# Symptom severity is a major determinant of cannabis-based products use among people with multiple sclerosis

Tangui Barré, Damien Testa, Melina Santos, Fabienne Marcellin, Perrine Roux, Patrizia Carrieri, Lise Radoszycki, Camelia Protopopescu

<figure><img src="image_1.png" /></figure>

## To cite this version:

Tangui Barré, Damien Testa, Melina Santos, Fabienne Marcellin, Perrine Roux, et al.. Symptom severity is a major determinant of cannabis-based products use among people with multiple sclerosis. Journal of Clinical Nursing, 2023, 32, pp.6460 - 6473. 10.1111/jocn.16674. inserm-04303022

HAL Id: inserm-04303022

https://inserm.hal.science/inserm-04303022

Submitted on 23 Nov 2023

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

<figure><img src="image_2.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
<figure><img src="image_3.png" /></figure>

# Symptom severity is a major determinant of cannabis-based products use among people with multiple sclerosis

Tangui Barré PhD, Researcher<fnref n="1" />

<figure><img src="image_4.png" /></figure>

Damien Testa PhD, Data Scientist<fnref n="2" />

Melina Santos PhD, Researcher<fnref n="1" />

Fabienne Marcellin PhD, Researcher<fnref n="1" />

Perrine Roux PhD, Researcher<fnref n="1" />

Patrizia Carrieri PhD, Researcher<fnref n="1" />

Lise Radoszycki MSc, Data Scientist<fnref n="2" />

Camelia Protopopescu PhD, Researcher<fnref n="1" />

## Correspondence

Patrizia Carrieri, Faculté de Médecine de la Timone, Aile Bleue, 35 boulevard Jean Moulin, Marseille, France.

Email: pmcARRIERI@aol.com

## Abstract

**Aims and Objectives:** We aimed to identify correlates of cannabinoid-based products (CBP) use in patients with multiple sclerosis (MS) in France and Spain.

**Background:** MS is responsible for a wide range of symptoms, including pain. Access to CBP differs according to local legislation. The French context is more restrictive than the Spanish one, and no data regarding cannabis use among MS patients has yet been published. Characterizing MS patients who use CBP constitutes a first step toward identifying persons most likely to benefit from them.

**Design:** An online cross-sectional survey was submitted to MS patients who were members of a social network for people living with chronic diseases and were living in France or Spain.

**Methods:** Two study outcomes measured therapeutic CBP use and daily therapeutic CBP use. Seemingly unrelated bivariate probit regression models were used to test for associations between the outcomes and patients' characteristics while accounting for country-related differences. STROBE guidelines were followed in reporting this study.

**Results:** Among 641 study participants (70% from France), the prevalence of CBP use was similar in both countries (23.3% in France vs. 20.1% in Spain). MS-related disability was associated with both outcomes, with a gradient observed between different degrees of disability. MS-related pain level was associated with CBP use only.

**Conclusions:** CBP use is common in MS patients from both countries. The more severe the MS, the more participants turned to CBP to alleviate their symptoms. Easier access to CBP should be ensured for MS patients in need of relief, especially from pain.

Tangui Barré and Damien Testa equally contributed to this work.

Lise Radoszycki and Camelia Protopopescu equally contributed to this work.

There is a statistician on the author team: C. Protopopescu.

This is an open access article under the terms of the [Creative Commons Attribution-NonCommercial License](https://creativecommons.org/licenses/by-nc), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

© 2023 The Authors. *Journal of Clinical Nursing* published by John Wiley & Sons Ltd.

<footnote n="1">¹Aix Marseille Univ, Inserm, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France</footnote>

<footnote n="2">²Carenity, Paris, France</footnote>
**Relevance to clinical practice:** This study highlights the characteristics of MS patients using CBP. Such practices should be discussed by healthcare professional with MS patients.

KEYWORDS

cannabis, multiple sclerosis, patient-reported outcomes, symptom management

# 1 | INTRODUCTION

Multiple sclerosis (MS) is an incurable immune-mediated inflammatory disease of the central nervous system whose underlying causes are unclear. It is responsible for chronic neurological disability (Dobson & Giovannoni, 2019). Global prevalence in 2015 was estimated at more than two million people (Feigin et al., 2017), and is on the rise (Walton et al., 2020). MS is generally diagnosed during young adulthood or middle age (Gilmour et al., 2018) and is more frequent in women (Dobson & Giovannoni, 2019).

The phenotypes commonly used to characterise MS are clinically isolated syndrome, relapsing–remitting MS (RRMS), primary progressive MS (PPMS) and secondary progressive MS (SPMS; Lublin et al., 2020; Thompson et al., 2018). RRMS is characterised by relapses–acute or subacute episodes of new or increasing neurologic dysfunction–followed by full or partial recovery (Lublin et al., 2014). Progressive MS is characterised by steadily increasing objectively documented neurologic dysfunction/disability without unequivocal recovery (Lublin et al., 2014). More specifically, PPMS is characterised by a progressive state of MS from onset, while in SPMS, the progressive state follows one or more relapses (Lublin et al., 2014).

Multiple sclerosis is responsible for a wide range of potentially debilitating symptoms including spasticity, pain, fatigue, depression, impairment of cognitive functions, reduced mobility and decreased bladder function. Symptoms tend to worsen with time (Kister et al., 2013, 2020). Despite advances in treatment, there is still no cure (Dobson & Giovannoni, 2019; McGinley et al., 2021). Disease-modifying therapies and symptomatic therapies are also often used to treat its symptoms (Dobson & Giovannoni, 2019).

The medical use of cannabinoids to reduce MS symptoms is still controversial. Research evidence for the potential benefits of cannabinoids on MS-related pain is not as strong as for spasticity (Nielsen et al., 2018; Rice & Cameron, 2017). Nabiximols—an oromucosal spray with a balanced mixture of tetrahydrocannabinol (THC) and cannabidiol (CBD)—is approved by health regulatory authorities in several countries for adult patients with moderate to severe MS-related spasticity who do not respond adequately to other anti-spasticity medication (Agence Nationale de Sécurité du Médicament et des Produits de Santé, 2014; Electronic Medicines Compendium, 2020). A number of countries, including Canada, also authorise its use for MS-associated neuropathic pain (Auhasira et al., 2018). However, this is not the case in France or Spain. Access to cannabis and to cannabinoid-based products (CBP), whether for

What does this paper contribute to the wider global clinical community?

* This study reveals that French and Spanish multiple sclerosis patients commonly use cannabis-based products.

* The more severe the multiple sclerosis, the more participants turned to cannabis-based products to alleviate their symptoms.

therapeutic or recreational purposes, varies according to local legislation. In France, while cannabis consumption is very common, it is criminalised by law. Furthermore, despite nabiximols being the only legal cannabinoid-based medical drug in the country, it is unavailable because of failures in price negotiations between its producer and French health authorities. Since March 2021, a national experimental test has been implemented in France to assess the relevance and feasibility of making medical cannabis available, with 3000 participants expected. Among the conditions for enrolment are neuropathic pain refractory to accessible therapies and painful refractory MS-related spasticity (Agence Nationale de Sécurité du Médicament et des Produits de Santé, 2021). Conversely, in Spain, cannabis use is decriminalised. Social clubs are organised for cannabis production and distribution (Belackova & Wilkins, 2018). Just as in France, nabiximols is the country's only legal cannabinoid-based medical drug available (nabilone and dronabinol are only authorised for "exceptional cases of MS" in Spain (Gorospe Elezcano, 2020)). It can only be dispensed in hospital pharmacies. Therefore, depending on the national legal context (i.e. France vs. Spain), people with MS may self-medicate with cannabis and/or cannabinoid-based drugs, or use them under medical supervision to alleviate their symptoms (Gupta et al., 2019; Gustavsen et al., 2019; Weinkle et al., 2019). Despite these legal and medical possibilities for cannabis use, no guidelines exist in either country for physicians who wish to counsel their patients with MS about the putative therapeutic use of cannabis (Calcaterra et al., 2020). Characterising CBP use in MS patients constitutes a first step in understanding the potential therapeutic benefits of cannabinoids, and therefore in identifying patients most likely to benefit from them.

Moreover, as cannabis-based self-medication does not come without risks (e.g. side effects and drug-drug interactions (Brown & Winterstein, 2019)), identifying patients most likely to use CBP,
as well as their motivations to do so, may help healthcare providers initiate discussion with them on this issue, and provide proper guidelines and harm reduction counselling. Due to the sensitive nature of issues related to the use of (formerly) illicit substances, some patients may be reluctant to talk about their consumptions with their healthcare providers, especially physicians, or may underreport their use, by fear of stigmatisation (Hulaihel et al., 2022; Nayak et al., 2022; Troup et al., 2022). They may more openly talk about this with nurses, as the latter may have better listening skills, be less prone to top-down decision making, and have more positive attitude toward CBP (and thus lower stigma) compared to physicians (HaGani et al., 2022; Melnikov et al., 2021; Ubel et al., 2017). Providing detailed information to nurses about CBP use in MS patients is thus important to help them contextualise this issue and to guide them in their routine interactions with MS patients.

This study aimed to identify correlates of CBP use in patients with MS in France and Spain.

