Medical cannabis patterns of use and substitution for opioids & other pharmaceutical drugs, alcohol, tobacco, and illicit substances; results from a cross-sectional survey of authorized patients.

BACKGROUND: A 239-question cross-sectional survey was sent out via email in January 2017 to gather comprehensive information on cannabis use from Canadian medical cannabis patients registered with a federally authorized licensed cannabis producer, resulting in 2032 complete surveys. METHODS: The survey gathered detailed demographic data and comprehensive information on patient patterns of medical cannabis use, including questions assessing the self-reported impact of cannabis on the use of prescription drugs, illicit substances, alcohol, and tobacco. RESULTS: Participants were 62.6% male (n = 1271) and 91% Caucasian (n = 1839). The mean age was 40 years old, and pain and mental health conditions accounted for 83.7% of all respondents (n = 1700). Then, 74.6% of respondents reported daily cannabis use (n = 1515) and mean amount used per day was 1.5 g. The most commonly cited substitution was for prescription drugs (69.1%, n = 953), followed by alcohol (44.5%, n = 515), tobacco (31.1%, n = 406), and illicit substances (26.6%, n = 136). Opioid medications accounted for 35.3% of all prescription drug substitution (n = 610), followed by antidepressants (21.5%, n = 371). Of the 610 mentions of specific opioid medications, patients report total cessation of use of 59.3% (n = 362). CONCLUSIONS: This study offers a unique perspective by focusing on the use of a standardized, government-regulated source of medical cannabis by patients registered in Canada's federal medical cannabis program. The findings provide a granular view of patient patterns of medical cannabis use, and the subsequent self-reported impacts on the use of opioids, alcohol, and other substances, adding to a growing body of academic research suggesting that increased regulated access to medical and recreational cannabis can result in a reduction in the use of and subsequent harms associated with opioids, alcohol, tobacco, and other substances.

Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science.

BACKGROUND: Comprehensive literature reviews of historical perspectives and evidence supporting cannabis/cannabinoids in the treatment of pain, including migraine and headache, with associated neurobiological mechanisms of pain modulation have been well described. Most of the existing literature reports on the cannabinoids Δ9 -tetrahydrocannabinol (THC) and cannabidiol (CBD), or cannabis in general. There are many cannabis strains that vary widely in the composition of cannabinoids, terpenes, flavonoids, and other compounds. These components work synergistically to produce wide variations in benefits, side effects, and strain characteristics. Knowledge of the individual medicinal properties of the cannabinoids, terpenes, and flavonoids is necessary to cross-breed strains to obtain optimal standardized synergistic compositions. This will enable targeting individual symptoms and/or diseases, including migraine, headache, and pain. OBJECTIVE: Review the medical literature for the use of cannabis/cannabinoids in the treatment of migraine, headache, facial pain, and other chronic pain syndromes, and for supporting evidence of a potential role in combatting the opioid epidemic. Review the medical literature involving major and minor cannabinoids, primary and secondary terpenes, and flavonoids that underlie the synergistic entourage effects of cannabis. Summarize the individual medicinal benefits of these substances, including analgesic and anti-inflammatory properties. CONCLUSION: There is accumulating evidence for various therapeutic benefits of cannabis/cannabinoids, especially in the treatment of pain, which may also apply to the treatment of migraine and headache. There is also supporting evidence that cannabis may assist in opioid detoxification and weaning, thus making it a potential weapon in battling the opioid epidemic. Cannabis science is a rapidly evolving medical sector and industry with increasingly regulated production standards. Further research is anticipated to optimize breeding of strain-specific synergistic ratios of cannabinoids, terpenes, and other phytochemicals for predictable user effects, characteristics, and improved symptom and disease-targeted therapies.

Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort.

