Article

Effects of Medical Marijuana on Migraine Headache Frequency in an Adult Population

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Abstract

Study Objective No clinical trials are currently available that demonstrate the effects of marijuana on patients with migraine headache; however, the potential effects of cannabinoids on serotonin in the central nervous system indicate that marijuana may be a therapeutic alternative. Thus, the objective of this study was to describe the effects of medical marijuana on the monthly frequency of migraine headache. DesignRetrospective chart review. SettingTwo medical marijuana specialty clinics in Colorado. PatientsOne hundred twenty-one adults with the primary diagnosis of migraine headache who were recommended migraine treatment or prophylaxis with medical marijuana by a physician, between January 2010 and September 2014, and had at least one follow-up visit. Measurements and ResultsThe primary outcome was number of migraine headaches per month with medical marijuana use. Secondary outcomes were the type and dose of medical marijuana used, previous and adjunctive migraine therapies, and patient-reported effects. Migraine headache frequency decreased from 10.4 to 4.6 headaches per month (p<0.0001) with the use of medical marijuana. Most patients used more than one form of marijuana and used it daily for prevention of migraine headache. Positive effects were reported in 48 patients (39.7%), with the most common effects reported being prevention of migraine headache with decreased frequency of migraine headache (24 patients [19.8%]) and aborted migraine headache (14 patients [11.6%]). Inhaled forms of marijuana were commonly used for acute migraine treatment and were reported to abort migraine headache. Negative effects were reported in 14 patients (11.6%); the most common effects were somnolence (2 patients [1.7%]) and difficulty controlling the effects of marijuana related to timing and intensity of the dose (2 patients [1.7%]), which were experienced only in patients using edible marijuana. Edible marijuana was also reported to cause more negative effects compared with other forms. Conclusion The frequency of migraine headache was decreased with medical marijuana use. Prospective studies should be conducted to explore a cause-and-effect relationship and the use of different strains, formulations, and doses of marijuana to better understand the effects of medical marijuana on migraine headache treatment and prophylaxis.

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... A total of 12 studies with 1,980 participants were included. The included studies were seven peer-reviewed publications (19)(20)(21)(22)(23)(24)(25) and five conference abstracts, including two case reports (26,27), one case series (28), one retrospective chart review (29), and one randomized control trial (30). The seven peer-reviewed publications were retrospective cohort study (22), retrospective analysis of medical charts of migraine patients who used MC (19,25) or analysis of MC Application (App) (20,21) and online surveys (23,24). ...
... The included studies were seven peer-reviewed publications (19)(20)(21)(22)(23)(24)(25) and five conference abstracts, including two case reports (26,27), one case series (28), one retrospective chart review (29), and one randomized control trial (30). The seven peer-reviewed publications were retrospective cohort study (22), retrospective analysis of medical charts of migraine patients who used MC (19,25) or analysis of MC Application (App) (20,21) and online surveys (23,24). The study selection process is shown in Figure 1. ...
... Migraine sufferers, ranging in age from 18 to 89, were treated with medical cannabis in various forms and doses (19). Oral drops of a THC and CBD formulation were administered in three studies (26,28,30). ...
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Background Medical cannabis (MC) has been hypothesized as an alternative therapy for migraines, given the undesirable side effects of current migraine medications. The objective of this review was to assess the effectiveness and safety of MC in the treatment of migraine in adults. Methods We searched PubMed, EMBASE, PsycINFO, CINAHL, and Web of Science for eligible studies in adults aged 18 years and older. Two reviewers independently screened studies for eligibility. A narrative synthesis of the included studies was conducted. Results A total of 12 publications involving 1,980 participants in Italy and the United States of America were included. Medical cannabis significantly reduced nausea and vomiting associated with migraine attacks after 6 months of use. Also, MC reduced the number of days of migraine after 30 days, and the frequency of migraine headaches per month. MC was 51% more effective in reducing migraines than non-cannabis products. Compared to amitriptyline, MC aborted migraine headaches in some (11.6%) users and reduced migraine frequency. While the use of MC for migraines was associated with the occurrence of medication overuse headaches (MOH), and the adverse events were mostly mild and occurred in 43.75% of patients who used oral cannabinoid preparations. Conclusions There is promising evidence that MC may have a beneficial effect on the onset and duration of migraine headaches in adults. However, well-designed experimental studies that assess MC's effectiveness and safety for treating migraine in adults are needed to support this hypothesis.
... Later in 2018, he and his team conducted another survey and identified different patterns of medical marijuana treatment in migraine headaches [20]. Rhyne et al., in 2016, did a retrospective study from medical record reviews, analyzed the frequency of headaches with medical marijuana as a primary goal, and focused on the type, dosage use, previous migraine therapies used, and patient-reported data as secondary outcomes [21]. ...
... They showed a significant reduction in migraine frequency with medical marijuana [21]. Leroux et al. conducted a survey and demonstrated that the prevalence of cannabis use is higher in patients with cluster headaches than in the general population [22]. ...
... This survey is limited as it did not examine "combination" medication use (antidepressant + sleep aid), and the data were designed to be interpretable by the general population [31]. Rhyne et al., in 2016, conducted a retrospective, observational review of patients in Colorado [21]. Patients between the ages of 18 and 89 years old with a diagnosis of migraines were included in the study [21]. ...
Article
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Cannabis has been long used since ancient times for both medical and recreational use. Past research has shown that cannabis can be indicated for symptom management disorders, including cancer, chronic pain, headaches, migraines, and psychological disorders (anxiety, depression, and post-traumatic stress disorder). Active ingredients in cannabis that modulate patients' perceptions of their conditions include Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), flavonoids, and terpenes. These compounds work to produce effects within the endocannabinoid system to decrease nociception and decrease symptom frequency. Research within the United States of America is limited to date due to cannabis being classified as a schedule one drug per the Drug Enforcement Agency. Few anecdotal studies have found a limited relationship between cannabis use and migraine frequency. The purpose of the review article is to document the validity of how medical cannabis can be utilized as an alternative therapy for migraine management. Thirty-four relevant articles were selected after a thorough screening process using PubMed and Google Scholar databases. The following keywords were used: "Cannabis," "Medical Marijuana," "Headache," "Cannabis and Migraine," "Cannabis and Headache." This literature study demonstrates that medical cannabis use decreases migraine duration and frequency and headaches of unknown origin. Patients suffering from migraines and related conditions may benefit from medical cannabis therapy due to its convenience and efficacy.
... A recent retrospective study conducted by Rhyne et al. (2016) showed that migraine patients who inhaled MC had a significant reduction in migraine frequency [30], which is in line with the results demonstrated here, and supports our finding of high rates of patient reporting of migraine frequency reduction. Migraine is classified as a pain condition. ...
... A recent retrospective study conducted by Rhyne et al. (2016) showed that migraine patients who inhaled MC had a significant reduction in migraine frequency [30], which is in line with the results demonstrated here, and supports our finding of high rates of patient reporting of migraine frequency reduction. Migraine is classified as a pain condition. ...
... Currently, there are no clinical trials on migraine and MC [42]. Previous studies on migraine did not assess the phytocannabinoids mentioned in our study [43], and usually regarded "cannabis" as a single adherent medication [30], therefore disregarding the inherent complexity in MC treatment, with differences in over 90 phytocannabinoids [18] between cannabis cultivars [44]. ...
Article
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Background: Medical cannabis (MC) treatment for migraine is practically emerging, although sufficient clinical data are not available for this indication. This cross-sectional questionnaire-based study aimed to investigate the associations between phytocannabinoid treatment and migraine frequency. Methods: Participants were migraine patients licensed for MC treatment. Data included self-reported questionnaires and MC treatment features. Patients were retrospectively classified as responders vs. non-responders (≥50% vs. <50% decrease in monthly migraine attacks frequency following MC treatment initiation, respectively). Comparative statistics evaluated differences between these two subgroups. Results: A total of 145 patients (97 females, 67%) with a median MC treatment duration of three years were analyzed. Compared to non-responders, responders (n = 89, 61%) reported lower current migraine disability and lower negative impact, and lower rates of opioid and triptan consumption. Subgroup analysis demonstrated that responders consumed higher doses of the phytocannabinoid ms_373_15c and lower doses of the phytocannabinoid ms_331_18d (3.40 95% CI (1.10 to 12.00); p < 0.01 and 0.22 95% CI (0.05-0.72); p < 0.05, respectively). Conclusions: These findings indicate that MC results in long-term reduction of migraine frequency in >60% of treated patients and is associated with less disability and lower antimigraine medication intake. They also point to the MC composition, which may be potentially efficacious in migraine patients.
... The medical literature regarding treatment of headache, migraine, and facial pain disorders shows supporting evidence for cannabis/cannabinoids in the treatment of chronic headaches, 65-68 migraine including chronic migraine, 13,14,39,66,[69][70][71][72][73][74][75][76][77][78][79][80][81][82] medication overuse headache, 83 cluster headache, 82,84-86 idiopathic intracranial hypertension, 87 and multiple sclerosis (MS) associated trigeminal neuralgia. 88 At the time of this writing, this majority of supporting literature consists primarily of case series, case studies, case reports, surveys, clinical/anecdotal reports, and one retrospective analysis. ...
... There has been one retrospective study of cannabis use in the treatment of migraine, and it was strongly positive, although limitations exist. 74 In this study, the investigators reviewed charts of 121 adults from 2 medical marijuana specialty clinics in Colorado. These patients had the primary diagnosis of migraine and had been recommended by a physician for acute and/or preventive treatment with medicinal cannabis. ...
Article
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 diseasetargeted therapies.
... One study found that 85 % of individuals using medically prescribed cannabis to treat migraines reported a decrease in migraine frequency. 29 Negative effects, notably somnolence and difficulty controlling drug effects, were reported in 11.6 % of participants, and were experienced only after the use of edible, rather than inhaled, cannabis. 29 A qualitative study of online migraine forums found that migraineurs frequently discussed cannabis as an effective acute and prophylactic migraine treatment, noting its ability to alleviate migraine symptoms and reduce the frequency of migraine attacks. ...
... 29 Negative effects, notably somnolence and difficulty controlling drug effects, were reported in 11.6 % of participants, and were experienced only after the use of edible, rather than inhaled, cannabis. 29 A qualitative study of online migraine forums found that migraineurs frequently discussed cannabis as an effective acute and prophylactic migraine treatment, noting its ability to alleviate migraine symptoms and reduce the frequency of migraine attacks. 3 Interestingly, the same study also discussed the potential for higher doses of cannabis to trigger or exacerbate, rather than alleviate, migraine symptoms. ...