## 2 | METHODS

### 2.1 | Study design and participants

Carenity is a social network for people living with chronic conditions, created in 2011 to provide high quality medical information to an online patient community and to help patients and caregivers find support and share their experiences about chronic diseases via online forums. This community has more than 500000 members from six different countries and generates real-world patient insights through online surveys (Carenity, 2019).

Carenity members living with MS (as self-reported), aged 18 years and older, and living in France or Spain were eligible for inclusion in this study. Participants voluntarily enrolled from April to July 2019, provided signed informed consent, and responded to a confidential web-based survey. No financial incentive was provided to participate in the survey.

### 2.2 | Questionnaire and data collection

Participants completed a self-administered online questionnaire comprising one open and 30 closed questions exploring sociodemographic characteristics, clinical and psychosocial aspects of MS, and CBP use patterns in the context of coping with MS.

The sociodemographic characteristics collected included gender, age, country of residence, city size and highest educational level attained. With regard to clinical and psychosocial aspects of MS, we collected data on the type of MS (RRMS, SPMS, PPMS, unknown), presence of MS-related spasticity (yes, no, unknown), time since diagnosis, self-perceived global health level (visual analogue scale from 0 indicating the worst imaginable health state, to 10 indicating the best imaginable health state; Atkinson & Lennox, 2006), and

MS-related pain level (visual analogue scale from 0, indicating no pain to 10, indicating extreme pain; Karcioglu et al., 2018). The severity of MS-related disability was estimated by a neurologic and walking impairment score, adapted from the Expanded Disability Status Scale (EDSS). As clinical evaluation was not available, 11 pre-determined items were proposed to obtain a self-assessed EDSS level for each participant (see Table S2 for the complete list). The score quantified the level of disability from 0 to 10, based on a neurologic evaluation of eight functional systems and walking impairment; a higher score represented a higher level of disability (Kurtzke, 1983).

The frequency of CBP use was collected for those who declared using it for therapeutic purposes (in any form, including herb and cannabinoid-based forms, whether plant-derived or synthetically manufactured) to alleviate their MS symptoms. We also collected data on the type of CBP they used, and where they bought products. To collect these two data, participants could choose one or more options from a pre-defined list.

### 2.3 | Study outcomes

Two outcomes were defined, both based on therapeutic CBP use frequency: CBP use (vs. no use) and daily CBP use (vs. no use or less than daily use). In both outcomes, the term CBP encompassed all cannabis and/or cannabinoid-based products (such as herb, nabiximols or CBD-rich oil).

### 2.4 | Statistical analyses

The characteristics of study participants were described using numbers and percentages for categorical variables and means (standard deviations) for continuous ones. They were described globally, according to country of residence (i.e. France or Spain) and according to CBP use frequency. Users' patterns of CBP use were also described.

For each outcome, we used a seemingly unrelated bivariate probit regression model, which allowed us to account for the potential bias related to the differences between participants' characteristics according to their country of residence. This approach was based on two simultaneous equations with correlated error terms and robust standard errors (Huber/White/sandwich estimator of the variance), estimated by the Stata "biprobit" command (Greene, 2017). In the first equation, the factors associated with the country of residence were identified using a multivariable probit regression model. The second equation, with each of the study outcomes as the dependent variable, was estimated by maximum likelihood together with the previously identified first equation. This second equation was adjusted for the country of residence in all univariable and multivariable analyses, the former effectively being bivariable analyses that included each of the explanatory variables plus the country variable.

A similar (univariable/multivariable) selection procedure was used for the two equations of the seemingly unrelated bivariate probit model. The threshold for identifying eligible variables in the
univariable analyses was *p*-value < 0.20 (Wald test). A backward selection procedure was then used to obtain the final multivariable models, with the *p*-value threshold for statistical significance set at 0.05. A positive/negative coefficient in the probit regression models indicates a direct/inverse association between the corresponding explanatory variable and the outcome.

The following explanatory variables were tested in the models: gender, city size (recoded into <1000; 10,000-100,000; and >100,000 inhabitants), educational level (recoded into > vs. ≤upper secondary school certificate), time since diagnosis, age at diagnosis, MS-related spasticity, type of MS, MS-related disability (none or minimal (score 0-2), moderate or substantial (score 3-7), and total disability (score 8-10)), self-perceived global health level and MS-related pain level.

The study was conducted according to the "strengthening the reporting of observational studies in epidemiology" (STROBE) statement for cross-sectional studies (see Table S1). Stata/SE 16.1 software (StataCorp LP) was used for all analyses.

## 2.5 | Ethical considerations

The study was conducted in accordance with the Declaration of Helsinki. According to the French law and thanks to the anonymity of data, no approval from ethics committee was needed. Informed written consent was obtained from all participants included in the study.

# 3 | RESULTS

## 3.1 | Study population characteristics

Our study population included 641 Carenity members, 447 (69.7%) of whom lived in France and 194 (30.3%) in Spain. The study population comprised mainly women (72.7%); the mean age was 47.1 years; most of them (73.2%) experienced MS-related spasticity; and 54.5% and 16.8% underwent moderate or substantial disability and total disability, respectively (Table 1). According to the univariable probit regression analyses, participants from Spain were less likely than those in France to live in cities with <1000 inhabitants. Instead, they were more likely to (i) have RRMS, (ii) not know whether they had spasticity, (iii) suffer from less severe MS-related disability, (iv) have been diagnosed for a shorter time, (v) have been diagnosed at a younger age, (vi) have a higher self-reported global health level and (vii) have a lower self-reported MS-related pain level (Table 1). After multivariable adjustment, differences remained for city size, type of MS, MS-related disability, time since diagnosis and age at diagnosis.

Less than a quarter (22.3%) of all the survey participants used CBP to alleviate their MS symptoms, and 70.0% of users used them daily (Figure 1). There was no between-country difference in the two measured frequencies of CBP use (CBP use prevalence was

23.3% in France vs. 20.1% in Spain, $\chi^2$ test *p*-value = 0.377; daily CBP use prevalence was 16.1% in France vs. 14.4% in Spain, *p* = 0.591; Figure 1).

Patterns of therapeutic CBP use revealed between-country differences for most variables, with noticeable exceptions being the use of herb/resin and purchasing on the street or from relatives (Table 2).

## 3.2 | Correlates of therapeutic CBP use in MS patients

According to the results from the bivariate probit models, in univariable analyses, the factors associated with therapeutic CBP use (yes/no) were male gender, MS-related disability and MS-related pain level (Table 3). After multivariable adjustment, male gender (probit coefficient [95% confidence interval (CI)]: 0.34 [0.09;0.58]), MS-related disability—with a gradient between the categories “moderate or substantial disability” (0.36 [0.05;0.67]) and “total disability” (0.51 [0.13;0.88]) versus “no or minimal disability”—and MS-related pain level (0.04 [0.00;0.09] per one-point increase on a 10-point visual analogue scale), were all independently associated with CBP use (Table 3).

In univariable analyses, daily CBP use (vs. no use or less than daily use) was associated with SPMS (vs. the reference RRMS), MS-related disability and MS-related spasticity (Table 4). After multivariable adjustment, this outcome was only associated with MS-related disability, with a similar gradient between the categories to that described above: coefficient [95% CI]: 0.40 [0.06;0.73] and 0.60 [0.20;0.99] for “moderate or substantial disability” and “total disability”, respectively, versus “no or minimal disability” (Table 4).

# 4 | DISCUSSION

This real-world international study based on patient-reported outcomes from a web-based survey showed that patients with MS who had higher levels of related disability and those with higher levels of pain were more likely to use CBP for therapeutic purposes. Moreover, despite different legislation contexts, including the difficulty for French patients to obtain cannabinoid-based pharmaceutical products, the prevalence of CBP use was similar in patients from both Spain and France, and most users in both countries consumed CBP daily. Given that the French participants generally had a more advanced stage of the disease (i.e. more progressive forms of MS, longer time since diagnosis and increased MS-related disability) than their Spanish counterparts, the similar prevalences of CBP use in both countries suggests that people living with MS in France use CBP for therapeutic purposes as a last resort at an advanced stage of their disease.

