Cannabis health survey on usage in women with spinal cord injury and knowledge among physicians: A cross-sectional study

Objective: Individuals with spinal cord injury (SCI) report using cannabis to self-manage chronic pain and spasticity. However, its safety and efficacy are not well understood. As more women with SCI are pursuing motherhood, clinicians must consider the possibility of maternal cannabis use and its impact on fetal development. Moreover, due to the lack of current evidence for cannabis, it is important to characterize the perceptions and knowledge of physicians towards both recreational and synthetic cannabinoids. Design: Two anonymous surveys (10-items each) were conducted. Setting and Participants: Women with SCI (n = 20) completed an anonymous, online survey regarding cannabis use. Physicians at a Canadian SCI rehabilitation center (n = 15) completed a survey on their knowledge of recreational and synthetic cannabinoids among individuals with SCI. Outcome measures: Survey 1 evaluated cannabis use patterns and perceptions before/after SCI in women, including during pregnancy and breastfeeding. The aim of Survey 2 was to understand the perception and current knowledge of physicians regarding recreational cannabis and synthetic cannabinoid use by patients with SCI. Results: At the time of survey, 7 women with SCI reported use of cannabis, only 4 of them used prior to injury. Managing tone/spasticity (n = 5) was the major reported benefit of cannabis use. Women used cannabis during pregnancy and/or breastfeeding as a sleep aid or relief for morning sickness (n = 1 pregnancy, n = 1 breastfeeding, n = 1 both). The most-reported challenge with cannabis use was difficulty obtaining consistent, desirable effects (n = 5). Almost all physicians (n = 13) described their knowledge on recreational cannabis products as “none, very little or poor”, with greater overall comfort and knowledge of synthetic cannabinoids. Conclusion: Due to the reported use of cannabis during pregnancy/breastfeeding and current impoverishment of physicians’ knowledge (particularly regarding recreational cannabis products), it is imperative to further investigate the safety and efficacy of cannabis use in women with SCI.


Introduction
Negative sequelae such as chronic pain and spasticity are experienced in approximately 60% and 80% of Canadians with spinal cord injury (SCI), respectively. 1 These secondary conditions can detrimentally impact activities of daily living and health-related quality of life (HRQOL), 1 but current therapeutics have demonstrated limited efficacy. 2 Therefore, many individuals with SCI are open to exploring cannabis as an alternative therapy to improve HRQOL. 3,4 However, despite the rise of cannabis use among the wider general Canadian population since its legalization, 5 its effects are poorly understood in the SCI population. Individuals with SCI have rated cannabis as the most effective pain medication, even above opioids, and with fewer adverse drug reactions. 6 Cannabis was also described as effective in treating spasticity in this unique population. 7 However, negative consequences of cannabis use include fatigue, confusion, impaired memory, and nausea, which have been reported among individuals with SCI, 8 and increased risk of psychosis in the general population. 9 Since the majority of individuals who have sustained a traumatic SCI are men, 10 women with SCI are often understudied; however this represents a substantial population roughly estimated to be 715,000-850,000 worldwide. 11,12 Furthermore, women with SCI face sex-specific health challenges, including concerns relating to pregnancy and breastfeeding. 13 Pregnant women may use cannabis to ameliorate pregnancy-related symptoms such as mood changes, pain, nausea and/ or vomiting (morning sickness). 14 A recent study demonstrated increased medicinal and non-medicinal cannabis use among pregnant women from 2002 to 2017, particularly in the first trimester, a sensitive period for developmental toxicity. 15 Cannabis use during pregnancy has been reported to have negative impacts on offspring, including impaired cognitive function, 16 disrupted attention and visual-motor coordination, greater impulsivity 17 and increased rates of depression, 18 anemia, low birth weight 19 and preterm birth. 20 Nonetheless, the scarcity of literature precludes a clear understanding of the patterns and modes of cannabis ingestion, as well as putative therapeutic efficacy and adverse drug reactions among women with SCI. Consequently, it is exceedingly difficult for physicians to manage patient care. Therefore, we conducted a two-part cross-sectional study. For part 1, the aim was to determine cannabis use patterns and perceptions before/after SCI in women, including during pregnancy and breastfeeding. For part 2, the aim was to understand the perception and current knowledge of physicians regarding recreational cannabis and synthetic cannabinoid use by patients with SCI.

