Cannabinol (CBN) and Sleep: Separating Fact from Fiction
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Corroon J. Cannabinol and Sleep: Separating Fact from Fiction. Cannabis Cannabinoid Res. 2021 Aug 31. doi: 10.1089/can.2021.0006. Epub ahead of print. PMID: 34468204.
In recent years, marketers of cannabis (i.e., marijuana) products have claimed that cannabinol (CBN) has unique sleep-promoting effects. Despite a plausible mechanism, it is possible that such claims are merely rooted in cannabis lore. The aim of this narrative review was to answer the question: "Is there sufficient clinical evidence to support claims that CBN has sleep-promoting effects?" A systematic search of PubMed/MEDLINE was performed to evaluate the published evidence. The abstracts of 99 human studies were screened for relevance by the author and reviewed for compliance with the inclusion criteria. The characteristics and principal findings were extracted from eight full-text articles that met inclusion criteria for detailed review. Pre-clinical and clinical research investigating the effects of CBN is dated and limited, with the preponderance of human studies occurring in the 1970-1980s with small sample sizes lacking diversity in sociodemographic characteristics. Studies specifically assessing subjective effects associated with sleep, such as sedation or fatigue, are rare. Most importantly, published clinical trials investigating associations between CBN and validated sleep questionnaires and/or formal polysomnography were not identified in this review. In addition, evidence demonstrating that CBN itself elicits cannabis-like effects in humans is mixed, with the majority of available evidence demonstrating a lack of such an effect. Consequently, there is insufficient published evidence to support sleep-related claims. Randomized controlled trials are needed to substantiate claims made by manufacturers of cannabis products containing CBN. These studies should specifically evaluate its effects on sleep through polysomnography, or at minimum, through validated sleep questionnaires, and use dosages significantly higher than those found in currently available cannabis products marketed for sleep (typically ≤5 mg). Individuals seeking cannabis-derived sleep aids should be skeptical of manufacturers' claims of sleep-promoting effects.
Labeling of Cannabidiol Products: A Public Health Perspective
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Corroon J, MacKay D, Dolphin W (2020) Labeling of cannabidiol products: a public health perspective, Cannabis and Cannabinoid Research X:X, 1–5, DOI: 10.1089/can.2019.0101.
Interest in the therapeutic use of cannabidiol (CBD) has reached a fever-pitch in recent months, as CBD-containing products appear everywhere from online retailers to grocery stores and gas stations. The widespread availability of hemp-derived CBD products is confounding given that CBD is a U.S. Food and Drug Administration (FDA)-approved drug, and thus precluded from being added to food and beverages, or included in dietary supplements. The use by manufacturers of disease-related claims on marketing materials and product labels, along with the federal legalization of hemp in December 2018, has created political pressure on FDA to promulgate regulations.
Accurate and informative labeling of hemp-derived CBD products is an important public health issue. FDA-regulated product labels are considered an essential tool for protecting consumers and enabling informed decision-making. Untruthful or unsubstantiated health-related claims, and unallowed Drug Claims, in marketing materials and on labels of CBD products may create harm by enticing consumers to forgo more evidence-based medical interventions. Furthermore, missing or inaccurate labeling of the amount of CBD, delta-9 tetrahydrocannabinol (THC), and potentially harmful contaminants such as pesticides, naturally- occurring yeast and mold or heavy metals may result in harm and/or lack of efficacy. Manufacturers of these products may reasonably be expected to understand and adhere to FDA regulations for labeling and marketing of food, dietary supplements and drugs, both over-the-counter (OTC) and prescription, even though FDA has interpreted federal law as excluding them from these categories. As manufacturers prepare for forthcoming regulations, a better understanding of the basic framework for FDA labeling and marketing regulations for food, dietary supplements and drugs is warranted.
Indications and administration practices amongst medical cannabis healthcare providers: a cross-sectional survey
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Corroon, J., Sexton, M. & Bradley, R. Indications and administration practices amongst medical cannabis healthcare providers: a cross-sectional survey. BMC Fam Pract 20, 174 (2019) doi:10.1186/s12875-019-1059-8
The medical use of cannabis has been legislatively restricted for decades in the US and abroad. In recent years, changing local and national policies have given rise to a community of healthcare providers who may be recommending the medical use of cannabis without the benefit of formal clinical practice guidelines or sufficient training and education. In addition, a citizen science movement has emerged whereby unlicensed and untrained individuals are acting as healthcare provider proxies, offering cannabis-specific clinical care to “patients”. This study sought to characterize the clinical practice characteristics of these provider groups.
An anonymous, online survey was designed to describe levels of cannabis-specific education, practice characteristics, indications for medical use, dose, administration forms and adverse effects related to cannabis use. The questionnaire was disseminated via professional medical cannabis associations and by word-of-mouth. It was accessed between June 31–December 31, 2018. A self-selecting sample of respondents (n = 171) completed the survey.
Formal education or training in the medical use of cannabis was significantly more common among licensed respondents than unlicensed respondents (95.5% vs 76.9% respectively, OR, 6.3, 95% CI, 1.2–32.3, p = 0.03). The vast majority (n = 74, 83.15%) of licensed respondents reported having recommended cannabis as an adjunct to an existing prescription drug. Almost two-thirds (n = 64, 71.9%) reported having recommended it as a substitute. When delta-9-tetrahydrocannabinol (THC) is the principal therapeutic constituent of interest, vaporization is the most common method of administration recommended (n = 94 responses, 71.4% of respondents). In contrast, when cannabidiol (CBD) is the principal therapeutic constituent of interest, oral administration (sublingual or oromucosal absorption) is the most common method (n = 70 responses, 71.4% of respondents).
