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Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

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Open Access  Full Text Article                                                                                          Research Article

Knowledge and perceptions about Cannabidiol use

Abigail Calleja, Janis Vella Szijj, Anthony Serracino-Inglott, Lilian M. Azzopardi

Department of Pharmacy, Faculty of Medicine and Surgery, University of Malta, Msida, Malta

 

 

INTRODUCTION

Cannabis is being increasingly researched due to its different therapeutic properties¹ . The cannabis plant contains a large number of cannabinoids which are bioactive molecules and effects of these are primarily mediated by cannabinoid (CB) receptors². The two most researched cannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD). Both cannabinoids can be found in the cannabis plant however ratios vary according to species. Other cannabinoids include cannabinol, cannabigerol, cannabivarin and cannabinodiol^3,4. 

THC is known to produce psychoactive effects and increase stress and anxiety whilst CBD, exhibits antipsychotic effects and generally reduces anxiety and stress^5,6. The demand for CBD grew over time with more individuals consuming CBD products due to its potential therapeutic uses⁷. The anticonvulsant activity of CBD led to the approval of CBD for the treatment of treatment-resistant epilepsy^8-10. 

CBD is reported not to have any psychoactive or psychotropic effects unlike THC^5,6 . Russo (2017) views this as an inaccurate claim since CBD has been reported to produce pharmacological benefits on mental health disorders such as schizophrenia, depression, anxiety and addiction^10,11. 

A study by García-Gutiérrez et al., (2020) reported that CBD does not have sedating properties and Russo (2017) explained that products containing CBD may be sedating but pure CBD does not produce sedation^3,11. Sedation and somnolence are listed as very common adverse effects which can occur with use of Epidyolex®/ Epidiolex® which consists of 100mg pure CBD, indicated for treatment-resistant epilepsies¹². 

Different perceptions and levels of knowledge related to CBD use have been reported by patients and healthcare professionals (HCPs). According to Link et al., (2020), pharmacists working in the United States lacked knowledge about over-the-counter (OTC) CBD products and felt unprepared in giving advice to patients about CBD and discussing the use of OTC CBD products with other HCPs. Two major concerns that pharmacists reported were the safety and quality of OTC CBD products¹³. Patient concerns related to CBD reported by Wershoven et al., (2020) included limited scientific data to help guide HCPs, adverse effects of cannabinoids, potential for abuse and potential effects on driving¹⁴. Leszko and Meenrajan (2021) showed that a common concern of patients was that they might be judged or misunderstood by physicians if they knew that CBD was being used by them. Caregivers suggested that CBD should not be available over the counter but should be regulated by the government and labelled as a medicine¹⁵. The concern of being judged or misunderstood for using cannabis was reported as a barrier to CBD use¹⁶. Leszko and Meenrajan (2021) demonstrated the need for awareness about the difference between CBD and Medicinal Cannabis (MC) as the general public often confuse CBD with MC¹⁵. In a study by Schilling et al., (2021), the majority of participants knew the difference between MC and CBD¹⁷.

In 2018 the Maltese Drug Dependence Act was amended, allowing HCPs to prescribe and dispense medicinal preparations of cannabis¹⁸. The attitudes, beliefs and knowledge on medical cannabis of Maltese students was assessed and respondents considered cannabis to have therapeutic properties but felt that its use could lead to addiction and misuse¹⁹. 

The aim of the study was to assess the knowledge and perceptions of Maltese (i) members of the public (ii) HCPs about CBD. 

METHODS

Study was conducted whilst following guidelines described in the Standards for Reporting Qualitative Research²⁰. A survey to assess the knowledge and perception of the public and HCPs about CBD was conducted. Two questionnaires, one for the general public and one for HCPs were developed. The two questionnaires were divided into 4 sections: (i) demographic information (ii) knowledge about CBD (iii) perceptions about CBD (iv) potential barriers related to CBD use. 

Questions were presented in close-ended format and as statements. For each statement participants had to select whether they ‘strongly disagree’, ‘disagree’, ‘neither agree or disagree’, ‘agree’ and ‘strongly agree’.  Mean rating scores were given for each statement, where a score of 1 was given if the participant ‘strongly disagreed’ and a score of 5 was given if the participant ‘strongly agreed’ with the statement provided. Comparative analysis was univariate. The Kruskal Wallis test was used to compare rating scores provided to a statement between groups of participants clustered by demographic variables such as age. 

Validation of the questionnaires was carried out through discussion with a panel consisting of: three pharmacists, one general practitioner, one physiotherapist and two lay persons. The lay persons were not asked to validate the questionnaire intended for HCPs. 

Research ethics approval was granted by the Faculty Research Ethics Committee, Faculty of Medicine and Surgery of the University of Malta prior to dissemination of the questionnaire. 

