CBD Oil Scientific Research

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Public and medical interest in cannabidiol (CBD) has been rising, and CBD is now available from various sources. Research into the effects of low-dose CBD on outcomes like stress, anxiety, and sleep problems have been scarce, so we conducted an online survey of CBD users to better understand patterns of use, dose, and self-perceived effects of CBD. The sample consisted of 387 current or past-CBD users who answered a 20-question online survey. The survey was sent out to CBD users through email databases and social media. Participants reported basic demographics, CBD use patterns, reasons for use, and effects on anxiety, sleep, and stress. The sample (N = 387) consisted of 61.2% females, mostly between 25 and 54 years old (72.2%) and primarily based in the UK (77.4%). The top 4 reasons for using CBD were self-perceived anxiety (42.6%), sleep problems (42.5%), stress (37%), and general health and wellbeing (37%). Fifty-four per cent reported using less than 50 mg CBD daily, and 72.6% used CBD sublingually. Adjusted logistic models show females had lower odds than males of using CBD for general health and wellbeing [OR 0.45, 95% CI 0.30–0.72] and post-workout muscle-soreness [OR 0.46, 95%CI 0.24–0.91] but had higher odds of using CBD for self-perceived anxiety [OR 1.60, 95% CI 0.02–2.49] and insomnia [OR 1.87, 95% CI 1.13–3.11]. Older individuals had lower odds of using CBD for general health and wellbeing, stress, post-workout sore muscles, anxiety, skin conditions, focusing, and sleep but had higher odds of using CBD for pain. Respondents reported that CBD use was effective for stress, sleep problems, and anxiety in those who used the drug for those conditions. This survey indicated that CBD users take the drug to manage self-perceived anxiety, stress, sleep, and other symptoms, often in low doses, and these patterns vary by demographic characteristics. Further research is required to understand how low doses, representative of the general user, might impact mental health symptoms like stress, anxiety, and sleep problems. Questions and answers about FDA regulation of cannabis and cannabis-derived products

Reasons for cannabidiol use: a cross-sectional study of CBD users, focusing on self-perceived stress, anxiety, and sleep problems

Public and medical interest in cannabidiol (CBD) has been rising, and CBD is now available from various sources. Research into the effects of low-dose CBD on outcomes like stress, anxiety, and sleep problems have been scarce, so we conducted an online survey of CBD users to better understand patterns of use, dose, and self-perceived effects of CBD.

Methods

The sample consisted of 387 current or past-CBD users who answered a 20-question online survey. The survey was sent out to CBD users through email databases and social media. Participants reported basic demographics, CBD use patterns, reasons for use, and effects on anxiety, sleep, and stress.

Results

The sample (N = 387) consisted of 61.2% females, mostly between 25 and 54 years old (72.2%) and primarily based in the UK (77.4%). The top 4 reasons for using CBD were self-perceived anxiety (42.6%), sleep problems (42.5%), stress (37%), and general health and wellbeing (37%). Fifty-four per cent reported using less than 50 mg CBD daily, and 72.6% used CBD sublingually. Adjusted logistic models show females had lower odds than males of using CBD for general health and wellbeing [OR 0.45, 95% CI 0.30–0.72] and post-workout muscle-soreness [OR 0.46, 95%CI 0.24–0.91] but had higher odds of using CBD for self-perceived anxiety [OR 1.60, 95% CI 0.02–2.49] and insomnia [OR 1.87, 95% CI 1.13–3.11]. Older individuals had lower odds of using CBD for general health and wellbeing, stress, post-workout sore muscles, anxiety, skin conditions, focusing, and sleep but had higher odds of using CBD for pain. Respondents reported that CBD use was effective for stress, sleep problems, and anxiety in those who used the drug for those conditions.

Conclusion

This survey indicated that CBD users take the drug to manage self-perceived anxiety, stress, sleep, and other symptoms, often in low doses, and these patterns vary by demographic characteristics. Further research is required to understand how low doses, representative of the general user, might impact mental health symptoms like stress, anxiety, and sleep problems.

Introduction

In the past years, cannabidiol (CBD), one amongst hundreds of naturally occurring phytocannabinoids found in the Cannabis sativa plant, has received a lot of attention from scientific communities, politicians, and mainstream media channels. CBD is the second most abundant cannabinoid in the Cannabis sativa plant after delta-9-tetrahydrocannabinol (THC), but unlike THC, CBD is not intoxicating (Pertwee 2008). In many countries, including the UK, there is unsanctioned availability of products containing CBD, from oils and capsules to chewing gums, mints, soft drinks, gummies, and intimate lubrication gels.

CBD has not demonstrated any potential for abuse or dependency and is considered well tolerated with a good safety profile, according to a report released by the World Health Organization (WHO) (Geneva CANNABIDIOL (CBD) n.d.). Since January 2019, the European Union (EU) has classified CBD as a novel food, implying that before 1997, consumption was insignificant. Each country has implemented the regulation of CBD differently. In the UK, The Food Standards Agency (FSA) recommends limiting the daily dose of CBD to 70 mg (Cannabidiol (CBD) n.d.). However, researchers have used doses up to 1200 mg without serious side-effects (Davies and Bhattacharyya 2019). Conversely, few clinical trials involving children with treatment-resistant epilepsy who received either 10 or 20 mg/kg of CBD (Epidiolex) for 12 weeks recorded side-effects, such as a reversible rise in liver enzymes (Devinsky et al. 2018a; Thiele et al. 2018).

The popularity of CBD can be partly explained by an increasing number of preclinical and clinical studies indicating a range of potential health benefits. However, mass media interest also plays a significant role. Studies suggest CBD might help with mental health symptoms and neurological conditions like experimentally induced anxiety (Zuardi et al. 1993), generalised social anxiety disorder (Bergamaschi et al. 2011), social phobia (de Faria et al. 2020), and conditions like PTSD (Elms et al. 2019; Shannon and Opila-Lehman 2016) schizophrenia (Zuardi et al. 2006; Leweke et al. 2012; Morgan and Curran 2008; Schubart et al. 2011), addiction (Hurd et al. 2019; Hindocha et al. 2018; Galaj et al. 2020), and epilepsy (Devinsky et al. 2017; Devinsky et al. 2018b; Cunha et al. 1980). These mental health disorders are often co-morbid and include other symptoms CBD might help with, e.g. sleep and impaired cognition. There is also data to suggest CBD could help treat neurodegenerative diseases like Alzheimer’s disease (Watt and Karl 2017; Fernández-Ruiz et al. 2013; Esposito et al. 2006), Parkinson’s disease (Fernández-Ruiz et al. 2013; García-Arencibia et al. 2007), and chronic pain conditions including fibromyalgia (Van De Donk et al. 2019), either alone or with THC (Rog et al. 2005; Berman et al. 2004; Wade et al. 2003; Svendsen et al. 2004; Notcutt et al. 2004). Additionally, in more than 30 countries, health authorities have approved CBD, under the name Epidiolex, to treat two severe forms of treatment-resistant childhood epilepsy (Dravet and Lennox-Gastaut syndrome) (Devinsky et al. 2016; Silvestro et al. 2019). Sativex, a sublingual spray containing an equal amount of THC and CBD, is also approved to treat multiple sclerosis in more than 30 countries (Keating 2017).

When used in high doses, somnolence is a primary adverse effect (Machado Bergamaschi et al. 2011). Patients in CBD clinical trials were more likely to experience sedation (OR 4.21, 95% CI 1.18–15.01) and somnolence (OR 2.23, 95% CI 1.07–4.64) in comparison to placebo (Chesney et al. 2020). Despite this preclinical and experimental research, there is a lack of human clinical trials to establish the efficacy and appropriate CBD indications fully. The effective dose for most of the above indications is still to be determined. In much of the research, high doses of CBD are used (between 300 and 1200 mg), whilst at the same time, globally, millions of CBD users are using low dose CBD. Thus, a disconnect exists between clinical research and the current state of the market.

