New treatments are needed to counteract the often debilitating effects of headaches and migraines; the results for cannabinoids available so far are encouraging.
Sufferers know how much headaches can affect quality of life, and even the World Health Organisation recognises their negative impact, classifying them among the ten main causes of disability.
The effectiveness of drug therapies, for the acute phase as well as for preventative purposes, has been shown to be limited and they are linked to side effects which, in some cases, mean they are poorly tolerated, such as fatigue, skin rashes, dizziness, constipation and weight gain. Furthermore, the abuse of medications to counteract headaches may result in a worsening of the condition, thus establishing a vicious circle that is difficult to break.
There is, therefore, a need to develop new treatments. In this sense, cannabis-based medicinal products provide an interesting option: indeed, promising evidence from clinical trials is available for the treatment of chronic pain, including headache, as well as real-life data that point to their potential efficacy.
The state of the art
In a review published in 2021, a US research group collected data from the literature with the aim of establishing whether cannabis-based medicinal products can be used as an alternative treatment for the management of headaches and migraines [1].
The researchers selected and analysed 34 studies published between 1987 and 2020, in which medical cannabis had been used for the treatment of migraine and headaches.
The data that emerged from the analysis of the literature were encouraging, albeit not always in agreement, indicating the therapeutic efficacy of cannabis in mitigating migraines and in reducing the duration and frequency of attacks. The studies report both short- and long-term benefits, in terms of decrease in the daily intake of painkillers, addiction and intensity of pain.
In some cases, the patients reported persistent improvements in physical and psychological well-being with the long-term use of cannabis-based medicinal products.
Furthermore, despite some side effects, patients on the whole are in favour of the use of medical cannabis in addition to or as a replacement for drug therapies, and there is substantial consensus on the indicated use of these products in the event of failure of first- and second-line treatments.
The analysis also highlighted that the main method for taking cannabis is smoking, followed by vaping.
An ideal dosage could not be identified due to the high variability between studies and between patients, but some studies show good results for the use of THC+CBD combinations for prophylactic purposes or during an acute episode.
“The therapeutic benefits of cannabis should be studied in depth with high-quality trials, to also establish the type of product, the most suitable administration method and dose for chronic migraines and headaches, and the possible long-term effects”, is the conclusion of the authors of the review.
New data on the treatment of headaches
A study conducted in the United Kingdom focused on the efficacy of cannabinoids in the treatment of headaches specifically, assessing clinical and quality of life outcomes [2].
The researchers analysed a series of cases included in the UK Medical Cannabis Registry, with the aim of evaluating variations in the patient-reported outcome measurements after treatment with cannabinoids.
The study included 97 patients (55 men and 42 women) whose average age was 38 and who had been diagnosed with headache. The data regarding the patient-reported outcomes were collected through validated questionnaires at baseline and at the 1-, 3- and 6-month follow-up.
77% of the subjects included (75) had never smoked or had quit smoking, while over half (54 patients, 56%) used cannabis habitually at the time of recruitment.
The most common type of headache was migraine (82 subjects, 84.5%).
In most cases, the cannabinoids were either administered through flos vaporisation, or orally or sublingually in oil form.
As patient-reported outcomes, the researchers considered the impact of the headache/migraine in terms of:
- extent of the pain
- degree of disability and psychological stress (measured through the Headache Impact Test-6, HIT-6, and the Migraine Disability Assessment, MIDAS)
- effect on quality of life (measured with EQ-5D-5L)
- severity of the generalised anxiety disorder (measured with the Generalized Anxiety Disorder-7, GAD-7)
- sleep quality (measured with the Single-Item Sleep Quality Scale, SQS).
The analysis of the data pointed to a statistically significant improvement compared to baseline for HIT-6, MIDAS, EQ-5D-5L and SQS values, at 1, 3 and 6 months, whereas for GAD-7 the difference was significant at the 1- and 3-month follow-up.
Adverse events were also analysed, 113 in all in 17 subjects: in most cases these were classified as mild, and the most common ones were dry mouth and headache.
“In patients with headache, treatment with cannabinoids has a good safety profile and is associated with an improvement in quality of life and specific patient-reported outcomes for the condition. These results can therefore be kept in mind for clinical practice”, is the British researchers’ comment. “Furthermore, it is desirable to conduct randomised controlled trials to confirm the efficacy of these products for headaches”.
Focus on migraine
To gain further knowledge on the possible mechanisms of action of cannabinoids in migraine, an international research group, also including Italian researchers from the Ferrara and Padua universities, has developed an animal model of migraine to investigate the effects of cannabidiol (CBD), one of the main components of cannabis, in mitigating the significant symptoms of this condition [3].
An animal model of acute and chronic migraine was therefore developed, involving the onset of cephalic allodynia, pain, photophobia and anxiety-like behaviour triggered by the administration of exogenous CGRP (Calcitonin Gene-Related Peptide) in male and female mice.
First, the effects of the peptide were evaluated: a single administration of CGRP triggered facial hypersensitivity in mice of both sexes, while repeated treatment caused a progressive reduction in threshold levels for allodynia in females, but not in males.
The researchers then carried out a single administration of CBD before injecting the peptide, ascertaining a protective effect against periorbital allodynia in both male and female mice. However, the repeated treatment prevented the increase in basal levels of allodynia induced by the continued administration of CGRP in females only.
The researchers then injected CBD after CGRP, to assess its effects on the symptoms induced by the peptide: CBD reversed the allodynia effect, reduced pain in female mice, blocked anxiety in male mice, but did not protect females from photophobia.
“The data obtained with this model show the efficacy of CBD when it is injected before the migraine trigger factor as well as when it is administered afterwards”, the researchers commented. “This finding points to the efficacy of CBD in preventing as well as treating episodic and chronic migraine-like conditions, with a reduced risk of causing headaches due to the overuse of medications.”
References
- Poudel S, Quinonez J, Choudhari J, et al. Medical cannabis, headaches, and migraines: a review of the current literature. Cureus. 2021 Aug 24;13(8):e17407.
- Nicholas M, Erridge S, Bapir L, et al. UK medical cannabis registry: assessment of clinical outcomes in patients with headache disorders. Expert Rev Neurother. 2023;23(1):85-96.
- Sturaro C, Fakhoury B, Targowska-Duda KM, et al. Preclinical effects of cannabidiol in an experimental model of migraine. Pain. 2023 Nov 1;164(11):2540-2552.