Article
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Objectives As the legal and cultural landscape surrounding cannabis use in the United States continues to evolve, more Americans are turning to cannabis to self-medicate a number of ailments, including migraines. The purpose of the present study was to examine patterns of cannabis use and its associated relief among migraineurs. Design Participants were N = 589 adult cannabis users living in states with full legal access. Using a cross-sectional design, participants completed an online survey assessing their cannabis use profiles, migraine experience, and self-reported relief from cannabis and non-cannabis treatments. Results 161 participants (27.3 %) reported experiencing migraines. 76.4 % of migraineurs (N = 123) endorsed using cannabis to treat their migraines. 69.9 % (N = 86) of migraineurs using cannabis for migraine relief also endorsed using non-cannabis products (e.g., over-the-counter pain medication, triptans) to treat their migraines. Although their subjective health was similar (p = .17), migraineurs who endorsed using cannabis to treat their migraines reported more severe migraines compared to those who did not (p = .02). Migraineurs reported significantly more migraine relief from cannabis compared to non-cannabis products, even after controlling for migraine severity (p = .03). The majority of migraineurs using cannabis to treat their migraines were not medical cardholders (65.0 %), suggesting that these individuals were self-medicating in lieu of physician guidance. Conclusions The present study provides insight into the prevalence of cannabis use for migraine relief in a sample of cannabis users, and suggests that these migraineurs experience a high level of migraine relief from cannabis. Future studies are needed to determine the cannabis forms, potencies, and dosages that are most effective at treating migraine pain.
... The high clinical complexity of the analyzed sample could also account for the discrepancies between the present study's results and those of the study conducted by Rhyne and co-workers [24], who detected a significant reduction in the number of headache days per month in a cohort of 121 patients treated with medical marijuana. However, the study by Rhyne et al. assessed people with episodic migraine and a low acute medication intake, who thus gained higher clinical benefits from cannabinoid administration [24]. ...
... The high clinical complexity of the analyzed sample could also account for the discrepancies between the present study's results and those of the study conducted by Rhyne and co-workers [24], who detected a significant reduction in the number of headache days per month in a cohort of 121 patients treated with medical marijuana. However, the study by Rhyne et al. assessed people with episodic migraine and a low acute medication intake, who thus gained higher clinical benefits from cannabinoid administration [24]. The lack of a significant reduction of the MMD in the present study could be attributable to the worse impairment of patients at the baseline and reflects the central action of the ECS on pain; indeed, the ECS acts as a tonic regulator of the trigeminal system and of those brain areas involved in trigeminal pain perception [4], thus justifying the higher reduction in pain intensity rather than frequency. ...
Article
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Objective To explore the effectiveness and safety of 3 oral cannabinoid preparations (FM2®, Bedrocan® and Bediol®) in the treatment of chronic migraine. Design Retrospective, cohort study. Subjects Patients with chronic migraine who received FM2®, Bedrocan® or Bediol® daily for the off-label treatment of their headache, up to 6 months. Methods The number of migraine days per month, pain intensity, the number of acute medications taken per month, the number of days per month when the patient took at least one acute medication, and adverse events were recorded at baseline, 3 months, and 6 months after the start of treatment with oral cannabinoid preparations. Results The number of migraine days didn’t change significantly after the 3rd and the 6th month when compared to baseline (P = 0.1182). The pain intensity (P = 0.0004), the acute medication consumption (P = 0.0006) and the number of days per month in which patients took, at least, one acute medication, (P = 0.0004) significantly decreased when compared to the baseline. No significant differences were found between patients who were still taking a preventive treatment for chronic migraine and those who weren’t (all P > 0.05). Different oral cannabinoid preparations displayed similar effectiveness (all P > 0.05). The AEs were mostly mild and occurred in the 43.75% of patients. Conclusions Oral cannabinoid preparations may have a role in reducing pain intensity and acute medication intake in patients with chronic migraine, but the magnitude of the effect seems modest; further studies are needed.
... Supporting evidence also exists for cannabis/cannabinoids in the treatment of migraine and/or chronic migraine [1,[40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56], cluster headache [56][57][58][59], chronic headaches [13,44,60,61], medication overuse headache [62], idiopathic intracranial hypertension [63], and multiple sclerosis associated trigeminal neuralgia [64]. Publications detailing this headache, migraine, and facial pain literature, as well as described mechanisms of pain relief with cannabis and cannabinoids are available and should be reviewed, but are beyond the scope of this paper [1,2,28,51,65]. ...
... THC is 20 times more anti-inflammatory than aspirin, twice as anti-inflammatory as hydrocortisone [128], and has well documented analgesic and anti-inflammatory benefits including arthritic and inflammatory conditions [83,114,127,. There have been many positive studies across various chronic pain syndromes, showing benefit of THC in trials with smoked or vaporized cannabis comparing between different doses of THC, with benefit often noted at higher percentages [28,47,[157][158][159][160][161][162][163][164][165][166][167][168][169]. However, compositions of other cannabinoids including CBD, minor cannabinoids, and other important compounds such as terpenes were not assessed in most of these trials. ...
Article
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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 β-caryophyllene and β-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 β-caryophyllene and β-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.
... Another study conducted in 589 adult cannabis users reported that migraine sufferers experienced significant migraine relief using medical cannabis [41]. Rhyne et al. retrospectively evaluated the effects of medical cannabis in 121 EM sufferers attending two medical marijuana specialty clinics in Colorado (United States), reporting a global decrease in migraine frequency [42]. However, most of these patients used different formulae of marijuana, even on the same day, and through different routes of administration [42]. ...
... Rhyne et al. retrospectively evaluated the effects of medical cannabis in 121 EM sufferers attending two medical marijuana specialty clinics in Colorado (United States), reporting a global decrease in migraine frequency [42]. However, most of these patients used different formulae of marijuana, even on the same day, and through different routes of administration [42]. Another study explored the effect of different oral formulae of phytocannabinoids in CM sufferers. ...
Article
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The endocannabinoid system (ECS) influences many biological functions, and hence, its pharmacological modulation may be useful for several disorders, such as migraine. Preclinical studies have demonstrated that the ECS is involved in the modulation of trigeminal excitability. Additionally, clinical data have suggested that an endocannabinoid deficiency is associated with migraine. Given these data, phytocannabinoids, as well as synthetic cannabinoids, have been tried as migraine treatments. In this narrative review, the current clinical evidence of potential ECS involvement in migraine pathogenesis is summarized. Furthermore, studies exploring the clinical effects of phytocannabinoids and synthetic cannabinoids on migraine patients are reviewed.
... Another retrospective review evaluating 121 adult migraine sufferers authorized to use cannabis over a period of 57 months showed a decrease in migraine headache frequency from 10.4 to 4.6 per month [79]. A recent study evaluating real-time effects collected via mobile educational software application (n=699) of consumption of common and commercially available cannabis products for the treatment of headache and migraine under naturalistic conditions showed that 94% of users experienced symptom relief within a 2-h observation window [80]. ...
Article
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Purpose of Review Public acceptance of Cannabis sativa L. (cannabis) as a therapeutic option grows despite lags in both research and clinician familiarity. Cannabis—whether as a medical, recreational, or illicit substance—is and has been commonly used by patients. With ongoing decriminalization efforts, decreased perception of harms, and increased use of cannabis in the treatment of symptoms and disease, it is critical for clinicians to understand the rationale for specific therapies and their medical and practical implications for patients. In view of the opioid crisis, overall patient dissatisfaction, and lack of adherence to current chronic pain and headache therapies, this review provides up-to-date knowledge on cannabis as a potential treatment option for headache pain. Recent Findings Research into the use of cannabinoids for disease treatment have led to FDA-approved drugs for seizures, nausea, and vomiting caused by cancer chemotherapy; and for decreased appetite and weight loss in people with HIV/AIDS. For a wide variety of conditions and symptoms (including chronic pain), cannabis has gained increasing acceptance in society. The effects of cannabidiol (CBD) and tetrahydrocannabinol (THC) in pain pathways have been significantly elucidated. An increasing number of retrospective studies have shown a decrease in pain scores after administration of cannabinoids, as well as long-term benefits such as reduced opiate use. Yet, there is no FDA-approved cannabis product for headache or other chronic pain disorders. More is being done to determine who is likely to benefit from cannabis as well as to understand the long-term effects and limitations of the treatment. Summary Cannabis can refer to a number of products derived from the plant Cannabis sativa L. Relatively well-tolerated, these products come in different configurations, types, and delivery forms. Specific formulations of the plant have been shown to be an effective treatment modality for chronic pain, including headache. It is important for clinicians to know which product is being discussed as well as the harms, benefits, contraindications, interactions, and unknowns in order to provide the best counsel for patients.
... It would be interesting to explore whether migraine, anxiety and sleep disorders in patients with rare deleterious variants in CNR1 could be alleviated by treatment with THC or other CB1 agonists that may effectively stimulate the impaired and/or remaining functional CB1 receptors. In this regard, we note that a recent observational study of 121 adults with migraine reported a decrease in mean headache frequency from 10.4 to 4.6 headaches per month (p<0.0001) for patients receiving medicinal cannabis [71]. ...
Preprint
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Rare genetic variants in the core endocannabinoid system genes CNR1 , CNR2 , DAGLA , MGLL and FAAH were identified in molecular testing data from up to 6.032 patients with a broad spectrum of neurological disorders. The variants were evaluated for association with phenotypes similar to those observed in the orthologous gene knockouts in mice. Heterozygous rare coding variants in CNR1 , which encodes the type 1 cannabinoid receptor (CB1), were found to be significantly associated with pain sensitivity (especially migraine), sleep and memory disorders - alone or in combination with anxiety - compared to a set of controls without such CNR1 variants. Similarly, heterozygous rare variants in DAGLA , which encodes diacylglycerol lipase alpha, were found to be significantly associated with seizures and developmental disorders, including abnormalities of brain morphology, compared to controls. Rare variants in MGLL , FAAH and CNR2 were not associated with any neurological phenotypes in the patients tested. Diacylglycerol lipase alpha synthesizes the endocannabinoid 2-AG in the brain, which interacts with CB1 receptors. The phenotypes associated with rare CNR1 variants are reminiscent of those implicated in the theory of clinical endocannabinoid deficiency syndrome. The severe phenotypes associated with rare DAGLA variants underscore the critical role of rapid 2-AG synthesis and the endocannabinoid system in regulating neurological function and development. Mapping of the variants to the 3D structure of the type 1 cannabinoid receptor, or primary structure of diacylglycerol lipase alpha, reveals clustering of variants in certain structural regions and is consistent with impacts to function.