A cross-sectional study of 2409 cannabidiol users from the USA found that the top three medical conditions reported were chronic pain, arthritis/joint pain, and anxiety, followed by depression and insomnia (Corroon and Phillips 2018). A recent survey carried out by Wheeler et al. of 340 young adults, some of whom were CBD users, found the top reasons to be stress relief, relaxation, and sleep improvement. They found edible CBD products to be the most prevalent (Wheeler et al. 2020). Another study of 400 CBD patients in New Zealand observed an increase in overall quality of life, a decrease in perceived pain, depression, and anxiety symptoms, as well as an increase in appetite and better sleep (Gulbransen et al. 2020).

A national survey indicated that in the UK, 8–11% of the adult population had tried CBD by June 2019 (Andrew et al. 2019). Studies of Google searches have shown considerable increases in CBD interest, with 6.4 million unique searchers in the USA in April 2019 (Leas et al. 2019). Yet it is clear that scientists, physicians, and governments were not prepared for the rapid surge in CBD use.

The regulatory confusion, along with recent media hype, has made it hard for most people to understand the true nature of CBD. Being classified as both a medicine and a supplement in some forms, whilst an illegal substance in others leads to consumer and patient confusion and potential frustration. Therefore, this study aimed to understand users’ consumption patterns regarding dose, route of administration, and reasons for using CBD. We hypothesised that out of all reasons for using CBD, the top three would be anxiety, sleep disturbances, and stress.

Methods

We developed an anonymous online questionnaire to collect CBD users’ self-reported characteristics, preferred method/s, and reason/s for using CBD. The survey was hosted on Survey Monkey Inc. (San Mateo, CA, USA). Data was collected between 10 January 2020 and 18 March 2020. The 20 questions were designed as multiple-choice questions with the option to choose either one or more answers. For some questions, respondents could write an alternative response if no option matched. We collected demographic information (age, sex, and location), CBD use patterns, reasons for use, other medication use, perceived effects, and side effects. The full questionnaire is provided in the supplementary materials.

To access actual CBD users, we collaborated with four different CBD brands and retailers (TheDrug.Store, OTO CBD, With Pollen and Grass & Co.), based in the UK, who sent out the survey to their email databases. The survey was sent out to 14,743 unique email addresses. Two thousand five hundred thirty-four were opened and 475 clicked through to the survey. We also shared the survey with CBD user groups on social media channels like Facebook and LinkedIn. We did not collect any personal data or IP addresses. Ethical approval was not required since this research investigated non-sensitive information using anonymous survey procedures with participants not defined as “vulnerable”. In addition, participation was deemed unlikely to induce undue psychological stress or anxiety based on ethics committee guidelines (UCL REC n.d.).

Statistical analysis

All analyses were conducted in SPSS version 24 (IBM Corporation, Armonk, NY). Valid percentages are reported rather than absolute values for descriptive statistics to account for missing data. We only report data on those reporting using CBD themselves equivalent to 90% of the respondents (e.g., not for veterinary use, not those who had not tried it, and those reporting on behalf of other users). An analysis of non-responders can be found in supplementary materials. We conducted logistic regression models to investigate associations between sex (males [reference category] and females), age (recoded to < 34 years old [reference category], between 35 and 54 years old, and 55+) and location (UK [reference category], other). For CBD use patterns, we used separate models to compare those who did and did not report their primary use of CBD for self-perceived anxiety, stress, and sleep whilst controlling for sex, age, and location. We dummy-coded “time of day” as each category versus all others. We report adjusted odds ratios with 95% confidence intervals and p values with a defined cut-off of 0.05.

Results

The most significant findings were that many CBD users reported that CBD could improve sleep problems, stress, and anxiety and be used for general health and wellbeing. In the detailed results below, you can find the demographics of our survey population (Table 1), the CBD use patterns (Table 2), and logistic regression and OR’s for the different subgroups. The indications for CBD use are shown (Fig. 1), as well as how CBD affects sleep (Fig. 2), and other effects of CBD (Fig. 3). Using CBD for sleep was associated with taking it in the evening, and using CBD for anxiety or stress was associated with the sublingual route. Females had higher odds of using CBD for anxiety and men for post-workout. Details of the results can be found below.

Reasons for cannabidiol use amongst 397 adult cannabidiol users who were allowed to respond to more than one option leading to a total of 1622 responses. Y-axis represents percentage based on total responses

Perceived effects of cannabidiol on sleep amongst adult cannabidiol users responding to the question “how does cannabidiol affect your sleep?” Participants were allowed to select multiple options. Y-axis represents percentage of total responses (n = 522)

Other perceived benefits of cannabidiol amongst adult cannabidiol users. Respondents were asked what other benefits or effects they feel from using cannabidiol. Participants were allowed to select multiple options. X-axis is the percentage of total responses (n = 906)

Demographic characteristics

A total of 430 people started the survey, of whom 15 (3.48%) did not respond to any questions, and 28 (6.5%) reported they did not use CBD themselves (analysis of these non-users can be found in the supplementary materials). Non-CBD-users skipped most questions and had sociodemographic characteristics similar to those of CBD users. Three hundred eighty-seven (90%) reported using CBD themselves. The majority of users were females from the UK (see Table 1). In regards to other medication use, there were a total of 467 responses. 39.4% of respondents reported not taking any other medication, 14.7% “painkillers”, and 14.7% “other” (40% anxiolytics and antidepressants). No other medication was reported by more than 10% of responses.

Logistic regression on location purchased (CBD shop or other) found that those who lived outside of the UK (aOR 2.286, [95% CI 1.35–3.86], p = 0.002) and males (aOR 1.75, [95% CI 1.06–2.88], p = 0.02) had greater odds of purchasing CBD from an “other” location. Each of the primary disorders was included in the model individually, and did not significantly alter the model and were not associated with location purchased.

CBD use patterns

The majority of users take CBD sublingually for 3–6 months (see Table 2). Those 35–54 years old (aOR 1.67 [95% CI 1.02–2.72], p = 0.04) and those 55+ (aOR 2.01, [95% CI 1.11–3.64], p = 0.02) had greater odds of using CBD daily in comparison to less than daily. There were no associations with self-perceived anxiety, stress, or sleep improvement. Females had lower odds of using CBD for greater than 1 year versus less than 1 year (aOR 0.54, [95% CI 0.38–0.88], p = 0.013) suggesting females had used CBD for less time. No associations emerged for self-perceived anxiety, stress, or sleep. There were no sex or age associations for the frequency of use, duration of use, or number of times per day. Females had a greater odds of responding that they take CBD when they need it versus males (aOR 1.79, [95% CI 1.036–3.095], p = 0.037). However, no other associations with age and sex on time of day emerged.

Compared with people not using CBD for anxiety, those who did self-medicate used CBD multiple times a day (aOR 3.44, [95% CI 1.70, 7.00], p = 0.001). Moreover, compared with those not using CBD for self-perceived stress, those who were self-medicating also used CBD multiple times a day (aOR 1.97, [95% CI 1.034–3.77], p = 0.039). Those using CBD for sleep improvement had greater odds of using CBD in the evening (aOR 3.02, [95% CI 1.86, 4.93], p ≤ 0.001) and lower odds of using CBD in the morning (aOR 0.157, [95% CI 0.07–0.38], p ≤ 0.001). Those using CBD for self-perceived anxiety had lower odds of using CBD in the evening (aOR 0.56, [95% CI 0.14–0.45], p ≤ 0.001). No associations emerged between those who did and did not use CBD for self-perceived stress on the time of day they used CBD.

CBD dose and route of administration

Route of administration did not vary by sex. There were lower odds of those aged 55+ of vaping CBD (aOR 0.176, [95% CI 0.04–0.80], p = 0.025) as well as lower odds of those aged 35–55 (aOR 0.245, [95% CI 0.10–0.59], p = 0.002) and 55+ (aOR 0.115, [95% CI 0.025–0.520], p = 0.005) in comparison to 18–34 years old for drinking CBD. Self-reported anxiety (aOR 1.78, [95% CI 1.08–2.92], p = 0.023) and those using CBD for sleep improvement (aOR 1.945, [95% CI 1.152–3.285], p = 0.013) were associated with the sublingual route. Stress was not associated with route of administration.