BACKGROUND: Medicinal cannabis registries typically report pain as the most common reason for use. It would be clinically useful to identify patterns of cannabis treatment in migraine and headache, as compared to arthritis and chronic pain, and to analyze preferred cannabis strains, biochemical profiles, and prescription medication substitutions with cannabis. METHODS: Via electronic survey in medicinal cannabis patients with headache, arthritis, and chronic pain, demographics and patterns of cannabis use including methods, frequency, quantity, preferred strains, cannabinoid and terpene profiles, and prescription substitutions were recorded. Cannabis use for migraine among headache patients was assessed via the ID Migraine™ questionnaire, a validated screen used to predict the probability of migraine. RESULTS: Of 2032 patients, 21 illnesses were treated with cannabis. Pain syndromes accounted for 42.4% (n = 861) overall; chronic pain 29.4% (n = 598;), arthritis 9.3% (n = 188), and headache 3.7% (n = 75;). Across all 21 illnesses, headache was a symptom treated with cannabis in 24.9% (n = 505). These patients were given the ID Migraine™ questionnaire, with 68% (n = 343) giving 3 "Yes" responses, 20% (n = 102) giving 2 "Yes" responses (97% and 93% probability of migraine, respectively). Therefore, 88% (n = 445) of headache patients were treating probable migraine with cannabis. Hybrid strains were most preferred across all pain subtypes, with "OG Shark" the most preferred strain in the ID Migraine™ and headache groups. Many pain patients substituted prescription medications with cannabis (41.2-59.5%), most commonly opiates/opioids (40.5-72.8%). Prescription substitution in headache patients included opiates/opioids (43.4%), anti-depressant/anti-anxiety (39%), NSAIDs (21%), triptans (8.1%), anti-convulsants (7.7%), muscle relaxers (7%), ergots (0.4%). CONCLUSIONS: Chronic pain was the most common reason for cannabis use, consistent with most registries. The majority of headache patients treating with cannabis were positive for migraine. Hybrid strains were preferred in ID Migraine™, headache, and most pain groups, with "OG Shark", a high THC (Δ9-tetrahydrocannabinol)/THCA (tetrahydrocannabinolic acid), low CBD (cannabidiol)/CBDA (cannabidiolic acid), strain with predominant terpenes ß-caryophyllene and ß-myrcene, most preferred in the headache and ID Migraine™ groups. This could reflect the potent analgesic, anti-inflammatory, and anti-emetic properties of THC, with anti-inflammatory and analgesic properties of ß-caryophyllene and ß-myrcene. Opiates/opioids were most commonly substituted with cannabis. Prospective studies are needed, but results may provide early insight into optimizing crossbred cannabis strains, synergistic biochemical profiles, dosing, and patterns of use in the treatment of headache, migraine, and chronic pain syndromes.

Case Report of Debilitating Headaches and a Coexisting Ophthalmic Artery Aneurysm: An Indication for Treatment?

OBJECTIVE: We present a case of a patient who had severe unilateral headaches related to a small, unruptured ophthalmic artery aneurysm, who experienced complete headache cessation following endovascular coiling. BACKGROUND: Small unruptured intracranial aneurysms are generally managed and followed conservatively due to minimal risk of rupture. Headaches are frequently reported in patients with intracranial aneurysms, but these aneurysms are typically considered incidental and unrelated, given the undefined association between headaches and most aneurysms. CONCLUSION: There may be some unruptured intracranial aneurysms that can cause intractable headaches and warrant interventional treatment. Future prospective studies are needed that compare pre- and post-procedure headache character and diagnosis, aneurysm characteristics such as size, location, orientation, and shape, type of aneurysm repair with materials used, and other potential risk factors for worsening post-procedure headache in order to better predict headache association to aneurysms, as well as outcomes following endovascular aneurysm treatment.

Headache, cerebral aneurysms, and the use of triptans and ergot derivatives.