Recruitment of participants was carried out by means of convenience sampling. The questionnaire for the public was uploaded as Google Forms through social media via Facebook and LinkedIn and that for HCPs was disseminated through professional associations and community pharmacies. Prior to completing questionnaire, participants were given an information sheet explaining the nature and scope of the study. When data collection was executed in person, a box was used for respondents to place the completed questionnaire in it and remain anonymous. Responses were collected between June 2021 and December 2021. 

RESULTS 

Questionnaire for the Public 

Four hundred participants completed the questionnaire of who 63% (n=250) were female. Forty-two percent (n= 166) of the participants were aged between 26-40 years and 42% (n=166) had a tertiary level of education. Prior to completing the questionnaire, 90% (n=361) of respondents had heard about CBD before and 77% (n=277) gained their knowledge about CBD from social media or news. 

Ninety-six percent of participants (n=384) agreed that CBD has a therapeutic effect and 79% (n=314) believed that CBD has an analgesic effect whilst 45% (n= 180) believed that CBD has an anti-epileptic effect. Results of correlation between mean rating scores and age of participants were all statistically significant. When it comes to knowledge of participants about CBD, varying mean rating scores for provided statements were given with the highest mean rating scores seen in participants aged between 18-25 years of age indicating higher level of knowledge about CBD in this group of patients (Table 1).

 

 

Table 1: Knowledge of the public about CBD and age (N=400)

                                  

Statement	Age	Sample size	Mean Score	Std. Dev	P-value
CBD and THC are naturally occurring compounds derived from cannabis	18-25	89	4.39	0.685	<0.001
	26-40	166	4.32	0.771
	41-60	107	4.01	0.976
	60+	38	3.32	0.989
CBD and THC produce different biological effects because they work differently	18-25	89	4.18	0.806	<0.001
	26-40	166	4.10	0.868
	41-60	107	3.88	1.016
	60+	38	3.21	0.963
CBD has a lower risk of producing mental effects compared to THC	18-25	89	3.96	0.852	<0.001
	26-40	166	3.90	0.909
	41-60	107	3.49	1.093
	60+	38	3.08	0.969
CBD is available in several formulations	18-25	89	4.48	0.725	<0.001
	26-40	166	4.45	0.798
	41-60	107	4.02	1.046
	60+	38	3.24	1.051
Legality of CBD in the EU is unclear	18-25	89	3.57	0.976	0.034
	26-40	166	3.55	1.006
	41-60	107	3.41	1.064
	60+	38	3.05	1.038
CBD dosing depends on weight, but there is no standard dose	18-25	89	3.81	0.928	<0.001
	26-40	166	3.80	0.820
	41-60	107	3.58	0.962
	60+	38	3.11	0.981
CBD products do not interact with other medications	18-25	89	2.53	0.918	0.009
	26-40	166	2.92	1.012
	41-60	107	2.74	0.935
	60+	38	2.82	0.834
CBD can cause a euphoric/high sensation	18-25	89	2.48	1.216	0.046
	26-40	166	2.39	1.089
	41-60	107	2.42	1.158
	60+	38	2.92	0.850

 

 

 

The majority of participants (86%; n= 342) believed that CBD products without a marketing authorization should be legally available in Malta. Forty-seven percent (n=161) of participants who believed that CBD products should be available in Malta believed that it should be classified as prescription only medicine (POM) and 31% (n=106) believed it should be over the counter. The rest of the participants believed it should be available in general sales. 

Participants who believed that CBD products should be available in Malta agreed more that CBD products available in health shops and pharmacies are of the same safety, quality and efficacy, that CBD products should be used in preference to conventional medicine and that HCPs should be able to prescribe or recommend CBD products (Table 2).

 

 

Table 2: Perceptions of the public about CBD (N=400)

Statements	Mean	Std. Dev
CBD products available in retail shops and pharmacies are of the same quality, safety and efficacy	3.15	1.294
Potential use of CBD might cause judgement or conflicts between healthcare professionals and patients	3.34	1.028
CBD products should not be used due to potential impairing effects on driving	2.51	1.135
CBD should only be legally available in pharmacies	3.47	1.356
CBD should be legally available in retail shops	2.47	1.387
CBD products recommended or prescribed by a healthcare professional (e.g., pharmacist, physician, nurse) are more likely to be used by patients	3.91	.950
CBD products should be used in preference to conventional medicine	3.04	1.154
CBD products should be used for minor ailments (e.g., headache, joint pain, minor sleep disorders)	3.25	1.274
CBD products should be used for major medical conditions (e.g., mental illness, epilepsy, cancer)	3.78	1.050
CBD should be classified as dangerous or harmful	2.11	1.149
Healthcare professionals should be able to recommend or prescribe CBD products	4.22	.853
CBD products intended for medicinal use should only be considered if there is no viable alternative medicine	2.58	1.248
CBD is very safe and has minimal side effects since it is a naturally occurring compound derived from cannabis	3.53	1.073
CBD use can lead to the use of more dangerous drugs (e.g., cocaine, heroin)	2.03	1.126
CBD products used for recreational purposes should be decriminalised	3.46	1.352

 

The major potential barrier to CBD use (66%; n= 262) was believed to be social stigma associated with the use of CBD for medicinal purposes. Fifty-six percent (n=224) of participants felt that personal beliefs of HCPs was another barrier to CBD use. 

