Characterizing Cannabis Use and Perceived Benefit in a Tertiary Headache Center Patient Sample

Abstract

Background and Objectives

Research suggests a potential role for cannabinoids in the etiology and treatment of migraine. However, there is a paucity of research on usage patterns and perceived benefits of cannabis use in clinical headache patient populations.

Methods

Patients from a tertiary headache center completed a 1-time online survey regarding cannabis use patterns and perceived benefits of cannabis-based products in treating migraine symptoms, clinical features, and risk factors (e.g., depression, sleep disturbance). Descriptive analyses were performed.

Results

Data were collected from 1373 patients (response rate 25.4% [1,373/5,400]), with 55.7% reporting cannabis-based product use in the past 3 years and 32.5% indicating current use. The most frequently cited reasons for cannabis-based product use were treating headache (65.8%) and sleep concerns (50.8%). Inhaled products (i.e., smoked/vaped) and edibles were the most commonly reported delivery methods, with THC/CBD (∆9 tetrahydrocannabinol/cannabidiol) blends as the most-cited product composition. A majority of participants reported cannabis-related improvements in migraine headache characteristics (i.e., intensity: 78.1%; duration: 73.4%; frequency: 62.4%), nausea (56.3%), and risk factors (sleep disturbance: 81.2%; anxiety: 71.4%; depression: 57.0%). Over half (58.0%) of the respondents reported only using cannabis products when experiencing a headache, while 42.0% used cannabis most days/daily for prevention. Nearly half (48.9%) of the respondents reported that cannabis use contributed to a reduction in medication amount for headache treatment, and 14.5% reported an elimination of other medications. A minority (20.9%) of participants reported experiencing side effects when using cannabis products for headache, most commonly fatigue/lethargy. For those participants who reported no use of cannabis-based products in the previous 3 years, approximately half indicated not knowing what cannabis product to take or the appropriate dosage.

Discussion

This is the largest study to date to document cannabis product usage patterns and perceived benefits for migraine management in a clinical headache patient sample. A majority of patients surveyed reported using cannabis products for migraine management and cited perceived improvements in migraine characteristics, clinical features, and associated risk factors. The findings warrant experimental trials to confirm the perceived benefits of cannabis products for migraine prevention and treatment.

Introduction

In the United States, migraine affects nearly 40 million people (12% of the general population) and is the second leading cause of years lived with disability globally.^1-3 Migraine is characterized by debilitating headaches and associated clinical features, including nausea, vomiting, aura, and sensitivities to light, sound, and smell. Standard preventive and abortive pharmacologic therapies (even newer calcitonin gene-related peptide antagonists) and supplementary procedural therapies often do not provide adequate relief, and associated side effects can be difficult to tolerate.^4,5 According to a survey of American Headache Society members, 5–31% of the patients with migraine are treatment-resistant or treatment refractory.⁶ Thus, it is imperative to continue efforts to discover and determine the safety and efficacy of novel treatments for migraine.⁷

Research studies have suggested a potential role for cannabinoids in the etiology and treatment of migraine.⁸ The endocannabinoid system (ECS) is a neuromodulatory system comprising endogenous cannabinoids (CBs), receptors, and enzymes within the body. It is known to play a critical role in CNS development, synaptic plasticity, and the body's response to endogenous and environmental insults.^9,10 Both preclinical and clinical studies suggest abnormal functioning of the ECS in migraine, including lower concentrations of anandamide in cerebral spinal fluid and high concentrations of palmitoylethanolamide.^9,11 Some findings suggest trait-specific sex differences in endogenous lipid signals of 2-arachidonoylglycerol and anandamide, with lower levels found in pain modulatory networks in female (vs male) animal models; this may also help explain why some pain disorders (i.e., migraine, fibromyalgia) have a higher prevalence in female patients.¹² Taken together, there is considerable evidence to suggest a role for cannabis (including its constituents ∆9 tetrahydrocannabinol, THC, and cannabidiol, CBD) in effective migraine management.