... Since the Health Canada review, many survey studies, [149][150][151][152] and a chart review 153 have studied the therapeutic efficacy of MM in the treatment of headaches, however only one controlled clinical trial was conducted. 154 In this trial, nabilone (0.5 mg) was used in a randomized, double-blind, crossover design against ibuprofen (400 mg) in 30 patients with a medication-overuse headache (MOH) and daily analgesic intake. ...
Article
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With the proposed Canadian July 2018 legalization of marijuana through the Cannabis Act, a thorough critical analysis of the current trials on the efficacy of medicinal marijuana (MM) as a treatment option is necessary. This review is particularly important for primary care physicians whose patients may be interested in using MM as an alternative therapy. In response to increased interest in MM, Health Canada released a document in 2013 for general practitioners (GPs) as an educational tool on the efficacy of MM in treating some chronic and acute conditions. Although additional studies have filled in some of the gaps since the release of the Health Canada document, conflicting and inconclusive results continue to pose a challenge for physicians. This review aims to supplement the Health Canada document by providing physicians with a critical yet concise update on the recent advancements made regarding the efficacy of MM as a potential therapeutic option. An update to the literature of 2013 is important given the upcoming changes in legislation on the use of marijuana. Also, we briefly highlight the current recommendations provided by Canadian medical colleges on the parameters that need to be considered prior to authorizing MM use, routes of administration as well as a general overview of the endocannabinoid system as it pertains to cannabis. Lastly, we outline the appropriate medical conditions for which the authorization of MM may present as a practical alternative option in improving patient outcomes as well as individual considerations of which GPs should be mindful. The purpose of this paper is to offer physicians an educational tool that provides a necessary, evidence-based analysis of the therapeutic potential of MM and to ensure physicians are making decisions on the therapeutic use of MM in good faith.
... Marijuana has been suggested for a variety of chronic and neurological diseases common to older adults, including headaches, chronic noncancer pain, Alzheimer's disease, Parkinson's disease, insomnia, and glaucoma. [5][6][7][8][9][10][11][12][13] An international survey of the use of marijuana that the International Association of Cannabinoid Medicine conducted found that, in adults aged 50 and older, the most common indications for marijuana use were chronic pain, anxiety, weight loss, depression, and disordered sleep, 8 but little research has been conducted on the efficacy and adverse effects of marijuana in older adults despite evidence suggesting impaired bone health, hallucinations, impaired short-term memory, high blood pressure, dizziness, gastrointestinal distress, and hypersomnolence. 4,10,[14][15][16] There is also limited research on the epidemiology and health status of older marijuana users and even less information comparing medicinal and recreational users. ...
Article
Objectives To understand patterns of marijuana use in community‐dwelling older adults in Colorado. Design Anonymous survey. Setting Two academic geriatric primary care clinics. Participants English‐speaking individuals. Measurements We assessed self‐reported characteristics and patterns of marijuana use and effect on targeted symptoms. Survey analysis focused on current users, defined as individuals who had used marijuana in the past 3 years. Results Three hundred forty‐five individuals completed the survey (55% response rate); 113 (32%) had used marijuana in the past, of whom 55 (16%) had used since legalization. More than half of current users were aged 75 and older, and one‐quarter were aged 85 and older. Most current users were white women. Of current users, 44% used marijuana products at least weekly for common conditions including chronic pain, depression, anxiety, and insomnia, and most found marijuana helpful for these conditions. Most respondents reported obtaining marijuana recreationally (67%) without a prescription. Nine respondents reported negative side effects attributable to marijuana use. Conclusion To our knowledge, this is the first study to characterize marijuana use of older adults in a state in which it is legal for medical and recreational use. Marijuana was used for several common geriatric conditions, and respondents reported few side effects. The small number of survey respondents, the lack of generalizability in states where marijuana sales are illegal, and participation bias were the main study limitations. Further research is needed to better understand useful or harmful effects in this population.
... These developments did not escape notice of the giants of neurology on both sides of the Atlantic, who similarly adopted its use in these indications: Silas Weir Mitchell, Seguin, Gowers and Osler (Mitchell, 1874;Seguin, 1877;Gowers, 1888;Osler and McCrae, 1915). While medicinal cannabis suffered a period of obscurity and quiescence, mainly attributable to quality control issues and political barriers, modern data on migraine (Russo, 2004(Russo, , 2016bRhyne et al., 2016) and neuropathic pain, whether central or peripheral support its common application by affected patients (Rog et al., 2005;Nurmikko et al., 2007;Russo and Hohmann, 2013;Serpell et al., 2014), additionally supported by the National Academies of Science, Engineering and Medicine (National Academies of Sciences Engineering and Medicine (U.S.). Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda, 2017). ...
Article
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Neurological therapeutics have been hampered by its inability to advance beyond symptomatic treatment of neurodegenerative disorders into the realm of actual palliation, arrest or reversal of the attendant pathological processes. While cannabis-based medicines have demonstrated safety, efficacy and consistency sufficient for regulatory approval in spasticity in multiple sclerosis (MS), and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges remain. This review will examine the intriguing promise that recent discoveries regarding cannabis-based medicines offer to neurological therapeutics by incorporating the neutral phytocannabinoids tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), and cannabis terpenoids in the putative treatment of five syndromes, currently labeled recalcitrant to therapeutic success, and wherein improved pharmacological intervention is required: intractable epilepsy, brain tumors, Parkinson disease (PD), Alzheimer disease (AD) and traumatic brain injury (TBI)/chronic traumatic encephalopathy (CTE). Current basic science and clinical investigations support the safety and efficacy of such interventions in treatment of these currently intractable conditions, that in some cases share pathological processes, and the plausibility of interventions that harness endocannabinoid mechanisms, whether mediated via direct activity on CB1 and CB2 (tetrahydrocannabinol, THC, caryophyllene), peroxisome proliferator-activated receptor-gamma (PPARγ; THCA), 5-HT1A (CBD, CBDA) or even nutritional approaches utilizing prebiotics and probiotics. The inherent polypharmaceutical properties of cannabis botanicals offer distinct advantages over the current single-target pharmaceutical model and portend to revolutionize neurological treatment into a new reality of effective interventional and even preventative treatment.
... Rhyne et al. [88] did a retrospective chart review of 121 adults with migraine headache referred for treatment with medical marijuana and had at least one follow-up visit. Migraine headache frequency decreased from 10.4 to 4.6 headaches per month (P < 0.0001) and self-reported positive effects were recorded in 48 patients (39.7%). ...
Article
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Purpose of review: Migraine is a common, highly disabling disorder. Its treatment involves acute and preventive therapy. Many of available preventive medications are not well tolerated, which results in poor compliance and limited effectiveness. Cannabinoids have been proposed for the treatment of migraine but their efficacy and tolerability are controversial. Recent findings: Cannabinoids modulate functions and activity of signaling pathways that have a key role in pain control. Growing preclinical evidence and initial clinical findings suggest that modulation of the endocannabinoid system, via endogenous or exogenous cannabinoids may be relevant for migraine via multiple mechanisms. Summary: The endocannabinoid system qualifies as an interesting area of research worth exploration in the quest for therapeutic targets for the treatment of migraine.
... Reports of marijuana use for acute migraine treatment through self-medication or as a substitute for analgesics are increasingly common (10)(11)(12)47). Medical marijuana has been reported to reduce the frequency of attacks in patients with migraine (19,48). The distribution of cannabinoid receptors is consistent with potential anti-migraine effects that have been reported in preclinical studies (16,17,49,50). ...
Article
Aim Evaluation of cannabinoid receptor agonists in a preclinical model of medication overuse headache. Methods Female Sprague Dawley rats received graded intraperitoneal doses of WIN55,212-2 or Δ-9-tetrahydrocannabinol (Δ-9-THC). Antinociception (tail-flick test), catalepsy and hypomotility (open field test) and impairment of motor function (rotarod test) were assessed to establish effective dosing. Rats were then treated twice daily with equianalgesic doses of WIN55,212-2 or Δ-9-THC, or vehicle, for 7 days and cutaneous tactile sensory thresholds were evaluated during and three weeks following drug discontinuation. Rats then received a one-hour period of bright light stress (BLS) on two consecutive days and tactile sensory thresholds were re-assessed. Results WIN55,212-2 and Δ-9-THC produced antinociception as well as hypomotility, catalepsy and motor impairment. Repeated administration of WIN55,212-2 and Δ-9-THC induced generalized periorbital and hindpaw allodynia that resolved within 3 weeks after discontinuation of drug. Two episodes of BLS produced delayed and long-lasting periorbital and hindpaw allodynia selectively in rats previously treated with WIN55,212-2, and Δ-9-THC. Interpretation Cannabinoid receptor agonists including Δ-9-THC produce a state of latent sensitization characterized by increased sensitivity to stress, a presumed migraine trigger. Overuse of cannabinoids including cannabis may increase the risk of medication overuse headache in vulnerable individuals.
... Otras investigaciones le otorgan utilidad para el alivio de la ansiedad y el insomnio (Aggarwal et al., 2013;Pedersen & Sandberg, 2013;Walsh et al., 2013;Webb & Webb, 2014) y para reducir los síntomas del trastorno de estrés postraumático en algunos pacientes (Greer, Grob, & Halberstadt, 2014), como también para disminuir la frecuencia de migrañas (Rhyne, Anderson, Gedde, & Borgelt, 2016). Un estudio reciente señala que el aceite de cannabis sería seguro y eficaz para los síntomas conductuales y psicológicos de la demencia, por lo que sugieren agregarlo a la farmacoterapia de los pacientes con Alzheimer como una opción de tratamiento (Shelef et al., 2016). ...
Article
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Resumen Este estudio pretende reportar la evidencia actual sobre el uso medicinal de cannabis existente en la base de datos Scopus. Se llevó a cabo una revisión sistemática de las publicaciones científicas, entre el periodo 2013-2017, disponibles en Scopus sobre el uso medicinal de cannabis. Estados Unidos es el país con mayor cantidad de publicaciones, seguido de Canadá e Israel; existiendo un aumento progresivo y constante de la evidencia entre los años 2013 y 2017. Los contenidos de las publicaciones versan sobre efectos beneficiosos y adversos para la salud, consecuencias de la legislación del cannabis y su asociación con diversas variables. Existe una falta de estudios en uso medicinal de cannabis respecto a tratamientos y enfermedades, su estandarización, vías de administración y dosis, dando cuenta de la necesidad de un volumen mayor de investigaciones al respecto.