Questionnaire for HCPs 

One hundred and fifty HCPs completed the questionnaire of who 59% (n=88) were female. The majority of HCPs (49%; n=73) were pharmacists. Most HCPs (43%; n= 64) had between 1 to 5 years of practice. 

Prior to completing the questionnaire, 97% (n= 146) of HCPs had heard about CBD before and the majority (71%; n= 98) heard about CBD from social media or news. Sixty-one percent (n=91) encountered patients who asked them about CBD and its use. 

When it came to HCPs’ knowledge about CBD, respondents felt they were most knowledgeable about the ‘different biological effects of CBD and THC’, the ‘effects of CBD on driving’ and the ‘legal status of CBD in Malta’ (Table 3). There was no significant difference between the knowledge mean rating scores and profession or years of practice.

 

 

 

Table 3: Knowledge of healthcare professionals about CBD (n= 150)

‘I feel knowledgeable about’:	Mean	Std. Deviation
Mechanism of action of CBD	2.09	0.951
Mechanism of action of THC	2.01	0.966
Different biological effects of CBD and THC	2.21	1.001
Different toxic effects of CBD and THC	2.12	1.003
Different therapeutic effects of CBD and THC	2.21	0.971
EMA approved indications of CBD	1.83	0.995
FDA approved indications of CBD	1.65	0.956
Ratio of CBD/THC in Bediol®	1.89	1.344
Ratio of CBD/THC in Bedrocan®	1.92	1.344
Ratio of CBD/THC in Pedanios 20/1®	1.89	1.344
Ratio of CBD/THC in Pedanios 22/1®	1.89	1.344
Pharmacology of CBD	1.76	0.946
Safety profile of CBD (e.g., contraindications, cautions, drug interactions)	1.89	0.959
Likelihood of dependence or addiction from CBD use	2.18	1.081
Effects of CBD on driving	2.23	1.100
Likelihood of withdrawal symptoms upon stopping use of CBD	2.15	1.132
Legal status of CBD in Malta	2.52	1.180
Legal status of CBD in other European countries	2.02	1.108

 

 

 

HCPs believed that CBD has mostly an anxiolytic (n=60), analgesic (n=83) and anti-inflammatory effect (n= 39). The majority of HCPs believed that sedation and somnolence are common to very common side effects caused by CBD followed by fatigue (n=79) and increased appetite (n=79). Fever (n=90) was believed to be a rare to very rare side effect of CBD followed by infections (n=80). One HCP believed that incontinence when overdosing was a very common side effect of CBD and another HCP believed that nausea was a common side effect of CBD. 

One hundred and twelve (75%) HCPs were not aware that there is only one Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved CBD-based product called Epidiolex/Epidyloex and out of these, 54 were pharmacists and 25 medical doctors. 

Sixty percent (n=90) of HCPs believed that Epidyolex should be available in Malta and 67% (n=101) of HCPs believed that CBD products should be classified as Prescription Only Medication. The HCPs who believed that CBD should be classified as general sales had between 1 and 5 years of practice. 

HCPs feel that there is a lack of education and misconceptions among the general public about CBD and its use in medical conditions. They believed that CBD for medicinal use should be manufactured only in appropriately licensed EU Good Manufacturing Practice certified facilities (Table 4).

 

 

 

 

 

Table 4: Perception of Healthcare Professionals about CBD (N=150)

Statements	Mean	Std. Deviation
There is a lack of education among the general public about CBD and its use in medical conditions	4.41	0.812
There is not enough data about the side effects of CBD-only products	3.31	1.081
CBD products for medicinal use should be available for prescribing or recommending	3.99	0.969
CBD-only products should only be legally available in pharmacies	4.17	1.048
CBD-only products should be legally available in retail shops	1.84	1.087
CBD-only products should not be prescribed or recommended due to potential impairing effects on driving	2.37	1.007
CBD-only products should be prescribed or recommended for minor ailments (e.g., headache, joint pain, minor sleep disorders) in preference to conventional medicine	2.57	1.138
CBD is very safe and has minimal side effects since it is a naturally occurring compound derived from cannabis	2.89	1.150
CBD-only products intended for medicinal use should only be considered if there is no viable alternative medicine	2.99	1.187
CBD-only products should be available on prescription only, to avoid misuse and abuse of such products	3.66	1.345
CBD-only should be classified as a dangerous or harmful drug	2.59	1.265
There are misconceptions among general public about CBD use	4.00	0.941
Healthcare professionals are concerned about a patient’s perception of a healthcare professional prescribing or recommending CBD for medicinal use	3.38	1.008
CBD use will lead to the use of more dangerous drugs (e.g., cocaine, heroin)	2.27	1.053
CBD for medicinal use should be manufactured only in appropriately licensed EU GMP certified facilities	4.31	0.962
The quality between CBD products used for recreational purposes and for medicinal use should be the same	3.24	1.422
The use of CBD-only products for recreational purposes should be decriminalised	3.17	1.308