This is the very first time that CBP use is documented among people living with MS in the sociocultural and legislative context of France. Previous studies focused on cannabis, while we provided
<table><caption>TABLE 1 Characteristics of the study participants according to country of residence and factors associated with living in Spain (probit regression, univariable and multivariable analyses, Carenity survey, n = 641).</caption><thead><tr><th rowspan="2"></th><th colspan="2">Total (n = 641)</th><th colspan="2">France (n = 447)</th><th colspan="2">Spain (n = 194)</th><th colspan="2">Univariable analyses</th><th colspan="2">Multivariable analysis</th></tr><tr><th>No. of participants (%) or mean (SD)</th><th>No. of participants (%) or mean (SD)</th><th>No. of participants (%) or mean (SD)</th><th>No. of participants (%) or mean (SD)</th><th>Coeff [95% CI]</th><th>aCoeff [95% CI]</th><th>p-value</th><th>p-value</th><th>aCoeff [95% CI]</th><th>p-value</th></tr></thead><tbody><tr><td>Gender</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Female (ref.)</td><td>466 (72.7)</td><td>331 (74.0)</td><td>135 (69.6)</td><td>1</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Male</td><td>175 (27.3)</td><td>116 (26.0)</td><td>59 (30.4)</td><td>0.13 [-0.09;0.36]</td><td>.246</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Age (years)<sup>a</sup></td><td>47.1 (11.1)</td><td>49.1 (11.5)</td><td>42.5 (8.7)</td><td>-0.04 [-0.05; -0.03]</td><td>&lt;10<sup>-3</sup></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Town/city size (no. of inhabitants)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>&lt;1000 (ref.)</td><td>254 (39.6)</td><td>208 (46.5)</td><td>46 (23.7)</td><td>1</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>10,000-100,000</td><td>226 (35.3)</td><td>154 (34.5)</td><td>72 (37.1)</td><td>0.44 [0.20;0.69]</td><td>.001</td><td>1</td><td></td><td></td><td></td><td></td></tr><tr><td>&gt;100,000</td><td>161 (25.1)</td><td>85 (19.0)</td><td>76 (39.2)</td><td>0.84 [0.58;1.11]</td><td>&lt;10<sup>-3</sup></td><td>0.85 [0.57;1.13]</td><td></td><td></td><td></td><td></td></tr><tr><td>Educational level</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>&lt;upper secondary school certificate (ref.)</td><td>330 (51.5)</td><td>239 (53.5)</td><td>91 (46.9)</td><td>1</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>&gt;upper secondary school certificate</td><td>311 (48.5)</td><td>208 (46.5)</td><td>103 (53.1)</td><td>0.15 [-0.05;0.36]</td><td>.127</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Time since diagnosis (years)</td><td>12.4 (9.2)</td><td>13.1 (9.7)</td><td>10.9 (7.6)</td><td>-0.02 [-0.03; -0.01]</td><td>.002</td><td>-0.02 [-0.03; -0.00]</td><td>.019</td><td></td><td></td><td></td></tr><tr><td>Age at diagnosis (years)</td><td>34.7 (10.3)</td><td>36.0 (10.7)</td><td>31.6 (8.5)</td><td>-0.03 [-0.04; -0.02]</td><td>&lt;10<sup>-3</sup></td><td>-0.02 [-0.04; -0.01]</td><td>&lt;10<sup>-3</sup></td><td></td><td></td><td></td></tr><tr><td>MS-related spasticity</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Yes (ref.)</td><td>469 (73.2)</td><td>340 (76.1)</td><td>129 (66.5)</td><td>1</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>No</td><td>98 (15.3)</td><td>63 (14.1)</td><td>35 (18.0)</td><td>0.23 [-0.05;0.51]</td><td>.107</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Unknown</td><td>74 (11.5)</td><td>44 (9.8)</td><td>30 (15.5)</td><td>0.36 [0.05;0.67]</td><td>.025</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Type of MS<sup>b</sup></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>RRMS (ref.)</td><td>365 (56.9)</td><td>221 (49.4)</td><td>144 (74.2)</td><td>1</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>PPMS</td><td>95 (14.8)</td><td>80 (17.9)</td><td>15 (7.7)</td><td>-0.74 [-1.07; -0.40]</td><td>&lt;10<sup>-3</sup></td><td>-0.52 [-0.90; -0.14]</td><td>.007</td><td></td><td></td><td></td></tr><tr><td>SPMS</td><td>135 (21.1)</td><td>114 (25.5)</td><td>21 (10.8)</td><td>-0.75 [-1.03; -0.46]</td><td>&lt;10<sup>-3</sup></td><td>-0.59 [-0.95; -0.23]</td><td>.001</td><td></td><td></td><td></td></tr><tr><td>Unknown</td><td>46 (7.2)</td><td>32 (7.2)</td><td>14 (7.2)</td><td>-0.24 [-0.65;0.16]</td><td>.233</td><td>-0.12 [-0.52;0.28]</td><td>.552</td><td></td><td></td><td></td></tr><tr><td>Disease disability score (adapted from the EDSS)<sup>c</sup></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>No or minimal disability (ref.)</td><td>184 (28.7)</td><td>97 (21.7)</td><td>87 (44.8)</td><td>1</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Moderate or substantial disability</td><td>349 (54.5)</td><td>268 (60.0)</td><td>81 (41.8)</td><td>-0.66 [-0.90; -0.43]</td><td>&lt;10<sup>-3</sup></td><td>-0.33 [-0.59; -0.07]</td><td>.013</td><td></td><td></td><td></td></tr><tr><td>Total disability</td><td>108 (16.8)</td><td>82 (18.3)</td><td>26 (13.4)</td><td>-0.64 [-0.95; -0.32]</td><td>&lt;10<sup>-3</sup></td><td>0.06 [-0.34;0.47]</td><td>.759</td><td></td><td></td><td></td></tr></tbody></table>
<table><caption>TABLE 1 (Continued)</caption><thead><tr><th rowspan="2"></th><th>Total (n = 641)</th><th>France (n = 447)</th><th>Spain (n = 194)</th><th>Univariable analyses</th><th colspan="2">Multivariable analysis</th></tr><tr><th>No. of participants (%) or mean (SD)</th><th>No. of participants (%) or mean (SD)</th><th>No. of participants (%) or mean (SD)</th><th>Coeff [95% CI]</th><th>p-value</th><th>aCoeff [95% CI]</th><th>p-value</th></tr></thead><tbody><tr><td>Global health level (VAS)<sup>d</sup></td><td>5.9 (2.3)</td><td>5.7 (2.2)</td><td>6.3 (2.5)</td><td>0.07 [0.03;0.12]</td><td>.002</td><td></td><td></td></tr><tr><td>MS-related level of pain (VAS)<sup>e</sup></td><td>4.2 (2.7)</td><td>4.3 (2.6)</td><td>3.8 (3.0)</td><td>-0.04 [-0.08; -0.00]</td><td>.035</td><td></td><td></td></tr><tr><td>Intercept</td><td></td><td></td><td></td><td></td><td></td><td>0.48 [-0.06;1.01]</td><td>.081</td></tr></tbody></table>

Abbreviations: aCoeff, adjusted probit coefficient; CI, confidence interval; Coeff, probit coefficient; EDSS, Expanded Disability Status Scale; MS, multiple sclerosis; ref., reference; SD, standard deviation; VAS, visual analogue scale.

<sup>a</sup>Statistics for age are provided for descriptive purposes only. This variable was not entered in the models.

<sup>b</sup>Type of MS: relapsing–remitting MS (RRMS), primary progressive MS (PPMS), secondary progressive MS (SPMS), unknown.

<sup>c</sup>Disease severity score (adapted from the EDSS): no or minimal disability (0–2), moderate or substantial disability (3–7), total disability (8–10).

<sup>d</sup>Global health level (VAS): from 0 (the worst imaginable health state) to 10 (the best imaginable health state).

<sup>e</sup>MS-related pain level (VAS): from 0 (no pain) to 10 (extreme pain).

data for CBP as a whole. This original international study revealed that despite CBD or cannabis-based products being partly available, herb/resin remain the most commonly used products.

Despite the potential barriers to CBP access, the prevalence of use we found here would suggest that patients use cannabis or CBP because they alleviate their symptoms, especially neurologic/walking impairments, and pain. Nabiximols is generally approved for spasticity treatment but not for MS-related pain (Electronic Medicines Compendium, 2020). In countries where medical cannabis is approved, chronic pain is one of the most common conditions for its prescription (Boehnke et al., 2019; Schmidt-Wolf & Cremer-Schaeffer, 2021). In their systematic review, Nielsen et al. (2018) concluded that "recent high quality reviews supported the clinical use of cannabinoids for spasticity and pain in MS". With regard to pain, they reported one low-quality randomised controlled trial which highlighted positive effects for smoked cannabis, and 15 studies of varying quality which highlighted mixed effects for products based on a THC/CBD mixture. The responsiveness to the ataxic, antinociceptive and hypothermic effects of THC seems to be partially genetically determined (Parks et al., 2020), and may therefore partly explain the mixed results cited above.

Our results regarding pain are consistent with patient-reported outcomes from MS patients using cannabis for therapeutic reasons in different countries (Guarnaccia et al., 2021; Martínez-Rodríguez et al., 2008; Page & Verhoef, 2006). They reflect results from the French sub-sample of the present survey, in which 75% of CBP users reported positive CBP-related change in pain (Barré et al., 2022). They also echo previous evidence that cannabis and/or cannabinoids are beneficial in MS-related spasticity and neuropathic pain (Nielsen et al., 2018; Rice & Cameron, 2017). More broadly, MS patient-reported data elsewhere highlighted insomnia, mood disorders, nausea, and bladder problems as other MS-related symptoms which were alleviated by the use of cannabis (Clark et al., 2004; Guarnaccia et al., 2021; Page & Verhoef, 2006).

Our results for the prevalence of "natural" (i.e. non-synthetic) cannabis use—approximately 10% of the study population if we consider that half of those taking CBP used herb/resin-based products—are also consistent (despite being in the lower range) with previous reported cannabis use prevalence of 10%–50% in MS patients (Banwell et al., 2016; Chong et al., 2006; Clark et al., 2004; Gupta et al., 2019; Gustavsen et al., 2019; Martínez-Rodríguez et al., 2008; Ware et al., 2005). Specifically, the prevalence we found for Spain is consistent with that found by Martínez-Rodríguez et al. (2008) (17.1%). The lower values we found for cannabis use may be explained by the sampling process, which may have over-represented MS patients who were more informed about the disease and/or were more health-conscious, as well as those who preferred less harmful (i.e. non-smoked) routes of administration. They may also be explained by the all-encompassing definition used for cannabis in other studies (i.e. where all types of CBP, not only herb or resin, were considered as cannabis).

