Facebook, LinkedIn, and ResearchGate. CBD product manufacturers and herbal vaporizer manufacturers assisted in recruitment by promoting links to the survey on their Facebook pages and/or via email to their customers. The only inclusion criterion was current or prior use of CBD. Respondents could skip any question(s) they did not wish to answer.

Data analyses

Descriptive statistics including simple proportions were used to describe demographics, usage characteristics, medical conditions, perceived efficacy, side effects, and other CBD use preferences. Data analyses were conducted using SAS University Edition (SAS 9.4; SAS Institute Inc., Cary, NC). Univariate and bivariate comparisons were conducted using PROC FREQ and chi-square tests. Odds ratios (ORs) were used to estimate strength of association using PROC LOGISTIC. Statistical significance was assessed using α=0.05. Figures were produced using DeltaGraph version 4.5 for Mac.

Results

Demographics

A total of 2490 responses were collected. Eighty-one respondents were excluded from the analysis for failure to answer the first question regarding stated use of CBD, leaving 2409 respondents included in the final study population. The sample was balanced in terms of gender (female: 50.87%; male: 47.40%) with most respondents reporting ages between 55 and 74 years (39.97%). Most were either graduates of, or currently enrolled in, college or a postgraduate program (71.22%). The vast majority resided in the United States (91.23%). Respondents from all 50 U.S. states were represented in the survey with the majority residing in California (n=412, 21.90%; Table 1 ). In addition, there were survey respondents from 23 other countries. Regular Cannabis use was reported by 55.17% of respondents.

Table 1.

Sociodemographic and Other Characteristics of Survey Respondents (n=2409)

n (%)
Gender
Male 1013 (47.40)
Female 1087 (50.87)
Decline to state 37 (1.73)
Missing 272
Age (years)
≤24 138 (6.33)
25–34 292 (13.40)
35–44 400 (18.36)
45–54 404 (18.54)
55–64 532 (24.41)
65–74 339 (15.56)
≥75 74 (3.40)
Missing 230
Education
Primary/middle school 22 (1.01)
High school/GED 503 (23.13)
College 1138 (52.32)
Postgraduate 411 (18.90)
Other 101 (4.64)
Missing 234
Geography
United States 1987 (91.23)
Canada/Mexico 103 (4.73)
Other 88 (4.04)
Missing 231
Geography—U.S. states (top 5)
California 412 (21.90)
Texas 93 (4.94)
Oregon 83 (4.41)
Florida 79 (4.20)
Colorado 76 (4.04)
Missing 528
Cannabis use
Regular 1189 (55.17)
Nonregular 966 (44.83)
Missing 254
CBD use
General health and well-being 926 (38.44)
Medical condition 1483 (61.56)
Missing

CBD, cannabidiol; GED, General Educational Development.

Stated use: medical versus general health and well-being

More than 60% (61.56%) reported using CBD to treat a medical condition(s) ( Table 1 ). The odds of using CBD to treat a medical condition were 1.65 (95% confidence interval [CI], 1.39–1.97) times greater among women than among men, higher with age, and roughly equal among residents and nonresidents of the United States (OR, 1.06; 95% CI, 0.9–2.5; Table 2 ). Respondents n=25) and wide CI (OR, 18.72; 95% CI, 4.20–83.39, compared with those between 18 and 24 years of age. Data not included in Table 2 ). This additional analysis was based on the established use of CBD to treat pediatric seizure disorders 6,7,16 and the percentage of respondents in that age category reporting using CBD to treat a medical condition (n=23; 92%).

Table 2.