 

 

The majority of HCPs felt comfortable prescribing or recommending CBD for pain conditions (69%; n=104) and insomnia (50%; n=75). HCPs were not comfortable with prescribing or recommending CBD for schizophrenia (63%; n=95), autism (57.3%; n= 86) and Alzheimer’s disease (54%; n=81)  (Table 5). 

 

 

Table 5: Healthcare professionals’ level of comfort in prescribing or recommending CBD in various medical conditions (N=150)

Would you feel comfortable prescribing or recommending CBD in?
	Yes	No	Maybe
Anxiety	44.7%	24.7%	30.6%
Arthritis	42%	28.7%	29.3%
Alzheimer’s Disease	20%	54%	26%
Autism	16.7%	57.3%	26%
Cancer	45.3%	29.3%	25.3%
Depression	36%	28.7%	35.3%
Epilepsy	37.3%	35.3%	27.3%
Hypertension	10%	57.3%	32.7%
Inflammation	35.3%	34%	30.7%
Insomnia	50%	25.3%	24.7%
Migraine	41.3%	29.3%	29.3%
Multiple Sclerosis	36.7%	32%	31.3%
Nausea and vomiting	26.7%	47.3%	26%
Pain	69.3%	16%	14.7%
Parkinson’s Disease	32.7%	43.3%	24%
Post-Traumatic Stress Disorder	38%	38%	24%
Schizophrenia	16%	63.3%	20.7%
Skin conditions e.g., eczema, psoriasis	26.7%	51.3%	22%

The most common potential barrier related to CBD use was believed to be personal beliefs of HCPs (65%; n= 98). There was no significant association between potential barriers related to CBD use and HCP’s gender, age, profession and years of practice. 

 

DISCUSSION 

Although members from the general public heard about CBD and agreed that it has therapeutic effects, less than half of the respondents knew that it has an anti-epileptic effect. The majority of respondents believe that CBD has an analgesic effect, even though to date, there is no FDA or EMA approved CBD medicinal product indicated for pain. Pain is a common indication for which CBD is used²¹. A lack of knowledge amongst members of the general public and consumers on CBD was reported in other studies^22-24. In this study the highest mean knowledge rating scores were attained by the younger participants aged between 18-25 years of age. A study conducted by Casanova et al, reported that awareness on CBD was associated with a younger age²⁵. More permissive attitudes related to cannabis amongst young people are more evident in countries where medical cannabis laws are passed, such as Malta²⁶. 

Participants believed that CBD-only products should be classified as POM. These results agree with findings from the study conducted by Leszko and Meenrajan where participants suggested that CBD products should not be OTC¹⁵. Participants perceive that CBD products available in health shops and pharmacies have the same quality, safety and efficacy. Bonn-Miller et al and Mazzetti et al claimed that analysed cannabinoid concentrations in CBD products differed from the ones stated on the product label^27,28. To date there is no locally conducted study describing analysis of cannabinoids in commercially available cannabis products. There is a need for analysing CBD products available on the Maltese market to verify whether concentrations stated on product labels reflect actual cannabinoid concentrations in the products. 

Respondents from the public agreed that HCPs should be able to recommend or prescribe CBD products with the majority of participants believing that CBD products recommended by HCPs such as a pharmacists, physicians or nurses are more likely to be used by patients. In a study conducted by Schilling et al, participants disagreed that CBD is a dangerous or harmful drug¹⁷. Individuals who believed that CBD-only products should be available in Malta believe that CBD products should be used in preference to conventional medicine and that CBD products should be used for both minor and major ailments. Studies conducted by Berg et al and Lovecchio et al found CBD to be beneficial in the management of pain, insomnia and anxiety among other conditions^22,29. Although CBD is found effective in reducing pain¹⁷ there are limited high quality randomized control trials about the use of CBD in reducing and managing pain and other conditions and about the efficacy and safety of cannabis products^30,31 . 

Social stigma associated with the use of CBD and potential judgement of HCPs were barriers to CBD use reported by members of the public which were also concerns reported in other studies^15,16,32,33. 