The association we found between self-reported MS-related pain and disability and CBP use is consistent with previous results
<figure><img src="image_5.png" /><figcaption>(b) Spain</figcaption></figure>

<figure><img src="image_6.png" /><figcaption>FIGURE 1 Cannabis-based products use in people with multiple sclerosis according to disease disability score as a function of country of residence: (a) France; (b) Spain (Carenity survey, n = 641).</figcaption></figure>

<table><caption>TABLE 2 Patterns of cannabis-based products and purchase location by users according to their country of residence (Carenity survey, n = 143).</caption><thead><tr><th rowspan="2"></th><th colspan="1">All participants<br>(n = 143)</th><th colspan="1">France (n = 39)</th><th colspan="1">Spain (n = 104)</th><th rowspan="2">p-value<sup>a</sup></th></tr><tr><th>No. of participants<br>(%)</th><th>No. of<br>participants (%)</th><th>No. of participants<br>(%)</th></tr></thead><tbody><tr><th colspan="5">Cannabis-based product<sup>b</sup></th></tr><tr><td>Nabiximols</td><td>19 (13.3)</td><td>3 (2.9)</td><td>16 (41.0)</td><td>&lt;10<sup>-3</sup></td></tr><tr><td>Edible</td><td>6 (4.2)</td><td>2 (1.9)</td><td>4 (10.3)</td><td>.047</td></tr><tr><td>Vaping</td><td>24 (16.8)</td><td>24 (23.1)</td><td>0 (0.0)</td><td>&lt;10<sup>-3</sup></td></tr><tr><td>Pills/capsules</td><td>10 (7.0)</td><td>10 (9.6)</td><td>0 (0.0)</td><td>.062</td></tr><tr><td>Dried herb/<br>resin</td><td>67 (46.8)</td><td>47 (45.2)</td><td>20 (51.3)</td><td>.516<sup>c</sup></td></tr><tr><td>Oil</td><td>53 (37.1)</td><td>48 (46.1)</td><td>5 (12.8)</td><td>&lt;10<sup>-3c</sup></td></tr><tr><td>Ointment</td><td>4 (2.8)</td><td>3 (2.9)</td><td>1 (2.6)</td><td>1.000</td></tr><tr><td>Spray</td><td>3 (2.1)</td><td>0 (0.0)</td><td>3 (7.7)</td><td>.019</td></tr><tr><th colspan="5">Purchase location<sup>b</sup></th></tr><tr><td>Pharmacy</td><td>22 (15.4)</td><td>4 (3.8)</td><td>18 (46.1)</td><td>&lt;10<sup>-3</sup></td></tr><tr><td>Internet</td><td>46 (32.2)</td><td>43 (41.3)</td><td>3 (7.7)</td><td>&lt;10<sup>-3</sup></td></tr><tr><td>Bordering<br>country</td><td>19 (13.3)</td><td>19 (18.3)</td><td>0 (0.0)</td><td>.002</td></tr><tr><td>From relatives</td><td>40 (28.0)</td><td>29 (27.9)</td><td>11 (28.2)</td><td>.970<sup>c</sup></td></tr><tr><td>On the street</td><td>26 (18.2)</td><td>21 (20.2)</td><td>5 (12.8)</td><td>.309<sup>c</sup></td></tr></tbody></table>

for Spain (Martínez-Rodríguez et al., 2008) and the UK (Chong et al., 2006). This association also suggests that CBP start to be used as a therapeutic strategy when MS symptoms become unbearable and/or other treatment options have failed to alleviate them. This is in line with the approval of nabiximols by the French and Spanish health authorities for non-respondent patients (i.e. who do not respond adequately to other anti-spasticity medication; Agence

Nationale de Sécurité du Médicament et des Produits de Santé, 2014; Almirall, 2010). Our results indirectly suggest that patients tend to assess for themselves the benefit-risk balance of CBP use, and that the more severe the disability and/or pain, the more likely they are to try using CBP to alleviate symptoms. Among the barriers that patients may have to overcome in this context, we can cite illegality (Banwell et al., 2016), fear of side effects (Pratt et al., 2019; Urits

<footnote><sup>a</sup>Fisher's exact test by default.</footnote>

<footnote><sup>b</sup>Multiple responses were possible.</footnote>

<footnote><sup>c</sup>Chi-squared test.</footnote>
<table><caption>TABLE 3 Factors associated with cannabis-based products use in people with multiple sclerosis, taking into account differences in participants' characteristics according to country of residence (seemingly unrelated bivariate probit regression, univariable and multivariable analyses, Carenity survey, n = 641).</caption><thead><tr><th rowspan="2"></th><th rowspan="2">Total<br>(n = 641)<br>No. of<br>participants<br>(%) or mean<br>(SD)</th><th colspan="2">Cannabis-based products use</th><th rowspan="2">Univariable<br>analyses<sup>a</sup><br>Coeff [95% CI]</th><th rowspan="2">p-value</th><th rowspan="2">Multivariable<br>analysis<sup>b</sup><br>aCoeff [95% CI]</th><th rowspan="2">p-value</th></tr><tr><th>No (n = 498)<br>No. of<br>participants (%)<br>or mean (SD)</th><th>Yes (n = 143)<br>No. of<br>participants (%)<br>or mean (SD)</th></tr></thead><tbody><tr><td>Country of residence</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>France (ref.)</td><td>447 (69.7)</td><td>343 (68.9)</td><td>104 (72.7)</td><td>1</td><td></td><td>1</td><td></td></tr><tr><td>Spain</td><td>194 (30.3)</td><td>155 (31.1)</td><td>39 (27.3)</td><td>-0.50 [-1.10;0.10]</td><td>.100</td><td>0.20 [-0.54;0.95]</td><td>.589</td></tr><tr><td>Gender</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Female (ref.)</td><td>466 (72.7)</td><td>375 (75.3)</td><td>91 (63.6)</td><td>1</td><td></td><td>1</td><td></td></tr><tr><td>Male</td><td>175 (27.3)</td><td>123 (24.7)</td><td>52 (36.4)</td><td>0.31 [0.07;0.55]</td><td>.012</td><td>0.34 [0.09;0.58]</td><td>.006</td></tr><tr><td>Age (years)</td><td>47.1 (11.1)</td><td>46.9 (11.1)</td><td>47.9 (11.3)</td><td>-0.00 [-0.02;0.01]</td><td>.695</td><td></td><td></td></tr><tr><td>Town/city size (no.<br>of inhabitants)</td><td></td><td></td><td></td><td></td><td></td><td>.910</td><td></td></tr><tr><td>&lt;1000 (ref.)</td><td>254 (39.6)</td><td>194 (39.0)</td><td>60 (42.0)</td><td>1</td><td></td><td></td><td></td></tr><tr><td>10,000-100,000</td><td>226 (35.3)</td><td>176 (35.3)</td><td>50 (35.0)</td><td>0.04 [-0.23;0.31]</td><td>.764</td><td></td><td></td></tr><tr><td>&gt;100,000</td><td>161 (25.1)</td><td>128 (25.7)</td><td>33 (23.1)</td><td>0.08 [-0.29;0.44]</td><td>.669</td><td></td><td></td></tr><tr><td>Educational level</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>&le;upper<br>secondary<br>school<br>certificate<br>(ref.)</td><td>330 (51.5)</td><td>260 (52.2)</td><td>70 (49.0)</td><td>1</td><td></td><td></td><td></td></tr><tr><td>&gt;upper<br>secondary<br>school<br>certificate</td><td>311 (48.5)</td><td>238 (47.8)</td><td>73 (51.1)</td><td>0.10 [-0.11;0.31]</td><td>.372</td><td></td><td></td></tr><tr><td>Time since<br>diagnosis (years)</td><td>12.4 (9.2)</td><td>12.1 (8.9)</td><td>13.5 (9.8)</td><td>0.01 [-0.01;0.02]</td><td>.260</td><td></td><td></td></tr><tr><td>Age at diagnosis<br>(years)</td><td>34.7 (10.3)</td><td>34.8 (10.3)</td><td>34.4 (10.5)</td><td>-0.01 [-0.02;0.00]</td><td>.139</td><td></td><td></td></tr><tr><td>MS-related<br>spasticity<br>related to MS</td><td></td><td></td><td></td><td></td><td></td><td>.052</td><td></td></tr><tr><td>Yes (ref.)</td><td>469 (73.2)</td><td>353 (70.9)</td><td>116 (81.1)</td><td>1</td><td></td><td></td><td></td></tr><tr><td>No</td><td>98 (15.3)</td><td>86 (17.3)</td><td>12 (8.4)</td><td>-0.44 [-0.80;-0.08]</td><td>.016</td><td></td><td></td></tr><tr><td>Unknown</td><td>74 (11.5)</td><td>59 (11.9)</td><td>15 (10.5)</td><td>-0.12 [-0.47;0.23]</td><td>.500</td><td></td><td></td></tr><tr><td>Type of MS<sup>c</sup></td><td></td><td></td><td></td><td></td><td></td><td>.233</td><td></td></tr><tr><td>RRMS (ref.)</td><td>365 (56.9)</td><td>288 (57.8)</td><td>77 (53.9)</td><td>1</td><td></td><td></td><td></td></tr><tr><td>PPMS</td><td>95 (14.8)</td><td>71 (14.3)</td><td>24 (16.8)</td><td>0.05 [-0.33;0.43]</td><td>.787</td><td></td><td></td></tr><tr><td>SPMS</td><td>135 (21.1)</td><td>98 (19.7)</td><td>37 (25.9)</td><td>0.12 [-0.23;0.47]</td><td>.514</td><td></td><td></td></tr><tr><td>Unknown</td><td>46 (7.2)</td><td>41 (8.2)</td><td>5 (3.5)</td><td>-0.46 [-0.96;0.04]</td><td>.073</td><td></td><td></td></tr><tr><td>Disease disability<br>score (adapted<br>from the EDSS)<sup>d</sup></td><td></td><td></td><td></td><td></td><td></td><td>.004</td><td>.024</td></tr><tr><td>No or minimal<br>disability (ref.)</td><td>184 (28.7)</td><td>159 (31.9)</td><td>25 (17.5)</td><td>1</td><td></td><td>1</td><td></td></tr></tbody></table>