Reasons for use of CBD

42.6% endorsed using CBD for self-perceived anxiety, followed by 37.5% for stress, 37% for general health and wellbeing, and 37% for improving sleep (see Fig. 1). 24.6% reported use for self-perceived insomnia. Overall, 42.5% of respondents said they were using CBD for some sleep issue, either to improve sleep or for self-perceived insomnia. In the supplementary materials (see Table 2), we show reasons for use broken down by sex, age, and location.

In adjusted logistic models, more males (47.4%) were using CBD for general health and wellbeing than females (30.7%; aOR 0.464, [95% CI 0.30–0.72], p = 0.001). More females were using CBD for self-perceived anxiety (47.9%) than males (34.2%; aOR 1.595, [95% CI 1.021, 2.49], p = 0.04), and for self-perceived insomnia (females 28.6%, males 17.8%; aOR 1.871, [95% CI 1.125–3.112], p = 0.015). More males (14.1%) than females (7.1%) were using CBD for post-workout sore muscles (aOR 0.462, [95% CI 0.236–0.905], p = 0.024).

Self-perceived anxiety

One hundred sixty-five of 387 (42.6%) endorsed using CBD for self-perceived anxiety. In response to the question “how does CBD affect your anxiety levels”, participants responded that they felt less anxious (141/163 (86.5%)), followed by “no difference (I still suffer from the same degree of anxiety)” (21/163; 12.8%), and one person (0.6%) noted greater anxiety. Moreover, participants were asked how often they thought about problems when they were supposed to be relaxing, compared with before they started taking CBD. We found that just 96/163 (58.9%) of respondents thought about their problems less than before, followed by “it hasn’t changed (I still think a lot about problems” (55/163; 33.7%), followed by “it hasn’t changed (I did not think about problems a lot before)” (11/163; 6.7%), followed by (1/163; 0.6%) of respondents reporting thinking about problems more than before.

Amongst those who reported experiencing anxiety, adjusted logistic models comparing those who responded that CBD reduces their self-perceived anxiety with those who responded that they still suffer from anxiety found no associations with age, sex, or location. Similar results emerged for “thinking about problems”.

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Self-perceived stress

One hundred forty-five of 387 (37.5%) of respondents endorsed the use of CBD for self-perceived stress. Amongst those using CBD for stress, in response to the question “how does CBD affect your stress level”, participants responded that they felt less stressed (130/141; 92.2% followed by it does not affect my stress levels (I still feel stressed) (11/141; 7.8%). No respondent said that it increased their stress level. Adjusted logistic models comparing those who responded that CBD reduces their stress versus those who responded that they still have stress found no associations with age, sex, or location.

Self-perceived sleep problems

As we initially designed the study to address sleep, we asked detailed questions regarding this. Improving sleep (125/387; 32.3%) and self-perceived insomnia (95/387; 24.5%) were the fourth and fifth-ranked endorsed reasons for using CBD, overall 42.5% endorsed sleep as a reason for use. Respondents said that CBD helped them sleep (see Fig. 2). As we restricted this analysis to respondents who selected using CBD for sleep improvement, there was considerable overlap between using CBD for sleep improvement and self-perceived insomnia. Regarding questions about the time it takes to fall asleep, 48.2%(73/124;) said CBD led them to fall asleep faster, followed by 29/124 (23.4%) who said it did not make a difference and still have a hard time falling asleep, followed by 22/124 (17.7%) who said it did not make a difference because they did not have a problem falling asleep beforehand. Age, sex, and location were not associated with the speed of falling asleep.

Other reported benefits

We asked participants to report on other effects they experience. From a total of 960 responses, the most prevalent effect was calm (21.3%), followed by decreased pain (19.5%) (see Fig. 3). One per cent reported feeling euphoric/high. In examining the “other” responses, 27/960 (9.3%) reported that they did not feel any benefits from the use of CBD.

Sex was associated with sexual enhancement where males reported experiencing more sexual enhancement (9.9%) than females (2.9%) (aOR 0.274, [95% CI 0.11–0.70], p = 0.007). There were no other associations between sex and other CBD benefits. Those aged 55+ (23.1%; aOR 3.8, [95% CI 1.63–8.87], p = 0.002) and those aged 35–54 years old (16.8%; aOR 2.72, [95% CI 1.258–5.876], p = 0.011) reported taking less of their other medications in comparison to those aged under 34 years old (9.9%). Those ages 55+ reported experiencing more “no positive experiences” (14.3%) in comparison to those under 34 (2.7%; aOR 5.31, [95% CI 1.45–19.41], p = 0.012).

CBD side-effects

A total of 388 responses were made, of whom 277/388 (71%) were logged as not experiencing any side-effects. Dry mouth was experienced by 44/388 (11%), and 13/288 (3%) experienced fatigue. All other side-effects were reported less than 2% (e.g. dizziness, nausea, upset stomach, rapid heartbeat, diarrhoea, headache, anxiety, psychotic symptoms, sexual problems, trouble concentrating). No respondents reported vomiting, fainting, liver problems (raised liver enzymes in blood test), or seizures. Adjusted logistic models show no associations of age, of sex with “no side effects” or fatigue. Location of the participants was associated with dry mouth, those who lived outside of the UK had greater odds of experiencing dry mouth (aOR 2.44, [95% CI 1.25–4.75], p = 0.009). No other side-effects were analysed due to the small number of respondents citing other side-effects.

Discussion

This study aimed to investigate CBD use patterns in the general population regarding the route of administration, dose, and indications for use. We found that the main indications for using CBD were self-perceived anxiety, stress, general health and wellbeing, sleep, and pain.

User characteristics and reason for use

More than half of the users were using a daily dose below 50 mg via a sublingual route of administration. Most were using CBD daily, sometimes multiple times per day. We found that respondents who use CBD for self-perceived anxiety and stress tend to use it several times per day, whilst respondents endorsing using CBD for sleep take it in the evening, indicating that user patterns vary according to the symptoms. A recent review suggests half-life is between 1.4 and 10.9 h after oromucosal spray and 2–5 days after chronic oral administration (Iffland and Grotenhermen 2017). In the light of these findings, it may be that people are dosing CBD several times per day to maintain stable plasma levels throughout the day if managing symptoms of stress and anxiety, whilst only using CBD at night if managing sleep problems.

We found that 69.7% of users had been using CBD for less than 1 year. Moreover, only 4.1% had used CBD for more than 5 years, reflecting both that it is a fairly new phenomenon and an increasing interest in CBD in the UK, compared with the USA. A similar American survey reported that 34.6% had used CBD for less than 1 year and 53.2% more than 5 years (Corroon and Phillips 2018). At the time of writing, CBD is legal in all but three, out of fifty, American states, and many of these allow the products to contain THC. In the UK and Europe, non-prescription CBD products are not allowed to contain any THC (< 0.01%). These differences might create a divergence between European vs American consumers’ experiences, and stresses the urgency for internal and external regulation, and education about cannabinoids in Europe.

We found age and sex differences in the reason for CBD use. Most of the sample was female, but males had greater odds of using CBD for general health and wellbeing and post-workout for sore muscles. In contrast, females were more likely to use CBD for self-perceived anxiety and insomnia, reflecting the higher prevalence of both symptoms amongst women (McLean et al. 2011; Li et al. 2002). We also found more females using CBD for fibromyalgia, possibly reflecting the much higher prevalence of fibromyalgia amongst women (Yunus 2002). A recent study compared the subjective effects of 100 mg oral versus vaporised and smoked CBD and found that women reported experiencing more subjective effects of CBD than men (Spindle et al. 2020), which may reflect why women were using CBD for more chronic symptomology. There were also significant age differences, with more people under 34 years old using CBD for general health and wellbeing than older age groups, which might be explained in part by the fact that disease burden generally increases with age. More young people use CBD to reduce self-perceived stress and anxiety, aligning with studies finding young people are more troubled by symptoms of anxiety than older people (Brenes et al. 2008).

In the present study, we found that the largest proportion of respondents used CBD to help with mental health symptoms like perceived anxiety, stress, and sleep problems. This finding aligns with a previous CBD survey that found that anxiety and insomnia were amongst the top 6 reasons for using CBD (Corroon and Phillips 2018). However, Corroon et al. found that the two main reasons for using CBD was arthritis/joint pain and chronic pain, whereas these ranked number six and seven amongst reasons from our respondents. This result may reflect the younger demographics of our sample compared with Corroon et al.