... After the 61 first cycle of BTX, she had a significant decrease in headache frequency and severity, 62 3 3 similar to her previous response prior to cannabis use, down to 8-headache days/month. shown to affect the endocannabinoid system by downregulation of brain cannabinoid 83 receptor type 1, and this may affect the modulation of neuropathic, visceral, and 84 inflammatory pain (1,4). It has been demonstrated that chronic migraineurs with or 85 4 4 without MOH responded well to BTX treatment similarly and in the chronic migraineurs 86 with MOH group, they started to decrease their daily abortive medications overtime due 87 to their response to BTX (5). ...
Article
Chronic cannabis use and treatment failure of onabotulinum toxin A for chronic migraine - Tommy L.H. Chan, Niushen Zhang
... These findings suggest the analgesic effect of medical cannabis in patients with headache and migraine [32]. Similarly, a retrospective, observational chart review by Rhyne et al. found that migraine headache frequency decreased significantly with medical marijuana use (P < 0.0001) [33]. Research suggests a role for medicinal cannabis in migraine headaches; however, there are no randomized controlled trials (RCTs) for validation and further evaluation. ...
Article
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Purpose of Review This review discusses the recent advancements in research on Cannabinoids’ role in pain, including its use in cancer pain, neuropathic pain, fibromyalgia, headache, visceral pain, postoperative and failed back pain management, and concurrent use with opioids. Recent Findings Current research suggests that a potential role exists for medical cannabis in pain management, although research shows varied effectiveness by the type of pain. Moreover, its coadministration with opioids may result in reduced opioid requirements. Summary Patients with neuropathic pain, cancer pain, and migraine headache may benefit from the analgesic effects of a cannabis-based medicine (CBM), but not necessarily patients with chronic abdominal pain. Equivocal results were shown in fibromyalgia and postoperative orthopedic pain. Interestingly, the opioid-sparing properties of CBM make it an attractive option for pain management. However, the scale and quality of studies conducted are limited. Further research is necessary to establish recommendation guidelines for medical cannabis in pain management.
... Nearly 36% of medical cannabis users reported using cannabis to treat headache/migraine; moreover, they retrospectively reported an average 3.6-point decrease (on a 10-point scale) in headache severity after cannabis use [26]. Similarly, 40% of patients for whom medical cannabis was recommended for migraine reported a positive effect, with a decrease in migraine frequency from 10.4 to 4.6 migraines/month [22]. Moreover, another study found that approximately 2/3 of cannabis users indicated slight to substantial decreases in use of other migraine medications after initiating medical cannabis use [21]. ...
Article
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Use of cannabis to alleviate headache and migraine is relatively common, yet research on its effectiveness remains sparse. We sought to determine whether inhalation of cannabis decreases headache and migraine ratings as well as whether gender, type of cannabis (concentrate vs. flower), THC, CBD, or dose contribute to changes in these ratings. Finally, we explored evidence for tolerance to these effects. Archival data were obtained from StrainprintTM, a medical cannabis app that allows patients to track symptoms before and after using different strains and doses of cannabis. Latent change score models and multilevel models were used to analyze data from 12,293 sessions where cannabis was used to treat headache and 7,441 sessions where cannabis was used to treat migraine. There were significant reductions in headache and migraine ratings after cannabis use. Men reported larger reductions in headache than women and use of concentrates was associated with larger reductions in headache than flower. Further, there was evidence of tolerance to these effects. Perspective: Inhaled cannabis reduces self-reported headache and migraine severity by approximately 50%. However, its effectiveness appears to diminish across time and patients appear to use larger doses across time, suggesting tolerance to these effects may develop with continued use.
... A large meta-analysis by Whiting et al. and other studies showed that cannabinoids are effective with neuropathic pain, fibromyalgia, cancer, and diabetic neuropathy, refractory pain due to multiple sclerosis and other neurological conditions, including rheumatoid arthritis, noncancer pain, central pain, musculoskeletal problems, and chemotherapy-induced pain [15][16]. Its efficacy with migraines and mood disorders has been consistently noted in the literature as well [17][18][19]. A recent preclinical study demonstrated effective neuropathic pain and comorbid anxiety and depression reduction through its interaction with the serotonin 5-HT 1A receptor [20]. ...
Article
Neurofibromatosis type 1 (NF1) is a common genetic disorder. Pain is a major symptom of this disease which can be secondary to the development of plexiform and subcutaneous neurofibromas, musculoskeletal symptoms (such as scoliosis and pseudoarthrosis), and headaches. Visible neurofibromas add significant psychosocial distress for NF1 patients. Along with the chronic pain, psychosocial distress contributes to associated mood disorders, such as depression and anxiety. Cannabis has been the focus of many studies for treating multiple conditions, including epilepsy, multiple sclerosis, Parkinsonism disease, and many chronic pain conditions. Cannabidiol (CBD) is the major non-psychotropic component of cannabis. CBD has shown anti-inflammatory and analgesic properties, as well as having mood stabilizer and anxiolytic effects. In this report, we present the use of cannabidiol (CBD) for the management of chronic pain and concomitant mood disorder in an NF1 patient.
... There are studies available that have proven cannabinoids can decrease the pain from headaches as well as the frequency of headaches. Rhyne D, et al. [7] states that migraine headache frequency does decrease with the use of medical marijuana, which contains high doses of THC. Cannabinoids are a common treatment modality for headaches as mentioned [8]. ...
... (23,24) También existe evidencia del cannabis para el tratamiento de la migraña, cefalea crónica, hipertensión intracraneal idiopática y esclerosis múltiple asociada con neuralgia del trigémino. (24,25,26) Aunque estos últimos usos no están avalados por ensayos clínicos bien Este es un artículo en Acceso Abierto distribuido según los términos de la Licencia Creative Commons Atribución-NoComercial 4.0 que permite el uso, distribución y reproducción no comerciales y sin restricciones en cualquier medio, siempre que sea debidamente citada la fuente primaria de publicación. ...
Article
Introducción: En la actualidad, uno de los temas más polémicos que involucra en gran proporción al campo de la Medicina es el uso terapéutico de la marihuana y su legalización. Esta planta de reconocimiento milenario ha desatado en las últimas décadas disímiles de controversias dado el descubrimiento del sistema endocannabinoide que revolucionó la investigación sobre ella. Objetivo: Describir la situación actual del cannabis, sus beneficios terapéuticos y sus efectos adversos. Material y métodos: Se realizó una exhaustiva búsqueda y revisión empleando los Descriptores en Ciencias de la Salud, en idioma inglés y español, consultando las bases de datos Pubmed, Scielo, Lilacs, Cochrane Library y Web of Science, para los últimos 10 años, empleándose un total de 45 artículos como referencias bibliográficas. Desarrollo: Al Cannabis se le han atribuido efectos farmacológicos, tales como: antinociceptivo, antiepiléptico, inmunosupresivo, antiemético, estimulante del apetito, antimicrobiano, antiinflamatorio y neuroprotector. A su vez, presenta disímiles reacciones adversas como son la predisposición a varios tipos de cáncer, empeoramiento de desórdenes mentales, dificultades en el aprendizaje y el rendimiento escolar, que constituye una droga portera, entre otros. A pesar de las tendencias legalizadoras no son suficientes las razones para la legalización de esta droga, cuando su principal blanco resulta ser los adolescentes, donde los daños neurológicos que causa son irreversibles. Conclusiones: Se debe continuar explorando las potencialidades terapéuticas de los cannabinoides a partir de la elaboración de productos farmacológicos bien dosificados y controlados, pues el riesgo de sus efectos adversos es innegable y contundente.
... Most of the included participants took marijuana in more than one form on a regular basis for prevention. A reduced incidence of migraine headache was observed in 24 patients and abandoned migraine headache in 14 patients (Rhyne et al., 2016). Various randomized trials showing positive effects of cannabidiol in treating epilepsy have been carried out (Hess et al., 2016;Devinsky et al., 2017Devinsky et al., , 2018Schoedel et al., 2018). ...
Article
In the present review article, we have compiled and analysed ethnomedicinal knowledge on the plants used to manage CNS and memory-related problems by various indigenous communities of the two Union Territories of India viz., Jammu and Kashmir (J&K), and Ladakh. Ethnomedicinal studies conducted in J&K and Ladakh, India up till the year 2020, were searched from journals, edited books, and scientific databases such as Google Scholar, SciFinder, Scopus, CAB international, DOAJ, Science direct, PubMed and Web of Science. More than 100 ethnobotanical studies were reviewed during the present study. The reviewed studies covered various indigenous communities from the study area, such as Gujjar, Bakerwal, Amchis, Dard, Pathan, Gaddi, Pahari, and other local and ethnic communities. A total of 116 plants belonging to the 94 genera of 32 families were found to be used by different communities of the study area to manage CNS and memory-related problems. Some of the most used plant species were Centella asiatica, Cannabis sativa, Datura stramonium, Valeriana jatamansi, Hyoscyamus niger, Hypericum perforatum, Heracleum candicans, Euphorbia wallichii, Potentilla multifida, Atropa acuminata, and Prunella vulgaris. The maximum numbers of plant species used in the study area belonged to the family Asteraceae (15 spp.), followed by family Apiaceae (9 spp.), Lamiaceae (9 spp.), Solanaceae (6 spp.), Rosaceae (5 spp.), and so on. The whole plant of 34 plant species was used, followed by roots, leaves, seeds, fruits, and flowers for the treatment of CNS and memory-related ailments. The majority of the plants were used as a sedative or narcotic. Large numbers of plants were used to manage epilepsy, memory, or as a brain/nerve tonic. Further scientific validation studies are required to prove claimed neuroprotective uses of some of the highly used plant species in the region, such as E. wallichii, P. multifida, A. acuminata, P. vulgaris, Malva neglecta, Plantago himalaica, Pedicularis pectinata, and Nepeta leucolaena.