Odds of Using Cannabidiol for a Medical Condition by Sociodemographic and Other Characteristics (n=2409)

General health and well-being, (n=926) n (%) Medical condition, (n=1483) n (%) OR (95% CI)
Gender ***
Male 454 (44.82) 559 (55.18) 1.00 (reference)
Female 358 (32.93) 729 (67.07) 1.65 (1.39–1.97)
Decline to state 12 (32.43) 25 (67.57) 1.69 (0.84–3.41)
Missing 102 170
Age (years) ***
≤24 72 (52.17) 66 (47.83) 1.00 (reference)
25–34 153 (52.40) 139 (47.60) 0.99 (0.66–1.49)
35–44 170 (42.50) 230 (57.50) 1.48 (1.00–2.18)
45–54 150 (37.13) 254 (62.87) 1.85 (1.30–2.73)
55–64 180 (33.83) 352 (66.17) 2.13 (1.50–3.12)
65–74 98 (28.91) 241 (71.09) 2.68 (1.80–4.04)
≥75 19 (25.68) 55 (74.32) 3.16 (1.70–5.86)
Missing 84 146
Education ***
College 478 (42.00) 660 (58.00) 1.00 (reference)
Primary/middle school 1 (4.55) 21 (95.45) 15.18 (2.04–113.09)
High school/GED 172 (34.19) 331 (65.81) 1.39 (1.12–1.73)
Postgraduate 153 (37.23) 258 (62.77) 1.22 (0.97–1.54)
Other 34 (33.66) 67 (66.34) 1.43 (0.93–2.19)
Missing 88 146
Geography
United States 763 (38.40) 1224 (61.60) 1.00 (reference)
Canada/Mexico/other 76 (39.79) 115 (60.21) 1.06 (0.78–1.44)
Missing 87 144
Cannabis use ***
Regular 509 (42.81) 680 (57.19) 1.00 (reference)
Nonregular 320 (33.13) 646 (66.87) 1.44 (1.16–1.79)
Missing 97 157

CI, confidence interval; OR, odds ratio.

The odds of using CBD to treat a medical condition were 1.44 (95% CI, 1.16–1.79) times greater among nonregular users of Cannabis when compared with regular users.

Medical conditions

There were 1483 respondents who reported using CBD to treat at least one medical condition. A minimum of 3963 medical conditions were reported. This represents an average of more than two and a half (mean: 2.67) different medical conditions per respondent.

In order of frequency, the top three medical conditions reported were chronic pain, arthritis/joint pain, and anxiety ( Fig. 1 ).

Number of medical conditions for which respondents reported using CBD, by medical condition (n=3963). CBD, cannabidiol; COPD, chronic obstructive pulmonary disease; PTSD, post-traumatic stress disorder.

Respondents selected “Other” 362 times. The most common “Other” conditions reported were neuropathy (n=48), autoimmune conditions (n=38), and fibromyalgia (n=37).

Methods of administration

A total of 4135 methods of administration were reported by 2200 respondents. This represents an average of almost two (mean: 1.88) different methods of administration per respondent. Overall, the most common method reported was the administration of CBD in a sublingual form ( Fig. 2 ). This includes liquids administered as sprays, drops, and tinctures. The least common method was topical use.

Number and percentage of methods of administering CBD (n=4135).

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More than half (51.36%) of those reporting a method of administration reported using only one method (n=1130; missing=209; not including “Other,” n=31). On average, respondents who reported using one method of administration were 1.6 times more likely to use CBD for a medical condition than for general health and well-being (medical condition, n=691; general health and well-being, n=439). Medical users reporting one method of administration were 2.4 times more likely to use a topical form, 2.0 times more likely to use an edible form of CBD, and 1.8 times more likely to use CBD in a sublingual or pill or capsule form than general health and well-being users reporting one method.

Learning about CBD, frequency and duration of use

Overall, 75.85% of respondents reported learning about CBD from internet research, family members, or friends. Of the remaining respondents, medical users were more likely to learn about CBD from a Medical Doctor or Naturopathic Doctor and to use it more frequently than those using it for general health and well-being. The odds of using CBD to treat a medical condition were 1.79 (95% CI, 1.46–2.19) times greater among respondents using it more than once per day compared with those using it daily ( Table 3 ). Duration of use was more variable, but the odds of using CBD to treat a medical condition were greater among those using it for

Table 3.