While growing evidence provides biological plausibility for cannabis as a migraine treatment, there is relatively little known about attitudes toward cannabis, usage rates, reasons for use, and perceived benefits for treating headaches, migraine-related clinical features, and risk factors (i.e., sleep, psychiatric symptoms). To date, the few studies which have surveyed cannabis use in patients with headache and migraine suggest that cannabis may reduce migraine frequency, related disability, clinical features (i.e., nausea, vomiting), medication use, and headache pain ratings.^8,13 However, these studies have been limited by several factors, including small subsamples of patients with migraine and headache within larger samples of patients with and without pain conditions. Other studies have highlighted the risks of cannabis use among patients with headache disorders, including the potential for cannabinoid agonists to increase the risk of medication overuse headache (MOH) and sensitivity to headache risk factors, including environmental stress.¹⁴ Other studies have highlighted concerns with chronic cannabis use, particularly the use of THC-containing compounds, including the triggering or exacerbation of psychiatric symptoms (e.g., psychosis, paranoia, anxiety)^15,16 and the potential for hyperemesis syndrome with overuse.^17,18 Additional research is warranted to explore the relationships between cannabis use and medical/psychiatric symptoms and comorbidities to better understand the safety and efficacy of cannabis use in individuals with headache disorders.

Only 1 study to date has examined cannabis use in a tertiary headache center patient sample, comprising 200 patients in a Canadian clinic.¹⁹ Active cannabis use was reported by 34% of the respondents, as well as reductions in headache severity and frequency associated with cannabis use. Participants also reported benefits to nausea symptoms and migraine-related risk factors (anxiety, stress, depression). In summary, there is a paucity of research concerning patterns and benefits of cannabis use in patient populations with headache or migraine, particularly in the United States, where sociopolitical considerations related to legality of cannabis use are evolving and vary among states.

This study surveys a clinical headache patient sample regarding cannabinoid use characteristics and perceived benefits in treating migraine symptoms, clinical features, and associated risk factors. It expands on previous work, with a sample size that is nearly 7 times larger, and was conducted in a state where recreational cannabis use was recently legalized; thus, sociopolitical viewpoints and laws are in a state of change. The aim of this study was also to address important knowledge gaps in cannabis use among patients with migraine, including reasons for cannabis use (not only limited to migraine treatment), reasons for cannabis abstinence or discontinuation, benefits cannabis may have in treating headache duration and other risk factors, and statistical comparisons of differences in perceived helpfulness of cannabis by headache characteristics.

Methods

Standard Protocol Approvals, Registrations, and Patient Consents

This study was approved by the healthcare organization's Institutional Review Board, and participants provided electronic consent via an information sheet (waiver of signed consent).

Participants and Survey Dissemination Procedures

This study was cross-sectional and exploratory. The cannabis use survey was developed and approved by a multidisciplinary team, including a board-certified headache specialist, a psychiatrist with cannabis research expertise, a psychologist, a lawyer with migraine research experience, a behavioral headache researcher, and the institution's research director. Survey creation, thorough testing, and distribution occurred via REDCap (Research Electronic Data Capture), and the voluntary survey link was sent electronically to all patients seen within a 3-month time period (n = 5,400; May–August 2022) at a tertiary headache center in a nonprofit healthcare system. The 3-month window was chosen based on the expectation that a majority of the center's patient population would be seen in that time frame for follow-up. Patients who had not consented to electronic communication did not receive the survey link, and were excluded from participation. Patients received 2 electronic message reminders about the survey during the 3 months it was accessible. All survey communications stated that they only took the survey once. To ensure anonymity, no identifying information was collected, including IP address. Participants were not compensated.

Cannabis Survey Characteristics

Survey items queried several aspects of cannabis use: use of cannabis-based products in the past 3 years, reasons for use, length of time of use, reasons for stopping (if no longer using), constituent types (i.e., CBD only; CBD/THC combination), product types (i.e., inhaled products, edibles), method for obtaining products (i.e., medical dispensary), perceived benefits in treating both health concerns and migraine-related symptoms, benefit to risk factors (i.e., anxiety, sleep), changes in other migraine medications based on cannabis use, side effects, and reasons for not using cannabis (if participant indicated no use in the last 3 years). Participants also reported the number of monthly headache days, including moderate-to-severe intensity headache days. For questions related to perceived benefits of cannabis in treating headache symptoms, migraine-related clinical features, and other migraine risk factors, a 6-point Likert scale was used (not at all, slightly, somewhat, very, extremely, not applicable). Branching logic was used, in that those who indicated no cannabis use in the past 3 years were not shown additional questions about cannabis use. All participants saw questions in the same order on a single page. Participants were permitted to review/change their answers before submission.