BACKGROUND: Uncertainty exists regarding the correlation between unruptured cerebral aneurysms and their role in headache etiology. It is also unclear whether surgical endovascular treatment may improve or worsen the headache, and if there are predictable factors for headache outcome such as pre-existing headache features, aneurysm characteristics, or other medical history. There is debate regarding safe treatment of migraine in patients with aneurysms, both before and after endovascular treatments. Particularly, there is hesitancy to use the triptans and ergot derivatives such as dihydroergotamine because of their vasoconstrictive effects and concern for adverse events related to the aneurysm such as aneurysmal instability and rupture. OBJECTIVE: To review the literature regarding the anatomy, pathophysiology, and association between headache, untreated vs surgically treated aneurysms, and the use of triptans and ergot derivatives for migraine treatment in this setting. CONCLUSION: Associations between some headaches and aneurysms may exist. Some chronic headaches may respond to surgical aneurysm repair while others may worsen. These associations are undefined by current literature because of variable results, study methods, and limited data. Prospective studies are needed which incorporate pre- and post-procedure headache character and diagnosis, aneurysm characteristics, type of aneurysm repair, associated risk factors for worsening post-procedure headache, and ultimately combining all of these data to better predict headache outcome following surgical aneurysm treatment. Lastly, the caution and avoidance of triptan and ergot derivative use for migraine in the setting of aneurysm is not supported by the current evidence, and much of this concern may be excessive and unwarranted, although more evidence confirming safety is needed.

Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It's Been .

BACKGROUND: The use of cannabis, or marijuana, for medicinal purposes is deeply rooted though history, dating back to ancient times. It once held a prominent position in the history of medicine, recommended by many eminent physicians for numerous diseases, particularly headache and migraine. Through the decades, this plant has taken a fascinating journey from a legal and frequently prescribed status to illegal, driven by political and social factors rather than by science. However, with an abundance of growing support for its multitude of medicinal uses, the misguided stigma of cannabis is fading, and there has been a dramatic push for legalizing medicinal cannabis and research. Almost half of the United States has now legalized medicinal cannabis, several states have legalized recreational use, and others have legalized cannabidiol-only use, which is one of many therapeutic cannabinoids extracted from cannabis. Physicians need to be educated on the history, pharmacology, clinical indications, and proper clinical use of cannabis, as patients will inevitably inquire about it for many diseases, including chronic pain and headache disorders for which there is some intriguing supportive evidence. OBJECTIVE: To review the history of medicinal cannabis use, discuss the pharmacology and physiology of the endocannabinoid system and cannabis-derived cannabinoids, perform a comprehensive literature review of the clinical uses of medicinal cannabis and cannabinoids with a focus on migraine and other headache disorders, and outline general clinical practice guidelines. CONCLUSION: The literature suggests that the medicinal use of cannabis may have a therapeutic role for a multitude of diseases, particularly chronic pain disorders including headache. Supporting literature suggests a role for medicinal cannabis and cannabinoids in several types of headache disorders including migraine and cluster headache, although it is primarily limited to case based, anecdotal, or laboratory-based scientific research. Cannabis contains an extensive number of pharmacological and biochemical compounds, of which only a minority are understood, so many potential therapeutic uses likely remain undiscovered. Cannabinoids appear to modulate and interact at many pathways inherent to migraine, triptan mechanisms ofaction, and opiate pathways, suggesting potential synergistic or similar benefits. Modulation of the endocannabinoid system through agonism or antagonism of its receptors, targeting its metabolic pathways, or combining cannabinoids with other analgesics for synergistic effects, may provide the foundation for many new classes of medications. Despite the limited evidence and research suggesting a role for cannabis and cannabinoids in some headache disorders, randomized clinical trials are lacking and necessary for confirmation and further evaluation.

Triptan education and improving knowledge for optimal migraine treatment: an observational study.