Odds of Using Cannabidiol for a Medical Condition, by Cannabidiol Usage Characteristics (n=2409)

General health and well-being, (n=926) n (%) Medical condition, (n=1483) n (%) OR (95% CI)
Learned about CBD **
Family member/friend 320 (41.24) 456 (58.76) 1.00 (reference)
Internet research 337 (38.04) 549 (61.96) 1.14 (0.94–1.39)
Physician/naturopathic doctor 58 (27.36) 154 (72.64) 1.86 (1.33–2.60)
Other (please specify) 131 (41.32) 186 (58.68) 1.00 (0.76–1.30)
Missing 80 138
Frequency of use ***
Daily 418 (39.70) 635 (60.30) 1.00 (reference)
227 (56.47) 175 (43.53) 0.51 (0.40–0.64)
>Once per day 196 (26.92) 532 (73.08) 1.79 (1.46–2.19)
Missing 85 141
Duration of use (years) *
>5 134 (53.17) 118 (46.83) 1.00 (reference)
2–5 151 (35.61) 273 (64.39) 2.05 (1.50–2.82)
1–2 202 (42.98) 268 (57.02) 1.51 (1.11–2.05)
364 (34.57) 689 (65.43) 2.15 (1.63–2.84)
Missing 75 135

Treatment efficacy

Only respondents who reported using CBD to treat a medical condition were asked about its efficacy (n=1483). Almost 36% (35.80%) of respondents reported that CBD treats their medical condition(s) “very well by itself,” while only 4.30% reported “not very well” ( Table 4 ). Respondents most frequently reported feeling that CBD treated their medical condition(s) “very well by itself” or “moderately well by itself” for the following three conditions: chronic pain, arthritis/joint pain, and anxiety ( Fig. 3 ).

Number of medical conditions for which respondents report CBD treating “Very Well by Itself” or “Moderately Well by Itself,” by medical condition (n=2557).

Table 4.

Number and Percentage of Respondents Using Cannabidiol for a Medical Condition, by Treatment Efficacy and Regular Cannabis Use

How well do you feel CBD treats your medical condition(s)? (n=1483) Regular cannabis use (n=674) n (%) Nonregular cannabis use (n=628) n (%) OR (95% CI)
Not very well 57 (4.30) 18 (31.58) 39 (68.42) 1.00 (reference)
Well in combination with conventional medicine * 404 (30.44) 195 (49.24) 201 (50.76) 2.11 (1.170–3.82)
Moderately well by itself *** 391 (29.46) 221 (57.40) 164 (42.60) 2.92 (1.61–5.29)
Very well by itself 475 (35.80) 240 (51.72) 224 (48.28) 2.32 (1.29–4.18)
Missing ** 156

The odds of regular Cannabis use were two to three times greater among those who reported feeling that CBD treated their medical condition “very well by itself” (OR, 2.32; 95% CI, 1.29–4.18) or “moderately well by itself” (OR, 2.92; 95% CI, 1.61–5.29; see Table 4 ).

Side effects

A minimum of 1314 side effects were reported across 2409 respondents (missing, n=1095). Seven hundred eighty-five (59.74%) of these effects were categorized as adverse ( Table 5 ). On average, this represents at least one reported adverse effect in approximately one out of every three (3.07) users of CBD.

Table 5.

Most Common Adverse Effects Reported by Survey Respondents (n=742)

Adverse effect Medical condition (n=1483) n (%) General health and well-being (n=926) n (%) Total (n=2409) n (%)
Dry mouth 174 (11.73%) 94 (10.15%) 268 (11.12%)
Euphoria 59 (3.98%) 96 (10.37%) 155 (6.43%)
Hunger 80 (5.39%) 73 (7.88%) 153 (6.35%)
Other 46 (3.10%) 11 (1.19%) 57 (2.37%)
Red eyes 34 (2.29%) 32 (3.46%) 66 (2.74%)
Sleepy/groggy 29 (1.96%) 14 (1.51%) 43 (1.78%)
Total adverse effects 422 (28.46%) 320 (34.56%) 742 (30.80%)

The top five most frequently reported adverse effects were dry mouth (n=268, 11.12% of all CBD users), euphoria (n=155, 6.43%), hunger (n=153, 6.35%), red eyes (n=66, 2.74%), and sedation/fatigue (n=43, 1.78%). Just under 30% (28.46%) of medical users reported an adverse effect when compared with 34.56% of general health and well-being users.