(Continues)
<table><caption>TABLE 3 (Continued)</caption><thead><tr><th rowspan="3"></th><th rowspan="2">Total<br>(n = 641)</th><th colspan="2">Cannabis-based products use</th><th rowspan="2">Univariable<br>analyses<sup>a</sup></th><th rowspan="2">Multivariable<br>analysis<sup>b</sup></th></tr><tr><th>No (n = 498)</th><th>Yes (n = 143)</th></tr><tr><th>No. of<br>participants<br>(%) or mean<br>(SD)</th><th>No. of<br>participants (%)<br>or mean (SD)</th><th>No. of<br>participants (%)<br>or mean (SD)</th><th>Coeff [95% CI]</th><th>p-value</th><th>aCoeff [95% CI]</th><th>p-value</th></tr></thead><tbody><tr><td>Moderate or<br>substantial<br>disability</td><td>349 (54.5)</td><td>263 (52.8)</td><td>86 (60.1)</td><td>0.45 [0.14;0.76]</td><td>.004</td><td>0.36 [0.05;0.67]</td><td>.025</td></tr><tr><td>Total disability</td><td>108 (16.9)</td><td>76 (15.3)</td><td>32 (22.4)</td><td>0.60 [0.23;0.96]</td><td>.001</td><td>0.51 [0.13;0.88]</td><td>.008</td></tr><tr><td>Global health level<br>(VAS)<sup>e</sup></td><td>5.9 (2.3)</td><td>5.9 (2.3)</td><td>5.7 (2.4)</td><td>-0.00 [-0.06;0.05]</td><td>.866</td><td></td><td></td></tr><tr><td>MS-related level of<br>pain (VAS)<sup>f</sup></td><td>4.2 (2.7)</td><td>4.0 (2.7)</td><td>4.7 (2.9)</td><td>0.04 [0.00;0.09]</td><td>.036</td><td>0.04 [0.00;0.09]</td><td>.045</td></tr><tr><td>Intercept</td><td></td><td></td><td></td><td></td><td>-1.40<br>[-1.81;-1.00]</td><td></td><td>&lt;10<sup>-3</sup></td></tr></tbody></table>

Abbreviations: aCoeff, adjusted probit coefficient; CI, confidence interval; Coeff, probit coefficient; EDSS, Expanded Disability Status Scale; MS, multiple sclerosis; ref., reference; SD, standard deviation; VAS, visual analog scale.

<sup>a</sup>Adjusted for country of residence, seemingly unrelated bivariate probit, with the second equation for country of residence containing the explicative variables listed in the multivariable model in Table 1.

<sup>b</sup>Seemingly unrelated bivariate probit, with the second equation for country of residence containing the explicative variables listed in the multivariable model in Table 1.

<sup>c</sup>Type of MS: relapsing–remitting MS (RRMS), primary progressive MS (PPMS), secondary progressive MS (SPMS), unknown.

<sup>d</sup>Disease disability score (adapted from the EDSS): no or minimal disability (0–2), moderate or substantial disability (3–7), total disability (8–10).

<sup>e</sup>Global health level (VAS): from 0 (the worst imaginable health state) to 10 (the best imaginable health state).

<sup>f</sup>MS-related pain level (VAS): from 0 (no pain) to 10 (extreme pain).

et al., 2021), lack of information on the practical use and efficacy of cannabis use for patients and doctors alike (Alexander, 2020; Temple et al., 2019), social or moral considerations (Page & Verhoef, 2006), and high prices.

We found that patients with MS in France use CBP for therapeutic purposes, and that cannabis herb/resin (mostly from street) and oil are the most common forms of CBP used. Herb/resin is also the most common form of CBP in Spain, far exceeding nabiximols, which can only be dispensed in the country's hospital pharmacies. While Canada, the USA and 23 European countries have approved several CBP, only five reviewed by Abuhasira et al. (2018) (Canada, Germany, Israel and the Netherlands, and over 50% of the states in the United States) have fully authorised the medical use of herbal cannabis. Moreover, those authors reported that most regulators allow physicians to decide what specific indications they will prescribe cannabis for (Abuhasira et al., 2018). This finding reflects a void in the counselling of physicians on cannabis use, as highlighted elsewhere (Calcaterra et al., 2020).

Our results add to the body of literature suggesting that cannabis and CBP use helps alleviate symptoms for patients with more severe MS. Physicians, if properly trained and brought up to date on CBP, can therefore be encouraged to explore MS patients' attitudes regarding cannabis and CBP use and, according to their disease severity and symptom patterns, can prescribe or counsel CBP and/or provide state-of-the-art information about the potential benefits of CBP use for therapeutic purposes. However, in the

context of France, none of this can happen before policy makers and law enforcers remove the legal barriers to cannabis and CBP use. Therefore, all healthcare professionals involved in MS patients care may participate in screening for and assessing cannabis use in those patients, keeping in mind that stronger pain and disability increase the likelihood of use. Moreover, as herb/resin is likely to be the most commonly used product, professionals' knowledge on harm reduction practices (Fischer et al., 2017; Meffert et al., 2019) may benefit to patients.

Setting up an appropriate regulation toward the therapeutic use of CBP would improve access to them, but would also avoid patients' exposure to uncontrolled and potentially adulterated and/or mislabeled CBP. This is for instance acutely needed in France, where cannabis flowers must come from the black market, which provides increasingly potent cannabis (Freeman et al., 2021).

We found that CBP use was lower in men than in women, which is inconsistent with results for cannabis from Canada (Clark et al., 2004), the UK (Ware et al., 2005) and the USA (Gupta et al., 2019). This difference may be related to the recent proliferation of CBD products (Walker et al., 2020), which can be legally sold in France and Spain, and which seem to attract more female than male buyers (Moltke & Hindocha, 2021; Wheeler et al., 2020).