With few variations, the reasons for use in our study were somewhat similar to the results from another study of 400 patients in New Zealand, who were all prescribed sublingual CBD oil with doses ranging from 40 to 300 mg/day (Gulbransen et al. 2020). This study found that the patients had an increase in overall quality of life, including improved sleep and decreased self-perceived anxiety levels and reduced pain scores.

Route of administration, dosing, and side-effects

Younger respondents were more likely to use novel routes of administration, e.g., vaping or drinking. This trend correlates with data showing that more people have tried vaping (in general) amongst younger age groups (Vaping and e-cigarette use by age U.S 2018). Only 9.3% reported vaping CBD in our sample, compared with 19% in the study by Corroon et al. (Corroon and Phillips 2018). The fast onset of vaporised CBD might explain why inhaled CBD is popular for self-perceived anxiety and stress.

Corroon et al. found a more even distribution between various application methods with the most popular being sublingual CBD (23% vs 72,6% in our study sample). Our approach of recruiting respondents through email databases of non-vape CBD brands may explain why the sublingual administration route is much more frequent in our study than in the American survey.

The bioavailability of CBD varies by route of administration (Millar et al. 2019), but is generally low, between 10 and 31% (Millar et al. 2018). Oral routes have the lowest bioavailability due to first-pass metabolism, whilst inhaled routes have the highest bioavailability (Ohlsson et al. 1986). The bioavailability of sublingual CBD is between 13 and 19% (Mechoulam et al. 2002), and greater than the oral route, thus exerting effects at much lower doses, making it more efficient for users. Investigating plasma levels of low-dose sublingual CBD users, and correlating them to the subjective experience, might give important insights into the optimal dose for treating these low-level mental health problems like self-perceived stress, anxiety, and sleep problems.

Most people were using less than 100 mg (72.9%) per day. Due to the high price and the lack of medical supervision, it is not surprising that non-medical CBD users are taking much lower doses than those used in clinical studies, and those prescribed for specific medical conditions (Davies and Bhattacharyya 2019; Szaflarski et al. 2018). It is important to highlight that 16.8% reported using more than 100 mg per day, and 10.2% did not know how much CBD they were using. The use of high doses CBD is concerning in light of the current FSA recommendation of restricting the dose to 70 mg CBD per day (Cannabidiol (CBD) n.d.), and it stresses the importance of better public information and communication and improved packaging and guidance from brands to consumers.

Amongst our study sample, almost 11% experienced having a dry mouth, most likely indicating levels of THC in the product, as this is a common side effect of THC rather than CBD (Darling and Arendorf 1993; LaFrance et al. 2020). People living outside of the UK had higher odds of experiencing a dry mouth, which might be explained by the different legislation regarding permitted THC content and CBD quality between countries. This differentiation leads to some concerns about product safety, consistency, and ultimately trust amongst CBD consumers. A recent study of 29 CBD products showed that only 11% contained within 10% of the advertised CBD concentration, 55% of the products had traces of controlled substances such as THC (Liebling et al. 2020). There is still a need for external and internal control within the CBD industry to ensure consumer safety is prioritised.

CBD and self-perceived stress

37.5% of respondents reported using CBD for perceived stress, with 92.2% reporting reduced stress levels, making it the third-highest ranking reason for CBD use amongst our sample. Yet, no studies are looking directly at how CBD affects perceived stress levels. This might in part be because stress, apart from post-traumatic stress disorder, is not classified as a disease according to international disease classification (WHO | Burn-out an “occupational phenomenon”: International Classification of Diseases 2019). With more than 12.8 million working days lost because of work-related stress, anxiety, or depression in the UK (Hse 2019), the relationship between CBD and stress is an area of interest for further research. A recent study surveying social media for comments about perceived therapeutic effects of CBD products revealed that the most frequently discussed symptoms, which are not addressed in the research literature, are indeed stress and nausea (Tran and Kavuluru 2020).

CBD and self-perceived anxiety

Self-perceived anxiety was the top-ranked reason for the use of CBD with 42.6% reporting they take CBD for this reason. Of these, 86.5% reported they felt less anxiety. There are biologically plausible reasons for the use of CBD in anxiety. Pharmacological research suggests CBD is a partial 5-HT1a receptor agonist which supports anxiolytic and stress-reducing properties (Russo et al. 2005; Resstel et al. 2009), the activation of which has been associated with anxiolytic, antidepressant, and antipsychotic effects (Zuardi et al. 1993; Bergamaschi et al. 2011; de Faria et al. 2020; Vilazodone for major depressive disorder | MDedge Psychiatry n.d.; Newman-Tancredi and Kleven 2011). CBD also modulates specifically configured GABAA receptors that may be relevant to anxiolytic effects (Bakas et al. 2017; Deshpande et al. 2011). CBD is anxiolytic under experimental conditions in animals, healthy humans and in those with generalised social anxiety disorder (de Faria et al. 2020; Elms et al. 2019; Newman-Tancredi and Kleven 2011) although large clinical trials have not been conducted. Crippa et al. administered an oral dose of 400 mg CBD or placebo, in a double-blind procedure. They found it significantly lowered feelings of anxiety, accompanying changes in limbic areas, in subjects with social anxiety disorder (SAD) (Crippa et al. 2011). Similar results were seen in a small randomised trial using a public speaking test with 600 mg CBD vs placebo (Bergamaschi et al. 2011).

CBD and self-perceived sleep problems

In our survey, sleep was the second-highest-ranking reason for CBD use. We found that 42.5% used CBD to help with sleep, which is higher than for previously published data on adult CBD users, where it was the fifth-highest reason (Corroon and Phillips 2018). It is well-known that a lack of sleep can cause a variety of physical and mental health effects including raised levels of cortisol(Leproult et al. 1997), anxiety (Babson et al. 2010), and mood disturbances (Brazeau et al. 2010), and both short and long duration of sleep is a significant predictor of death (Cappuccio et al. 2010). A recent controlled study of 300 mg CBD found no effect on any sleep indices (Linares et al. 2018), whilst observational and cross-sectional studies showed improvement in sleep outcomes (Corroon and Phillips 2018; Gulbransen et al. 2020). Preclinical studies have shown mixed results with some doses showing an increase in total sleep time (Chagas et al. 2013) and another study indicating that CBD causes increased wakefulness (Murillo-Rodríguez et al. 2006). Thus, the research on CBD and sleep thus far is mixed. However, as sedation and somnolence are regarded as common adverse effects of CBD in a meta-analysis of clinical trials where high doses are used (Chesney et al. 2020), it may not be surprising that CBD at low doses improved sleep quality and duration.

Given the low quality of CBD available on the market, it may be that these individuals were not taking CBD, or that CBD is not efficacious in sleep, so many individuals report better sleep by virtue of the placebo effect, fuelled by marketing (Haney 2020). Another reason may be that CBD is acting on other aspects of stress and anxiety that indirectly reduce sleep problems. Still, in this survey, participants directly attributed improved sleep to CBD. This points to the need for RCTs, as the effect of expectations (i.e. the result of the placebo effect), particularly with compounds advertised as cure-alls (Haney 2020). Suggesting that the placebo effect may contribute to the purported impact of CBD does not reject the potential medical value of CBD, but it does mean we must be wary of the results of observational studies (Haney 2020).

Strengths and limitations

Our measures were retrospective self-reported symptoms, rather than contemporaneous reports or object assessments, and thus prone to recall bias. This approach may lead to over- or under-estimation of benefits and harms. In reporting anxiety symptoms, it should be noted that many anxiety measures are self-reported, and scales are often an accurate measure of anxiety. Stress itself is not often measured, but scales assessing self-reported stress are reliable (Morgan et al. 2014). Regarding sleep problems, our measures do not accurately correspond with objective measures of sleep such as actigraphy (Girschik et al. 2012), which has implications in the epidemiology of sleep, including in the present study. Future research should use validated measures of anxiety, stress, and sleep. However, it should be noted we included responses to gain an insight where CBD may not help, with about 20% responding that CBD did not help with sleep or anxiety and about 10% saying CBD did not help with stress. There is also a risk of selection biases regarding our recruitment method from email databases of current users and social media recruiting. As we had a self-selected sample, we do not represent the general population or even the overall population of CBD users. It is more likely that respondents with a positive experience have responded to this survey, and continue to use CBD. Still, users with a negative experience may have stopped using CBD and therefore were not reached by this survey, which might further contribute to the selection biases.