... Cannabinoids: A fast-growing field of therapeutic intervention in different brain disorders is to modulate the endocannabinoid (eCB) system to harness favorable outcomes [205,284]. Cannabis-based research has come a long way from its introduction in 1838 by William O'Shaughnessy [285] for the treatment of migraines [286,287] and neuropathic pain [285,288,289]. The current cannabis preparations available clinically are Cesamet (nabilone), Marinol (dronabinol: ∆9-tetrahydrocannabinol [∆9-THC]), and Sativex also branded as Nabiximols (∆9-THC with cannabidiol) [290]. ...
Article
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Studying the complex molecular mechanisms involved in traumatic brain injury (TBI) is crucial for developing new therapies for TBI. Current treatments for TBI are primarily focused on patient stabilization and symptom mitigation. However, the field lacks defined therapies to prevent cell death, oxidative stress, and inflammatory cascades which lead to chronic pathology. Little can be done to treat the mechanical damage that occurs during the primary insult of a TBI; however, secondary injury mechanisms, such as inflammation, blood-brain barrier (BBB) breakdown, edema formation, excitotoxicity, oxidative stress, and cell death, can be targeted by therapeutic interventions. Elucidating the many mechanisms underlying secondary injury and studying targets of neuroprotective therapeutic agents is critical for developing new treatments. Therefore, we present a review on the molecular events following TBI from inflammation to programmed cell death and discuss current research and the latest therapeutic strategies to help understand TBI-mediated secondary injury.
... Previous prospective studies have demonstrated QoL improvement and decrease in opioids consumption following cannabis treatment (Haroutounian et al., 2016), however, none of these studies explored which MC compounds may be responsible for these phenomena. Thus, regarding 'cannabis' as if it was a single adherent medication (Rhyne et al., 2016) could lead to major bias due to cannabis treatment complexities with different concentrations of over 90 phytocannabinoids (Baram et al., 2019) and similar amounts of terpenoids (Shapira et al., 2019) between cannabis cultivars (Hazekamp and Fischedick, 2012). ...
Article
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Introduction: Chronic non-cancer pain (CNCP) is one of the most prevalent indications for medical cannabis (MC) treatment globally. In this study, we investigated CNCP parameters in patients during prolonged MC treatment, and assessed the interrelation between CNCP parameters and the chemical composition of MC chemovar used. Methods: A cross-sectional questionnaire-based study was performed in one-month intervals for the duration of six months. Subjects were adult patients licensed for MC treatment who also reported a diagnosis of CNCP by a physician. Data included self-reported questionnaires. MC treatment features included administration route, cultivator, cultivar name and monthly dose. Comparison statistics were used to evaluate differences between the abovementioned parameters and the monthly MC chemovar doses at each time point. Results: 429, 150, 98, 71, 77 and 82 patients reported fully on their MC treatment regimens at six one-month intervals, respectively. Although pain intensities did not change during the study period, analgesic medication consumption rates decreased from 46 to 28% ( p < 0.005) and good Quality of Life (QoL) rates increased from 49 to 62% ( p < 0.05). These changes overlapped with increase in rates of (-)-Δ ⁹ - trans -tetrahydrocannabinol (THC) and α -pinene high dose consumption. Conclusion: Even though we observed that pain intensities did not improve during the study, QoL did improve and the rate of analgesic medication consumption decreased alongside with increasing rates of high dose THC and α -pinene consumption. Understanding MC treatment composition may shed light on its long-term effects.
... Previous prospective studies have demonstrated QoL improvement and decrease in opioids consumption following cannabis treatment (Haroutounian et al., 2016), however, none of these studies explored which MC compounds may be responsible for these phenomena. Thus, regarding 'cannabis' as if it was a single adherent medication (Rhyne et al., 2016) could lead to major bias due to cannabis treatment complexities with different concentrations of over 90 phytocannabinoids (Baram et al., 2019) and similar amounts of terpenoids (Shapira et al., 2019) between cannabis cultivars (Hazekamp and Fischedick, 2012). ...
Article
Full-text available
Introduction: Chronic non-cancer pain (CNCP) is one of the most prevalent indications for medical cannabis (MC) treatment globally. In this study, we investigated CNCP parameters in patients during prolonged MC treatment, and assessed the interrelation between CNCP parameters and the chemical composition of MC chemovar used. Methods: A cross-sectional questionnaire-based study was performed in one-month intervals for the duration of six months. Subjects were adult patients licensed for MC treatment who also reported a diagnosis of CNCP by a physician. Data included self-reported questionnaires. MC treatment features included administration route, cultivator, cultivar name and monthly dose. Comparison statistics were used to evaluate differences between the abovementioned parameters and the monthly MC chemovar doses at each time point. Results: 429, 150, 98, 71, 77 and 82 patients reported fully on their MC treatment regimens at six one-month intervals, respectively. Although pain intensities did not change during the study period, analgesic medication consumption rates decreased from 46 to 28% (p < 0.005) and good Quality of Life (QoL) rates increased from 49 to 62% (p < 0.05). These changes overlapped with increase in rates of (-)-Δ 9-trans-tetrahydrocannabinol (THC) and α-pinene high dose consumption. Conclusion: Even though we observed that pain intensities did not improve during the study, QoL did improve and the rate of analgesic medication consumption decreased alongside with increasing rates of high dose THC and α-pinene consumption. Understanding MC treatment composition may shed light on its long-term effects.
... [17][18][19] There is currently limited evidence suggesting that cannabis could be helpful for the treatment of migraine. 20 There are no randomized controlled clinical trials that support this hypothesis. However, there is emerging anecdotal clinical evidence that use of cannabis may lead to medication overuse. ...
Article
Objective: To examine whether cannabis use predicts medication overuse headache (MOH) in patients with chronic migraine (CM). Methods: Electronic chart review was conducted by combining the terms "CM," "medication overuse," "cannabis," "cannabidiol," and "tetrahydrocannabinol" for patients seen at our headache clinics from 2015 to 2019. Of 729 charts consecutively screened, 368 met our inclusion criteria, that is, adult patients with CM with ≥1-year CM duration. The following variables were extracted from the included patient charts: MOH diagnosis, age, sex, migraine frequency, current CM duration, current cannabis use duration, overused acute migraine medications, current MOH duration, and types of cannabis products used. Logistic regression was used to identify variables predicting MOH while controlling for remaining predictors. Agglomerative hierarchical clustering (AHC) was conducted to explore natural clusters using all predictor variables. Results: There were 212 patients with CM and MOH (cases; median age 43 years, interquartile range [IQR] 33-54; 177 [83%] females) and 156 patients with CM without MOH (referents; median age 40 years, IQR 31-49; 130 [83%] females). MOH was present in 81% (122/150) of current cannabis users compared with 41% (90/218) in those without cannabis use-adjusted odds ratio 6.3 (95% CI: 3.56 to 11.1, p < 0.0001). Current cannabis use was significantly associated with opioid use (Spearman's rho 0.26, p < 0.0001). Both current cannabis use (rho 0.40, p < 0.0001) and opioid use (rho 0.36, p < 0.0001) were significantly associated with MOH. Similarly, AHC revealed two major natural clusters. Cluster I patients featured 9.3 times higher current cannabis use, 9.2 times higher current opioid use, and 1.8 times higher MOH burden than those in Cluster II (p < 0.0001). Conclusion: Cannabis use was significantly associated with increased prevalence of MOH in CM. Bidirectional cannabis-opioid association was observed-use of one was associated with use of the other. Advising patients with CM and MOH to reduce cannabis use may help treat MOH effectively.
... It can prevent migraine attacks when used daily. Interestingly, when acute migraine occurred, the commonly used form was inhalation [110]. [111]. ...
Article
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Objective: The purpose of this review was to present general data of cannabinoids, its function related to orofacial pain management, and its adverse effects. Methods: The data was searched through PubMed database and Google Scholars by various keywords without time limits. Hand searching and citation mining were also applied. Unpublished, incomplete, non-English data were excluded. Results: The presence of cannabinoids receptors throughout orofacial tissues has been reported, which could be a therapeutic site of action. Only in neuropathic pain, cannabinoids have been proven to be successful over conventional treatment. More clinical approvals of its analgesic effects are extremely required for pain originating from other tissues. When prescribing cannabis, dentists should be cautious about its adverse effects in many systems. Conclusion: Currently, cannabinoids have not been officially endorsed for analgesic effects in orofacial area. It can be useful for neuropathic orofacial pain especially when the standard treatment was unsuccessful.
... Known from ancient times [15], cannabinoids emerged recently as a promising analgesic approach to treat migraine pain [16][17][18]. In particular, cannabis, now legalized in many countries, has shown a therapeutic effect in migraine [16,19]. Indeed, marijuana had been used in the past for medicinal purposes to relieve headaches [20]. ...
Article
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In migraine pain, cannabis has a promising analgesic action, which, however, is associated with side psychotropic effects. To overcome these adverse effects of exogenous cannabinoids, we propose migraine pain relief via activation of the endogenous cannabinoid system (ECS) by inhibiting enzymes degrading endocannabinoids. To provide a functional platform for such purpose in the peripheral and central parts of the rat nociceptive system relevant to migraine, we measured by activity-based protein profiling (ABPP) the activity of the main endocannabinoid-hydrolases, mon-oacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH). We found that in trigeminal ganglia, the MAGL activity was nine-fold higher than that of FAAH. MAGL activity exceeded FAAH activity also in DRG, spinal cord and brainstem. However, activities of MAGL and FAAH were comparably high in the cerebellum and cerebral cortex implicated in migraine aura. MAGL and FAAH activities were identified and blocked by the selective and potent inhibitors JJKK-048/KML29 and JZP327A, respectively. The high MAGL activity in trigeminal ganglia implicated in the generation of nociceptive signals suggests this part of ECS as a priority target for blocking peripheral mechanisms of migraine pain. In the CNS, both MAGL and FAAH represent potential targets for attenuation of migraine-related enhanced cortical excitability and pain transmission.
... However, other studies show cannabis use to be a risk factor for abuse or dependence of prescription opioids and other drugs [17][18][19] . There is currently limited evidence suggesting that cannabis could be helpful for treatment of migraine 20 . There are no randomized controlled clinical trials that support this hypothesis. ...