To our knowledge, this is the first study to report the prevalence and correlates of CBP use in French patients with MS. Another strength is the international sampling design. By including patients from two countries—France and Spain—while statistically taking
<table><caption>TABLE 4 Factors associated with daily use of cannabis-based products in people with multiple sclerosis, accounting for differences in participants' characteristics by country of residence (seemingly unrelated bivariate probit regression, univariable and multivariable analyses, Carenity survey, n = 641).</caption><thead><tr><th rowspan="2"></th><th rowspan="2">Total (n = 641)<br>No. of<br>participants<br>(%) or mean<br>(SD)</th><th colspan="2">Daily use of cannabis-based products</th><th rowspan="2">Univariable<br>analyses<sup>a</sup><br>Coeff [95% CI]</th><th rowspan="2">p-value</th><th rowspan="2">Multivariable<br>analysis<sup>b</sup><br>aCoeff [95% CI]</th><th rowspan="2">p-value</th></tr><tr><th>No (n = 541)<br>No. of<br>participants (%)<br>(%) or mean (SD)</th><th>Yes (n = 100)<br>No. of participants<br>(%) or mean (SD)</th></tr></thead><tbody><tr><td>Country of residence</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>France (ref.)</td><td>447 (69.7)</td><td></td><td></td><td>1</td><td></td><td>1</td><td></td></tr><tr><td>Spain</td><td>194 (30.3)</td><td></td><td></td><td>-0.27 [-0.98;0.43]</td><td>.445</td><td>0.32 [-0.53;1.17]</td><td>.461</td></tr><tr><td>Gender</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Female (ref.)</td><td>466 (72.7)</td><td>399 (73.7)</td><td>67 (67.0)</td><td>1</td><td></td><td></td><td></td></tr><tr><td>Male</td><td>175 (27.3)</td><td>142 (26.2)</td><td>33 (33.0)</td><td>0.18 [-0.09;0.44]</td><td>.191</td><td></td><td></td></tr><tr><td>Age (years)</td><td>47.1 (11.1)</td><td>47.1 (11.0)</td><td>47.5 (11.5)</td><td>-0.00 [-0.02;0.01]</td><td>.746</td><td></td><td></td></tr><tr><td>Town/city size (no.<br>of inhabitants)</td><td></td><td></td><td></td><td></td><td></td><td>.320</td><td></td></tr><tr><td>&lt;1000 (ref.)</td><td>254 (39.6)</td><td>215 (39.7)</td><td>39 (39.0)</td><td>1</td><td></td><td></td><td></td></tr><tr><td>10,000-100,000</td><td>226 (35.3)</td><td>193 (35.7)</td><td>33 (33.0)</td><td>0.06 [-0.24;0.35]</td><td>.712</td><td></td><td></td></tr><tr><td>&gt;100,000</td><td>161 (25.1)</td><td>133 (24.6)</td><td>28 (28.0)</td><td>0.26 [-0.10;0.63]</td><td>.154</td><td></td><td></td></tr><tr><td>Educational level</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>≤upper<br>secondary<br>school<br>certificate<br>(ref.)</td><td>330 (51.5)</td><td>283 (52.3)</td><td>47 (47.0)</td><td>1</td><td></td><td></td><td></td></tr><tr><td>&gt;upper<br>secondary<br>school<br>certificate</td><td>311 (48.5)</td><td>258 (47.7)</td><td>53 (53.0)</td><td>0.13 [-0.10;0.37]</td><td>.275</td><td></td><td></td></tr><tr><td>Time since<br>diagnosis (years)</td><td>12.4 (9.2)</td><td>12.3 (9.1)</td><td>13.1 (9.6)</td><td>0.00 [-0.01;0.02]</td><td>.551</td><td></td><td></td></tr><tr><td>Age at diagnosis<br>(years)</td><td>34.7 (10.3)</td><td>34.8 (10.2)</td><td>34.4 (10.7)</td><td>-0.01 [-0.02;0.01]</td><td>.370</td><td></td><td></td></tr><tr><td>MS-related<br>spasticity</td><td></td><td></td><td></td><td></td><td></td><td>.033</td><td></td></tr><tr><td>Yes (ref.)</td><td>469 (73.2)</td><td>387 (71.5)</td><td>82 (82.0)</td><td>1</td><td></td><td></td><td></td></tr><tr><td>No</td><td>98 (15.3)</td><td>91 (16.8)</td><td>7 (7.0)</td><td>-0.53 [-0.93;-0.13]</td><td>.009</td><td></td><td></td></tr><tr><td>Unknown</td><td>74 (11.5)</td><td>63 (11.7)</td><td>11 (11.0)</td><td>-0.10 [-0.48;0.28]</td><td>.599</td><td></td><td></td></tr><tr><td>Type of MS<sup>c</sup></td><td></td><td></td><td></td><td></td><td></td><td>.035</td><td></td></tr><tr><td>RRMS (ref.)</td><td>365 (56.9)</td><td>315 (58.2)</td><td>50 (50.0)</td><td>1</td><td></td><td></td><td></td></tr><tr><td>PPMS</td><td>95 (14.8)</td><td>78 (14.4)</td><td>17 (17.0)</td><td>0.24 [-0.14;0.61]</td><td>.223</td><td></td><td></td></tr><tr><td>SPMS</td><td>135 (21.1)</td><td>105 (19.4)</td><td>30 (30.0)</td><td>0.39 [0.05;0.73]</td><td>.025</td><td></td><td></td></tr><tr><td>Unknown</td><td>46 (7.2)</td><td>43 (8.0)</td><td>3 (3.0)</td><td>-0.39 [-0.98;0.19]</td><td>.190</td><td></td><td></td></tr><tr><td>Disease disability<br>score (adapted<br>from the EDSS)<sup>d</sup></td><td></td><td></td><td></td><td></td><td></td><td>.011</td><td>.011</td></tr><tr><td>No or minimal<br>disability<br>(ref.)</td><td>184 (28.7)</td><td>166 (30.7)</td><td>18 (18.0)</td><td>1</td><td></td><td>1</td><td></td></tr></tbody></table>

(Continues)
<table><caption>TABLE 4 (Continued)</caption><thead><tr><th rowspan="2"></th><th rowspan="2">Total (n = 641)<br>No. of<br>participants<br>(%) or mean<br>(SD)</th><th colspan="2">Daily use of cannabis-based products</th><th rowspan="2">Univariable<br>analyses<sup>a</sup><br>Coeff [95% CI]</th><th rowspan="2">p-value</th><th rowspan="2">Multivariable<br>analysis<sup>b</sup><br>aCoeff [95% CI]</th><th rowspan="2">p-value</th></tr><tr><th>No (n = 541)<br>No. of<br>participants (%)<br>or mean (SD)</th><th>Yes (n = 100)<br>No. of participants<br>(%) or mean (SD)</th></tr></thead><tbody><tr><td>Moderate or<br>substantial<br>disability</td><td>349 (54.5)</td><td>291 (53.8)</td><td>58 (58.0)</td><td>0.40 [0.06;0.73]</td><td>.020</td><td>0.40 [0.06;0.73]</td><td>.020</td></tr><tr><td>Total disability</td><td>108 (16.8)</td><td>84 (15.5)</td><td>24 (24.0)</td><td>0.060 [0.20;0.99]</td><td>.003</td><td>0.60 [0.20;0.99]</td><td>.003</td></tr><tr><td>Global health level<br>(VAS)<sup>e</sup></td><td>5.9 (2.3)</td><td>5.9 (2.3)</td><td>5.7 (2.3)</td><td>-0.01 [-0.07;0.04]</td><td>.701</td><td></td><td></td></tr><tr><td>MS-related level of<br>pain (VAS)<sup>f</sup></td><td>4.2 (2.7)</td><td>4.1 (2.7)</td><td>4.6 (3.0)</td><td>0.03 [-0.02;0.08]</td><td>.194</td><td></td><td></td></tr><tr><td>Intercept</td><td></td><td></td><td></td><td></td><td></td><td>-1.43 [-1.84;-1.03]</td><td>&lt;10<sup>-3</sup></td></tr></tbody></table>

Abbreviations: aCoeff, adjusted probit coefficient; CI, confidence interval; Coeff, probit coefficient; EDSS, Expanded Disability Status Scale; MS, multiple sclerosis; ref., reference; SD, standard deviation; VAS, visual analogue scale.

<sup>a</sup>Adjusted for country of residence, seemingly unrelated bivariate probit, with the second equation for country of residence containing the explicative variables listed in the multivariable model in Table 1.

<sup>b</sup>Seemingly unrelated bivariate probit, with the second equation for country of residence containing the explicative variables listed in the multivariable model in Table 1.

<sup>c</sup>Type of MS: relapsing–remitting MS (RRMS), primary progressive MS (PPMS), secondary progressive MS (SPMS), unknown.

<sup>d</sup>Disease disability score (adapted from the EDSS): no or minimal disability (0–2), moderate or substantial disability (3–7), total disability (8–10).

<sup>e</sup>Global health level (VAS): from 0 (the worst imaginable health state) to 10 (the best imaginable health state).

<sup>f</sup>MS-related pain level (VAS): from 0 (no pain) to 10 (extreme pain).

into account the differences between socio-demographic and MS-related characteristics according to the country of residence, we highlighted correlates of CBP use common to both.

Our study sample cannot be considered representative of all Spanish or French patients with MS, and therefore we cannot generalise our results. More specifically, we recruited participants who were familiar with social media and internet platforms, and who engaged in community-based exchange. However, the fact that the majority of our study population were women with RRMS is consistent with the general features of populations with MS (Biernacki et al., 2020; Ramagopalan et al., 2010; Romanelli et al., 2020). Moreover, online surveying is likely to reduce the desirability bias which is expected to lead to under-reporting of CBP use, for instance in case of face-to-face interview with physician. Finally, MS-related disability was assessed through a self-administered questionnaire, and therefore, has not been clinically validated.

## 5 | CONCLUSION

To conclude, in a sample of French and Spanish patients with MS, patients experiencing higher levels of MS-related disability and/or pain were more likely to use CBP to alleviate their symptoms, and herb/ resin was the most common form of administration. Further studies are needed to shed more light on patients' practices and on the clinical efficacy of cannabis-based treatments for MS-related symptoms. Results from these studies may encourage health authorities

to consider relaxing the barriers to cannabis use for MS patients in need for relief from pain.

## 6 | RELEVANCE TO CLINICAL PRACTICE

CBP are used by MS patients, especially those with more severe symptoms. There is a need to be aware of it and discuss this topic with them. Taking into account such use may help in properly assessing the patients' symptoms, as well as their unmet needs. Moreover, subsequent checking for drug-drug interactions between cannabinoids and current treatments may prevent drug-related risks. Finally, nurses and healthcare professionals may provide CBP and harm reduction counselling to optimise patients' benefits from such a use. When possible, access to safe CBP may be eased.

### AUTHOR CONTRIBUTIONS

*Project Conception:* Tangui Barré, Damien Testa, Melina Santos, Fabienne Marcellin, Perrine Roux, Patrizia Carrieri, Lise Radoszycki and Camelia Protopopescu. *Project organisation:* Tangui Barré, Damien Testa, Melina Santos, Fabienne Marcellin, Perrine Roux, Patrizia Carrieri, Lise Radoszycki and Camelia Protopopescu. *Project execution:* Tangui Barré and Patrizia Carrieri. *Statistical analysis design:* Tangui Barré, Patrizia Carrieri and Camelia Protopopescu. *Statistical analysis–execution:* Camelia Protopopescu. *Statistical analysis–review and critique:* Tangui Barré and Camelia Protopopescu. *Preparation of the first draft of manuscript:* Tangui Barré. *Review and*
critique of manuscript: Tangui Barré, Damien Testa, Melina Santos, Fabienne Marcellin, Perrine Roux, Patrizia Carrieri, Lise Radoszycki and Camelia Protopopescu.