Results from the HCPs questionnaire demonstrated that HCPs were somewhat knowledgeable about certain aspects on CBD such as biological effects and not knowledgeable about others such as available FDA/EMA approved products. Link et al claimed that pharmacists lacked knowledge about CBD products and felt unprepared or incompetent in advising patients¹³. Unpreparedness and lack of knowledge could be due to the limited available scientific data on CBD to help guide professionals and inadequate training^14,34. Being more knowledgeable about CBD could lead to a more positive attitude towards prescribing it^35. 

More HCPs agreed that CBD produces an analgesic effect rather than an anti-epileptic effect. Although CBD is found effective in reducing pain¹⁷, pain is not an indication for which Epidyolex/Epidiolex is approved for. Sedation and somnolence were believed to be common to very common side effects caused by CBD whilst fever and infections were considered to be rare to very rare side effects. These results indicate varying levels of knowledge since side effects listed in the questionnaire were all common to very common side effects cause by Epidyolex/Epidiolex¹². The majority of HCPs were not aware of Epidyolex/Epidiolex, the only FDA/EMA approved CBD-based product^9,21. 

The majority of HCPs believe that CBD-only products should be classified as POM. CBD is qualified as a novel food and under European law is not considered as being a narcotic drug ⁹. In this study, HCPs with the least years of practice stated that CBD should be available in general sales rather than as POM or OTC. The way practitioners regard MC and CBD is related to the circumstances encountered throughout their career³⁶. HCPs with fewer years of practice might be more willing and open and might have had positive experiences related to CBD and the advocacy of its use. 

HCPs claimed that CBD products should be available for prescribing or recommending. Should CBD be classified as an OTC product, pharmacists would play an important role when it comes to recommending it as a non-prescription medicine³⁷. Patients have reported to be more comfortable if HCPs prescribed CBD products for use¹⁷. The majority of HCPs would feel comfortable in prescribing CBD products for pain and insomnia. Schizophrenia, autism and Alzheimer’s Disease were the conditions for which HCPs were the least comfortable prescribing CBD. Haug et al reported that HCPs would likely recommend CBD for Alzheimer’s Disease and epilepsy³⁸. 

Personal beliefs of HCPs and risk of being judged by HCPs were the main barriers to CBD use reported in both questionnaires. Patients’ fear of being judged by their HCPs due to their personal beliefs on CBD and social stigma related to CBD use were also barriers reported in a study by Sharma et al³⁹. 

Study Strengths and Limitations

The study is the first to gather the knowledge and perceptions about CBD use of members of the Maltese pubic and Maltese HCPs and sheds light on the need for more research and education about CBD and MC. Limitations of the study included the lack of open-ended questions in the questionnaire which could have gathered more data regarding knowledge and perceptions about CBD from respondents. Having a larger number of respondents for both questionnaires would yield more representative data. During dissemination of the questionnaires four MC products (Bedrocan® 22/1, Bediol®, Pedanios® 20/1 and Pedanios® 22/1) were available on the market and mentioned in the questionnaire for the HCPs. Since then, more MC products are available on the Maltese market. During dissemination of the questionnaires CBD products (excluding CBD found in MC) were not legally available in Malta, as they are now and responses provided might not be indicative of the current knowledge and perceptions about CBD. 

 CONCLUSION

Respondents from the general public were mostly knowledgeable about CBD and its use even though HCPs claim that there is a lack of education among the general public about CBD and its use in medical conditions. Members of the public had positive perceptions in relation to CBD and like HCPs, feel more comfortable should CBD be a POM or be recommended by a HCP. HCPs were not so knowledgeable about certain aspects on CBD. There is a need for increased research, awareness, education and training about cannabis and CBD to HCPs and students^1,39-47. Increased research, knowledge and availability of prescribing information and guidelines related CBD use might lead to an increased willingness of HCPs to recommend CBD and lead to a decrease in potential barriers associated with its use. 

FUNDING DECLARATION

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors

CONFLICT OF INTEREST

The authors declare that there is no conflict of interest.

AUTHOR CONTRIBUTIONS

Abigail Calleja: Main researcher, collected and analyzed data. 

Janis Vella Szijj: Supervisor, drafted manuscript and corresponding author.

Anthony Serracino Inglott: Supervisor and reviewer. 

Lilian M. Azzopardi: Head of Department and Reviewer.