Conclusion

The survey demonstrated that CBD is used for a wide range of physical and mental health symptoms and improved general health and wellbeing. A majority of the sample surveyed in this study found that CBD helped their symptoms, and they often used doses below 50 mg. Out of the four most common symptoms, three were related to mental health. Self-perceived stress, anxiety, and sleep problems constitute some of society’s biggest health problems, but we lack adequate treatment options. Further research is needed into whether CBD can efficiently and safely help treat these symptoms.

Availability of data and materials

The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD)

There is a significant interest in the development of therapies and other consumer products derived from cannabis and its components, including cannabidiol (CBD). FDA recognizes the potential opportunities that cannabis or cannabis-derived compounds may offer and acknowledges the significant interest in these possibilities. However, 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 is committed to protecting the public health while also taking steps to improve the efficiency of regulatory pathways for the lawful marketing of appropriate cannabis and cannabis-derived products. FDA has a number of resources available that address cannabis and cannabis-derived products, such as CBD, and the agency wants to ensure that consumers and other stakeholders have access to these resources in a centralized location.

Consumer Information

FDA Communications

Regulatory Resources

Questions and Answers

Below are a number of frequently asked questions and answers on this topic.

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1. What are cannabis and marijuana?

A. Cannabis is a plant of the Cannabaceae family and contains more than eighty biologically active chemical compounds. The most commonly known compounds are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Parts of the Cannabis sativa plant have been controlled under the Controlled Substances Act (CSA) since 1970 under the drug class “Marihuana” (commonly referred to as “marijuana”) [21 U.S.C. 802(16)]. “Marihuana” is listed in Schedule I of the CSA due to its high potential for abuse, which is attributable in large part to the psychoactive effects of THC, and the absence of a currently accepted medical use of the plant in the United States.

2. How does the 2018 Farm Bill define hemp? What does it mean for FDA-regulated products?

A. At the federal level, the Agriculture Improvement Act of 2018, Pub. L. 115-334, (the 2018 Farm Bill) was signed into law on Dec. 20, 2018. Among other things, this new law changes certain federal authorities relating to the production and marketing of hemp, defined as “the plant Cannabis sativa L. and any part of that plant, including the seeds thereof and all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers, whether growing or not, with a delta-9 tetrahydrocannabinol concentration of not more than 0.3 percent on a dry weight basis.” These changes include removing hemp from the CSA, which means that cannabis plants and derivatives that contain no more than 0.3 percent THC on a dry weight basis are no longer controlled substances under federal law.

The 2018 Farm Bill, however, explicitly preserved FDA’s authority to regulate products containing cannabis or cannabis-derived compounds under the FD&C Act and section 351 of the Public Health Service Act (PHS Act). FDA treats products containing cannabis or cannabis-derived compounds as it does any other FDA-regulated products — meaning they’re subject to the same authorities and requirements as FDA-regulated products containing any other substance. This is true regardless of whether the cannabis or cannabis-derived compounds are classified as hemp under the 2018 Farm Bill.

3. Has FDA approved any medical products containing cannabis or cannabis-derived compounds such as CBD?

A. To date, the agency has not approved a marketing application for cannabis for the treatment of any disease or condition. FDA has, however, approved one cannabis-derived and three cannabis-related drug products. These approved products are only available with a prescription from a licensed healthcare provider.

FDA has approved Epidiolex, which contains a purified form of the drug substance CBD for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 1 years of age and older. It has also approved Epidiolex for the treatment of seizures associated with tuberous sclerosis complex in patients 1 year of age or older. That means FDA has concluded that this particular drug product is safe and effective for its intended use.

The agency also has approved Marinol and Syndros for therapeutic uses in the United States, including for the treatment of anorexia associated with weight loss in AIDS patients. Marinol and Syndros include the active ingredient dronabinol, a synthetic delta-9- tetrahydrocannabinol (THC) which is considered the psychoactive component of cannabis. Another FDA-approved drug, Cesamet, contains the active ingredient nabilone, which has a chemical structure similar to THC and is synthetically derived.

4. Aside from Epidiolex, are there other CBD drug products that are FDA-approved? What about the products I’ve seen in stores or online?

A. No. There are no other FDA-approved drug products that contain CBD. We are aware that some firms are marketing CBD products to treat diseases or for other therapeutic uses , and we have issued several warning letters to such firms. Under the FD&C Act, any product intended to have a therapeutic or medical use, and any product (other than a food) that is intended to affect the structure or function of the body of humans or animals, is a drug. Drugs must generally either receive premarket approval by FDA through the New Drug Application (NDA) process or conform to a “monograph” for a particular drug category, as established by FDA’s Over-the-Counter (OTC) Drug Review. CBD was not an ingredient considered under the OTC drug review. An unapproved new drug cannot be distributed or sold in interstate commerce.

FDA continues to be concerned at the proliferation of products asserting to contain CBD that are marketed for therapeutic or medical uses although they have not been approved by FDA. Often such products are sold online and are therefore available throughout the country. Selling unapproved products with unsubstantiated therapeutic claims is not only a violation of the law, but also can put patients at risk, as these products have not been proven to be safe or effective. This deceptive marketing of unproven treatments also raises significant public health concerns, because patients and other consumers may be influenced not to use approved therapies to treat serious and even fatal diseases.

Unlike drugs approved by FDA, products that have not been subject to FDA review as part of the drug approval process have not been evaluated as to whether they work, what the proper dosage may be if they do work, how they could interact with other drugs, or whether they have dangerous side effects or other safety concerns.

The agency has and will continue to monitor the marketplace and take action as needed to protect the public health against companies illegally selling cannabis and cannabis-derived products that can put consumers at risk and that are being marketed for therapeutic uses for which they are not approved. At the same time, FDA recognizes the potential therapeutic opportunities that cannabis or cannabis-derived compounds could offer and acknowledges the significant interest in these possibilities. FDA continues to believe that the drug approval process represents the best way to help ensure that safe and effective new medicines, including any drugs derived from cannabis, are available to patients in need of appropriate medical therapy. The Center for Drug Evaluation and Research (CDER) is committed to supporting the development of new drugs, including cannabis and cannabis-derived drugs, through the investigational new drug (IND) and drug approval process (see Question #16).

5. Why hasn’t FDA approved more products containing cannabis or cannabis-derived compounds for medical uses?

A. FDA is aware that unapproved cannabis or cannabis-derived products are being used for the treatment of a number of medical conditions including, for example, AIDS wasting, epilepsy, neuropathic pain, spasticity associated with multiple sclerosis, and cancer and chemotherapy-induced nausea.

To date, FDA has not approved a marketing application for cannabis for the treatment of any disease or condition and thus has not determined that cannabis is safe and effective for any particular disease or condition. The agency has, however, approved one cannabis-derived and three cannabis-related drug products (see Question #2).

FDA relies on applicants and scientific investigators to conduct research. The agency’s role, as laid out in the FD&C Act, is to review data submitted to the FDA in an application for approval to ensure that the drug product meets the statutory standards for approval.

The study of cannabis and cannabis-derived compounds in clinical trial settings is needed to assess the safety and effectiveness of these substances for the treatment of any disease or condition. FDA’s December 2016 Guidance for Industry: Botanical Drug Development provides specific recommendations on submitting INDs for botanical drug products, such as those derived from cannabis, in support of future marketing applications for these products. The agency’s July 2020 draft guidance, Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research Guidance for Industry, highlights quality considerations for anyone wishing to conduct clinical research in this area, particularly those who are less familiar with the FDA.