Discussion

To our knowledge, this is the first published survey (aside from industry reports) that specifically analyzes CBD users, as opposed to overall Cannabis or medical Cannabis users. The results of this study suggest that CBD is used more frequently as a specific therapy for medical conditions than for general health and well-being. This stands in contrast to the majority of marijuana users, who largely use THC-dominant Cannabis for recreational or nonmedical reasons. 38

The most common medical condition for which CBD was reportedly used was pain. In preclinical studies, CBD-based analgesia is associated with potent immune-modulatory, anti-inflammatory, and antioxidant activity. 39–47 CBD acts as an agonist for a wide variety of cell-surface receptors including adenosine A2A, 5-HT1A, TRPV1, α7nAch, α3 glycine receptors, and the peroxisome proliferator-activated receptor gamma (PPAR-γ) nuclear receptor. These receptors are all associated with anti-inflammatory activity. 48–58 Consistent with the efficacy reported by survey respondents, CBD has been shown to reduce inflammatory cytokines in murine models of inflammatory disease and chronic and acute pain. 59

The endocannabinoid system may also play a role in CBD-mediated analgesia. CBD inhibits enzymes (i.e., fatty acid amide hydrolase and monoacylglycerol lipase) that degrade endocannabinoids. This inhibition is associated with increased endocannabinoid levels, analgesia, and opioid-sparing effects in preclinical models of pain. 60

Anxiety and depression were also commonly reported reasons for CBD use in this survey. CBD has long been proposed to inhibit THC-associated anxiety by antagonizing cannabinoid receptor activation by THC. 61–63 CBD may also reduce anxiety via the serotonin 5-HT1A and/or GABAA receptors. 14,64 These receptor pathways are being explored in hopes of novel therapeutic strategies for phobias, post-traumatic stress disorder, and drug abuse. 65,66

The majority of survey respondents learned about CBD from internet research, family members, or friends. This was the case for both medical and general health and well-being users. Over 74% of respondents reported using CBD daily or more than daily. Sublingual delivery was the most common route of administration in both groups. The frequency of use of sublingual preparations found in this study contradicts a recent industry-funded CBD survey where respondents reported more frequent vaping, smoking, and topical use. 67 This industry survey was collected from customers of an online medical marijuana recommendation service. Presumably, these respondents were seeking marijuana-derived products, so the frequency of inhalation as a method of administration is consistent with marijuana users overall. 68 Our finding may be in part due to the fact that hemp-derived CBD products are largely distributed online and in health-food stores and widely offered as oral preparations.

The percentage of respondents (55.17%) who reported regular Cannabis use is markedly higher than national estimates. In 2015, an estimated 8.3% (∼22.2 million people) of individuals aged 12 years or older had used marijuana in the past month. 69 The reason for the higher rate of Cannabis use among survey respondents is not clear, although one possibility is that Cannabis users would be more likely to have heard of CBD. However, CBD use by a relatively high percentage (44.83%) of nonregular Cannabis users suggests that individuals are not using CBD as a perceived legal route to THC consumption.