Statistical Analyses

This was the primary analysis of these data, and statistical tests were selected a priori. A REDCap report identified duplicate cases for removal from the dataset before analysis. Statistical software IBM SPSS for Windows (version 27) was utilized. Descriptive analyses were conducted for survey responses (i.e., frequency/percentage, median/interquartile range, IQR). Kruskal–Wallis tests examined differences in perceived cannabis benefit Likert scores based on the number of monthly headache days (<15 days vs ≥ 15 days) and number of reasons for cannabis use (1 or 2 reasons vs 3+ reasons). Face validity of survey items was evaluated by research team members during survey construction. To evaluate the internal reliability and relationships between survey items measuring similar constructs with the same Likert scale, Cronbach's alpha and Spearman rank correlation analyses were performed on the following items: helpfulness of cannabis-based products in treating headache frequency, duration, and intensity, photophobia, phonophobia, nausea, appetite, brain fog, other general pain, sleep, depression, and anxiety. No statistical power calculation was conducted before this study, and sample size was based on the available data for respondents who completed the survey during the 3-month window. Hypothesis testing was two-tailed; the criterion for statistical significance was p < 0.05.

Data Availability

Data will be made available from the corresponding author upon reasonable request.

Results

Of 5,400 patients who received the survey, 1,691 individuals (31.3%) agreed to participate. After data cleaning (i.e., removing duplicate cases, removing cases who gave electronic consent but did not complete any survey questions), the final dataset was 1,373 cases, representing a response rate of 25.4%. Of these, 1,137 (82.8%) completed the survey, while 236 (17.2%) provided partial responses. All responses were included in the final analyses. Missing data ranged from 0.0% to 31.8% for each question, with an average of 15.0% missing data per question. Table legends contain additional information about missing data. Internal consistency (Cronbach's alpha) of 12 items, which queried helpfulness of cannabis-based products in treating headache-related symptoms, clinical features, and risk factors, was found to be α = 0.92. Spearman rank-order correlational analyses of the same 12 items revealed positive, significant relationships between all items (all p < 0.001), with r-values between 0.29 and 0.90.

Headache Days

Participants reported a median of 12.0 headache days per month (IQR: 6.0, 20.0; n = 1,141), with 44.9% (512/1,141) experiencing 15 or more headache days per month suggestive of chronic migraine. Participants reported a median of 6.0 moderate-to-severe headache days per month (IQR: 3.0, 12.0; n = 1,137), with 43.9% (499/1,137) having 8 or more moderate-to-severe headache days per month.

Cannabis Use Patterns and Characteristics

Over half of the respondents (55.7%; 765/1,373) indicated they had used a cannabis-based product in the past 3 years, with 58.9% (446/758) of these reporting current active use (32.5% of the total sample). Other participants with a recent history of cannabis-based product use indicated trying it once or twice (15.8%; 120/758), while others tried it more than once or twice but have since stopped (25.3%; 192/758). Table 1 summarizes different aspects of self-reported cannabis use, including reasons for use, methods, product composition, and source of products; data were organized for all cannabis users (n = 765) and cannabis use characteristics for only those who endorsed using it for headache treatment (n = 503). For all cannabis users, more than half indicated that they started using cannabis products to treat headache (503/765; 65.8%) or to help with sleep (389/765; 50.8%). Regarding reasons for cannabis use, 43.4% (330/759) endorsed 3 or more reasons for starting cannabis, while 56.5% (429/759) reported 1 or 2 reasons. The most frequently reported methods of cannabis use included inhaled products (smoking products: 55.3% [420/759]; vaping products: 48.2% [366/759]) and edibles (75.4%; 572/759), and the most-cited cannabis product composition was a THC/CBD blend (44.4%; 320/721). Nearly half of the respondents reported that they obtained cannabis-based products from a medical dispensary (49.0%; 373/762) or a store (42.4%; 323/762). For participants who endorsed using cannabis-based products for headache treatment, similar results and proportions were observed for methods of cannabis use, product composition, and sources of products (Table 1). For those participants who reported trying cannabis and then discontinuing use (n = 413), reasons for discontinuation included expense (26.9%; 111/413), difficulty obtaining product (19.1%; 79/413), and lack of benefit (18.2%; 75/413). In addition, 121 individuals (29.3%) selected “other” for reason for discontinuation of cannabis use, with most frequent “other” reasons including pregnancy (12.4%; 15/121), concerns about side effects/impact on functioning (9.1%; 11/121), concerns about taking other medications (8.3%; 10/121), and issues with obtaining cannabis (8.3%; 10/121).