The FDA will continue to facilitate the work of companies interested in appropriately bringing safe, effective, and quality products to market, including scientifically-based research concerning the medicinal uses of cannabis. Additional information concerning research on the medical use of cannabis is available from the National Institutes of Health, particularly the National Cancer Institute (NCI) and National Institute on Drug Abuse (NIDA).

6. What is FDA’s reaction to states that are allowing cannabis to be sold for medical uses without the FDA’s approval?

A. The FDA is aware that several states have either passed laws that remove state restrictions on the medical use of cannabis and its derivatives or are considering doing so. It is important to conduct medical research into the safety and effectiveness of cannabis products through adequate and well-controlled clinical trials. We welcome the opportunity to talk with states who are considering support for medical research of cannabis and its derivatives, so that we can provide information on Federal and scientific standards.

7. Has the agency received any adverse event reports associated with cannabis use for medical conditions?

A. The agency has received reports of adverse events in patients using cannabis or cannabis-derived products to treat medical conditions. The FDA reviews such reports and will continue to monitor adverse event reports for any safety signals, with a focus on serious adverse effects. Consumers and healthcare providers can report adverse events associated with cannabis or cannabis-derived products via the FDA’s MedWatch reporting system, either online or by phone at 1-800-FDA-1088. For more information, please see the FDA’s webpage on MedWatch.

Information from adverse event reports regarding cannabis use is extremely limited; the FDA primarily receives adverse event reports for approved products. General information on the potential adverse effects of using cannabis and its constituents can come from clinical trials that have been published, as well as from spontaneously reported adverse events sent to the FDA. Additional information about the safety and effectiveness of cannabis and its constituents is needed. Clinical trials of cannabis conducted under an IND application could collect this important information as a part of the drug development process.

8. Is it legal for me to sell CBD products?

A. It depends, among other things, on the intended use of the product and how it is labeled and marketed. Even if a CBD product meets the definition of “hemp” under the 2018 Farm Bill (see Question #2), it still must comply with all other applicable laws, including the FD&C Act. The below questions and answers explain some of the ways that specific parts of the FD&C Act can affect the legality of CBD products.

We are aware that state and local authorities are fielding numerous questions about the legality of CBD. There is ongoing communication with state and local officials to answer questions about requirements under the FD&C Act, to better understand the landscape at the state level, and to otherwise engage with state/local regulatory partners.

9. Can THC or CBD products be sold as dietary supplements?

A. No. Based on available evidence, FDA has concluded that THC and CBD products are excluded from the dietary supplement definition under section 201(ff)(3)(B) of the FD&C Act [21 U.S.C. § 321(ff)(3)(B)]. Under that provision, if a substance (such as THC or CBD) is an active ingredient in a drug product that has been approved under section 505 of the FD&C Act [21 U.S.C. § 355], or has been authorized for investigation as a new drug for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public, then products containing that substance are excluded from the definition of a dietary supplement. FDA considers a substance to be “authorized for investigation as a new drug” if it is the subject of an Investigational New Drug application (IND) that has gone into effect. Under FDA’s regulations (21 CFR 312.2), unless a clinical investigation meets the limited criteria in that regulation, an IND is required for all clinical investigations of products that are subject to section 505 of the FD&C Act.

There is an exception to section 201(ff)(3)(B) if the substance was “marketed as” a dietary supplement or as a conventional food before the drug was approved or before the new drug investigations were authorized, as applicable. However, based on available evidence, FDA has concluded that this is not the case for THC or CBD.

FDA is not aware of any evidence that would call into question its current conclusions that THC and CBD products are excluded from the dietary supplement definition under section 201(ff)(3)(B) of the FD&C Act. Interested parties may present the agency with any evidence that they think has bearing on this issue. Our continuing review of information that has been submitted thus far has not caused us to change our conclusions.

When a substance is excluded from the dietary supplement definition under section 201(ff)(3)(B) of the FD&C Act, the exclusion applies unless FDA, in the agency’s discretion, has issued a regulation, after notice and comment, finding that the article would be lawful under the FD&C Act. To date, no such regulation has been issued for any substance.

Ingredients that are derived from parts of the cannabis plant that do not contain THC or CBD might fall outside the scope of this exclusion, and therefore might be able to be marketed as dietary supplements. However, all products marketed as dietary supplements must comply with all applicable laws and regulations governing dietary supplement products. For example, manufacturers and distributors who wish to market dietary supplements that contain “new dietary ingredients” (i.e., dietary ingredients that were not marketed in the United States in a dietary supplement before October 15, 1994) generally must notify FDA about these ingredients (see section 413(d) of the FD&C Act [21 U.S.C. § 350b(d)]). Generally, the notification must include information demonstrating that a dietary supplement containing the new dietary ingredient will reasonably be expected to be safe under the conditions of use recommended or suggested in the labeling. A dietary supplement is adulterated if it contains a new dietary ingredient for which there is inadequate information to provide reasonable assurance that the ingredient does not present a significant or unreasonable risk of illness or injury (see section 402(f)(1)(B) of the FD&C Act [21 U.S.C. 342(f)(1)(B)]).

Numerous other legal requirements apply to dietary supplement products, including requirements relating to Current Good Manufacturing Practices (CGMPs) and labeling. Information about these requirements, and about FDA requirements across all product areas, can be found on FDA’s website.

10. Is it legal, in interstate commerce, to sell a food (including any animal food or feed) to which THC or CBD has been added?

A. No. Under section 301(ll) of the FD&C Act [21 U.S.C. § 331(ll)], it is prohibited to introduce or deliver for introduction into interstate commerce any food (including any animal food or feed) to which has been added a substance which is an active ingredient in a drug product that has been approved under section 505 of the FD&C Act [21 U.S.C. § 355], or a drug for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public. There are exceptions, including when the drug was marketed in food before the drug was approved or before the substantial clinical investigations involving the drug had been instituted or, in the case of animal feed, that the drug is a new animal drug approved for use in feed and used according to the approved labeling. However, based on available evidence, FDA has concluded that none of these is the case for THC or CBD. FDA has therefore concluded that it is a prohibited act to introduce or deliver for introduction into interstate commerce any food (including any animal food or feed) to which THC or CBD has been added. FDA is not aware of any evidence that would call into question these conclusions. Interested parties may present the agency with any evidence that they think has bearing on this issue. Our continuing review of information that has been submitted thus far has not caused us to change our conclusions.

When this statutory prohibition applies to a substance, it prohibits the introduction into interstate commerce of any food to which the substance has been added unless FDA, in the agency’s discretion, has issued a regulation approving the use of the substance in the food (section 301(ll)(2) of the FD&C Act [21 U.S.C. § 331(ll)(2)]). To date, no such regulation has been issued for any substance.

Ingredients that are derived from parts of the cannabis plant that do not contain THC or CBD might fall outside the scope of 301(ll), and therefore might be able to be added to food. For example, as discussed in Question #12, certain hemp seed ingredients can be legally marketed in human food. However, all food ingredients must comply with all applicable laws and regulations. For example, by statute, any substance intentionally added to food is a food additive, and therefore subject to premarket review and approval by FDA, unless the substance is generally recognized as safe (GRAS) by qualified experts under the conditions of its intended use, or the use of the substance is otherwise excepted from the definition of a food additive (sections 201(s) and 409 of the FD&C Act [21 U.S.C. §§ 321(s) and 348]). Aside from the three hemp seed ingredients mentioned in Question #12, no other cannabis or cannabis-derived ingredients have been the subject of a food additive petition, an evaluated GRAS notification, or have otherwise been approved for use in food by FDA. Food companies that wish to use cannabis or cannabis-derived ingredients in their foods are subject to the relevant laws and regulations that govern all food products, including those that relate to the food additive and GRAS processes.

11. In making the two previous determinations about THC, why did FDA conclude that THC is an active ingredient in a drug product that has been approved under section 505 of the FD&C Act? In making the two previous determinations about CBD, why did FDA determine that substantial clinical investigations have been authorized for and/or instituted, and that the existence of such investigations has been made public?

A. THC (dronabinol) is the active ingredient in the approved drug products, Marinol capsules (and generics) and Syndros oral solution. CBD is the active ingredient in the approved drug product, Epidiolex.