DATA AVAILABILITY STATEMENT

Data underlying this article is available in the University of Malta Open Access Repository at https://www.um.edu.mt/library/oar/handle/123456789/103954 

REFERENCES 

1. Szaflarski M, McGoldrick P, Currens L, Blodgett D, Land H, Szaflarski J et al. Attitudes and knowledge about cannabis and cannabis-based therapies among US neurologists, nurses, and pharmacists. Epilepsy Behav. 2020; 107102. https://doi.org/10.1016/j.yebeh.2020.107102 PMid:32442891

2. Sharpe L, Sinclair J, Kramer A, de Manincor M, Sarris J. Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties. Journal of Translational Medicine. 2020;18(1):374. https://doi.org/10.1186/s12967-020-02518-2 PMid:33008420 PMCid:PMC7531079

3. García-Gutiérrez MS, Navarrete F, Gasparyan A, Austrich-Olivares A, Sala F, Manzanares J. Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders. Biomolecules. 2020; 10(11): 1575. https://doi.org/10.3390/biom10111575 PMid:33228239 PMCid:PMC7699613

4. Gonçalves ECD, Baldasso GM, Bicca MA, Paes RS, Capasso R, Dutra RC. Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant. Molecules. 2020; 25(7): 1567. https://doi.org/10.3390/molecules25071567 PMid:32235333 PMCid:PMC7181184

5. Pellati F, Borgonetti V, Brighenti V, Biagi M, Benvenuti S, Corsi L. Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer. BioMed Research International. 2018; 2018: 1691428. https://doi.org/10.1155/2018/1691428 PMid:30627539 PMCid:PMC6304621

6. Afrin F, Chi M, Eamens AL, Duchatel RJ, Douglas AM, Schneider J, et al. Can Hemp Help? Low-THC Cannabis and Non-THC Cannabinoids for the Treatment of Cancer. Cancers. 2020; 12(4): 1033. https://doi.org/10.3390/cancers12041033 PMid:32340151 PMCid:PMC7226605

7. Salami SA, Martinelli F, Giovino A, Bachari A, Arad N, Mantri N. It Is Our Turn to Get Cannabis High: Put Cannabinoids in Food and Health Baskets. Molecules. 2020; 25(18): 4036. https://doi.org/10.3390/molecules25184036 PMid:32899626 PMCid:PMC7571138

8. Britch SC, Babalonis S, Walsh SL. Cannabidiol: pharmacology and therapeutic targets. Psychopharmacology. 2020;238(1):9-28. https://doi.org/10.1007/s00213-020-05712-8 PMid:33221931 PMCid:PMC7796924

9. Brunetti P, Lo Faro AF, Pirani F, Berretta P, Pacifici R, Pichini S, et al. Pharmacology and legal status of cannabidiol. Annali dell'Istituto Superiore di Sanità. 2020;56(3):285-91. doi: 10.4415/ANN_20_03_06

10. Kicman A, Toczek M. The Effects of Cannabidiol, a Non-Intoxicating Compound of Cannabis, on the Cardiovascular System in Health and Disease. Int J Mol Sci. 2020;21(18):6740. https://doi.org/10.3390/ijms21186740 PMid:32937917 PMCid:PMC7554803

11. Russo EB. Cannabidiol Claims and Misconceptions. Trends in Pharmacological Sciences. 2017;38(3):198-201. https://doi.org/10.1016/j.tips.2016.12.004 PMid:28089139

12. Huestis M.A, Solimini R, Pichini S, Pacifici R, Carlier J, Busardò F.P. Cannabidiol Adverse Effects and Toxicity. Current Neuropharmacology. 2019; 17(10): 974-989. https://doi.org/10.2174/1570159X17666190603171901 PMid:31161980 PMCid:PMC7052834

13. Link K, Deshpande M, Ferguson M. Illinois Pharmacists and Over the Counter Cannabidiol Products: A Survey on Knowledge and Educational Needs. INNOVATIONS in pharmacy. 2020;11(2):2. https://doi.org/10.24926/iip.v11i2.2968 PMid:34007603 PMCid:PMC8051912

14. Wershoven N, Kennedy AG, MacLean CD. Use and Reported Helpfulness of Cannabinoids Among Primary Care Patients in Vermont. Journal of Primary Care & Community Health. 2020;11:215013272094695. https://doi.org/10.1177/2150132720946954 PMid:32757826 PMCid:PMC7412898

15. Leszko M, Meenrajan S. Attitudes, beliefs, and changing trends of cannabidiol (CBD) oil use among caregivers of individuals with Alzheimer's disease. Complementary Therapies in Medicine. 2021;57:102660. https://doi.org/10.1016/j.ctim.2021.102660 PMid:33418066

16. Hua DY, Lees R, Brosnan M, Freeman TP. Cannabis and cannabidiol use among autistic and non-autistic adults in the UK: a propensity score-matched analysis. BMJ Open. 2021;11(12):e053814. https://doi.org/10.1136/bmjopen-2021-053814 PMid:34916323 PMCid:PMC8685162

17. Schilling JM, Hughes CG, Wallace MS, Sexton M, Backonja M, Moeller-Bertram T. Cannabidiol as a Treatment for Chronic Pain: A Survey of Patients' Perspectives and Attitudes. Journal of Pain Research. 2021;14:1241-1250. https://doi.org/10.2147/JPR.S278718 PMid:33981161 PMCid:PMC8107012

18. Malta Medicines Authority. Cannabis for medicinal and research purposes. 2023 [cited May 5 2023]. Available from: https://medicinesauthority.gov.mt/cannabisformedicinalandresearchpurposes?l=1#:~:text=In%202018%2C%20Malta%20enacted%20the,for%20medicinal%20and%20research%20purposes.

