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Abstract

Introduction:

Cannabinol (CBN) was discovered in 1896, but its commercial use did not take off until recently, and there have been few studies on its use, safety, and efficacy. Japan has strict regulations on cannabis, but CBN products have been legally distributed since late 2020. It is possible to speculate that these products are used for different purposes than in places such as some states of the United States where cannabis is legal, but no academic research has been conducted to date.

Objective:

To conduct a quantitative evaluation of the use, self-assessed efficacy, dependence, and adverse events of CBN products in Japan.

Methods:

An online questionnaire was created for CBN users, and a request for responses was disseminated via social networking service.

Results:

In total, 515 valid responses were obtained. Regarding the purpose of use, 174 (33.8%) were medical, 136 (26.4%) were recreational, and 199 (38.6%) were both. The most common medical purposes were sleeping disorder (N = 325), anxiety (N = 186), and depression (N = 181). Statistically significant subjective symptom improvement was observed before and after CBN use for sleeping disorder, anxiety, and chronic pain. In addition, 82.7% of users reported improved physical quality of life (QOL), 84.1% reported improved mental QOL, and 55.4% reported improved social QOL. The rate of adverse events experienced was 9.9%, and 5.2% were classified as substance use disorders.

Conclusions:

CBN is used in Japan primarily for self-mental-health care applications, not on a prescription basis, and contributes to improved QOL. The experience rate of adverse events was 10%, the severity was mild, and the dependence was considered milder than that of cannabis.

Introduction

Cannabinol (CBN) is a type of cannabinoid (CB), a group of chemical compounds that is specifically contained in Cannabis sativa L. Its discovery was first documented in 1896, and its structural formula was identified in 1932.^1,2 At the time of its discovery, CBN was considered to be the primary psychoactive component of cannabis. However, following the identification of delta-9-tetrahydrocannabinol (Δ9-THC) as the predominant psychoactive substance in cannabis in 1964, the social attention toward CBN decreased.^1,2 In the synthetic pathway, CBN is produced when Δ9-THC undergoes oxidation.²

CBN has approximately a quarter of the agonistic activity of tetrahydrocannabinol (THC at CB1 receptors.³ However, it is typically classified as a CB with no psychoactive effects. In the 1970s, safety tests were conducted on healthy subjects. In the basic research, it showed potential medical benefits such as analgesic, sedative, antibacterial, anti-inflammatory, anticonvulsant, and appetite-enhancing effects.^4–9 In recent years, clinical studies have been conducted for sleeping disorders, using various regimens containing CBN.^10–15

In the United States, the market for CBN products as dietary supplements is expanding after the legalization of hemp at the end of 2018. These products are primarily sold as supplements to improve sleep. A previous study conducted in the United States showed that the usage rate of CBN within the past year was 4.4%.¹⁶ Additionally, CBN is often present in trace amounts in full-spectrum cannabidiol (CBD) products.

Cannabis is currently regulated by the Cannabis Control Act (CCA) in Japan. The use of cannabis for medical purposes is prohibited under the CCA, so it is not possible to use cannabis flowers or extracts made from them. In addition, synthetic THC is regulated as a narcotic, so it is also not possible to use this. However, certain parts of the plant, such as seeds and mature stalks, are excluded from the definition of cannabis.¹⁷ This is due to the fact that, at the time the legislation was enacted in 1948, hemp was being cultivated for the purpose of extracting fiber and for food.¹⁸ This exception has become a legal loophole, and CBD products can be imported if they are accompanied by documents that declare they are THC-free and made from mature stalks or seeds. As a result, CBD products are legal, but there is no legal framework for quality control. CBD products containing trace amounts of CBN have also been legally distributed since 2013. Furthermore, products containing CBN as the primary ingredient appeared on the market in 2020. (Note: The CCA referred to in this paragraph is current as of October 2024, but a new regulation is scheduled to be enforced on December 12, 2024.)

