Dr. Ethan Russo ranks among the world’s most prolific researchers of medical cannabis, having published innumerous research and review articles in the field during the last two decades (many related to Sativex and intractable epilepsy). At the turn of the century, he authored three often cited articles in which he elaborated a theory of clinical endocannabinoid deficiency.
Seeing how many brain disorders were associated with neurotransmitter deficiencies—such as dopamine in Parkinson’s disease and serotonin and norepinephrine in depression—he suggested that a deficit in endocannabinoid signalling might also explain a set of conditions that had until then evaded a proper understanding.
Among the extensive list of conditions proposed to involve endocannabinoid dysfunction, three have gained a reasonable level of support since the publication of those seminal articles: migraines, fibromyalgia and irritable bowel syndrome. In a review article published recently in the open access journal Cannabis and Cannabinoid Research, Dr. Russo discusses the evidence accumulated in this direction.
Fibromyalgia is a condition characterized by pain in soft tissues, particularly in the regions of the shoulder or neck, which is intense or frequent enough to limit physical activity and affect sleep and long-term well-being. Surprisingly to the medical community, there is an absence of clear biomarkers in this disease, including the usual signs of inflammation that accompany other pain syndromes. This has led to a contentious debate about the validity of the diagnosis, but despite this, fibromyalgia ranks as the most common rheumatology diagnosis in the U.S.
In 1998, a team established a link between hyperalgesia (pain) and endocannabinoid hypofunction in the spinal cord, in line with the endocannabinoid deficiency theory. They further demonstrated that endocannabinoids were able to reduce hyperalgesia.
Instead of discussing any progress (or lack thereof) in understanding this mechanism, Dr. Russo then focuses on a trio of uncontrolled clinical trials of THC and cannabis which suggest modest improvements in the pain and discomfort felt by fibromyalgia patients. One of these was an open label trial in which 28 patients reported improvements in pain and stiffness merely 2 hours after cannabis administration, together with improvements in somnolence and well-being when compared to controls.
“While this degree of benefit is yet to be shown in formal RCTs (randomized controlled trials) in fibromyalgia, the court of public opinion supports its utility” he writes in relation to a survey of 1300 patients who overwhelmingly supported cannabis over other prescription medicines for the alleviation of fibromyalgia. This, he argues, is sufficient to justify more definitive clinical trials.
Migraines are a complex syndrome demarcated by strong headaches as well as other unusual symptoms including nausea and light- and sound-related anxiety (photophobia and sonophobia). It affects around 14% of the U.S. population, and is three times more common in women than men.
The evidence for an involvement of the endocannabinoid system starts with the finding that anandamide (an endogenous cannabinoid) modifies the response of serotonin receptors in a way that is strikingly similar to that of drugs deemed effective in treating migraines. In addition, this compound regulates several brain and nerve structures that are thought to be dysregulated in this condition, possibly even those involved in the strange epiphenomena of photo- and sonophobia.