Approximately half of all respondents reported using CBD for 5 years. Nonserious adverse effects were relatively common among respondents and higher among those using CBD for general health and well-being, despite the fact that this group reported less frequent use than medical users. While dry mouth, sedation/fatigue, decreased appetite, and diarrhea have previously been reported following CBD use, 6,7 other studies have demonstrated no adverse effects. 10,70–72 This dichotomy may be related to dose, interactions with prescription medications, or both. More broadly, adverse effects may also be related to the method of administration and/or the use of purified, high-dose CBD as opposed to CBD in a whole plant extract. These questions and more reinforce the need for more research on unanticipated consequences of CBD use, particularly the impact of long-term usage. 4,5 Many of the adverse effects reported in this study (i.e., euphoria, hunger, and red eyes) are commonly associated with THC use. 73 These analyses did not attempt to discriminate between hemp-derived CBD and marijuana-derived CBD products, which may have differing chemical constituents (including THC content) and therefore different effects. Further, no discrimination could be made between isolated CBD and CBD used as a constituent of a whole plant extract.

Industry-originated studies have found that users are confused about the source of their CBD and the concentration of CBD and other ingredients. 67–74 It is worth noting that independent research has confirmed that the CBD content in almost 70% of CBD-labeled products available online may be mislabeled. In one study, 43% of products were underlabeled and 26% were overlabeled for actual CBD content. More than 20% contained detectable levels of THC. 75 Since CBD-containing products are largely unregulated there is no obvious way for users to know the quantity of CBD, or other constituents, which may be present in the products they use. Given this uncertainty, it is possible that some of the reported efficacy and the adverse effects may be in part due to the inclusion of other compounds in the CBD preparation, including THC.

Strengths and limitations

This study has several strengths, including the size, geographic representation of the sample, wide age range of the respondents, and a focus on specific usage characteristics. In part, this was the result of utilizing multiple recruitment methodologies.

In terms of limitations, the study population was a self-selected convenience sample, and as such, may not be representative of the general population or the overall population of CBD users. Individuals with favorable opinions of or experiences with CBD or Cannabis are more likely to have responded to the questionnaire than those with negative opinions and experiences. In addition, “regular cannabis use” was not defined in the survey and “marijuana” was not distinguished from “Cannabis.” Since the survey was primarily circulated via the internet, CBD users with limited social media connectivity would be underrepresented. Finally, no mechanism for identifying repeat respondents was incorporated into the survey. Although results were examined manually, it is possible that repeat respondents may have distorted the results (i.e., Ballot stuffing).

Conclusion

The use of CBD among individuals for both specific health conditions and general health and well-being is widespread. The results of this study demonstrate that individuals are learning about CBD from the internet, friends, or family members, rather than from healthcare professionals. CBD is being used as a specific therapy for a number of diverse medical conditions—particularly pain and inflammatory disorders, in addition to anxiety, depression, and sleep disorders. A large percentage of respondents indicate that CBD treats their condition(s) effectively in the absence of conventional medicine and with nonserious adverse effects. These data provide a compelling rationale for further research to better understand the therapeutic potential of CBD in treating chronic pain, anxiety, depression, sleep disorders, and other medical conditions.

Abbreviations Used

CBD cannabidiol
CI confidence interval
COPD chronic obstructive pulmonary disease
FDA Food and Drug Administration
GED General Educational Development
IRB institutional review board
OR odds ratio
PTSD post-traumatic stress disorder
THC tetrahydrocannabinol

Acknowledgments

The authors thank Gina Spidel for help with survey design, proofreading, and assistance with the SDSU Electronic Internal Review Board; Edgar Herrera for setting up the survey Facebook page; Belle Della Cruz for help with survey wording; and Rod Kight, Esq., for assistance in clarifying the regulatory status of CBD in the United States.

Author Disclosure Statement

J.C. is the Medical Director at The Center for Medical Cannabis Education, a for-profit clinical, research and consulting entity.

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CBD: A User’s Guide

CBD is seemingly everywhere and in everything, from CBD-infused creams to CBD-infused oils, tinctures, gummies, juices, and lollipops. But does it work, and is it safe? We’ve got your questions covered.

I n case you haven’t heard, CBD is a cure for whatever ails you, from insomnia and inflammation to pandemic angst. Or at least that’s what retailers, supermarkets, mini-marts, beauty stores, and coffee and smoothie shops across America would have you believe. There are CBD-infused creams. CBD-infused oils. CBD-infused tinctures, gummies, juices, lollipops, lattes, nutritional supplements, and even a CBD oil–infused pillow! What’s next, CBD-infused tampons? (Actually, that already exists. Really.)