19. Bonnici J, Clark M. Maltese health and social wellbeing student knowledge, attitudes and beliefs about medicinal cannabis, Complementary Therapies in Medicine. 2021; 60: 102753. https://doi.org/10.1016/j.ctim.2021.102753 PMid:34139340

20. O'Brien BC, Harris IB, Beckman TJ, Reed DA, Cook DA. Standards for Reporting Qualitative Research: A Synthesis of Recommendations, Academic Medicine. 2014; 89:1245-1251. https://doi.org/10.1097/ACM.0000000000000388 PMid:24979285

21. Corroon J, Phillips JA. A Cross-Sectional Study of Cannabidiol Users. Cannabis and Cannabinoid Research. 2018;3(1):152-61. https://doi.org/10.1089/can.2018.0006 PMid:30014038 PMCid:PMC6043845

22. Lovecchio F, Langhans MT, Bennett T, Steinhaus M, Premkumar A, Cunningham M, et al. Prevalence of Cannabidiol Use in Patients With Spine Complaints: Results of an Anonymous Survey. International Journal of Spine Surgery. 2021;15(4):663-8. https://doi.org/10.14444/8087 PMid:34285125 PMCid:PMC8375682

23. Hammond D, Goodman S. Knowledge of tetrahydrocannabinol and cannabidiol levels among cannabis consumers in the United States and Canada. Cannabis and Cannabinoid Research. 2020; 7:3. https://doi.org/10.1089/can.2020.0092 PMid:33998866 PMCid:PMC9225412

24. Erridge S, Coomber R, Sodergren MH. Medical cannabis, CBD wellness products and public awareness of evolving regulation in the United Kingdom. Journal of Cannabis Research. 2022; 4:56. https://doi.org/10.1186/s42238-022-00165-6 PMCid:PMC9617440

25. Casanova C, Ramier C, Fortin D, Carrieri P, Mancini J, Barré T. Cannabidiol use and perceptions in France: a national survey. BMC Public Health. 2022; 22:1628. https://doi.org/10.1186/s12889-022-14057-0 PMid:36038869 PMCid:PMC9421113

26. Schmidt LA, Jacobs LM, Spetz J. Young people's more permissive views about marijuana: local impact of state laws or National Trend? Am J Public Health. 2016; 106: 1498-1503. https://doi.org/10.2105/AJPH.2016.303153 PMid:27196657 PMCid:PMC4940634

27. Bonn-Miller MO, Loflin MJE, Thomas BF, Marcu JP, Hyke T, Vandrey R. Labeling Accuracy of Cannabidiol Extracts Sold Online. JAMA. 2017;318(17):1708-9. https://doi.org/10.1001/jama.2017.11909 PMid:29114823 PMCid:PMC5818782

28. Mazzetti C, Ferri E, Pozzi M, Labra M. Quantification of the content of cannabidiol in commercially available e-liquids and studies on their thermal and photo-stability. Scientific Reports. 2021;11(1):16573. https://doi.org/10.1038/s41598-021-96039-7 PMid:34376801 PMCid:PMC8355102

29. Berg CJ, Getachew B, Pulvers K, Sussman S, Wagener TL, Meyers C, et al. Vape shop owners'/managers' attitudes about CBD, THC, and marijuana legal markets. Preventive Medicine Reports. 2020;20:101208. https://doi.org/10.1016/j.pmedr.2020.101208 PMid:32995147 PMCid:PMC7516178

30. Graham M, Bird S, Howard Z, Dobson M, Palazzi K, Lucas CJ et al. Cannabis Medicines Advisory Service preliminary survey results: enquirer perceptions and patient outcomes, Internal Medicine Journal. 2022; 52:228-37. https://doi.org/10.1111/imj.15635 PMid:34837455 PMCid:PMC9304266

31. Hachem Y, Abdallah SJ, Rueda S, Wiese J, Mehra K, Rup J et al. Healthcare practitioner perceptions on barriers impacting cannabis prescribing practices. BMC Complimentary Medicines and Therapy. 2022; 22: 237. https://doi.org/10.1186/s12906-022-03716-9 PMid:36076191 PMCid:PMC9453734

32. Garcia-Romeu A, Elmore J, Mayhugh RE, Schlienz NJ, Martin EL, Stickland JC et al. Online survey of medicinal cannabis users: qualitative analysis of patient-level data. Frontiers in Pharmacology. 2022; 13: 965535. https://doi.org/10.3389/fphar.2022.965535 PMid:36147312 PMCid:PMC9485457