Table 1.

Cannabis Use Patterns and Characteristics

	All cannabis users N = 765		Cannabis use for only headache N = 503
	Response (%)	N	Response (%)	N
Reasons for use (select all that apply)		759		503
Headache treatment	65.8	503	100.0	503
Sleep	50.8	389	60.0	302
Relaxation	48.8	373	54.5	274
Other medical concerns	31.6	242	29.0	146
Recreation/“to get high”	24.2	185	19.1	96
Curious	16.6	127	13.5	68
Method of cannabis use (select all that apply)		759		500
Edibles	75.4	572	76.4	382
Smoking	55.3	420	57.4	287
Vaping	48.2	366	52.4	262
Oils	36.1	274	36.6	183
Topicals	28.1	213	30.0	150
Dabs/concentrates	19.4	147	20.8	104
Drinks	15.5	118	16.8	84
Cannabis product composition (select all that apply)		720		473
THC/CBD combination	44.4	320	47.6	225
THC only	31.3	226	35.1	166
CBD only	20.8	150	21.1	100
Not sure	3.9	28	4.4	21
Not currently using	27.5	198	24.7	117
Source of cannabis products (select all that apply)		762		502
Medical dispensary	49.0	373	52.8	265
Store	42.4	323	42.0	211
Friend	34.1	260	33.3	167
Other	13.5	103	14.1	71

Missing data (left column): Reasons for use (6/765); methods of cannabis use (6/765); cannabis product composition (45/765); source of cannabis products (3/765). (Right column): Reasons for use (0/503); methods of cannabis use (3/503); cannabis product composition (30/503); source of cannabis products (1/503).

Perceived Cannabis Benefit for Migraine Characteristics

Headache

Participants who confirmed cannabis use in the past 3 years reported on perceived benefits for improving migraine symptoms, including headache frequency, intensity, and duration (Table 2). More than half (62.4%; 390/625) reported some level of improvement in headache frequency (slightly, somewhat, very, or extremely), with 24.5% (153/625) indicating “very” or “extremely” large improvements in monthly headache days. Over 70% (448/610) noted an improvement in headache duration, with 37.2% (227/610) reporting improvements of a “very” or “extreme” nature. Regarding headache intensity, 78.1% (477/611) noted improvement, with 47.8% (292/611) noting improvements of a “very” or “extremely” large magnitude. Over half of the respondents (58.0%; 302/521) reported using cannabis-based products only when experiencing a headache, while 42.0% (219/521) used cannabis most days or every day for prevention. When using cannabis-based products for migraine treatment, 48.9% (300/613) indicated that they were able to reduce the amount of medication used for headache treatment, and 14.5% (89/613) reported that they were able to eliminate other medications. However, over one-third (36.5%; 224/613) did not experience changes in headache-specific medication use by using cannabis-based products.

Table 2.

Symptom Improvement Ratings for Headache Characteristics, Migraine Clinical Features, and Migraine Risk Factors Based on Cannabis Use

	Not at all % (N)	Slightly % (N)	Somewhat % (N)	Very % (N)	Extremely % (N)	Not applicable % (N)
Headache characteristics
Days per month	18.2 (114)	14.4 (90)	23.5 (147)	14.4 (90)	10.1 (63)	19.4 (121)
Duration	13.8 (84)	12.6 (77)	23.6 (144)	22.5 (137)	14.8 (90)	12.8 (78)
Intensity	9.5 (58)	11.0 (67)	19.3 (118)	26.2 (160)	21.6 (132)	12.4 (76)
Migraine clinical features
Nausea	12.8 (77)	6.2 (37)	13.2 (79)	16.5 (99)	20.5 (123)	30.8 (185)
Photophobia	24.8 (150)	9.2 (56)	17.5 (106)	12.2 (74)	9.1 (55)	27.2 (165)
Phonophobia	23.4 (141)	9.3 (56)	17.9 (108)	12.6 (76)	8.3 (50)	28.4 (171)
Brain fog	29.4 (176)	12.2 (73)	15.0 (90)	8.0 (48)	4.7 (28)	30.7 (184)
Appetite disturbance	12.7 (76)	5.5 (33)	15.0 (90)	15.2 (91)	22.7 (136)	29.0 (174)
Risk factors
Sleep	7.9 (49)	4.7 (29)	12.6 (78)	24.0 (148)	39.9 (246)	10.9 (67)
Depression	13.6 (82)	8.3 (50)	17.4 (105)	15.7 (95)	15.7 (95)	29.4 (178)
Anxiety	9.7 (60)	9.4 (58)	14.9 (92)	21.8 (135)	25.2 (156)	18.9 (117)
General pain	7.2 (44)	10.0 (61)	18.8 (115)	22.4 (137)	22.9 (140)	18.8 (115)