BACKGROUND: It is generally felt that patient education and patient knowledge regarding triptan use for acute migraine management are important for successful and safe treatment. It is unclear how knowledgeable triptan users are regarding their triptan, how much education occurs when triptans are prescribed, and the impact patient education has on actual patient knowledge regarding triptan use. OBJECTIVE: The primary objective was to compare triptan users' self-perceived knowledge and actual knowledge about triptans in patients who report having received triptan education vs patients who report not having received triptan education. METHODS: This was a multicenter prospective observational study of 207 migraine patients who were using triptans for abortive therapy and who were being evaluated as new patients at academic headache specialty clinics in the United States. Patients completed standardized questionnaires regarding their self-perceived knowledge about triptans, their actual knowledge regarding triptans, and the perceived education about the triptan that they had received at the time of prescription. RESULTS: Although greater than 80% of the subjects reported receiving education about when to take the triptan and the number of doses they could take for headache, only 71.5% reported receiving education about triptan side effects, 64% for the number of triptan doses they could take each week/month, 64% for taking other medications with the triptan, and 49% for medical contraindications to triptan use. Compared with subjects who did not recall receiving education about when to take their triptan, subjects who recalled such education had a statistically significant greater actual knowledge for taking the triptan immediately after a headache begins (91% vs 77%, P = .049; confidence interval [CI]: 0.00-0.33), treating when pain is mild (75% vs 50%, P = .009; CI: 0.04-0.45), understanding that they do not need to fail treatment with over-the-counter medications before taking a triptan (74% vs 42%, P = .001; CI: 0.11-0.51), and recognizing that coronary artery disease is a contraindication to triptan use (40% vs 19%, P = .001; CI: 0.09-0.34). CONCLUSION: This study provides evidence that patients who recall having received education at the time of triptan prescribing have greater knowledge regarding optimal triptan use. Triptan users who recalled having received this education had greater recognition of the importance of taking the triptan immediately at the onset of a headache, treating when pain is mild, not needing to fail treatment with over-the-counter medications before taking a triptan, and understanding that coronary artery disease is a contraindication to triptan use.

Identifying the factors underlying discontinuation of triptans.

OBJECTIVE: To identify factors associated with triptan discontinuation among migraine patients. BACKGROUND: It is unclear why many migraine patients who are prescribed triptans discontinue this treatment. This study investigated correlates of triptan discontinuation with a focus on potentially modifiable factors to improve compliance. METHODS: This multicenter cross-sectional survey (n = 276) was performed at US tertiary care headache clinics. Headache fellows who were members of the American Headache Society Headache Fellows Research Consortium recruited episodic and chronic migraine patients who were current triptan users (use within prior 3 months and for ≥1 year) or past triptan users (no use within 6 months; prior use within 2 years). Univariate analyses were first completed to compare current triptan users to past users for: migraine characteristics, other migraine treatments, triptan education, triptan efficacy, triptan side effects, type of prescribing provider, Migraine Disability Assessment (MIDAS) scores and Beck Depression Inventory (BDI) scores. Then, a multivariable logistic regression model was selected from all possible combinations of predictor variables to determine the factors that best correlated with triptan discontinuation. RESULTS: Compared with those still using triptans (n = 207), those who had discontinued use (n = 69) had higher rates of medication overuse (30 vs. 18%, P = .04) and were more likely to have ever used opioids for migraine treatment (57 vs. 38%, P = .006) as well as higher MIDAS (mean 63 vs. 37, P = .001) and BDI scores (mean 10.4 vs. 7.4, P = .009). Compared with discontinued users, current triptan users were more likely to have had their triptan prescribed by a specialist (neurologist, headache specialist, or pain specialist) (74 vs. 54%, P = .002) and were more likely to report headache resolution (53 vs. 14%, P < .001) or a reduction in pain intensity (71 vs. 28%, P < .001) most of the time from their triptan. On a 1-5 scale (1 = disagree, 5 = agree), triptan users felt they had more: control over their migraine attacks (2.9 vs. 2.1), confidence in their prescribing provider (4.5 vs. 4.0), and were more educated about triptan use (4.2 vs. 3.7) compared with triptan discontinuers (P < .001 for all comparisons). Although both current and prior users reported similar rates of side effects (48 vs. 43%, P = .44), of those who discontinued use, the main reasons were for lack of effect (44%) and side effects (29%). Our multivariable modeling revealed that the strongest correlate of triptan discontinuation was lack of efficacy (odds ratio = 17, 95% confidence interval [8.8, 33.0]). Other factors associated with discontinuation included MIDAS > 24 (2.6, [1.5, 4.6]), BDI >4 (2.5, [1.4, 4.5]), and a history of ever using opioids for migraine therapy (2.2, [1.3, 3.8]). Having a triptan prescribed by a specialist and using at least 1 other abortive medication with the triptan were associated with a decreased likelihood of triptan discontinuation (0.41, [0.2-0.7] and 0.44 [0.3, 0.8], respectively). CONCLUSIONS: As expected, discontinuation was most correlated with lack of efficacy, but other important factors associated with those who had discontinued use included greater migraine-related disability, depression, and the use of opioids for migraine attacks. Compared with patients who had discontinued triptans, current triptan users felt more: educated about their triptan, control over their migraine attacks, and confidence in their prescribing provider. Current triptan users had their triptan prescribed by a specialist and used other abortive medications with their triptan more often compared with patients who had discontinued triptans. Given the cross-sectional nature of this study, we cannot determine if these factors contributed to triptan discontinuation or reflect the impact of such discontinuation. Interventions that address modifiable risk factors for triptan discontinuation may decrease the likelihood of triptan discontinuation and thus improve overall migraine control. Because lack of efficacy was most strongly associated with triptan discontinuation, future research should determine why triptans are effective for some patients but not others.