In Japan, CBs that act on the CB1 receptors and cause psychoactive effects are regulated as designated drugs. However, CBN was not subject to regulation as of February 2024, when this survey was conducted. It is therefore possible that CBN might be used in Japan as a substitute for THC-containing products, which is a different use from that in the United States. To address this issue, we conducted an online cross-sectional survey.

Subjects and Methods

Methods

An anonymous online questionnaire was created using Google Form to collect data on CBN use. Responses were solicited through the social networking service accounts operated by the lead author, specifically Facebook, Twitter (X), Instagram, and YouTube. The data were collected between February 8 and February 22, 2024. Responses were given using multiple-choice questions, and in instances where no option was applicable, free-form responses were allowed. The questions were based on the findings of a preliminary survey conducted by Masataka and Nagamine.¹⁹ The data collected included: 1)

Factors related to patient background

Age, gender, place of residence, educational background, household income, presence or absence of a medical history, medication history, and regular hospital visits. 2)

Factors related to the intake of CB products

Experience with CBN use, type of product used, dosage, ingredients contained in the product, frequency of consumption, duration of use, purpose of use, and the amount spent on the product. 3)

Factors related to effectiveness

In this survey, the purpose of using CBN was broadly divided into (1) medical purposes and (2) recreational purposes. Within the category of medical purposes, the three conditions that were most frequently mentioned in the preliminary survey—sleeping disorder, anxiety, and chronic pain—were evaluated using the NRS to assess the subjective symptoms before and after the start of CBN product use.

For recreational purposes, more specific multiple-choice questions were asked about situations in which CBN products were used. In addition, all users were asked to self-evaluate on a 5-point scale.What kind of changes had occurred in their quality of life (QOL) before and after starting to use CBN, dividing it into three categories: physical health, psychological and mental health, and social health. 4)

Factors related to adverse events

Undesired reactions associated with CBN use were defined as side effects, and users were asked to answer questions about the symptoms that occurred and their severity using a multiple-choice format. The severity was defined as follows: Very mild: no need for cessation or reduction of use; mild: cessation or reduction of use resulted in rapid disappearance of symptoms; moderate: consultation with a medical institution was required; and severe: hospitalization or some form of medical intervention was required.

Additionally, to assess the addictive properties of CBN products, respondents were asked to self-check whether they met the criteria for substance use disorder according to Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-V). (For details, please refer to the survey form in Supplementary Appendix S1.)

The data that support the findings of this study are not openly available due to reasons of sensitivity and are only available from the lead author upon a reasonable request.

Subjects

The following respondents were excluded from the analysis:

(1) Those who did not consent to the survey. (2) Those who did not use CBN products multiple times in the past year. (3) Those who indicated it was their second or subsequent response. (4) Those who indicated that they currently reside outside of Japan. When responding to the survey, any information that could be used to identify individuals, such as names, email addresses, or IP addresses, was not collected. This study was conducted in accordance with the Helsinki Declaration and was reviewed and approved by the Ethics Committee of the Japanese Clinical Association of Cannabinoids (Approval No. 0007, approved on January 27, 2024).

Statistical analysis

Simple tabulation was performed for each survey item. For the p-value of the degree of improvement in subjective symptoms before and after the use of CBN, a two-tailed test of the available t-test was used. For the significance level, a p-value of <0.05 was defined as significant.

Results

In total, 547 responses were received during the survey period, of which 515 were eligible for analysis.

Background of respondents

The background factors of the respondents are summarized in Table 1. There were 391 males (75.9%) and 124 females (24.1%). The ages of the users ranged from 6 to 87 years old, with an average age of 37.4 years old (standard deviation: 10.8). By gender, the average age was 35.9 years (±10.2) for males and 41.8 years (±11.5) for females. The average weight of all participants was 65.0 kg (±13.8 kg), with males weighing 68.0 kg (±13.3 kg) and females weighing 55.3 kg (±10.4 kg). In total, 38.6% of respondents had diagnosed conditions, 40.6% were visiting hospitals regularly, and 35.9% used prescription drugs. The most common illnesses (mentioned by 10% or more of respondents) were mental illness (N = 91, 45.7%), sleep disorders (N = 70, 35.2%), chronic pain (N = 35, 17.6%), skin disease (N = 32, 16.1%), asthma (N = 31, 15.6%), headache (N=23, 11.6%), and hypertension (N = 21, 10.6%).