Missing data: days per month (139/765); duration (155/765); intensity (153/765); nausea (164/765); photophobia (158/765); phonophobia (162/765); brain fog (165/765); appetite disturbance (164/765); sleep (147/765); depression (159/765); anxiety (146/765); general pain (152/765).

Clinical Features

Nausea was improved in a little over half of the respondents (56.3%; 338/600), of whom 37.0% (222/600) reported “very” or “extreme” improvement (Table 2). Relatedly, appetite was “very” or “extremely” improved in 37.8% of the participants (227/600). Photophobia and phonophobia demonstrated less improvement with cannabis product use than other migraine clinical features, with less than one-quarter reporting improvements of the “very” or “extreme” magnitude (21.3%, 129/606; 20.9%, 126/602, respectively). Brain fog was reported to be “very” or “extremely” improved in 12.7% of the respondents, representing the least improvement in all measured migraine clinical features. Participants selected “not applicable” for 28%–31% of these clinical features (Table 2), suggesting that they do not experience these symptoms.

Risk Factors

Regarding the perceived benefits of cannabis in treating migraine-related risk factors, respondents reported most improvement in sleep, with 81.2% (501/617) reporting any improvement and 63.8% (394/617) reporting sleep was “very” or “extremely” improved (Table 2). Anxiety and depression symptoms were also described as “very much” or “extremely” improved for 47.1% (291/618) and 31.4% (190/605) of respondents, respectively. General pain was “very” or “extremely” improved in 45.3% (277/612) of respondents. Participants selected “not applicable” for 10.9%–29.5% of these risk factors, with depression being the least reported (29.4%; 178/605) (Table 2).

Differences in Perceived Cannabis Benefit by Headache Characteristics

Headache Frequency

Patients who reported less than 15 headache days per month, compared with those who reported 15 or more days, indicated greater benefit of cannabis products for reducing monthly headache days (frequency), χ²(1) = 8.37, p = 0.004 and improving sleep, χ²(1) = 4.58, p = 0.032. No differences in cannabis benefit by monthly headache frequency were observed for other headache characteristics, clinical features, or related risk factors. In addition, no significant differences were observed when comparing perceived cannabis helpfulness for those with 8 or more moderate-to-severe headache days per month to those with less than 8 days.

Number of Reasons for Cannabis Use

Compared with participants who reported using cannabis for 1 or 2 reasons, participants who selected 3 or more reasons reported that cannabis products had greater perceived effectiveness for improving all headache symptoms, migraine clinical features, and related risk factors: headache frequency, χ²(1) = 4.66, p = 0.031; headache duration, χ²(1) = 6.74, p = 0.009; headache intensity, χ²(1) = 11.74, p = 0.001; nausea, χ²(1) = 14.00, p < 0.001; photophobia, χ²(1) = 8.15, p = 0.004; phonophobia, χ²(1) = 6.19. p = 0.013; brain fog, χ²(1) = 9.28, p = 0.002; appetite χ²(1) = 24.69, p < 0.001; sleep, χ²(1) = 35.50, p < 0.001; depression, χ²(1) = 14.17, p < 0.001; anxiety, χ²(1) = 21.70, p < 0.001; and general pain, χ²(1) = 23.69, p < 0.001.

Cannabis-Related Side Effects

When using cannabis-based products for headache, 20.9% (121/578) reported experiencing side effects. The most commonly reported side effects were fatigue/lethargy (18.6%; 21/113), anxiety (10.6%; 12/121), appetite change (10.6%; 12/113), and headache onset and/or worsening (8.8%; 10/113). Less frequently reported side effects included nausea/vomiting (4.4%; 5/113), brain fog (6.2%; 7/113), and paranoia (6.2%; 7/113).