ACKNOWLEDGEMENTS

We thank the participating patients. We also thank Jude Sweeney (Milan, Italy) for revising the English language and copyediting the manuscript.

FUNDING INFORMATION

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

CONFLICT OF INTEREST STATEMENT

The authors declare that there are no conflicts of interest relevant to this work. The authors also declare that there are no additional disclosures to report.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available on re-
quest from the corresponding author. The data are not publicly avail-
able due to privacy or ethical restrictions.

ETHICAL APPROVAL

The study was conducted in accordance with the Declaration of
Helsinki. According to French law and anonymity of data, no ap-
proval from ethics committee was needed. Informed written con-
sent was obtained from all individual participants included in the
study.

ORCID

Tangui Barré https://orcid.org/0000-0002-3439-8868

REFERENCES

Abuhasira, R., Shbiro, L., & Landschaft, Y. (2018). Medical use of cannabis and cannabinoids containing products—Regulations in Europe and North America. *European Journal of Internal Medicine, 49*, 2–6.
https://doi.org/10.1016/j.ejim.2018.01.001

Agence Nationale de Sécurité du Médicament et des Produits de Santé. (2014). Résumé des Caractéristiques du Produit. Retrieved February 22, 2022, from http://agence-prd.ansm.sante.fr/php/ecodex/rcp/R0242579.htm

Agence Nationale de Sécurité du Médicament et des Produits de Santé. (2021). Cadre et mise en oeuvre de l'expérimentation (Framework and implementation of the experimentation). Retrieved August 25, 2021, from https://ansm.sante.fr/dossiers-thematiques/cannabis-a-usage-medical/cadre-et-mise-en-oeuvre-de-l-experimentation-du-cannabis-medical

Alexander, S. P. (2020). Barriers to the wider adoption of medi-
nal cannabis. *British Journal of Pain*, 14(2), 122–132. https://doi.
org/10.1177/2049463720922884

Almirall. (2010). *Sativex® receives regulatory authorisation in Spain*.
Retrieved July 6, 2021, from https://www.almirall.de/documents/
portlet_file_entry/4257831/1401_EN_Spain_regulatoryAppro-
val_final_-with_MRP.pdf/953d6e94-0343-42e1-9eff-951cb
30c9f48

Atkinson, M., & Lennox, R. (2006). Extending basic principles of measurement models to the design and validation of patient reported outcomes. *Health and Quality of Life Outcomes, 4*, 65. https://doi.org/10.1186/1477-7525-4-65

Banwell, E., Pavisian, B., Lee, L., & Feinstein, A. (2016). Attitudes to cannabis and patterns of use among Canadians with multiple sclerosis. *Multiple Sclerosis and Related Disorders, 10*, 123–126. https://doi.org/10.1016/j.msdard.2016.09.008

Barré, T., Ramier, C., Protopopescu, C., Carrieri, P., & Radoszycki, L. (2022). Symptom improvements following therapeutic use of cannabis-based products in French people with multiple sclerosis. *Multiple Sclerosis and Related Disorders, 67*, 104093. https://doi.org/10.1016/j.msdard.2022.104093

Belackova, V., & Wilkins, C. (2018). Consumer agency in cannabis supply—Exploring auto-regulatory documents of the cannabis social clubs in Spain. *The International Journal on Drug Policy*, 54, 26–34. https://doi.org/10.1016/j.drugpo.2017.12.018

Biernacki, T., Sandi, D., Fricska-Nagy, Z., Kincses, Z. T., Füvesi, J., Laczkó, R., ... Bencsik, K. (2020). Epidemiology of multiple sclerosis in Central Europe, update from Hungary. *Brain and Behavior, 10*(5), e01598. https://doi.org/10.1002/brb3.1598

Boehnke, K. F., Gangopadhyay, S., Clauw, D. J., & Haffajee, R. L. (2019). Qualifying conditions of medical cannabis license holders in the United States. *Health Affairs (Project Hope)*, 38(2), 295–302. https://doi.org/10.1377/hlthaff.2018.05266

Brown, J. D., & Winterstein, A. G. (2019). Potential adverse drug events and drug-drug interactions with medical and consumer cannabis (CBD) use. *Journal of Clinical Medicine*, 8(7), 989. https://doi.org/10.3390/jcm8070989

Calcaterra, S. L., Cunningham, C. O., & Hopfer, C. J. (2020). The void in clinician counseling of cannabis use. *Journal of General Internal Medicine*, 35(6), 1875–1878. https://doi.org/10.1007/s11606-019-05612-4

Carenity. (2019). *Qui sommes-nous?* Retrieved July 15, 2020, from https://www.carenity.com/

Chong, M. S., Wolff, K., Wise, K., Tanton, C., Winstock, A., & Silber, E. (2006). Cannabis use in patients with multiple sclerosis. *Multiple Sclerosis Journal*, 12(5), 646–651. https://doi.org/10.1177/1352458506070947

Clark, A. J., Ware, M. A., Yazer, E., Murray, T. J., & Lynch, M. E. (2004). Patterns of cannabis use among patients with multiple sclerosis. *Neurology*, 62(11), 2098–2100. https://doi.org/10.1212/01.wnl.0000127707.07621.72

Dobson, R., & Giovannoni, G. (2019). Multiple sclerosis—A review. *European Journal of Neurology*, 26(1), 27–40. https://doi.org/10.1111/ene.13819

Electronic Medicines Compendium. (2020). *Sativex oromucosal spray—Summary of product characteristics*. Retrieved July 6, 2021, from https://www.medicines.org.uk/emc/product/602/smpc#gref

Feigin, V. L., Krishnamurthi, R. V., Theadom, A. M., Abajobir, A. A., Mishra, S. R., Ahmed, M. B., ... Zaki, M. E. (2017). Global, regional, and national burden of neurological disorders during 1990–2015: A systematic analysis for the global burden of disease study 2015. *The Lancet Neurology*, 16(11), 877–897. https://doi.org/10.1016/S1474-4422(17)30299-5

Fischer, B., Russell, C., Sabioni, P., van den Brink, W., Le Foll, B., Hall, W., ... Room, R. (2017). Lower-risk cannabis use guidelines: A comprehensive update of evidence and recommendations. *American Journal of Public Health*, 107(8), e1–e12. https://doi.org/10.2105/AJPH.2017.303818

Freeman, T. P., Craft, S., Wilson, J., Stylianou, S., ElSohly, M., Di Forti, M., & Lynskey, M. T. (2021). Changes in delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) concentrations in cannabis over time: Systematic review and meta-analysis. *Addiction* (Abingdon, England), 116(5), 1000–1010. https://doi.org/10.1111/add.15253
Gilmour, H., Ramage-Morin, P. L., & Wong, S. L. (2018). Multiple sclerosis: Prevalence and impact. *Health Reports*, 29(1), 3–8.

Gorospe Elezcano, J. (2020). *Respuesta del Gobierno (Government's reply)*. Retrieved August 4, 2022, from https://www.congreso.es/entradap/114p/e5/e_0054632_n_000.pdf

Greene, W. (2017). *Econometric analysis* (8th ed.). Pearson.

Guarnaccia, J. B., Khan, A., Ayettey, R., Treu, J. A., Comerford, B., & Njike, V. Y. (2021). Patterns of medical cannabis use among patients diagnosed with multiple sclerosis. *Multiple Sclerosis and Related Disorders*, 50, 102830. https://doi.org/10.1016/j.msdard.2021.102830

Gupta, S., Fellows, K., Weinstock-Guttman, B., Hagemeier, J., Zivadinov, R., & Ramanathan, M. (2019). Marijuana use by patients with multiple sclerosis. *International Journal of MS Care*, 21(2), 57–62. https://doi.org/10.7224/1537-2073.2017-112

Gustavsen, S., Søndergaard, H. B., Andresen, S. R., Magyari, M., Sørensen, P. S., Sellebjerg, F., & Oturai, A. B. (2019). Illegal cannabis use is common among Danes with multiple sclerosis. *Multiple Sclerosis and Related Disorders*, 33, 5–12. https://doi.org/10.1016/j.msdard.2019.05.008

HaGani, N., Sznitman, S., Dor, M., Bar-Sela, G., Oren, D., Margolis-Dorfman, L., ... Green, M. S. (2022). Attitudes toward the use of medical cannabis and the perceived efficacy, side-effects and risks: A survey of patients, nurses and physicians. *Journal of Psychoactive Drugs*, 54(5), 393–402. https://doi.org/10.1080/02791072.2021.2009598

Hulaihel, A., Gliksberg, O., Feingold, D., Brill, S., Amit, B. H., Lev-ran, S., & Sznitman, S. R. (2022). Medical cannabis and stigma: A qualitative study with patients living with chronic pain. *Journal of Clinical Nursing*. https://doi.org/10.1111/jocn.16340

Karcioglu, O., Topacoglu, H., Dikme, O., & Dikme, O. (2018). A systematic review of the pain scales in adults: Which to use? *The American Journal of Emergency Medicine*, 36(4), 707–714. https://doi.org/10.1016/j.ajem.2018.01.008

Kister, I., Bacon, T., & Cutter, G. R. (2020). A longitudinal study of symptom botheration in multiple sclerosis. *Multiple Sclerosis and Related Disorders*, 46, 102585. https://doi.org/10.1016/j.msdard.2020.102585

Kister, I., Bacon, T. E., Chamot, E., Salter, A. R., Cutter, G. R., Kalina, J. T., & Herbert, J. (2013). Natural history of multiple sclerosis symptoms. *International Journal of MS Care*, 15(3), 146–156. https://doi.org/10.7224/1537-2073.2012-053

Kurtzke, J. (1983). Rating neurological impairment in multiple sclerosis: An expanded disability status scale. *Neurology*, 33, 1444–1452.