Table 1.

Demographic Characteristics of 515 Cannabinol Users

	N (total n = 515)	Valid percentage (%)
Sex (% M)	391	75.9
Mean age	37.4 (±10.8)
Educational background
Underage or currently in school	25	4.8
Middle school	41	7.9
High school	143	27.7
Vocational school and college	109	21.1
University	166	32.1
Postgraduate or higher	32	6.2
Household income
Less than 3 million yen	83	16.1
3∼5 million yen	139	27.0
5∼7 million yen	110	21.4
7∼10 million yen	69	13.4
More than 10 million yen	66	12.8
I don’t know/no comments	48	9.3
Medical background
having a medical diagnosis (% yes)	199	38.6
Seeing doctor regularly (% yes)	209	40.6
Taking pharmaceutical drug (% yes)	185	35.9

Details of CBN use

Details of the respondents’ CBN use are summarized in Table 2. In total, 135 people (26.2%) were able to answer the question about the amount of CBN they used per day. The average was 184 mg (±275 mg) overall, 215 mg (±304 mg) for men, and 116 mg (±181 mg) for women. When divided by average body weight, the average was 2.83 mg/kg/day overall, 3.16 mg/kg/day for men, and 2.10 mg/kg/day for women. Among the respondents, the average amount used by the group (n = 29) that answered that they only used it for recreational purposes was 255.0 mg (±292.1), and the average amount used by the group (n = 49) that answered that they only used it for health care purposes was 131.2 mg (±317.0). There was no statistically significant difference between the two groups (p = 0.0905). Regarding the other ingredients contained in the CBN products they used, only 92 people (17.9%) said that it was only CBN, while 392 people (76.1%) said that the products contained other CBs. Thirty-one people (6.0%) answered that they did not know. When asked if they used other CBs or supplements, 76.5% of respondents answered that they did. The breakdown was 92% CBD, 73.5% cannabigerol (CBG), 56.3% new semisynthetic CBs, and 16.6% illegal cannabis products. (Multiple answers allowed.)

Table 2.

Details of CBN Use

	N (total n = 515)	Valid percentage (%)
Currently use CBN (yes)	460	89.3
Types of CBN product used
Vape/CBN herb	407	79.0
Oil	127	24.7
Topical	24	4.7
Edible/drink	238	46.2
Capsule/pill	31	6.0
Others	19	3.7
Product component
Isolate	92	17.9
Contain other cannabinoids	392	76.1
Not aware	31	6.0
Frequency
Less than once a week	75	14.6
Less than once a day	160	31.1
Once a day	155	30.1
Twice a day	54	10.5
Three times a day	24	4.7
More than three times a day	47	9.1
Duration of CBN use
Less than 1 month	26	5.0
1∼3 months	82	15.9
3∼6 months	89	17.3
6∼12 months	88	17.1
12∼24 months	146	28.3
More than 24 months	84	16.3
The amount of money spent per month
<5000 yen	187	36.3
>5000 yen, <10,000 yen	182	35.3
>10,000 yen, <15,000 yen	65	12.6
>15,000 yen, <20,000 yen	31	6.0
>20,000 yen, <25,000 yen	9	1.7
>25,000 yen, <30,000 yen	4	0.8
>30,000 yen	11	2.1
I don’t know/no comments	26	5.0

For the type of CBN product, respondents were allowed to select more than one option. For the product components, respondents were instructed to answer about the product they use most frequently.

CBN = cannabinol.

Purpose of CBN use

In total, 174 people (33.8%) said they used it in the hope of improving their health in some way, 136 people (26.4%) said they used it for recreational purposes, 199 people (38.6%) said it was both, and 6 people (1.2%) said it was neither. The details of the health-related uses are shown in Figure 1.