Methods
The two-part study was approved by the Behavioural Research Ethics Board of the University of British Columbia (H16-02495) and utilized a nonprobability purposive sampling design. Part 1 involved an online survey with a maximum of ten items over three pages, developed by our research team (Appendix A). The survey was distributed through email to women with SCI who had previously consented to being approached as prospective participants for future research studies. Primary outcomes of the survey included cannabis use patterns before and following SCI, and secondary outcomes included reasons for use, routes of administration, and perceived positive and negative outcomes of cannabis for three timepoints: (1) following SCI, (2) during pregnancy and (3) during breastfeeding. Data was collected from August to September of 2018. The email provided an external internet hyperlink to a secure website host that complies with the British Columbia (BC) Freedom of Information and Protection of Privacy Act (FOIPPA). 21 The informed consent form was on a separate page, allowing women to express their wish to participate or exit the survey. Further information on the survey administration was provided in accordance with the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) (Appendix B). Basic frequency descriptive statistics for each question comprised the planned statistical analyses, including range as a measure of variability.
Part 2 included a ten-item hardcopy survey for physicians, which was also developed by our research team (Appendices C-D). Physicians working at a SCI rehabilitation center in BC, were contacted by telephone calls and in-person recruitment. Survey distribution and collection occurred from September to October 2018. Primary outcome measures of the physician's survey included knowledge on therapeutic and adverse drug reactions of synthetic and recreational cannabis. Moreover, we also enquired about physicians' years of experience, volume of patients, comfort prescribing cannabis, and physicians' perceptions of reasons for use and areas requiring more research as secondary outcomes. Statistical analyses included frequency descriptive statistics, including range, as well as Spearman's rank-order correlations between total number of years of practice, total daily patients and total number of patients with SCI seen daily, with comfort prescribing medical cannabis, knowledge of cannabis benefits and knowledge of cannabis side effects.

Part 1: women with SCI cannabis use
Among the 59 women with SCI emailed for part 1, 21 women visited the link, and 20 completed the survey (one woman did not continue to the survey). Among the 20 women with SCI that started the survey, only seven completed the survey since 13 never used cannabis (Table 1). Notably, two women used cannabis, i.e. one during pregnancy, one during breastfeeding, and one during both. Most current users reported using cannabis for both medicinal and recreational purposes (n = 4), while some used cannabis only for either medicinal (n = 2) or recreational (n = 1) purpose. The most common route of cannabis administration included edible products (i.e. baked goods infused with cannabis) (n = 5) followed by inhalation/smoke (n = 4), oral use of oils (n = 2), topical use of oils (n = 1) and other unspecified means (n = 1).
The most commonly reported benefits of cannabis use following SCI included a reduction of tone and spasticity, pain, and depression/anxiety, improved sleep, and decreased morning sickness ( Table 2). The same results were also observed among the two women who used cannabis during pregnancy, and likewise with women during breastfeeding, excluding sleep aid. Perceived negative impacts included inconsistency of effects, the legality of obtaining cannabis, fatigue, and issues with mobility.

Part 2: physician perceptions and knowledge of cannabis
Fifteen physicians were recruited for part 2. At the time of survey completion, this group had practiced for a mean of 14 years, with all but one physician having seen patients with SCI in their practice (Table 3). Most physicians strongly agreed that they felt comfortable prescribing synthetic cannabinoids ( Figure 1) and rated their knowledge of its therapeutic and side effects as excellent ( Figure 2). Physicians considered pain relief as the most common reason for medical cannabis use, followed by spasticity relief and appetite stimulation. The majority of physicians reported their knowledge across five recreational cannabis products as being "none, very little or poor", as shown in the distribution of physician knowledge of recreational cannabis products ( Figure 3).
No significant Spearman's rank-order correlations were found between the number of total years of practice, total daily patients or total patients with SCI, and comfort or knowledge with medicinal synthetic cannabinoid therapeutic benefits or side effects (Table  4). Physicians indicated priority areas to address, that would help guide their practice regarding cannabis use. Physicians were able to indicate more than one topic due to the open-text entry format of the question. Priority areas indicated were: further research on compound composition (n = 6), product quality (n = 4), a comprehensive database of available products (n = 3), side effect profiles (n = 2), evidence of efficacy (n = 1) and impaired driving (n = 1) (multiple reasons permitted).