Lublin, F. D., Coetzee, T., Cohen, J. A., Marrie, R. A., & Thompson, A. J. (2020). The 2013 clinical course descriptors for multiple sclerosis: A clarification. *Neurology*, 94(24), 1088–1092. https://doi.org/10.1212/WNL.00000000000009636

Lublin, F. D., Reingold, S. C., Cohen, J. A., Cutter, G. R., Sørensen, P. S., Thompson, A. J., ... Polman, C. H. (2014). Defining the clinical course of multiple sclerosis: The 2013 revisions. *Neurology*, 83(3), 278–286. https://doi.org/10.1212/WNL.0000000000000560

Martínez-Rodríguez, J. E., Munteis, E., Carreño, M., Blanco, Y., Roquer, J., Abanades, S., ... Saiz, A. (2008). Cannabis use in Spanish patients with multiple sclerosis: Fulfilment of patients' expectations? *Journal of the Neurological Sciences*, 273(1), 103–107. https://doi.org/10.1016/j.jns.2008.06.037

McGinley, M. P., Goldschmidt, C. H., & Rae-Grant, A. D. (2021). Diagnosis and treatment of multiple sclerosis: A review. *JAMA*, 325(8), 765–779. https://doi.org/10.1001/jama.2020.26858

Meffert, B. N., Morabito, D. M., Mosich, M. K., Loflin, M. J., Sottile, J., & Heinz, A. J. (2019). Navigating blind in the Green rush: Clinical considerations and harm reduction practices for cannabis. *Current Drug Research Reviews*, 11(1), 3–11. https://doi.org/10.2174/2589977511666181109153958

Melnikov, S., Aboav, A., Shalom, E., Phriedman, S., & Khalaila, K. (2021). The effect of attitudes, subjective norms and stigma on health-care

providers' intention to recommend medicinal cannabis to patients. *International Journal of Nursing Practice*, 27(1), e12836. https://doi.org/10.1111/ijn.12836

Moltke, J., & Hindocha, C. (2021). Reasons for cannabidiol use: A cross-sectional study of CBD users, focusing on self-perceived stress, anxiety, and sleep problems. *Journal of Cannabis Research*, 3(1), 5. https://doi.org/10.1186/s42238-021-00061-5

Nayak, M. M., Revette, A., Chai, P. R., Lansang, K., Sannes, T., Tung, S., & Braun, I. M. (2022). Medical cannabis-related stigma: Cancer survivors' perspectives. *Journal of Cancer Survivorship: Research and Practice*. https://doi.org/10.1007/s11764-022-01297-7

Nielsen, S., Germanos, R., Weier, M., Pollard, J., Degenhardt, L., Hall, W., ... Farrell, M. (2018). The use of cannabis and cannabinoids in treating symptoms of multiple sclerosis: A systematic review of reviews. *Current Neurology and Neuroscience Reports*, 18(2), 8. https://doi.org/10.1007/s11910-018-0814-x

Page, S. A., & Verhoef, M. J. (2006). Medicinal marijuana use, experiences of people with multiple sclerosis. *Canadian Family Physician*, 52(1), 65.

Parks, C., Jones, B. C., Moore, B. M., & Mulligan, M. K. (2020). Sex and strain variation in initial sensitivity and rapid tolerance to Δ9-tetrahydrocannabinol. *Cannabis and Cannabinoid Research*, 5(3), 231–245. https://doi.org/10.1089/can.2019.0047

Pratt, M., Stevens, A., Thuku, M., Butler, C., Skidmore, B., Wieland, L. S., ... Hutton, B. (2019). Benefits and harms of medical cannabis: A scoping review of systematic reviews. *Systematic Reviews*, 8, 320. https://doi.org/10.1186/s13643-019-1243-x

Ramagopalan, S. V., Byrnes, J. K., Orton, S.-M., Dyment, D. A., Guimond, C., Yee, I. M., ... Sadovnick, A. D. (2010). Sex ratio of multiple sclerosis and clinical phenotype. *European Journal of Neurology*, 17(4), 634–637. https://doi.org/10.1111/j.1468-1331.2009.02850.x

Rice, J., & Cameron, M. (2017). Cannabinoids for treatment of MS symptoms: State of the evidence. *Current Neurology and Neuroscience Reports*, 18(8), 1–10. https://doi.org/10.1007/s11910-018-0859-x

Romanelli, R. J., Huang, Q., Lacy, J., Hashemi, L., Wong, A., & Smith, A. (2020). Multiple sclerosis in a multi-ethnic population from northern California: A retrospective analysis, 2010–2016. BMC Neurology, 20, 163. https://doi.org/10.1186/s12883-020-01749-6

Schmidt-Wolf, G., & Cremer-Schaeffer, P. (2021). Three years of cannabis as medicine-preliminary results of the survey accompanying the prescription of medical cannabis in Germany. *Bundesgesundheitsblatt*, *Gesundheitsforschung, Gesundheitsschutz*, 64(3), 368–377. https://doi.org/10.1007/s00103-021-03285-1

Temple, L. M., Lampert, S. L., & Ewigman, B. (2019). Barriers to achieving optimal success with medical cannabis: Opportunities for quality improvement. *Journal of Alternative and Complementary Medicine* (New York, NY), 25(1), 5–7. https://doi.org/10.1089/acm.2018.0250

Thompson, A. J., Banwell, B. L., Barkhof, F., Carroll, W. M., Coetzee, T., Comi, G., ... Cohen, J. A. (2018). Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. *The Lancet. Neurology*, 17(2), 162–173. https://doi.org/10.1016/S1474-4422(17)30470-2

Troup, L. J., Erridge, S., Ciesluk, B., & Sodergren, M. H. (2022). Perceived stigma of patients undergoing treatment with cannabis-based medicinal products. *International Journal of Environmental Research and Public Health*, 19(12), 7499. https://doi.org/10.3390/ijerph19127499

Ubel, P. A., Scherr, K. A., & Fagerlin, A. (2017). Empowerment failure: How shortcomings in physician communication unwittingly undermine patient autonomy. *The American Journal of Bioethics*, 17(11), 31–39. https://doi.org/10.1080/15265161.2017.1378753

Urits, I., Charipova, K., Gress, K., Li, N., Berger, A. A., Cornett, E. M., ... Viswanath, O. (2021). Adverse effects of recreational and medical cannabis. *Psychopharmacology Bulletin*, 51(1), 94–109.

Walker, L. A., Koturbash, I., Kingston, R., ElSohy, M. A., Yates, C. R., Gurley, B. J., & Khan, I. (2020). Cannabidiol (CBD) in dietary supplements: Perspectives on science, safety, and potential regulatory
approaches. *Journal of Dietary Supplements*, 17(5), 493-502. https://doi.org/10.1080/19390211.2020.1777244

Walton, C., King, R., Rechtman, L., Kaye, W., Leray, E., Marrie, R. A., ... Baneke, P. (2020). Rising prevalence of multiple sclerosis worldwide: Insights from the atlas of MS, third edition. *Multiple Sclerosis Journal*, 26(14), 1816-1821. https://doi.org/10.1177/1352458520970841

Ware, M. A., Adams, H., & Guy, G. W. (2005). The medicinal use of cannabis in the UK: Results of a nationwide survey. *International Journal of Clinical Practice*, *59*(3), 291-295. https://doi.org/10.1111/j.1742-1241.2004.00271.x

Weinkle, L., Domen, C. H., Shelton, I., Sillau, S., Nair, K., & Alvarez, E. (2019). Exploring cannabis use by patients with multiple sclerosis in a state where cannabis is legal. *Multiple Sclerosis and Related Disorders*, 27, 383-390. https://doi.org/10.1016/j.msard.2018.11.022

Wheeler, M., Merten, J. W., Gordon, B. T., & Hamadi, H. (2020). CBD (Cannabidiol) product attitudes, knowledge, and use among young adults. *Substance Use & Misuse*, 55(7), 1138-1145. https://doi.org/10.1080/10826084.2020.1729201

## SUPPORTING INFORMATION

Additional supporting information can be found online in the Supporting Information section at the end of this article.

**How to cite this article:** Barré, T., Testa, D., Santos, M., Marcellin, F., Roux, P., Carrieri, P., Radoszycki, L., & Protopopescu, C. (2023). Symptom severity is a major determinant of cannabis-based products use among people with multiple sclerosis. *Journal of Clinical Nursing*, 32, 6460-6473. https://doi.org/10.1111/jocn.16674