The existence of substantial clinical investigations regarding THC and CBD have been made public. For example, two such substantial clinical investigations include GW Pharmaceuticals’ investigations regarding Sativex. (See Sativex Commences US Phase II/III Clinical Trial in Cancer Pain )

12. Can hulled hemp seed, hemp seed protein powder, and hemp seed oil be used in human food?

A. In December 2018, FDA completed its evaluation of three generally recognized as safe (GRAS) notices for the following hemp seed-derived food ingredients: hulled hemp seed, hemp seed protein powder, and hemp seed oil. FDA had no questions regarding the company’s conclusion that the use of such products as described in the notices is safe. Therefore, these products can be legally marketed in human foods for the uses described in the notices, provided they comply with all other requirements. These GRAS notices related only to the use of these ingredients in human food. To date, FDA has not received any GRAS notices for the use of hemp-derived ingredients in animal food (see Question #25).

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Hemp seeds are the seeds of the Cannabis sativa plant. The seeds of the plant do not naturally contain THC or CBD. The hemp seed-derived ingredients that are the subject of these GRAS notices contain only trace amounts of THC and CBD, which the seeds may pick up during harvesting and processing when they are in contact with other parts of the plant. Consumption of these hemp seed-derived ingredients is not capable of making consumers “high.”

The GRAS conclusions can apply to ingredients for human food marketed by other companies, if they are manufactured in a way that is consistent with the notices and they meet the listed specifications. Some of the intended uses for these ingredients include adding them as source of protein, carbohydrates, oil, and other nutrients to beverages (juices, smoothies, protein drinks, plant-based alternatives to dairy products), soups, dips, spreads, sauces, dressings, plant-based alternatives to meat products, desserts, baked goods, cereals, snacks and nutrition bars. Products that contain any of these hemp seed-derived ingredients must declare them by name on the ingredient list.

These GRAS conclusions do not affect the FDA’s position on the addition of CBD and THC to food.

13. What is FDA’s position on cannabis and cannabis-derived ingredients in cosmetics?

A. A cosmetic is defined in 201(i) as “(1) articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance, and (2) articles intended for use as a component of any such articles; except that such term shall not include soap.”

Under the FD&C Act, cosmetic products and ingredients are not subject to premarket approval by FDA, except for most color additives. Certain cosmetic ingredients are prohibited or restricted by regulation, but currently that is not the case for any cannabis or cannabis-derived ingredients. Ingredients not specifically addressed by regulation must nonetheless comply with all applicable requirements, and no ingredient – including a cannabis or cannabis-derived ingredient – can be used in a cosmetic if it causes the product to be adulterated or misbranded in any way. A cosmetic generally is adulterated if it bears or contains any poisonous or deleterious substance which may render it injurious to users under the conditions of use prescribed in the labeling, or under such conditions of use as are customary or usual (section 601(a) of the FD&C Act [21 U.S.C. § 361(a)]).

If a product is intended to affect the structure or function of the body, or to diagnose, cure, mitigate, treat or prevent disease, it is a drug, or possibly both a cosmetic and a drug, even if it affects the appearance. (See Question #3 for more information about drugs.)

FDA can take action if it has information that an ingredient or cosmetic product is unsafe to consumers. Consumers can report adverse events associated with cosmetic products via the FDA’s MedWatch reporting system, either online or by phone at 1-800-FDA-1088, or by contacting your nearest FDA district office consumer complaint coordinator. For more information, please see the FDA’s webpage on how to report a cosmetic-related complaint.

14. Will FDA take action against cannabis or cannabis-related products that are in violation of the FD&C Act?

A. The FDA has sent warning letters in the past to companies illegally selling CBD products that claimed to prevent, diagnose, treat, or cure serious diseases, such as cancer. Some of these products were in further violation of the FD&C Act because they were marketed as dietary supplements or because they involved the addition of CBD to food.

When a product is in violation of the FD&C Act, FDA considers many factors in deciding whether or not to initiate an enforcement action. Those factors include, among other things, agency resources and the threat to the public health. FDA also may consult with its federal and state partners in making decisions about whether to initiate a federal enforcement action.

15. Can I import or export cannabis-containing or cannabis-derived products?

A. General information about the import/export of drug products regulated by FDA can be found online here. The Drug Enforcement Administration (DEA) is the federal agency responsible for enforcing the controlled substance laws and regulations in the U.S. and, as such, should be consulted with respect to any regulations/requirements they may have regarding the import or export of products containing cannabis. Please see here for information about importing or exporting food ingredients.

Regarding imports, if it appears that an article is adulterated, misbranded, in violation of section 505 of the FD&C Act, or prohibited from introduction or delivery for introduction into interstate commerce under section 301(ll) of the FD&C Act, such article will be refused admission (see section 801(a)(3) of the FD&C Act [21 U.S.C. § 381(a)(3)]).

Research and Expanded Access

16. What is FDA’s role when it comes to the investigation of cannabis and cannabis-derived products for medical use?

A. To conduct clinical research that can lead to an approved new drug, including research using materials from plants such as cannabis, researchers need to work with the FDA and submit an IND application to the Center for Drug Evaluation and Research (CDER). The IND application process gives researchers a path to follow that includes regular interactions with the FDA to support efficient drug development while protecting the patients who are enrolled in the trials. For research for use as an animal drug product, researchers would establish an investigational new animal drug (INAD) file with the Center for Veterinary Medicine to conduct their research, rather than an IND with CDER.

As discussed above (see Question #2), the 2018 Farm Bill removed hemp from the CSA. This change may streamline the process for researchers to study cannabis and its derivatives, including CBD, that fall under the definition of hemp, which could speed the development of new drugs.

As also discussed above (see Question #5) the agency also issued a draft guidance in July 2020, Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research Guidance for Industry, for individuals considering clinical research in this area.

Conducting clinical research using cannabis-related substances that are scheduled by the DEA often involves interactions with several federal agencies. This includes: a registration administered by the DEA; obtaining the cannabis for research from NIDA, within the National Institutes of Health, or another DEA-registered source; and review by the FDA of the IND or INAD application and research protocol. Additionally:

  • For a Schedule I controlled substance under the CSA, DEA provides researchers with investigator and protocol registrations and has Schedule I-level security requirements at the site cannabis will be studied.
  • NIDA provides research-grade cannabis for scientific study. The agency is responsible for overseeing the cultivation of cannabis for medical research and has contracted with the University of Mississippi to grow cannabis for research at a secure facility. Cannabis of varying potencies and compositions is available. DEA also may allow additional growers to register with the DEA to produce and distribute cannabis for research purposes.
  • Researchers work with the FDA and submit an IND application to the appropriate division in the Office of New Drugs in CDER depending on the therapeutic indication. Based on the results obtained in studies conducted at the IND stage, sponsors may submit a marketing application for formal approval of the drug.

17. Does the FDA object to the clinical investigation of cannabis for medical use?

A. No. The FDA believes that scientifically valid research conducted under an IND application is the best way to determine what patients could benefit from the use of drugs derived from cannabis. The FDA supports the conduct of that research by:

  1. Providing information on the process needed to conduct clinical research using cannabis.
  2. Providing information on the specific requirements needed to develop a drug that is derived from a plant such as cannabis. In December 2016, the FDA updated its Guidance for Industry: Botanical Drug Development, which provides sponsors with guidance on submitting IND applications for botanical drug products.
  3. Providing specific support for investigators interested in conducting clinical research using cannabis and its constituents as a part of the IND process through meetings and regular interactions throughout the drug development process.
  4. Providing general support to investigators to help them understand and follow the procedures to conduct clinical research through the FDA Center for Drug Evaluation and Research’s Small Business and Industry Assistance group.

18. How can patients gain access to cannabis or cannabis-derived products for medical use through expanded access?

A. Expanded access is a potential pathway for a patient with a serious or life-threatening disease or condition to try an investigational medical product (drug, biologic, or medical device) for treatment outside of clinical trials when there are no comparable or satisfactory therapies available. Manufacturers may be able to make investigational drugs available to individual patients in certain circumstances through expanded access, as described in the FD&C Act and implementing regulations.