Preprint
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Objective: To examine whether cannabis use predicts medication overuse headache (MOH) in chronic migraine (CM) patients. Methods: Electronic chart review was conducted by combining the terms “chronic migraine”, “medication overuse”, “cannabis”, “CBD”, “THC” for patients seen at our headache clinics from 2015 to 2019. Of 729 charts identified, 368 (150 using cannabis; 218 not using cannabis) met our inclusion criteria, i.e., adult CM patients with ≥ 1-year CM duration. The following variables were extracted from each patient’s chart: MOH diagnosis as dependent variable, and predictor variables as age, sex, migraine frequency, current CM duration, current cannabis use duration, overused acute migraine medications, current MOH duration, and types of cannabis products used. Logistic regression was employed to identify variables predicting MOH while controlling for remaining predictors. Agglomerative hierarchical clustering (AHC) was conducted to explore natural clusters using all predictor variables. Results: There were 212 CM patients with MOH ( cases ) and 156 CM patients without MOH ( referents ). Current cannabis use statistically significantly predicted cases with MOH – odds ratio 6.0 (3.45, 10.43), p < 0.0001. Current cannabis use, opioid use, and MOH were significantly associated. AHC revealed two major natural clusters. Cluster I patients were younger with less migraine frequency, higher MOH burden, more current cannabis and opioid users than cluster II. Conclusion: Cannabis use significantly contributes to the prevalence of MOH in CM. Bidirectional cannabis-opioid association was observed – use of one increased use of the other. Advising CM patients with MOH to reduce cannabis use may help treat MOH effectively.
... An earlier retrospective chart review of adults with migraine (n=121) treated with medical cannabis reported decreased headache frequency (p<0001) [110]; however, validity and interpretation is limited based on study design. Results are further limited by lack of control and sampling bias (likely over-representing users who find cannabis effective for headache). ...
Article
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Purpose of Review Headache affects and disables at least 1 billion people worldwide. Patients and providers seek new therapies to relieve headache without the side effects and financial burden of current treatments. This narrative review highlights recent treatment advances in integrative headache medicine: nutraceuticals and behavioral therapies. Recent Findings Growing use of complementary and alternative medicine (CAM) therapies for headache (riboflavin, coenzyme Q10, magnesium, vitamin D, melatonin) alongside mainstream treatments is increasing with improving evidence of quality, safety, and tolerability. Increasing interest in medical cannabis is tempered by lack of evidence regarding safety and efficacy. Behavioral therapies including cognitive behavioral therapy (CBT), biofeedback, mindfulness-based stress reduction (MBSR), and acceptance and commitment therapy (ACT) improve patient resiliency and self-efficacy outcomes and reduce disability. Summary The body of evidence for nutraceutical and behavioral CAM interventions for headache continues to grow and improve in quality. Providers and patients should educate themselves regarding CAM therapies as part of integrative headache management. Future studies should examine combinatorial trials of CAM therapies against current standards of headache care.
... Moreover, the limited data on clinical effectiveness should be weighed against the substantial evidence for marijuana-related harms, such as worsening respiratory symptoms, increased risk of motor vehicle accidents, lower birth rates, and increased risk for developing psychotic disorders (NASEM, 2017). More generally, marijuana's long-term therapeutic benefits versus costs (including tolerance, addiction, and withdrawal) are not yet known (Brigden & England, 2018;Rhyne et al., 2016;Wilkinson et al., 2016). ...
Article
Full-text available
Objective: Prior studies documenting more frequent and problematic use among young adults who have acquired medical marijuana (MM) cards have broadly compared those who use medically to those who use recreationally. Gaining a better picture of how health symptoms and problematic use vary both within those who have a MM card for specific condition domains and between those who do not have a MM card can provide key information for medical practitioners and states interested in adopting or updating MM policies. Method: The current study categorizes young adults authorized to use MM into three mutually exclusive groups based on endorsements of qualifying conditions: (1) Physical Health only (e.g., AIDS, arthritis, cancer; n = 34); (2) Behavioral Health only (e.g., anxiety, depression, sleep problems; n = 75); and (3) Multiple Conditions (a physical and behavioral health condition; n = 71). Multiple and logistic regression models examined differences across marijuana use, problems, mental health, physical health, and sleep quality for MM condition categories and for those that only use marijuana recreationally (n = 1,015). Results: After adjusting for socio-demographic factors (age, sex, sexual orientation, educational status, employment status, race/ethnicity, mother's education, prior intervention involvement in youth), MM card holders, particularly those with physical health or multiple health conditions, reported heavier, more frequent, and more problematic and risky marijuana use compared to those using recreationally. Despite this pattern, those in different MM condition categories were generally not found to be more symptomatic in domains of mental or physical health relevant to their respective conditions, compared to different category groups or to those using recreationally. Conclusions: Findings emphasize the importance of providers conducting a careful assessment of reasons for needing a card, along with use, to reduce potential harms while adding credibility to a medical movement with genuine promise of relief for many medical conditions.
Article
For centuries, cannabis has been used with many different purposes, including medicinal use, usually bypassing any formal approval process. However, during the last decade, interest in cannabis in medicine has been increasing, and several countries, including the United States and Canada, have produced their own legislation about marihuana and cannabis-based medicines. Because of this, interest in research has been increasing and evidence about its medical effects is becoming necessary. We conducted a review examining the evidence of cannabis in pain. Cannabis had been shown to be useful in acute and chronic pain, however recently these results have been controverted. Within the different types of chronic pain, it has a weak evidence for neuropathic, rheumatic pain, and headache, modest evidence for multiple sclerosis related pain, and as adjuvant therapy in cancer pain. There is no strong evidence to recommend cannabis in order to decrease opioids in patients with chronic use. Even though cannabis-based medications appear to be mostly safe, mild adverse effects are common; somnolence, sedation, amnesia, euphoric mood, hyperhidrosis, paranoia, and confusion may limit the use of cannabis in clinical practice. Risks have not been systematically analyzed. Special concern arises on how adverse effect might affect vulnerable population such as elderly patients. More research is needed in order to evaluate benefits and risks, as well as the ideal administration route and dosages. As cannabis use increases in several countries, answers to these questions might be coming soon.
Article
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Despite federal prohibition of medical marijuana possession, sale, and use, marijuana use continues to escalate as state legalization persists and expands. The purpose of this discussion is to provide a brief summary of the evidence regarding both potential benefits and risks of medical marijuana use.
Article
Background: With increasing popularity of marijuana, consumers are likely turning to the internet for information regarding medical marijuana. Accuracy of medical marijuana claims is a significant concern because consumers change their medication management based on information from a single website. Objective: The purpose of this study was to evaluate the accuracy and quality of medical marijuana claims on popular websites. Methods: Commonly used websites containing claims regarding medical marijuana were selected by utilizing three online marketing tools that rank websites based on number of views, number of visitors, and visitor engagement. Once the top ten most popular websites were selected, medical claims regarding marijuana were reviewed for accuracy and quality using evidence-based tools. Results: Seventy-six percent of claims made by websites were inaccurate and were based on low-quality evidence. Of the medical marijuana claims reviewed, 10% of websites made appropriate cause and effect conclusions. Furthermore, approximately 3% of the medical marijuana claims were written by a healthcare professional. Conclusion: The findings show there is misleading and inaccurate information readily available to consumers online.
Article
Background: Migraine may be described as a headache with moderate to extreme pain that is often accompanied by incapacitating neurological symptoms. It is estimated that 12% of the world population suffers from migraine. Although a number of drugs have been used for treatment of migraine, most of these are not effective for every patient and may have undesirable side-effects. Thus, there is an enormous unmet need in current migraine therapy for discovering safer and more effective agents. Methods: The information summarized in this review was obtained through extensive literature review and search of relevant books and articles with the use of Web of Knowledge and SciVerse Scopus databases. Results: Greater understanding of the molecular mechanisms underlying the etiopathogenesis of migraine is helpful in identifying novel targets for antimigraine drugs such as cannabinoid, histamine, and melatonin receptors. In the past, natural product-derived constituents have served as an invaluable source of numerous medicinally useful antimigraine agents and it may be expected that further promising drug candidates from natural products will be discovered for antimigraine pharmacotherapy with better efficacy and fewer adverse-effects. Conclusion: The discovery of novel targets in migraine therapy has opened new horizons for compounds that have not been clinically tested or that previously failed in clinical trials as potential antimigraine drugs. Ginkgolide B, melatonin, histamine, oxytocin, various ribosomal peptide toxins, kavalactones, devil's claw-derived compounds, salvinorin A and petasin are among those agents that show considerable promise as novel drugs in migraine prevention and treatment. It is necessary to conduct more research to better understand their antimigraine action, to confirm their effectiveness and safety, and to introduce them into clinical practice.
Article
Objective: To describe which cannabinoids and terpenes are effective for treating pain. Data sources: Peer-reviewed articles, book chapters. Conclusion: Cannabis and cannabinoid medicines, as modulators of the endocannabinoid system, offer novel therapeutic options for the treatment of cancer-related pain, not only for patients who do not respond to conventional therapies, but also for patients who prefer to try cannabis as a first treatment option. Implications for nursing practice: Understanding the endocannabinoid system, cannabinoids, terpenes, routes of administration, potential drug interactions, clinical implications, and potential side effects ensures nurses can better assist patients who use cannabis for the treatment of cancer pain.
Article
The naturally occurring Cannabis plant has played an established role in pain management throughout recorded history. However, in recent years, both natural and synthetic cannabis-based products for medicinal use (CBPMs) have gained increasing worldwide attention due to growing evidence supporting their use in alleviating chronic inflammatory and neuropathic pain associated with an array of conditions. In view of these products’ growing popularity in both the medical and commercial fields, we carried out a systematic review to ascertain the effects of cannabis and its synthetically derived products on orofacial pain and inflammation. The application of topical dermal cannabidiol formulation has shown positive findings such as reducing pain and improving muscle function in patients suffering from myofascial pain. Conversely, two orally administered synthetic cannabinoid receptor agonists (AZD1940 and GW842166) failed to demonstrate significant analgesic effects following surgical third molar removal. There is a paucity of literature pertaining to the effects of cannabis-based products in the orofacial region; however, there is a wealth of high-quality evidence supporting their use for treating chronic nociceptive and neuropathic pain conditions in other areas. Further research is warranted to explore and substantiate the therapeutic role of CBPMs in the context of orofacial pain and inflammation. As evidence supporting their use expands, healthcare professionals should pay close attention to outcomes and changes to legislation that may impact and potentially benefit their patients.