FIG. 1.

Respondents who selected “expecting health improvements” as the reason for using CBN were asked to select the diagnosis or symptom that was applicable to them. Participants were allowed to select more than one option.

Regarding the recreational use of CBN, 23 people (6.9%) said they used it to lift their mood, 305 people (91.0%) said they used it to relax, and 7 people (2.1%) said it was hard to say either way. The most common situations in which respondents used CBN were in order of frequency, sleeping and relaxing (282 respondents), listening to music or watching videos (221 respondents), eating and drinking (125 respondents), exercising (75 respondents), outdoor events (72 respondents), and other (21 respondents).

The degree of improvement in subjective symptoms before and after the introduction of CBN for sleep, anxiety, and chronic pain

Participants were instructed to self-evaluate the severity of their symptoms before and after the start of CBN use for the three conditions that were expected to be the most common purpose of CBN use—sleep, anxiety, and chronic pain. A statistical evaluation was conducted to determine whether there was a significant difference in the average scores (Table 3).

Table 3.

Improvement of Symptoms Before and After CBN Use

		Mean ± SD	p
Severity of sleeping disorder before the introduction of CBN	n = 338	6.25 ± 2.49	<0.001
Severity of sleeping disorder after the introduction of CBN	n = 338	2.59 ± 2.22	<0.001
Severity of anxiety before the introduction of CBN	n = 264	6.35 ± 2.66	<0.001
Severity of anxiety after the introduction of CBN	n = 264	2.80 ± 2.13	<0.001
Severity of pain before the introduction of CBN	n = 189	5.08 ± 3.30	<0.001
Severity of pain after the introduction of CBN	n = 189	2.30 ± 2.11	<0.001

In all three conditions, there was a statistically significant improvement in the participants’ subjective assessment before and after the introduction of CBN.

Effects on QOL

Table 4 presents a summary of the effects of CBN on the QOL of users. Respondents were asked to self-evaluate their physical, mental, and social well-being, and 426 respondents (82.7%) indicated some improvement in their physical QOL, 433 respondents (84.1%) in their mental QOL, and 285 respondents (55.4%) reported some improvement in social QOL. Three respondents (0.58%) indicated that their mental QOL declined following the introduction of CBN, while two respondents (0.39%) reported a similar deterioration in their social QOL.

Table 4.

Changes in Quality of Life Before and After CBN Intake

	N (total n = 515)	Valid percentage (%)
Physical functioning QOL
Much improved	177	34.4
Moderately improved	249	48.3
No change	88	17.1
Moderately deteriorated	1	0.2
Much deteriorated	0	0
Mental health QOL
Much improved	170	33.0
Moderately improved	263	51.1
No change	79	15.3
Moderately deteriorated	3	0.6
Much deteriorated	0	0
Social functioning QOL
Much improved	110	21.4
Moderately improved	175	34.0
No change	228	44.3
Moderately deteriorated	2	0.4
Much deteriorated	0	0

QOL = quality of life.

Adverse events and dependence

Fifty-one respondents (9.9%) reported symptoms that they suspected were related to the use of CBN. The details are summarized in Table 5. In terms of severity, 58.8% of the respondents did not require discontinuation or reduction of CBN, 39.2% indicated the symptoms improved quickly with discontinuation or reduction of CBN, 1 user required a hospital visit in addition to discontinuation, and no users required hospitalization or medical intervention. In addition, 27 users (5.2%) were found to have a possible substance use disorder (responding that they met two or more of the 11 diagnostic criteria).

Table 5.