Reasons for Cannabis Abstinence

For those participants who reported the absence of cannabis-based products in the previous 3 years (44.3%; 608/1373), 85.4% (519/608) gave at least 1 reason for abstinence. Over half (54.1%; 281/519) stated that they did not know what (cannabis product) to take, and 48.0% (249/519) did not know what dosage to take. Approximately 40% (210/519) were unsure where to obtain cannabis products, 28.9% (150/519) reported anxiety regarding using cannabis, and 13.9% (72/519) reported it was too expensive. Finally, 34.3% (178/519) selected “other” as a reason for abstinence, and 94.4% (168/178) of these individuals provided additional information. The most common write-in responses included not wanting to use cannabis/not having reason for use (19.0%; 32/168), concerns about using cannabis due to job or drug testing requirements (11.3%; 19/168), cannabis not being discussed by their doctor or recommended as a treatment (10.7%; 18/168), side effects (10.1%; 17/168), stigma/illegal status in the past (8.3%; 14/168), and feeling unsure if cannabis would help/worsen headache or migraine (8.3%; 14/168). Two respondents (1.2%) reported cannabis-based products “didn't work” or were “not effective,” and 2 additional participants (1.2%) noted that cannabis-based products caused or triggered migraine and/or headache for them in the past.

Discussion

This study is the largest to date to survey a clinical headache patient population on cannabis product use and perceived benefits for managing migraine, related symptoms, and risk factors. Findings provide several novel insights into frequency, method, and reasons for cannabis usage. Nearly 60% of the study respondents reported cannabis use in the past 3 years, with approximately one-third reporting active use. This is similar to the rate of active use (34%) reported by Melinyshyn et al.,¹⁹ who also surveyed patients in a tertiary headache center, and nearly double the estimated rate of marijuana use in the US general population.²⁰ In addition, approximately two-thirds of the cannabis users in this study reported using it to treat headache and migraine symptoms. High rates of use for headache or migraine treatment have been reported in other studies that surveyed more general samples of adult cannabis consumers.^8,21 Overall, among the participants who reported cannabis use products during the past 3 years, they attributed improvements in headache symptoms and migraine clinical features to these products. This finding is consistent with previous studies which reported perceived benefits from cannabis use for headache frequency and severity in subgroups of participants with headache or migraine.^{8-10,13,19,21-23} In addition, half of the participants in this study reported that cannabis use contributed to a reduction in headache-specific medications, while 14% reported being able to eliminate other such medications. Other studies have also reported a decrease in migraine medications after cannabis use, including less opioid and triptan consumption,^22,24 as well as reports of greater benefit of cannabis products (vs noncannabis products) in treating migraine.²¹ Additional research is needed to explore the relationship between cannabis use and migraine symptoms, particularly in the context of the effectiveness (or lack thereof) of available migraine treatments, patient perception of cannabis-related benefit, and other patient-related variables which may contribute to reported benefit.

Several novel findings emerged from this survey study. First, nearly 80% of the participants reported some degree of reduction in headache duration. This is notable given that past studies have focused only on headache frequency and severity, despite longer headache duration being associated with higher migraine-related disability and lower quality of life.²⁵ In addition, those participants with fewer headache days per month (less than 15 days vs ≥15 days) reported greater perceived benefits of cannabis-based products in reducing headache frequency, suggesting that individuals with chronic migraine perceived cannabis-based products to be less effective for migraine prevention. Additional research is warranted to further explore possible relationships between migraine chronicity, cannabis use, and MOH. A previous study found that MOH was approximately 6 times more likely to occur in patients with chronic migraine who also used cannabis compared with patients who did not use cannabis.²⁶ Little is known about how MOH may be related to episodic vs chronic migraine in individuals who report cannabis use.

This study also highlights patients' perceived benefits of cannabis-related products for reducing sleep disturbance. Approximately half of the cannabis users reported sleep as a reason for use, and over 80% reported some magnitude of improvement. The only other known study to explore the relationship between cannabis use and sleep in a migraine patient sample found that those participants whose migraine frequency improved with cannabis use (“responders”) also reported better sleep quality compared with “nonresponders.”²² Increasing evidence supports a bidirectional relationship between sleep and migraine due to the association between poor sleep quality and greater headache impact, as well as overlapping brain structures and neurotransmitters involved in both migraine and sleep regulation.²⁷ As with the aforementioned study, this study cannot distinguish whether sleep improvement is due to concurrent improvements in migraine symptoms (i.e., frequency, intensity) or directly to cannabis use.