Individuals who recommend the medical use of cannabis appear to be self-generating a community standard of practice in the absence of formal clinical guidelines on dosing, interactions and other characteristics. Reducing barriers to clinical research on cannabis products is needed, not only to better understand their risks and benefits, but also to augment the evidence-base for informing clinical practice.
The Endocannabinoid System and its Modulation by Cannabidiol (CBD)
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Corroon J, Felice J. The Endocannabinoid System and its Modulation by Cannabidiol (CBD). Altern Ther Health Med. 2019;25(S2):6-14.
As interest in, and use of, phytocannabinoids from Cannabis Sativa L (Cannabis) has increased with the number of state-regulated Cannabis programs, heightened scientific attention has been directed toward the mechanisms by which delta-9-tetrahydrocannabiniol (delta-9-THC), cannabidiol (CBD), and other phytocannabinoids exert their physiological effects in the body. These exogenous, plant-derived ligands interact with endogenously produced proteins, receptors, enzymes, and endogenous ligands, in one of the most evolutionarily preserved biological systems known to the life sciences, the endogenous cannabinoid signaling system or endocannabinoid system (ECS).
The ECS is thought to be 600-million-years-old. Present in every animal species, except insects, it evolved as a stress/ harm regulation network that functions to restore homeostasis following cellular stressors.1 The ECS is upregulated and downregulated on a continuous basis as needed. It communicates with all other systems in the body and has been implicated in multiple regulatory functions in both health and disease, including pain, perception, mood, memory, and reward. This vital physiological system is modulated by diet, sleep, exercise, stress, and a multitude of other factors, including exposure to phytocannabinoids. According to George Kunos, Scientific Director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) at the National Institutes of Health (NIH), “Modulating endocannabinoid system activity may have therapeutic potential in almost all diseases affecting humans.”
Regulatory Status of Cannabidiol (CBD) in the United States: A Perspective
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Corroon J, Kight R. Regulatory Status of Cannabidiol in the United States: A Perspective. Cannabis and cannabinoid research. 2018;3(1):190-194.
Cannabidiol (CBD) is 1 of > 100 cannabinoids found in Cannabis sativa L. (Cannabis spp. or Cannabis). Despite its complex and rapidly evolving regulatory status in the United States, projected retail sales of CBD products— hemp, Cannabis and pharmaceutical—are as high as $1.9 billion by 2020. CBD products can currently be pur- chased online, over the counter, and at Cannabis-specific dispensaries throughout most parts of the country, despite the fact that CBD is presently 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 (FDA). These products are largely unregulated, and are being used predominantly to treat specific medical con- ditions. Recent FDA approval of Epidiolex (CBD) as a treatment for certain pediatric seizure disorders will prompt scheduling of CBD and likely alter FDA enforcement of the Federal Food, Drug, and Cosmetic Act (FD&C), which to date has mostly been in the form of warning letters. Persuasive legal arguments contend that CBD’s legal sta- tus is based on its source. According to these arguments, there are three legal sources. CBD-derived from: (1) parts of the Cannabis plant that do not meet the definition of cannabis in the Controlled Substances Act (CSA); (2) imported ‘‘non-psychoactive hemp’’; and (3) ‘‘Industrial hemp’’ cultivated as part of a state pilot program per the 2014 Farm Act. Although CBD’s lawful status with respect to the CSA appears to be expanding, its future regulatory status with respect to the FD&C Act is difficult to predict.
A Cross-Sectional Study of Cannabidiol (CBD) Users
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Corroon J, Phillips JA. A Cross-Sectional Study of Cannabidiol Users. Cannabis Cannabinoid Res. 2018 Jul 1;3(1):152-161. doi: 10.1089/can.2018.0006. PMID: 30014038; PMCID: PMC6043845.
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 it 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.
Cannabis as a substitute for prescription drugs
a cross-sectional study
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Corroon JM, Jr., Mischley LK, Sexton M. Cannabis as a substitute for prescription drugs - a cross-sectional study. Journal of pain research. 2017;10:989-998.
Background: The use of medical cannabis is increasing, most commonly for pain, anxiety and depression. Emerging data suggest that use and abuse of prescription drugs may be decreasing in states where medical cannabis is legal. The aim of this study was to survey cannabis users to determine whether they had intentionally substituted cannabis for prescription drugs. Methods: A total of 2,774 individuals were a self-selected convenience sample who reported having used cannabis at least once in the previous 90 days. Subjects were surveyed via an online anonymous questionnaire on cannabis substitution effects. Participants were recruited through social media and cannabis dispensaries in Washington State.
Results: A total of 1,248 (46%) respondents reported using cannabis as a substitute for pre- scription drugs. The most common classes of drugs substituted were narcotics/opioids (35.8%), anxiolytics/benzodiazepines (13.6%) and antidepressants (12.7%). A total of 2,473 substitutions were reported or approximately two drug substitutions per affirmative respondent. The odds of reporting substituting were 4.59 (95% confidence interval [CI], 3.87–5.43) greater among medical cannabis users compared with non-medical users and 1.66 (95% CI, 1.27–2.16) greater among those reporting use for managing the comorbidities of pain, anxiety and depression. A slightly higher percentage of those who reported substituting resided in states where medical cannabis was legal at the time of the survey (47% vs. 45%, p=0.58), but this difference was not statistically significant.
Discussion: These patient-reported outcomes support prior research that individuals are using cannabis as a substitute for prescription drugs, particularly, narcotics/opioids, and independent of whether they identify themselves as medical or non-medical users. This is especially true if they suffer from pain, anxiety and depression. Additionally, this study suggests that state laws allowing access to, and use of, medical cannabis may not be influencing individual decision- making in this area.