According to the Brightfield Group, a market research firm, CBD sales were estimated to exceed $4 billion at the end of 2021, and by 2025, the industry’s total market value could reach a whopping $16 billion.

Put that in your pipe and smoke it.

But does CBD work?

That’s a question worthy of a Talmudic scholar, because the CBD world is complicated.

Some believe that it may have an important role to play in certain health outcomes.

Raphael Mechoulam, PhD, a professor of medicinal chemistry at Hebrew University in Jerusalem, Israel, has been studying the health benefits of cannabis and CBD since the early 1960s. Long considered the grandfather of cannabis research, Dr. Mechoulam and his team developed a process for synthesizing certain acids found in the cannabis plant. These acids — otherwise known as cannabidiolic acid (CBDA), and a methylated version of CBDA (CBDA-ME) — have been since studied for a variety of purposes, and might ultimately be used to develop new drugs for everything from arthritis and anxiety to inflammatory bowel disease and psoriasis.

Others believe CBD is unproven and risky.

The U.S. Food and Drug Administration (FDA) continues to investigate its potential harms, noting that while it recognizes the potential opportunity that cannabis-derived compounds (like CBD) can offer, it remains concerned about CBD products being marketed as supplements. (According to the FDA, THC and CBD products do not fit the definition of a dietary supplement.)

“FDA is aware that some companies are marketing products containing cannabis and cannabis-derived compounds in ways that violate the Federal Food, Drug, and Cosmetic Act (FD&C Act), and that may put the health and safety of consumers at risk,” the Agency wrote in its 2021 update, noting that it’s illegal to market CBD by adding it to a food or labeling it as a dietary supplement.

Among a number of problems with CBD, the FDA says, is that it can cause liver damage and diarrhea, it may impact the metabolism of other drugs, and it may cause male reproductive toxicity in humans, as has been found in animal studies.

Still, many consumers continue to believe CBD’s potential benefits. A report (PDF), also from the Brightfield Group, that analyzed 2,400 members of an online community of medical cannabis users found that 59 percent of CBD users say they use it for insomnia and 66 percent for anxiety, while 44 percent have taken it for depression and 49 percent for joint pain and inflammation.

With so much CBD noise out there, we’re feeling a little overwhelmed and confused about CBD. We want to know the real deal. For starters, is CBD the same as cannabis? Should we spend our hard-earned money on the stuff, or is it a scam? Is there any science to back up the claims that CBD is helping people sleep better, feel better, look better, or be an all-around better human? If so, is that in the form of CBD oil, tinctures, lotions, or should we vape it? But wait — isn’t vaping bad for you?

Relax. We’ve got you covered. Herewith, the real scoop on CBD. (Buyer beware: Abbreviations ensue.)

Common Questions & Answers

Endocannabinoids are molecules produced by the body to maintain homeostasis — stability — in response to changes in the environment. The endocannabinoid system interacts with all of the major systems and organs in the body to enable and restore optimal functioning.

The word “cannabinoid” usually refers to a chemical found in the cannabis (marijuana or hemp) plant. “Endo,” in this context, refers to substances produced inside the body. Endocannabinoids are, in effect, the body’s own source of cannabis-like substances.

CBD and THC are plant cannabinoids, which operate much as endocannabinoids do, by attaching to certain receptors on the outsides of cells and altering the behavior of those cells or the bodily systems they are a part of.

Cannabinoids and endocannabinoids can affect pain perception, memory, mood, appetite, and many other bodily systems. The endocannabinoid system regulates the release of other neurotransmitters — that’s how it maintains homeostasis — and helps the body heal from any damage it sustains. Plant cannabinoids can similarly enhance feelings of well-being, but they can have undesirable side effects as well, particularly in young people.