Adverse Events and Severity of CBN

	Total N (n = 51)	Very mild	Mild	Moderate
Intoxication	13	9	3	1
Anxiety, paranoia	5	2	3	0
Sleepiness, decreased activity	18	12	6	0
Insomnia, sleeping problems	2	2	0	0
Drowsiness	16	8	8	0
Palpitations, rapid heartbeat	3	1	2	0
Dry mouth	19	13	5	1
Dry or bloodshot eyes	10	9	1	0
Altered sense of time	7	5	2	0
Decreased appetite	2	1	1	0
Increased appetite	13	9	4	0
GI symptoms	7	5	2	0
Skin conditions	1	1	0	0
Others	14	5	9	0

51 respondents who answered that they noticed symptoms that made them suspect side effects of CBN were asked to choose specific symptoms from a list. Participants were allowed to choose multiple responses. They were also asked to choose the severity of the most severe side effect symptom.

GI = gastrointestinal.

Discussion

We conducted a cross-sectional survey of cannabis users in Japan in 2021,^20,21 as well as a similar cross-sectional survey of CBD product users,²² and this cross-sectional survey of CBN users is the third survey. Here we will discuss the result of the survey in comparison with the previous two surveys.

Respondent background

The gender of the respondents in this survey was 75.9% male. In the survey of cannabis users conducted previously, the proportion of male respondents was 82.2%,²⁰ and in the survey of CBD users, it was 60.6%.²² In terms of age, the average age of cannabis users was 32.7 years, and that of CBD users was 37.7 years, whereas in this survey of CBN users, the average age was 37.4 years. This may reflect the fact that CBN is positioned somewhere between cannabis and CBD products. Compared to the statistical data,^23,24 the respondents in this survey tended to be more highly educated and earn higher incomes than the general population in Japan. This may be related to the fact that CBN products are expensive. In addition, the proportion of CBN users who also use prescription drugs was higher than that of CBD users²² (CBD: 30.5% vs. CBN: 35.9%). This may reflect the fact that CBN is used for more serious health care applications than CBD.

Purpose and efficacy of CBN products

In terms of the form of CBN products, smoking products accounted for the overwhelming majority, followed by edibles, with oils accounting for only 24.7%. Considering that in a similar survey on CBD, Vape accounted for 62.5%, oils accounted for 59.6%, and food and beverages accounted for 34.0%,²² there seems to be a tendency for CBN to be used in the form of a recreational product. In this survey, an almost twofold difference was observed in the average amount used by men and women, and even after correcting for the average weight of men and women, a trend was observed in which men tended to consume 1.5 times more. (The difference between two groups was not statistically significant.) In addition, although no statistically significant difference was found between the health care group and the recreational group, a difference in usage amount was almost twofold. Given that cannabis users in Japan are predominantly male,²⁰ it is postulated that users who use CBN as a substitute for cannabis for recreational purposes tend to take larger doses to achieve a psychoactive effect.

In this survey, the main purposes of medical use of CBN were improving sleep, followed by mental symptoms such as anxiety and depression, and then pain-related symptoms such as headaches, chronic pain, and joint pain. This was a similar trend to our previous research on the uses of CBD,²² online surveys on the uses of CBD conducted mainly in the United States and Europe,^25,26 and an online survey on the uses of CBG conducted in the United States in 2021.²⁷ Although CBN is often used specifically to improve sleep, we can assume that other purposes overlap with those of CBD and CBG. Clinical research is progressing in the area of sleeping disorder,^10–15 but it seems that there is a potential for clinical application of CBN for anxiety and chronic pain. However, there is no research on the anxiolytic effects of CBN, and research on its analgesic effects is limited to preclinical research.⁴ However, considering that the precursor of CBN, Δ9-THC, has been shown to be effective against anxiety and pain,^28,29 it is reasonable to assume that CBN, which also acts on CB1 receptors, has anxiolytic and analgesic effects.

The details of recreational use showed that it tended to be used as a supplement to enhance indoor relaxation activities rather than as a party drug. This may be a contributing factor to the low number of medical consultations related to CBN. The fact that the majority of users, including those who reported using it for recreational purposes, were aware of an improvement in their QOL shows the significance of CBN in health care.