Headache following intracranial neuroendovascular procedures.

AIMS: Predicting who will develop post-procedure headache (PPH) following intracranial endovascular procedures (IEPs) would be clinically useful and potentially could assist in reducing the excessive diagnostic testing so often obtained in these patients. Although limited safety data exist, the use of triptans or dihydroergotamine (DHE) often raise concern when used with pre/post-coiled aneurysms. We sought to determine risk factors for PPH following IEP, to evaluate the utility of diagnostic testing in patients with post-coil acute headache (HA), and to record whether triptans and DHE have been used safely in this clinical setting. METHODS: We conducted a retrospective chart review of adult patients undergoing IEPs. Bivariate analyses were conducted to compare patients who did and did not develop PPH. RESULTS: We reviewed records pertaining to 372 patients, of whom 263 underwent intracranial coil embolizations, 21 acrylic glue embolizations, and 88 stent placements. PPH occurred in 72% of coil patients, 33% of glue patients, and 14% of stent patients. Significant risk factors for post-coil HA were female gender, any pre-coil HA history, smoking, and anxiety/depression. A pre-stent history of HA exceeding 1 year's duration, and smoking were risk factors for post-stent HA. A pre-glue history of HA exceeding 1 year was the only risk factor for post-glue HA. In the small subgroup available for study, treatment with triptans or DHE was not associated with adverse events in pre/post-coiled aneurysms. Diagnostic testing was low yield. CONCLUSIONS: Occurrence of PPH was common after IEPs and especially so with coiling and in women, smokers, and those with anxiety/depression, and was often of longer duration than allowed by current International Classification of Headache Disorders-II criteria. The yield of diagnostic testing was low, and in a small subgroup treatment with triptans or DHE did not cause adverse events in pre/post-coiled aneurysms. Prospective studies are needed to confirm these findings.

Revisiting the role of ergots in the treatment of migraine and headache.