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Działania niepożądane, interakcje lekowe, a także farmakooporność mogą w znacznym stopniu utrudniać farmakologiczne leczenie migreny. W związku z tym coraz częściej stosuje się niekonwencjonalne i niefarmakologiczne metody leczenia. W szczególności nieinwazyjna neuromodulacja, blokady nerwów obwodowych, nutraceutyki i metody behawioralne są dobrze tolerowane i wskazane dla określonych grup pacjentów, takich jak młodzież, kobiety w ciąży i pacjenci, którzy z różnych powodów muszą lub chcą ograniczyć farmakoterapię. Metody te są coraz częściej postrzegane jako ważna opcja terapeutyczna w leczeniu migreny, konieczne są jednak dalsze badania nad ich skutecznością, także w odniesieniu do efektów długoter minowych, zwłaszcza że skuteczności części metod niekonwencjona lnych (np. kannabinoidów) dotychczas nie zweryfikowano w dobrej jakości badaniach naukowych. Celem pracy jest przedstawienie i omówienie głównych metod wspomagających leczenie farmakologiczne migreny na podstawie aktualnego piśmiennictwa.
Article
Background: Based on recent research in political science, which has conceptualized political party affiliation as a form of social identity, the present study examined political ideology, party affiliation, and associated control measures as determinants of attitudes toward marijuana legalization. The research, which examined attitudes at 16 points in time across a 30-year period, anticipated an increasingly important role for party affiliation, given increased partisanship in the United States. Methods: Drawing on data gathered in the General Social Survey, the study used binary logistic regression analysis to test the explanatory effects of ideology, affiliation and control measures on support for marijuana legalization. Results: As anticipated, political ideology showed significance as an explanatory measure across the 30-year period, but party affiliation did not become a consistent, statistically controlled determinant until 2004, when Republicans began to express significantly less support than Democrats and Independents. In terms of demographic control measures, the study found males and younger respondents to express greater support for legalization. In recent periods of study, White and Black respondents expressed greater support than minorities apart from African Americans, while education level and region of the country showed sporadic explanatory significance. Conclusion: While political ideology, conceived as a form of personal identity, predicted attitudes toward marijuana legalization across 30 years of analysis, party affiliation, conceived as a form of group identity, became a consistently significant predictor in the 21st century. This finding suggests increases in partisanship and group identity, which in turn suggest potential increases in the politicization of drug policy. The article concludes with limitations and recommendations for future research.
Article
Resumen Introducción El uso de nutracéuticos o suplementos dietarios/herbales para el tratamiento de la migraña en pacientes adultos es objeto de estudio reciente debido a que estos contribuirían al alivio del dolor de una manera eficaz, y con una tolerabilidad que las terapias farmacológicas convencionales actuales no siempre ofrecen. Existe un creciente interés en el uso de esto como tratamiento profiláctico en pacientes con migraña. El tratamiento nutracéutico consiste en la administración de vitaminas, suplementos y preparaciones a base de hierbas. Objetivo Efectuar una revisión bibliografía sobre el potencial uso del tratamiento nutracéutico en la práctica clínica en el abordaje de pacientes con migraña. Métodos En esta revisión se identificaron estudios observacionales, ensayos controlados aleatorios, revisiones sistemáticas y metaanálisis sobre la eficacia y la seguridad de los nutracéuticos para el manejo de la migraña en adultos, a través de una búsqueda bibliográfica en las plataformas virtuales de PubMed, Medline, LILACS, SciELO, Medscape y Cochrane, entre otras. Los artículos fueron revisados y verificados por su contenido relevante. Conclusiones Esta revisión proporciona un resumen actualizado de las pautas existentes para el uso de ciertos nutracéuticos y suplementos dietarios en el abordaje de la migraña. Se provee información sobre la eficacia y los efectos secundarios potenciales de estos. El tratamiento nutracéutico individualizado sería de utilidad para disminuir la frecuencia, la intensidad y el impacto de la cefalea en los pacientes con migraña.
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Purpose of Review The use of cannabis for the treatment of migraine has become an area of interest with the legalization of medical cannabis in the USA. Understanding the mechanisms of cannabinoids, available studies, and best clinical recommendations is crucial for headache providers to best serve patients. Recent Findings Patients utilizing medical cannabis for migraine have reported improvement in migraine profile and common comorbidities. Reduction in prescription medication is also common, especially opioids. Side effects exist, with the majority being mild. Not enough data is available for specific dose recommendations, but THC and CBD appear to mediate these observed effects. Summary The purpose of this article is twofold: review the limited research surrounding cannabis for migraine disease and reflect on clinical management experiences to provide recommendations that best capture the potential use of cannabis for migraine.
Article
Archaeological evidence establishes cannabis as one of humanity’s oldest cultivated plants. Various authorities estimate that the history of its use began 5‐10,000 years ago, initially in Asia, where the plant is indigenous and spreading eventually worldwide. Commonly referred to in some countries as marijuana, the more universal nomenclature is “cannabis,” the genus name adopted from the main botanical sources of Cannabis sativa and Cannabis indica, and the less common Cannabis ruderalis.
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The utilization of illicit drugs in Nigeria has become a menace in our society which had equally aggravated the antisocial behaviours among the young and the old. This had tremendously increased the number of mentally ill individuals in the nation. Hence, this study employed a cross-sectional survey of quantitative research design to explore predictors and patterns of marijuana use among adolescents in Owo Local Government Area, Ondo State. The objectives of the study are to: assess adolescents’ level of knowledge about marijuana; assess the pattern of marijuana use among adolescents; examine the effect of socioeconomic status of parents on the adolescents’ use of marijuana; Find out the influence of peer groups on adolescents use of marijuana; determine the adolescents’ perception of marijuana as a drug of social influence. Multistage sampling techniques were used to select 432 respondents from four districts/areas of the local government. A self-designed semi-structured questionnaire was used in data collection that spanned seven months, and data were analyzed with descriptive and inferential statistics. The result revealed that the majority of the respondents were introduced to marijuana by friends. However, it was also revealed that most respondents disagreed that adolescents from rich parents smoke marijuana more than those from poor parents. In addition, the majority of the respondents admitted that marijuana is used to withstand stressful situations and obtain relief from social pressure. It was also revealed that marijuana as a drug has some therapeutic benefits to the body. In conclusion, utilization of marijuana among adolescents has become rampant to the extent that respondents believed in the positive effects without considering the long term negative effects of marijuana use.
Article
Objective Few studies to date have measured the real-time effects of consumption of common and commercially available Cannabis products for the treatment of headache and migraine under naturalistic conditions. This study examines, for the first time, the effectiveness of using dried Cannabis flower, the most widely used type of Cannabis product in the United States, in actual time for treatment of headache- and migraine-related pain and the associations between different product characteristics and changes in symptom intensity following Cannabis use. Methods Between 06/10/2016 and 02/12/2019, 699 people used the Releaf Application to record real-time details of their Cannabis use, including product characteristics and symptom intensity levels prior to and following self-administration; data included 1910 session-level attempts to treat headache- (1328 sessions) or migraine-related pain (582 sessions). Changes in headache- or migraine-related pain intensity were measured on a 0−10 scale prior to, and immediately, following Cannabis consumption. Results Ninety-four percent of users experienced symptom relief within a two-hour observation window. The average symptom intensity reduction was 3.3 points on a 0−10 scale (standard deviation = 2.28, Cohen’s d = 1.58), with males experiencing greater relief than females (P < 0.001) and a trend that younger users (< 35 years) experience greater relief than older users (P = 0.08). Mixed effects regression models showed that, among the known (i.e., labeled) product characteristics, tetrahydrocannabinol levels 10% and higher are the strongest independent predictors of symptom relief, and this effect is particularly prominent in headache rather than migraine sufferers (P < 0.05), females (P < 0.05) and younger users (P < 0.001). Females and younger users also appear to gain greater symptom relief from flower labeled as “C. indica” rather than “C. sativa” or other hybrid strains. Conclusion These results suggest that whole dried Cannabis flower may be an effective medication for treatment of migraine- and headache-related pain, but the effectiveness differs according to characteristics of the Cannabis plant, the combustion methods, and the age and gender of the patient.
Article
Marijuana has been used to treat medical disease since well before the 1800s. Recently, increased use of cannabinoids, the chemical components of marijuana, have been seen to treat neurologic illness in children and adults. Unfortunately, data are lacking in treating most neurologic illnesses except in the field of epilepsy and pain from spasticity in multiple sclerosis. Therefore, formal conclusions about the potential efficacy, benefit, and adverse effects for most marijuana based products cannot be made at this time. Further research using gold standard scientific methodology should be performed to help address potential uses and safety for cannabinoids to treat neurologic illnesses.
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Background: Migraine is a complex and highly disabling neurological disease whose treatment remains challenging in many patients, even after the recent advent of the first specific-preventive drugs, namely monoclonal antibodies that target calcitonin gene-related peptide. For this reason, headache researchers are actively searching for new therapeutic targets. Cannabis has been proposed for migraine treatment, but controlled clinical studies are lacking. A major advance in cannabinoid research has been the discovery of the endocannabinoid system (ECS), which consists of receptors CB1 and CB2; their endogenous ligands, such as N-arachidonoylethanolamine; and the enzymes that catalyze endocannabinoid biosynthesis or degradation. Preclinical and clinical findings suggest a possible role for endocannabinoids and related lipids, such as palmitoylethanolamide (PEA), in migraine-related pain treatment. In animal models of migraine-related pain, endocannabinoid tone modulation via inhibition of endocannabinoid-catabolizing enzymes has been a particular focus of research. Methods: To conduct a narrative review of available data on the possible effects of cannabis, endocannabinoids, and other lipids in migraine-related pain, relevant key words were used to search the PubMed/MEDLINE database for basic and clinical studies. Results: Endocannabinoids and PEA seem to reduce trigeminal nociception by interacting with many pathways associated with migraine, suggesting a potential synergistic or similar effect. Conclusions: Modulation of the metabolic pathways of the ECS may be a basis for new migraine treatments. The multiplicity of options and the wealth of data already obtained in animal models underscore the importance of further advancing research in this area. Multiple molecules related to the ECS or to allosteric modulation of CB1 receptors have emerged as potential therapeutic targets in migraine-related pain. The complexity of the ECS calls for accurate biochemical and pharmacological characterization of any new compounds undergoing testing and development.