Adverse events and dependence

The incidence of adverse events with CBN was 9.9%. This is a lower frequency than our previous survey results, which showed that 38.5% of cannabis users experienced acute and transient adverse events.²⁰ Considering that the rate of adverse events in a similar survey of CBD was 7.4%,²² it can be said that the frequency of adverse events for CBN is lower than for cannabis and higher than for CBD. The main symptoms of acute adverse events were dry mouth, drowsiness, and fatigue. Acute adverse events related to cannabis were anxiety, nausea and vomiting, and delusions.²⁰ The difference is probably due to the milder agonist activity of CBN on CB1 receptors.

In terms of the severity of adverse events, only one user (0.19%) out of 515 required a visit to the hospital. This suggests that safety issues are within acceptable limits. The percentage of users whose CBN use may qualify as substance use disorder is 5.2%, and this result suggests that there is a possibility of dependency on CBN. In a similar survey, the percentage of users with substance use disorders related to cannabis was 9.5% for current users.²⁰ Compared to these figures, it can be assumed that the dependence property of CBN is weaker than that of cannabis itself.

Limitations

There are three limitations to this survey. First, there is a selection bias in the group of respondents. It is highly likely that the group responding to the survey is biased toward those who feel they have benefited from CBN products. Second, as this survey is based on self-reporting, it is not possible to make an objective assessment of substance use disorders and the possibility of a placebo effect on the effectiveness of CBN cannot be ruled out. Because it is known that the placebo effect has a particularly large impact on CB products,³⁰ it is important to conduct randomized controlled trials (RCTs) in order to prove the pharmacological effects of CBN. However, since cannabis is a plant, it is difficult to monopolize rights through patents. It is also difficult to monopolize CBN and CBD through substance patents, as time has passed since their discovery. For these reasons, it seems that there is little economic return for companies to conduct large-scale RCTs. In fact, the only RCT for CB products currently being conducted in Japan is the Phase 3 trial for Epidiolex.³¹ Third, many of the users were also using other CBs in addition to CBN, so it is not possible to evaluate the effects of CBN alone. Despite these limitations, this survey is the first that investigates the purposes for which CBN is used, and merits reporting.

Summary

In Japan, CBN products are mainly used for mental health care purposes, targeting symptoms such as sleeping disorder, anxiety, and depression, contributing to improved QOL. The incidence of adverse events is 10%, with the severity being mild, and CBN is considered to have lower dependency compared to cannabis. CBN is used in an intermediate position between cannabis and CBD, and its safety profile is also considered to be intermediate between the two.

Footnotes

Authors’ Contributions

Y.M.: Project administration, methodology, writing—original draft, conceptualization, and investigation. F.U.: Data curation and formal analysis. A.N.: Investigation. N.M.: Writing—review and editing and conceptualization. Y.A.: Conceptualization. T.M.: Supervision and conceptualization. I.T.: Funding acquisition and conceptualization.

Author Disclosure Statement

A.N. is engaged in the sales of CBD products but is not involved in the analysis of the results or the preparation of the discussion. The rest of the authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this article.

Funding Information

Article submission fee of this report was funded by the Fiscal 2024 Health and Labor Sciences Research Grant, entitled “Regulatory oversight of cannabinoid pharmaceuticals and cannabinoid products 24CA2012 (to Y.M., N.M., and I.T.)” in part. Part of this study was also supported by the Japanese Clinical Association of Cannabinoids.

Supplementary Material

Abbreviations Used

References

Appendino

. The early history of cannabinoid research. Rend Fis Acc Lincei, 2020; 31(4):919–929; doi: 10.1007/s12210-020-00956-0

Maioli

, Mattoteia

, Amin

HIM

, et al. Cannabinol: History, syntheses, and biological profile of the greatest “Minor” cannabinoid. Plants (Basel), 2022; 11(21):2896; doi: 10.3390/plants11212896

Rhee

, Vogel

, Barg

, et al. Cannabinol derivatives: Binding to cannabinoid receptors and inhibition of adenylylcyclase. J Med Chem, 1997; 40(20):3228–3233; doi: 10.1021/jm970126f