Discussion
This study provides preliminary insight on cannabis use in women with SCI from the perspective of patients and knowledge of recreational cannabis and synthetic cannabinoids among physicians. Of the 20 women originally surveyed, seven (35%) were using cannabis and two (10%) women with SCI used cannabis during   both pregnancy and breastfeeding. Spasticity and pain management were the most common reasons for use. The most frequent challenges were inconsistent effects and issues acquiring cannabis legally, since retrospective responses likely reflected a pre-legalization period. Physicians reported a high level of knowledge and comfort prescribing synthetic cannabinoids and the contrary for recreational cannabis products. Demont-Heinrich et al. reported a more frequent use of cannabis use in the general population during pregnancy and breastfeeding in current cannabis users (i.e. 36% during their most recent pregnancy and 14% used while breastfeeding) compared to past users (5% during pregnancy and <1% while breastfeeding). 14 With respect to the former study, our cohort of women with SCI had a percentage of cannabis use during pregnancy and breastfeeding somewhere in between. Consistent with the literature, women with SCI in our study reported perceived benefits of cannabis use such as management of pain, spasticity, 22,23 depression and anxiety. These findings follow a recent study suggesting higher rates of postpartum depression and anxiety in mothers with SCI compared to the general maternal population. 24 Our study also reported Figure 1 Comfort prescribing synthetic cannabinoids among physicians. Physicians generally reported comfort in prescribing synthetic cannabinoids to patients with SCI. Figure 2 Knowledge of synthetic cannabinoids among physicians. Physicians self-reported having fair to excellent knowledge of synthetic cannabinoids within the context of therapeutic cannabinoid use by patients with SCI. Figure 3 Physician knowledge of recreational cannabis products. Between 47-87% of physicians reported their knowledge across five recreational cannabis products as being "none, very little or poor". Between 13% and 53% of physicians reported "fair, good or excellent" knowledge. No physician reported "excellent" knowledge for any listed product. cannabis use-associated fatigue, which potentially could have a negative effect on cognitive function. This is especially concerning as SCI can significantly impair various cognitive domains including; executive function, memory, attention, language and visuospatial domains. 4,[25][26][27] Women with SCI most commonly consumed edibles, contrary to two studies examining routes of administration across the general SCI population. 28,29 Notably, edible products were consumed by all three individuals who used cannabis during pregnancy and/ or breastfeeding. It is possible that edibles were utilized intentionally to avoid harms of smoking cannabis, such as carcinogen exposure and increased risk of cancers. 30,31 However, we did not examine participant attitudes on different routes of administration or perceived impact on their infants. The high prevalence of edibles may account for the reported inconsistent effects; both retail and homemade edibles are poorly regulated and vary widely in cannabinoid concentrations. 32 Ingestion of edibles can have a delayed onset of both initial (30-90 min) and peak subjective effects (2-4 h), which complicates appropriate dosing. 33 Our sample of physicians reported a substantially greater level of knowledge of medicinal synthetic cannabinoids than similar surveys, potentially due to their focus on SCI care. [34][35][36] However, up to 87% of physicians self-reported their knowledge of recreational cannabis products as limited. As individuals with SCI continue to explore alternative treatments to manage secondary conditions, the state of clinician knowledge on these now legal compounds seems alarmingly inadequate. This paucity of physician knowledge regarding recreational cannabis may be due to the myriad of such products available, the rapidly evolving nature of product development, the lack of transparency and regulation regarding composition, and the absence of a central recreational cannabis database. Clarity on THC:CBD ratios and compositional details in recreational cannabis products were identified as a clear area of need.
There are several limitations to our work which should be considered including the small sample size of this pilot study, from which definitive conclusions regarding patterns of cannabis use cannot be drawn. It has to be noted that women with SCI represent only about 20% of all individuals with SCI, 37 so information is limited related to their health and well being. Furthermore, the relatively high number of non-responders (i.e. almost two-thirds of women with SCI did not respond to the invitation), which could be due to stigmatization of cannabis use, especially during pregnancy and breastfeeding. Moreover, at the time when we invited women to answer the survey, there were still laws that criminalized cannabis use, which could have been a reason to not fully disclose cannabis use (i.e. frequency, dose, and occasion). Furthermore, the study design (i.e. cross-sectional and internet-based) does not allow to understand the pattern of cannabis use or confirm cannabis blood levels (i.e. the influence of maternal side-effects and infant physiology). Moreover, participants were limited to Vancouver, which may yield greater rates of cannabis use than rural settings, due to varying attitudes or access. 38 Similarly, physicians who work in a major city may be more knowledgeable and comfortable with cannabinoid prescriptions due to greater exposure to patients using cannabis. The self-reported nature of survey data may also affect the representation of knowledge among physicians on cannabis products.
Considering the aforementioned limitations of this study, future research may want to consider utilizing an international, multi-center, qualitative study design in order to gain a greater depth of knowledge into the population of interest, which is relatively small. Moreover, it would be beneficial to conduct longitudinal studies on the impact of maternal cannabis use on pre-and post-natal development with an emphasis on neurocognitive function. Emerging evidence has shown that cannabinoid exposure in utero or via lactation induces perturbations of brain circuitry that cause long-term disruption of cognition and increased psychiatric vulnerability. 39 Furthermore, infants of women with SCI are often born preterm, [40][41][42] with low gestational length 42 and birth weight. 42,43 As cannabis use has been documented to exert similar effects, cannabis exposure during early development may exacerbate these issues in neonates. 19,44 Different routes of administration, including edibles, should  also be evaluated to better represent the effects of everyday cannabis use. This study demonstrated for the first time that cannabis use occurs during pregnancy and breastfeeding among women with SCI, potentially at a greater frequency than the general population. 14 Moreover, it revealed a need for more information on recreational cannabis products to guide patient care. It is advisable for physicians of patients with chronic conditions such as SCI to closely monitor for cannabis use during the reproductive period. We advocate for further education of clinicians and additional research regarding safety and efficacy of cannabis use in women with SCI and their impacts on offspring, to improve long-term intergenerational health outcomes.