The most highly cited reasons for cannabis use included headache, sleep, relaxation, another medical condition, and recreational purposes (i.e., “to get high”). Forty percent of respondents reported 3 or more reasons for cannabis use, suggesting that many patients with headache and migraine use cannabis-based products for a variety of presenting concerns. Participants with more reasons for use also reported greater treatment benefit than those citing less reasons for use. This is a novel finding within the headache and migraine patient population and provides insight into potential cannabis use patterns that might contribute to greater levels of relief across multiple conditions. In more general studies of recreational or medical cannabis use in adults, chronic pain, sleep, and mental health (i.e., anxiety, depression) are often the most-cited reasons for cannabis-based product use.²⁸ Although this study did not query specific mental health symptoms as reasons for cannabis use (other than for “relaxation”), participants did endorse improvements in this realm, with 31% and 47% endorsing “very much” or “extreme” improvement in depression and anxiety symptoms, respectively. Research suggests potential benefit in cannabis-based products for the treatment of anxiety and depression symptoms, with nuances in dosages and formulations suggested (i.e., most benefit from lower doses or THC/CBD blends, with potential exacerbation of symptoms at higher doses).²⁹ Given the higher prevalence of anxiety and depression in patients with migraine compared with the general population, it is critical to better understand whether improvements in headache symptoms with cannabis use are subsequent to improvements in mental health symptoms, vs primary improvements in headache symptoms then helping alleviate psychological distress. This relationship may be bidirectional and dependent upon individual patient characteristics and history.

Compared with other studies in headache patient samples where cannabis concentrates were preferred, participants of this study favored edibles and inhaled products. This is consistent with at least 1 previous study where inhaled products were the most preferred.²³ Differences in product type preferences may speak to distinctions in cannabis legal status between study settings, as well as the more recent ease of obtaining products. At the time of this survey, cannabis was approved for medical use and in the process of recreational legalization in the state (Connecticut), although the sale of recreational products had not yet been launched. As nearly half (49%) of the respondents reported obtaining cannabis-based products from a dispensary and 42% from a store, it seems likely that participants were obtaining cannabis products via a medical certificate, traveling to neighboring states where recreational sales were legal, or purchasing legal products over the counter (i.e., CBD-based products). The most preferred product was a THC/CBD blend (44% reported this preference); additional research is needed to differentiate the perceived effectiveness of cannabis-based products by composition (i.e., THC, CBD, hybrid), any potential harmful effects of specific compositions (e.g., higher doses of THC), and administration method for migraine symptoms and associated features. Among the one-fifth of participants who reported side effects with cannabis use for headache treatment, nausea and vomiting (4.4%) and psychiatric symptoms (anxiety: 10.6%; paranoia: 6.2%) were less frequently reported than other side effects. However, given previous studies concerning the relationships between cannabis use and hyperemesis syndrome and psychiatric symptom exacerbation, additional research is warranted.

Finally, novel study findings highlight possible reasons why individuals with headache and migraine disorders may ultimately discontinue cannabis use, as well as reasons for overall abstinence. For respondents who reported no use of cannabis-based products in the past 3 years, most frequently cited reasons focused on lack of knowledge regarding what product to use, where to get it, and how to use it. Others also cited a general preference to not use cannabis-based products and concerns about its legality and how it might impact their employment. Given the sociopolitical landscape of the tertiary headache center's location and recent recreational legalization, it is likely that these factors contributed to responses, including lack of knowledge, challenges with access, and stigmatization of cannabis-based product use. As several others have noted, there is a strong need for rigorous, controlled clinical trials to ultimately help inform patients of what cannabis-based products may be most beneficial for migraine treatment, including information related to composition, dosage, and modality of use.

This study contained several strengths. As previously noted, it focuses on cannabis use in a US-based tertiary headache center patient sample, and sample size was considerably larger than that in previous studies. In addition, the survey was constructed by a multidisciplinary research team, and survey items were developed and refined through an expert consensus process. Survey findings expanded upon previous studies and added novelty, including differences in perceived cannabis benefit by headache characteristics and reasons for use, perceived helpfulness for sleep disturbance, and reasons for discontinuation or abstinence from cannabis-based products.