Wong

, Cairns

. Cannabidiol, cannabinol and their combinations act as peripheral analgesics in a rat model of myofascial pain. Arch Oral Biol, 2019; 104:33–39; doi: 10.1016/j.archoralbio.2019.05.028

Corroon

. Cannabinol and sleep: Separating fact from fiction. Cannabis Cannabinoid Res, 2021; 6(5):366–371; doi: 10.1089/can.2021.0006

Scott

, Agonh

, Lehmann

. Antibacterial effects of phytocannabinoids. Life (Basel), 2022; 12(9):1394; doi: 10.3390/life12091394

Gojani

, Wang

, Li

, et al. Anti-Inflammatory effects of minor cannabinoids CBC, THCV, and CBN in human macrophages. Molecules, 2023; 28(18):6487; doi: 10.3390/molecules28186487

Thornton

, Dickson

, Carty

, et al. Cannabis constituents reduce seizure behavior in chemically-induced and scn1a-mutant zebrafish. Epilepsy Behav, 2020; 110:107152; doi: 10.1016/j.yebeh.2020.107152

Farrimond

, Whalley

, Williams

. Cannabinol and cannabidiol exert opposing effects on rat feeding patterns. Psychopharmacology (Berl), 2012; 223(1):117–129; doi: 10.1007/s00213-012-2697-x

10.

Gannon

, Bronfein

, Jackson

, et al. Novel formulation of THC and CBN in a repeat-action tablet improves objective and subjective measurements of sleep. American Journal of Endocannabinoid Medicine, 2021; 3(1):12–18.

11.

Kaufmann

. Use of a water-soluble form of cannabinol for the treatment of sleeplessness. Ijcam, 2021; 14(4):186–190; doi: 10.15406/ijcam.2021.14.00558

12.

Saleska

, Bryant

, Kolobaric

, et al. The safety and comparative effectiveness of non-psychoactive cannabinoid formulations for the improvement of sleep: A double-blinded, randomized controlled trial. J Am Nutr Assoc, 2024; 43(1):1–11; doi: 10.1080/27697061.2023.2203221

13.

Walsh

, Maddison

, Rankin

, et al. Treating insomnia symptoms with medicinal cannabis: A randomized, crossover trial of the efficacy of a cannabinoid medicine compared with placebo. Sleep, 2021; 44(11):zsab149; doi: 10.1093/sleep/zsab149

14.

Lavender

, McCartney

, Marshall

, et al. Cannabinol (CBN; 30 and 300 mg) effects on sleep and next-day function in insomnia disorder (‘CUPID’ study): Protocol for a randomized, double-blind, placebo-controlled, cross-over, three-arm, proof-of-concept trial. BMJ Open, 2023; 13(8):e071148; doi: 10.1136/bmjopen-2022-071148

15.

Bonn-Miller

, Feldner

, Bynion

, et al. A double-blind, randomized, placebo-controlled study of the safety and effects of CBN with and without CBD on sleep quality. Exp Clin Psychopharmacol, 2024; 32(3):277–284; doi: 10.1037/pha0000682

16.

Wilson-Poe

, Smith

, Elliott

, et al. Past-Year Use Prevalence of Cannabidiol, Cannabigerol, Cannabinol, and Δ8-Tetrahydrocannabinol Among US Adults. JAMA Netw Open, 2023; 6(12):e2347373; doi: 10.1001/jamanetworkopen.2023.47373

17.

Ministry of Health, Labor and Welfare, Japan. Cannabis Control Act. Available from: https://www.mhlw.go.jp/web/t_doc?dataId=81108000&dataType=0&pageNo=1 [Last accessed 08 15, 2024].

18.

Mitchell

. The secret history of cannabis in Japan. Asia Paci J, 2014; 12:1.

19.

VMC. co. ltd. 91.1% of CBN use is for health care purposes. Available from: https://prtimes.jp/main/html/rd/p/000000013.000091758.html [Last accessed 08 15, 2024].

20.