19. Can patients gain access to cannabis or cannabis-derived products for medical use through Right to Try?

A. Information for patients on Right to Try (RTT) is available on our website. RTT is designed to facilitate access to certain investigational drugs through direct interactions between patients, their physicians and drug sponsors – FDA is not involved in these decisions. Sponsors developing drugs for life-threatening conditions are responsible for determining whether to make their products available to patients who qualify for access under RTT. If you are interested in RTT, you should discuss this pathway with your licensed physician. Companies who develop drugs and biologics, also known as sponsors, can provide information about whether their drug/biologic is considered an eligible investigational drug under RTT and if they are able to provide the drug/biologic under the RTT Act.

Children and Pregnant/Lactating Women

20. Does the FDA have concerns about administering a cannabis product to children?

A. We understand that parents are trying to find treatments for their children’s medical conditions. However, the use of untested drugs can have unpredictable and unintended consequences. Caregivers and patients can be confident that FDA-approved drugs have been carefully evaluated for safety, efficacy, and quality, and are monitored by the FDA once they are on the market. The FDA continues to support sound, scientifically-based research into the medicinal uses of drug products containing cannabis or cannabis-derived compounds, and will continue to work with companies interested in bringing safe, effective, and quality products to market. With the exception of Epidiolex, Marinol, and Syndros, no product containing cannabis or cannabis-derived compounds (either plant-based or synthetic) has been approved as safe and effective for use in any patient population, whether pediatric or adult.

21. Does the FDA have concerns about administering a cannabis product to pregnant and lactating women?

A. The FDA is aware that there are potential adverse health effects with use of cannabis products containing THC in pregnant or lactating women. Published scientific literature reports potential adverse effects of cannabis use in pregnant women, including fetal growth restriction, low birth weight, preterm birth, small-for-gestational age, neonatal intensive care unit (NICU) admission, and stillbirth. [1, 2, 3] Based on published animal research, there are also concerns that use of cannabis during pregnancy may negatively impact fetal brain development. [4, 5, 6 ] The American College of Obstetricians and Gynecologists (ACOG) recommends that women who are pregnant or contemplating pregnancy should be encouraged to discontinue cannabis use. In addition, ACOG notes that there are insufficient data to evaluate the effects of cannabis use on breastfed infants; therefore, cannabis use is discouraged when breastfeeding. [7] Pregnant and lactating women should talk with a health care provider about the potential adverse health effects of cannabis use.

22. What does the FDA think about making CBD available to children with epilepsy?

A. The FDA has approved Epidiolex, which contains a purified form of the drug substance CBD, for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 1 years of age and older. It has also approved Epidiolex for the treatment of seizures associated with tuberous sclerosis complex in patients 1 year of age or older. That means the FDA has concluded that this particular drug product is safe and effective for its intended use. Controlled clinical trials testing the safety and efficacy of a drug, along with careful review through the FDA’s drug approval process, is the most appropriate way to bring cannabis-derived treatments to patients. Because of the adequate and well-controlled clinical studies that supported this approval, and the assurance of manufacturing quality standards, prescribers can have confidence in the drug’s uniform strength and consistent delivery that support appropriate dosing needed for treating patients with these complex and serious epilepsy syndromes.

23. What should I do if my child eats something containing cannabis?

A. With the exception of products such as the hemp seed ingredients discussed in Question #12, which have been evaluated for safety, it is important to protect children from accidental ingestion of cannabis and cannabis-containing products. FDA recommends that these products are kept out of reach of children to reduce the risk of accidental ingestion. If the parent or caregiver has a reasonable suspicion that the child accidentally ingested products containing cannabis, the child should be taken to a physician or emergency department, especially if the child acts in an unusual way or is/feels sick.

Pets and other Animals

24. I’ve seen cannabis products being marketed for pets. Are they safe?

A. FDA is aware of some cannabis products being marketed as animal health products. We want to stress that FDA has not approved cannabis for any use in animals, and the agency cannot ensure the safety or effectiveness of these products. For these reasons, FDA cautions pet-owners against the use of such products and recommends that you talk with your veterinarian about appropriate treatment options for your pet.

Signs that your pet may be suffering adverse effects from ingesting cannabis may include lethargy, depression, heavy drooling, vomiting, agitation, tremors, and convulsions.

If you have concerns that your pet is suffering adverse effects from ingesting cannabis or any substance containing cannabis, consult your veterinarian, local animal emergency hospital or an animal poison control center immediately.

While the agency is aware of reports of pets consuming various forms of cannabis, to date, FDA has not directly received any reports of adverse events associated with animals given cannabis products. However, adverse events from accidental ingestion are well-documented in scientific literature. If you feel your animal has suffered from ingesting cannabis, we encourage you to report the adverse event to the FDA. Please visit Reporting Information about Animal Drugs and Devices to learn more about how to report an adverse event related to an animal drug or for how to report an adverse event or problem with a pet food.

25. Can hemp be added to animal food?

A. All ingredients in animal food must be the subject of an approved food additive petition or generally recognized as safe (GRAS) for their intended use in the intended species. If an animal food contains an ingredient that is not the subject of an approved food additive petition or GRAS for its intended use in the intended species, that animal food would be adulterated under section 402(a)(2)(C)(i) of the FD&C Act [21 U.S.C. § 342(a)(2)(C)(i)]. In coordination with state feed control officials, CVM also recognizes ingredients listed in the Official Publication (OP) of the Association of American Feed Control Officials (AAFCO) as being acceptable for use in animal food. At this time, there are no approved food additive petitions or ingredient definitions listed in the AAFCO OP for any substances derived from hemp, and we are unaware of any GRAS conclusions regarding the use of any substances derived from hemp in animal food. Learn more about animal food ingredient submissions here.

With respect to products labeled to contain “hemp” that may also contain THC or CBD, as mentioned above it is a prohibited act under section 301(ll) of the FD&C Act to introduce or deliver for introduction into interstate commerce any animal food to which THC or CBD has been added.

26. Can approved human drugs containing CBD or synthetic THC be used extralabel in animals?

A. The Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA), permits veterinarians to prescribe extralabel uses of approved human and animal drugs for animals under certain conditions. Extralabel use must comply with all the provisions of AMDUCA and its implementing regulation at 21 CFR § 530. Among other limitations, these provisions allow extralabel use of a drug only on the lawful order of a licensed veterinarian in the context of a valid veterinarian-client-patient relationship and only in circumstances when the health of an animal is threatened or suffering, or death may result from failure to treat.

In addition, under 21 CFR 530.20, extralabel use of an approved human drug in a food-producing animal is not permitted if an animal drug approved for use in food-producing animals can be used in an extralabel manner for the use. In addition, under 21 CFR 530.20(b)(2), if scientific information on the human food safety aspect of the use of the approved human drug in food-producing animals is not available, the veterinarian must take appropriate measures to ensure that the animal and its food products will not enter the human food supply.
For more information on extralabel use of FDA approved drugs in animals, see Extralabel Use of FDA Approved Drugs In Animals.

[1] Gray, et al. Identifying Prenatal Cannabis Exposure and Effects of Concurrent Tobacco Exposure on Neonatal Growth. Clinical Chemistry. 2010; 56(9): 1442-1450.

[2] Gunn, et al. Prenatal Exposure to cannabis and maternal and child health outcomes: a systematic review and meta-analysis. BMJ Open. 2016; 6:e009986.

[3] Hayatbakhsh, et al. Birth Outcomes associated with cannabis use before and during pregnancy. Pediatric Research. 2012; 71 (2): 215-219.

[4] Silva, et al. Prenatal tetrahydrocannabinol (THC) alters cognitive function and amphetamine response from weaning to adulthood in the rat. Neurotoxicol and Teratol 2012; 34(1): 63-71.

[5] Trezza, et al. Effects of perinatal exposure to delta-9-tetrahydrocannabinol on the emotional reactivity of the offspring: a longitudinal behavioral study in Wistar rats. Psychopharmacology (Berl) 2008; 198(4): 529-537.

[6] Campolongo, et al. Perinatal exposure to delta-9-tetrahydrocannabinol causes enduring cognitive deficits associated with alteration of cortical gene expression and neurotransmission in rats. Addict Biol 2007; 12(3-4): 485–495.

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