Research suggests that endocannabinoids can be boosted by certain foods, such as those containing essential fatty acids, chocolate, herbs, spices, and teas, as well as by stress-reducing activities.

CBD: The Good, the Bad, and the Confusing

Before we get too much into the, er, weeds, it’s important to understand what CBD is and where it comes from.

Cannabis refers to a group of three varieties of marijuana plants with psychoactive properties: Cannabis sativa, Cannabis indica, and Cannabis ruderalis.

Cannabis contains more than 400 compounds, known as cannabinoids (pronounced keh-NAB-eh-noyd). The most well-known and researched are cannabidiol (CBD), and delta-9-tetrahydrocannabidiol (THC). Other lesser known components — THCA, CBN, CBC, and CBG — play different roles and have different effects in the body. (See our CBD glossary for details.)

The component in cannabis that is linked to its intoxicating effects (in other words, the “high,”) is THC. Conversely, CBD won’t get you high. Depending on your goals, this is either a good or a bad thing.

“Hemp” (which incidentally, is considered part of the CBD family) refers to non-intoxicating varieties that are high fiber or high seed-yielding and often used for rope, clothing, or sails. (Cocktail party fact: “The word ‘canvas’ comes from ‘cannabis,’ as it was made from cannabis fiber varietals,” says Will Kleidon, the CEO of Ojai Energetics in Ojai, California..)

In the United States, the legal definition of hemp is any cannabis plant whose delta-9 THC is below 0.3 percent.

What’s the Endocannabinoid System and How Does It Work?

The endocannabinoid system (ECS) is a biological system first described in the 1990s, and it plays a big role in brain, endocrine, and immune function. Its main role, however, is to maintain homeostasis, the internal biological balancing mechanism of the brain and body.

Two main elements of the system are endocannabinoid receptors, classified as CB1 and CB2. The body makes its own cannabinoids, known as endocannabinoids, that can act upon these receptors. But other varieties of cannabinoids, such as CBD, can interact with them, too.

What Are Cannabinoid Receptors?

Cannabinoid receptors are laced throughout the body, brain, and nerves.

  • Cannabinoid 1 (CB1) Receptors Most of these are in the central nervous system, especially neurons (nerve cells) in the brain.
  • Cannabinoid 2 (CB2) Receptors These are located mainly on immune cells but are also found in the central nervous system.

Both receptor types are activated by cannabinoids, which can be generated naturally inside the body (known as endocannabinoids) or can be introduced through a form of cannabis.

What’s the ‘Entourage Effect’?

The entourage effect refers to a theory that the whole is more effective than each part — or that the various compounds of the cannabis plant work best synergistically.

“It’s the theory that the cannabinoids, flavonoids, terpenes, and fatty acids all work together like an orchestra, in which all the instruments complement each other so you get the maximum effect of the plant,” says the cannabis researcher Monica Taing, PharmD. “CBD by itself can be a pain reliever, and THC can be a pain reliever by itself, but when combined, they work better for pain relief. That’s the entourage or ensemble effect.”

Now that that’s out of the way, let’s get into the nitty-gritty.

What Are the Legal Implications of Using CBD?

The legality of CBD is confusing.

In 2018, the Agriculture Improvement Act of 2018 (aka that year’s Farm Bill), legalized CBD derived from hemp — with the important caveat that it could only contain 0.3 percent of THC by dry weight, to be grown legally. This type of CBD is legal in 47 U.S. states with some restrictions, but totally illegal in Idaho, South Dakota, and Mississippi. Plants with more than 0.3 percent of THC are considered marijuana, which is legal for recreational use in 19 states, Washington, DC, and Guam.

Despite state laws legalizing the sale of cannabis for recreational or medicinal use, the Drug Enforcement Administration (DEA) (PDF) still classifies it as a Schedule 1 drug: “substances or chemicals [that] are defined as drugs with no currently accepted medical use and a high potential for abuse.” So, while marijuana is illegal on a federal level, states have different laws regarding marijuana and CBD.