Masataka

, Sugiyama

, Akahoshi

, et al. Field survey using social media on the harm imposed by cannabis-use among the general public in Japan (The first report). Journal of the Japanese Society of Alcohol and Drug Medicine, 2021; 56(4):128–141.

21.

Masataka

, Sugiyama

, Akahoshi

, et al. Risk factors for cannabis use disorders and cannabis psychosis in Japan: Second report of a survey on cannabis-related health problems among community cannabis users using social networking services. Neuropsychopharmacol Rep, 2023; 43(1):85–94; doi: 10.1002/npr2.12307

22.

Masataka

, Sugiyama

, Akahoshi

, et al. Cross-Sectional Survey on the Use of Cannabidiol Products in Japan. Journal of the Japanese Society for Integrative Medicine, 2022; 15(2):92–101; doi: 10.50883/imj.15.2_92

23.

Ministry of Health, Labour and Welfare, Japan. Summary report of Comprehensive Survey of Living Conditions 2019-2020. Available from: https://www.mhlw.go.jp/english/database/db-hss/cslc-report2019.html [Last accessed 08 15, 2024].

24.

Statistics Bureau, Ministry of Internal Affairs and Communications, Japan. 2010 Population Census. Available from: https://www.stat.go.jp/data/kokusei/2010/users-g/wakatta.html#jump2 [Last accessed 08 15, 2024].

25.

Corroon

, Phillips

. A cross-sectional study of cannabidiol users. Cannabis Cannabinoid Res, 2018; 3(1):152–161; doi: 10.1089/can.2018.0006

26.

Moltke

, Hindocha

. Reasons for cannabidiol use: A cross-sectional study of CBD users, focusing on self-perceived stress, anxiety, and sleep problems. J Cannabis Res, 2021; 3(1):5; doi: 10.1186/s42238-021-00061-5

27.

Russo

, Cuttler

, Cooper

, et al. Survey of patients employing cannabigerol-predominant cannabis preparations: Perceived medical effects, adverse events, and withdrawal symptoms. Cannabis Cannabinoid Res, 2022; 7(5):706–716; doi: 10.1089/can.2021.0058

28.

Lichenstein

. THC, CBD, and Anxiety: A review of recent findings on the anxiolytic and anxiogenic effects of cannabis’ primary cannabinoids. Curr Addict Rep, 2022; 9(4):473–485; doi: 10.1007/s40429-022-00450-7

29.

Bilbao

, Spanagel

. Medical cannabinoids: A pharmacology-based systematic review and meta-analysis for all relevant medical indications. BMC Med, 2022; 20(1):259; doi: 10.1186/s12916-022-02459-1

30.

Gedin

, Blomé

, Pontén

, et al. Placebo response and media attention in randomized clinical trials assessing cannabis-based therapies for pain: A systematic review and meta-analysis. JAMA Netw Open, 2022; 5(11):e2243848; doi: 10.1001/jamanetworkopen.2022.43848

31.

National Institute of Health Sciences, Japan. Clinical Research Submission and Publication System. Available from: https://jrct.niph.go.jp/latest-detail/jRCT2031220041 [Last accessed 08 15, 2024].

Supplementary Material

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How Cannabinol Is Utilized in Japan,a Country with Strict Cannabis Regulations—Its Purposes,Medical Effects,Adverse Events,and Dependence

Abstract

Introduction:

Objective:

Methods:

Results:

Conclusions:

Introduction

Subjects and Methods

Methods

Subjects

Statistical analysis

Results

Background of respondents

Details of CBN use

Purpose of CBN use

The degree of improvement in subjective symptoms before and after the introduction of CBN for sleep, anxiety, and chronic pain

Effects on QOL

Adverse events and dependence

Discussion

Respondent background

Purpose and efficacy of CBN products

Adverse events and dependence

Limitations

Summary

Footnotes

Authors’ Contributions

Author Disclosure Statement

Funding Information

Supplementary Material

Abbreviations Used

References

Supplementary Material