Our findings should also be viewed in the context of several limitations, 1 of which is the lack of sociodemographic data for the study sample. Although recreational cannabis was recently legalized in the study's state, there is still stigma related to use, and thus, protection of patient privacy was of paramount concern. However, this precluded the ability to characterize cannabis use and perceived benefits by participant characteristics, limiting study generalizability. In addition, the study clinic's location and the corresponding sociopolitical and legal landscape regarding cannabis likely impacted cannabis use rates and attitudes (e.g., 60% of the sample reported cannabis use over the past 3 years) and may not be generalizable to clinics in other states/areas. Given the self-report nature of the survey, one would expect some recall bias of headache characteristics and cannabis use during the past 3 years that may skew the survey results. Participants were not asked about more remote cannabis use due to similar concerns of recall bias, as well as the desire to focus on more recent use; however, this may have resulted in underreporting of those who tried cannabis in the past and did not find benefit for headache disorder symptoms. Additional information regarding headache disorder diagnosis and monthly use of acute and preventive medications may have been beneficial in better understanding relationships between cannabis use, perceived benefits among differing diagnoses, and medication use/benefit. Given the finding of an association between migraine chronicity and perceived cannabis benefit, future research should also seek to assess for MOH and how it may relate to the aforementioned variables. Understanding the use of acute and preventive medications (or absence of) with cannabis-based products would be important to determine the optimization of treatment but was outside the scope of this study. Last, this study was limited to those who could read and speak English, and therefore, the results are not generalizable to non–English-speaking patient samples.

A majority of patients surveyed reported using cannabis products for migraine management and cited perceived improvements in migraine characteristics, clinical features, and associated risk factors. The findings warrant experimental trials to confirm the perceived benefits of cannabis products for migraine prevention and treatment.

TAKE-HOME POINTS

• → Over half of the participants reported cannabis-based product use in the past 3 years, with over 30% of the total study sample reporting current use; most frequently reported reasons for cannabis use were to treat headache symptoms and to help with sleep concerns.

• → In addition to reporting some level of improvement in headache frequency and intensity with cannabis use, over 70% of the participants reported improvement in headache duration. Improvements in other novel areas were also reported, including appetite disturbance, general pain, sleep, and psychiatric symptoms.

• → Participants who reported less than 15 headache days per month, compared with those who reported 15 or more days, indicated greater benefit of cannabis products for reducing monthly headache days and improving sleeping patterns.

• → For participants who had never used cannabis in the previous 3 years, the most-cited reasons for abstinence included not knowing what product(s) or dosages of cannabis-based products to use.

Appendix. Authors

Name	Location	Contribution
Brianna Starkey, MA	Hartford HealthCare Headache Center, Ayer Neuroscience Institute	Drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data
Godfrey D. Pearlson, MD	Olin Neuropsychiatric Research Center, Institute of Living; Department of Psychiatry and Neuroscience, Yale School of Medicine	Drafting/revision of the manuscript for content, including medical writing for content; study concept or design; analysis or interpretation of data
Dale Bond, PhD	Department of Research, Hartford Hospital/Hartford HealthCare	Drafting/revision of the manuscript for content, including medical writing for content; study concept or design; analysis or interpretation of data
Cathy Glaser, JD	Hartford HealthCare Headache Center, Ayer Neuroscience Institute	Drafting/revision of the manuscript for content, including medical writing for content; study concept or design
Aakash Bhargava, MD	Hartford HealthCare Headache Center, Ayer Neuroscience Institute	Drafting/revision of the manuscript for content, including medical writing for content
Brian M. Grosberg, MD	Hartford HealthCare Headache Center, Ayer Neuroscience Institute; Department of Neurology, University of Connecticut School of Medicine	Drafting/revision of the manuscript for content, including medical writing for content; study concept or design; analysis or interpretation of data
Allison Verhaak, PhD	Hartford HealthCare Headache Center, Ayer Neuroscience Institute; Department of Neurology, University of Connecticut School of Medicine; Division of Health Psychology, The Institute of Living/Hartford Hospital	Drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data

Study Funding

B.M. Grosberg acknowledges the generous support of (1) Barbara and John Heffer, and (2) Michael and Lisa Aleo, who underwrote the preparation of this manuscript.

Disclosure

B. Grosberg: Institutional research funds/educational grants from Theranica, Amgen, AbbVie, Eli Lilly, Teva, Electrocore, Dr. Reddy, Migraine Research Foundation, and Neurolief; Book royalties or honoraria from Wiley and Medlink neurology; serves on the Medical Advisory Board for the Migraine Research Foundation, Amgen, Lundbeck, Eli Lilly, Theranica, Neurolief, Biohaven Pharmaceuticals, and Allergan. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.