The harmful side effects of the ergots described by early civilizations have been overcome with efficacious treatment for headaches including migraine, cluster, and chronic daily headache. Use of ergots contributed to initial theories of migraine pathogenesis and provided the substrate for development of the triptans. Triptans are very efficacious for many migraineurs, and since their widespread use, use of ergots has significantly declined. Unfortunately, there remain many migraineurs who benefit little from triptans, yet respond very well to ergots. Discoveries in migraine pathophysiology have given us better understanding of the complex processes involved, although there remain many unknown factors in migraine treatment. Additional, unrecognized therapeutic targets may exist throughout the neuronal connections of the brainstem, cortex, and cerebral vasculature. Ergots interact with a broader spectrum of receptors than triptans. This lack of receptor specificity explains potential ergot side effects, but may also account for efficacy. The role of ergots in headache should be revisited, especially in view of newer ergot formulations with improved tolerability and side effect profiles, such as orally inhaled dihydroergotamine. Redefining where in the headache treatment spectrum ergots belong and deciding when they may be the optimal choice of treatment is necessary.

Acute treatment of basilar-type migraine with greater occipital nerve blockade.

Basilar-type migraine (BTM) precludes use of migraine-specific medications such as triptans and ergots based on concerns originating from the vascular theory of migraine, although data supporting this contraindication are lacking. Availability of effective treatments for acute BTM is limited. We report a case of BTM aborted with greater occipital nerve (GON) blockade given in the setting of prominent suboccipital tenderness. GON blockade may provide an additional option in acute management of BTM. It may be particularly useful when associated with prominent ipsilateral suboccipital tenderness.

New daily persistent headache in children and adolescents.

New daily persistent headache (NDPH) is a form of chronic daily headache (CDH) that may have features of both migraine and tension-type headache. In contrast with other types of CDH, NDPH is characterized by patients recalling the specific date their unremitting daily headache began. In comparison, chronic tension-type headache and chronic migraine are preceded by a gradually increasing frequency of headache. After several months, all three of these CDH forms often have a similar phenotype, making early history a key to diagnosing NDPH. Evaluations to exclude secondary causes are necessary but usually negative. NDPH is difficult to treat and requires a multimodal approach. Questions regarding NDPH remain unanswered. Additional prospective studies are necessary to further understand, characterize, diagnose, and treat NDPH.

Role of greater occipital nerve blocks and trigger point injections for patients with dizziness and headache.

BACKGROUND: The trigeminocervical system is integral in cervicogenic headache. Cervicogenic headache frequently coexists with complaints of dizziness, tinnitus, nausea, imbalance, hearing complaints, and ear/eye pain. Controversy exists as to whether this constellation of symptoms may be cervically mediated. OBJECTIVES: To determine whether a wider spectrum of cervically mediated symptoms exist, and to investigate a potential role of greater occipital nerve blocks (GON) and trigger point injections (TPI) in these patients. METHODS: Retrospective review of GON/TPI performed in a tertiary otoneurology/headache clinic from May 2006 to March 2007 for suspected cervically mediated symptoms. Data included chief complaint, secondary symptoms, response to injection, pre-GON/TPI posterior vertex sensation changes to pinprick, cervical spine examination, and response to vibration of cervical and suboccipital musculature. RESULTS: Total number of 147 patients were included. Chief complaints in decreasing frequency: dizziness (93%), tinnitus (4%), headache (3%), and ear discomfort (0.7%). Overall symptoms in decreasing frequency: dizziness (97%), headache (88%), neck pain (63%), tinnitus (23%), and ear discomfort (22%). Improvements after GON/TPI: neck range of motion (71%), headache (57%), neck pain (52%), ear discomfort (47%), dizziness (46%), and tinnitus (30%). Dizziness responders had neck position asymmetries (84%), reproducible dizziness by cervical and suboccipital musculature vibration (75%), and preinjection posterior vertex sensory changes (60%). CONCLUSIONS: A wider spectrum of cervically mediated symptoms may exist by influence of trigeminocervical and vestibular circuitry through cervical afferent neuromodulation. Certain examination findings may help to predict benefit from GON/TPI.