Only one cannabis-derived drug product has been FDA approved: cannabidiol sold under the brand name Epidiolex, which contains a purified form of high-dose CBD to treat a rare, hard-to-treat form of epilepsy in children ages 1 and up.

How Do I Find Safe CBD Products? How Do I Know What I’m Getting?

Short answer: You often don’t.

The situation is not unlike that of dietary supplements, except for in the case of supplements, the FDA has defined a very clear set of restrictions — and the Federal Trade Commission, strict reinforcement of health claims. While the FDA has sent warning letters to certain companies selling CBD products, many products slip under the radar. In addition, state and Federal CBD regulations are at odds, so oversight can be difficult. What’s more, every state where medical or recreational marijuana is legal has its own testing rules and regulations, so something that passes muster in Massachusetts might not in California.

People often buy their products online or at the local drugstore or gas station, meaning that they often don’t know what they’re getting.

“Some CBD products don’t contain CBD, but they contain THC and heavy metals, so we need strong regulations,” says Dr. Taing. Indeed, as of May 21, 2022, poison control centers have managed 2,652 cases related to CBD, per the American Association of Poison Control Centers.

Some people have failed drug tests because they’ve unwittingly taken THC that was in a product that was supposed to contain only CBD. A study published in the Journal of the American Medical Association (JAMA) in November 2017 found that 21 percent of CBD products derived from hemp and sold online contained THC, even though THC wasn’t listed on the packaging.

A more recent study in JAMA Psychiatry showed that even a high-quality, high-potency cannabidiol product labeled as carrying as much as tenfold less than the legal limits of THC permissible under law might still result in positive urine drug tests.

Findings from another study, published June 2022 in the Journal of Cannabis Research, showed that of the 80 products evaluated, 37 contained CBD concentrations that were at least 10 percent higher or lower than the concentration listed on the label: 12 products contained less than 90 of what was listed, while 25 products contained more than 110 percent.

Even more worrisome, a study published in January 2019 in Forensic Science International examined nine liquids that were advertised as 100 percent natural CBD extract and found they contained potentially problematic compounds. One contained dextromethorphan, which is used in over-the-counter cough medication and is considered addictive when abused. Four others had a synthetic cannabinoid that can cause, among other things, anxiety, psychosis, and even death.

“As with any other product you would ingest, you have to be smart,” says Jahan Marcu, PhD, the editor in chief of the American Journal of Endocannabinoid Medicine, and the cofounder and chief science officer at the International Research Center on Cannabis and Mental Health.

What’s more, he says, every product should have a certificate of analysis, or COA — a document generated by a laboratory certifying its legitimacy and also listing the ingredients.

The Mayo Clinic uses the following checklist to identify high-quality products, as described in a 2019 issue of Mayo Clinic Proceedings:

  1. Does it meet the following quality standards? These include Current Good Manufacturing Practices (CGMP) certification from the FDA; European Union (EU), Australian (AUS), or Canadian (CFIA) organic certification; National Science Foundation (NSF) International certification.
  2. Does the company have an independent adverse event reporting program?
  3. Is the product certified organic or eco-farmed?
  4. Have their products been laboratory tested by batch to confirm tetrahydrocannabinol levels below 0.3 percent and no pesticides or heavy metals?

For more information, Project CBD, Certified Kind, Clean Green, and WeedMaps offer information on dispensaries, cannabis products, and brands.

Does It Matter if the CBD Is Organic?

In theory, yes, because without an organic label, there’s a potential for ingesting pesticides and chemical fertilizers. If you have a COA, then you’ll know what’s in the product.

But here’s the rub: Organic products are regulated by the U.S. Department of Agriculture (USDA), which is a federal agency. Since cannabis is considered a Schedule 1 drug, technically, medical cannabis couldn’t be designated as “organic,” unless it’s made from hemp.

In May 2018, Palmetto Grow became the first company to have USDA Organic certification for hemp flower and seed. Since then, other organic growers have joined the market. You can find a list of some of the best organic CBD products from EcoWatch and The Honest Consumer.

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