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OBJECTIVES: This study examines the concept of clinical endocannabinoid deficiency (CECD), and the prospect that it could underlie the pathophysiology of migraine, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis. METHODS: Available literature was reviewed, and literature searches pursued via the National Library of Medicine database and other resources. RESULTS: Migraine has numerous relationships to endocannabinoid function. Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors supporting therapeutic efficacy in acute and preventive migraine treatment. Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects. AEA is tonically active in the periaqueductal gray matter, a migraine generator. THC modulates glutamatergic neurotransmission via NMDA receptors. Fibromyalgia is now conceived as a central sensitization state with secondary hyperalgesia. Cannabinoids have similarly demonstrated the ability to block spinal, peripheral and gastrointestinal mechanisms that promote pain in headache, fibromyalgia, IBS and related disorders. The past and potential clinical utility of cannabis-based medicines in their treatment is discussed, as are further suggestions for experimental investigation of CECD via CSF examination and neuro-imaging. CONCLUSION: Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines.
Article
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Delta(9)-Tetrahydrocannabinol (THC) is the main source of the pharmacological effects caused by the consumption of cannabis, both the marijuana-like action and the medicinal benefits of the plant. However, its acid metabolite THC-COOH, the non-psychotropic cannabidiol (CBD), several cannabinoid analogues and newly discovered modulators of the endogenous cannabinoid system are also promising candidates for clinical research and therapeutic uses. Cannabinoids exert many effects through activation of G-protein-coupled cannabinoid receptors in the brain and peripheral tissues. Additionally, there is evidence for non-receptor-dependent mechanisms. Natural cannabis products and single cannabinoids are usually inhaled or taken orally; the rectal route, sublingual administration, transdermal delivery, eye drops and aerosols have only been used in a few studies and are of little relevance in practice today. The pharmacokinetics of THC vary as a function of its route of administration. Pulmonary assimilation of inhaled THC causes a maximum plasma concentration within minutes, psychotropic effects start within seconds to a few minutes, reach a maximum after 15-30 minutes, and taper off within 2-3 hours. Following oral ingestion, psychotropic effects set in with a delay of 30-90 minutes, reach their maximum after 2-3 hours and last for about 4-12 hours, depending on dose and specific effect. At doses exceeding the psychotropic threshold, ingestion of cannabis usually causes enhanced well-being and relaxation with an intensification of ordinary sensory experiences. The most important acute adverse effects caused by overdosing are anxiety and panic attacks, and with regard to somatic effects increased heart rate and changes in blood pressure. Regular use of cannabis may lead to dependency and to a mild withdrawal syndrome. The existence and the intensity of possible long-term adverse effects on psyche and cognition, immune system, fertility and pregnancy remain controversial. They are reported to be low in humans and do not preclude legitimate therapeutic use of cannabis-based drugs. Properties of cannabis that might be of therapeutic use include analgesia, muscle relaxation, immunosuppression, sedation, improvement of mood, stimulation of appetite, antiemesis, lowering of intraocular pressure, bronchodilation, neuroprotection and induction of apoptosis in cancer cells.
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Based on experimental evidence of the antinociceptive action of endocannabinoids and their role in the modulation of trigeminovascular system activation, we hypothesized that the endocannabinoid system may be dysfunctional in chronic migraine (CM). We examined whether the concentrations of N-arachidonoylethanolamide (anandamide, AEA), palmitoylethanolamide (PEA), and 2-arachidonoylglycerol (2-AG) in the CSF of patients with CM and with probable CM and probable analgesic-overuse headache (PCM+PAOH) are altered compared with control subjects. The above endocannabinoids were measured by high-performance liquid chromatography (HPLC), and quantified by isotope dilution gas-chromatography/mass-spectrometry. Calcitonin gene-related peptide (CGRP) levels were also determined by RIA method and the end products of nitric oxide (NO), the nitrites, by HPLC. CSF concentrations of AEA were significantly lower and those of PEA slightly but significantly higher both in patients with CM and PCM+PAOH than in nonmigraineur controls (p<0.01 and p<0.02, respectively). A negative correlation was found between AEA and CGRP levels in CM and PCM+PAOH patients (r=0.59, p<0.01 and r=-0.65, p<0.007; respectively). A similar trend was observed between this endocannabinoid and nitrite levels. Reduced levels of AEA in the CSF of CM and PCM+PAOH patients may reflect an impairment of the endocannabinoid system in these patients, which may contribute to chronic head pain and seem to be related to increased CGRP and NO production. These findings support the potential role of the cannabinoid (CB)1 receptor as a possible therapeutic target in CM.
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Full-text available
This study examines the concept of clinical endocannabinoid deficiency (CECD), and the prospect that it could underlie the pathophysiology of migraine, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis. Available literature was reviewed, and literature searches pursued via the National Library of Medicine database and other resources. Migraine has numerous relationships to endocannabinoid function. Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors supporting therapeutic efficacy in acute and preventive migraine treatment. Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects. AEA is tonically active in the periaqueductal gray matter, a migraine generator. THC modulates glutamatergic neurotransmission via NMDA receptors. Fibromyalgia is now conceived as a central sensitization state with secondary hyperalgesia. Cannabinoids have similarly demonstrated the ability to block spinal, peripheral and gastrointestinal mechanisms that promote pain in headache, fibromyalgia, IBS and related disorders. The past and potential clinical utility of cannabis-based medicines in their treatment is discussed, as are further suggestions for experimental investigation of CECD via CSF examination and neuro-imaging. Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines.
Article
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.
Article
Cannabinoids, the active components of Cannabis sativa L., act in the body by mimicking endo- genous substances - the endocannabinoids - that activate specific cell surface receptors. Cannabi- noids exert palliative effects in cancer patients. For example, they inhibit chemotherapy-induced nausea and vomiting, stimulate appetite and inhibit pain. In addition, cannabinoids inhibit tumor growth in laboratory animals. They do so by modulating key cell signaling pathways, thereby in- ducing antitumoral actions such as the apoptotic death of tumor cells as well as the inhibition of tumor angiogenesis. Of interest, cannabinoids seem to be selective antitumoral compounds as they can kill tumor cells without significantly affecting the viability of their non-transformed counter- parts. On the basis of these preclinical findings a pilot clinical study of ∆ 9 -tetrahydrocannabinol (THC) in patients with recurrent glioblastoma multiforme has recently been run. The fair safety profile of THC, together with its possible growth-inhibiting action on tumor cells, may set the ba- sis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids.
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Most hallucinogens and cannabinoids fall into Federal Controlled Substances schedule 1, meaning they cannot be prescribed by practitioners, allegedly have no accepted medical use, and have a high abuse potential. The legal and regulatory status has inhibited clinical research on these substances such that there are no blinded studies from which to assess true efficacy. Despite such classification, hallucinogens and cannabinoids are used by patients with headache on occasion. Cannabinoids in particular have a long history of use for headache and migraine before prohibition and are still used by patients as a migraine abortive. Hallucinogens are being increasing used by cluster headache patients outside of physician recommendation mainly to abort a cluster period and to maintain quiescence for which there is considerable anecdotal success.
Article
Cannabinoids - the active components of Cannabis sativa and their derivatives - exert palliative effects in cancer patients by preventing nausea, vomiting and pain and by stimulating appetite. In addition, these compounds have been shown to inhibit the growth of tumour cells in culture and animal models by modulating key cell-signalling pathways. Cannabinoids are usually well tolerated, and do not produce the generalized toxic effects of conventional chemotherapies. So, could cannabinoids be used to develop new anticancer therapies?
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The University of Mississippi has a contract with the National Institute on Drug Abuse (NIDA) to carry out a variety of research activities dealing with cannabis, including the Potency Monitoring (PM) program, which provides analytical potency data on cannabis preparations confiscated in the United States. This report provides data on 46,211 samples seized and analyzed by gas chromatography-flame ionization detection (GC-FID) during 1993–2008. The data showed an upward trend in the mean Δ9-tetrahydrocannabinol (Δ9-THC) content of all confiscated cannabis preparations, which increased from 3.4% in 1993 to 8.8% in 2008. Hashish potencies did not increase consistently during this period; however, the mean yearly potency varied from 2.5–9.2% (1993–2003) to 12.0–29.3% (2004–2008). Hash oil potencies also varied considerably during this period (16.8 ± 16.3%). The increase in cannabis preparation potency is mainly due to the increase in the potency of nondomestic versus domestic samples.
Article
To provide updated evidence-based recommendations for the preventive treatment of migraine headache. The clinical question addressed was: What pharmacologic therapies are proven effective for migraine prevention? The authors analyzed published studies from June 1999 to May 2009 using a structured review process to classify the evidence relative to the efficacy of various medications available in the United States for migraine prevention. The author panel reviewed 284 abstracts, which ultimately yielded 29 Class I or Class II articles that are reviewed herein. Divalproex sodium, sodium valproate, topiramate, metoprolol, propranolol, and timolol are effective for migraine prevention and should be offered to patients with migraine to reduce migraine attack frequency and severity (Level A). Frovatriptan is effective for prevention of menstrual migraine (Level A). Lamotrigine is ineffective for migraine prevention (Level A).
Article
The pharmacokinetics and pharmacodynamics of cloprednol after oral administration in doses of 2.5 to 15 mg to healthy volunteers were determined. The half-life of cloprednol ranged from 1.8 h to 2.7 h, the oral clearance (CL/F) was determined to be 15-22 l/h. Since cloprednol shows nonlinear plasma protein binding, the plasma concentrations were converted to their free, unbound concentrations for the PK/PD-analysis. Due to this nonlinearity, the half-life of free, unbound cloprednol was shorter than that of the total drug. For the assessment of pharmacodynamics, differential white blood cell counts were obtained over 24 hours. An integrated pharmacokinetic-pharmacodynamic (PK/PD) approach using a modified Emax-model was applied to link unbound corticosteroid concentrations to the effect on lymphocytes and granulocytes. The E50 value for unbound cloprednol ranged from 3.6 to 4.7 ng/ml and 1.2 to 4.6 ng/ml for granulocytes and lymphocytes, respectively. The PK/PD model allowed a good prediction of the observed effects and was consistent with reported values for glucocorticoid receptor binding affinities for cloprednol.
Chronic migraine headache: Five cases successfully treated with marinol and/or illicit cannabis
  • T H Mikuriya
Mikuriya TH. Chronic migraine headache: Five cases successfully treated with marinol and/or illicit cannabis. 1991. Available from http://druglibrary.org/schaffer/hemp/migrn1.htm.
Handbook of Cannabis Therapeutics: From Bench to Bedside
  • Eb Russo
  • F Grotenhermen
Russo EB, Grotenhermen F, eds. Handbook of Cannabis Therapeutics: From Bench to Bedside. Binghamton, NY: Haworth Press; 2006:69–116.