33. Sabmeethavorn Q, Bonomo YA, Hallinan CM. Pharmacists' perceptions and experiences of medicinal cannabis dispensing: A narrative review with a systematic approach, International Journal of Pharmacy Practice. 2022; 30: 204-14. https://doi.org/10.1093/ijpp/riac005 PMid:35225341

34. Karanges EA, Suraev A, Elias N, Manocha R, McGregor IS. Knowledge and attitudes of Australian general practitioners towards medicinal cannabis: a cross-sectional survey. British Medical Journal Open. 2018;8(7):e022101. https://doi.org/10.1136/bmjopen-2018-022101 PMid:29970456 PMCid:PMC6042562

35. Rosenbaek F, Riisgaard H, Nielsen JB, Wehberg S, Waldorff FB, Pedersen LB et al. GPs' prescription patterns, experience and attitudes towards medicinal cannabis-a nationwide survey at the early stage of the Danish test scheme. BMC Primary Care. 2023;24:17. https://doi.org/10.1186/s12875-023-01971-4 PMid:36650442 PMCid:PMC9843989

36. Manoharan R, Kemper J, Young J. Exploring the medical cannabis prescribing behaviors of New Zealand physicians. Drug Alcohol Rev. 2022;1(6):1355-1366. https://doi.org/10.1111/dar.13476 PMid:35604868 PMCid:PMC9544511

37. Galea S, Zarb Adami M, Serracino-Inglott A, Azzopardi LM. Pharmacist interventions in non-prescription medicine use. Journal of Pharmaceutical Health Services Research. 2014; 5:55-9 https://doi.org/10.1111/jphs.12044

38. Haug NA, Kieschnick D, Sottile JE, Babson KA, Vandrey R, Bonn-Miller MO. Training and Practices of Cannabis Dispensary Staff. Cannabis and Cannabinoid Research. 2016;1(1):244-51. https://doi.org/10.1089/can.2016.0024 PMid:28861496 PMCid:PMC5531366

39. Sharma P, Holland A, Sheikh T, Novy B, Oesterle T, Platt R et al. Primary care provider attitudes, experiences and practices about cannabidiol (CBD) and barriers to patient-provider communication about CBD use: A qualitative study. PEC Innovation. 2022; 100044. https://doi.org/10.1016/j.pecinn.2022.100044 PMid:37213726 PMCid:PMC10194378

40. Dill J, Kurkowski A. CBD: Considerations for use within the health system. Hospital Pharmacy. 2020; 55(1): 9-11. https://doi.org/10.1177/0018578719873870 PMid:31983761 PMCid:PMC6961151

41. Moeller KE. McGuire JM, Melton BL. A nationwide survey of pharmacy students' knowledge and perceptions regarding medical cannabis. Journal of the American Pharmacists Association. 2020; 21-224. https://doi.org/10.1016/j.japh.2019.08.008 PMid:31585701

42. Felnhofer A, Kothgassner OD, Stoll A, Klier C. Knowledge about and attitudes towards medical cannabis among Austrian university students. Complementary therapies in medicine. 2021; 102700. https://doi.org/10.1016/j.ctim.2021.102700 PMid:33677020

43. Nichols MA, Arnett SJ, Fa B, Marchionda RA, Cutting MC, McDonald MR et al. National survey identifying community pharmacist preceptors' experience, knowledge, attitudes and behaviors influencing intent to recommend cannabidiol products. Journal of the American Pharmacists Association. 2021; S91-S104. https://doi.org/10.1016/j.japh.2021.01.016 PMid:33558186

44. Ukagbu O, Smith J, Hall D, Frain T, Abbasian C. Staff awareness of the use of cannabidiol (CBD): a trust-wide survey study in the UK. Journal of Cannabis Research. 2021; 3:51. https://doi.org/10.1186/s42238-021-00104-x PMid:34906259 PMCid:PMC8672615

45. Hassan KM, Oluwafemi O, Ketchatang W. Pharmacy students' knowledge, attitudes and awareness toward marijuana use. J Pharm Pract. 2022; 36; 1170-76. https://doi.org/10.1177/08971900221096969 PMid:35475401

46. Sokratous S, Kaikoush K, Mpouzika MD, Alexandrou G, Karanikola NM. Attitudes, beliefs and knowledge about medical cannabis among nurses and midwives in Cyprus: a cross-sectional descriptive correlational study. BMC Nursing. 2022; 21: 120. https://doi.org/10.1186/s12912-022-00887-1 PMid:35585574 PMCid:PMC9118681

47. Jankie S, Sewdass K, Smith W, Naraynsingh C, Johnson J, Farnon N. A cross-sectional survey of prospective healthcare professionals' knowledge, attitudes and perceptions of medical Cannabis, Exploratory Research in Clinical and Social Pharmacy. 2023; 10: 100275. https://doi.org/10.1016/j.rcsop.2023.100275 PMid:37168830 PMCid:PMC10165452