Fibromyalgia and the endocannabinoid system, John M. McPartland, 2010

Fibromyalgia and the endocannabinoid system

John M. McPartland

in Fibromyalgia syndrome : A practitioner’s guide to treatment, chapter 11, 2010, 263-277.

Doi : 10.1016/B978-0-443-06936-9.00011-1



Introduction . . . . . . . . . . . . . . . 263
Cannabis and cannabinoid receptors . . 264
Endocannabinoids and their enzymes . 266
Nociception and pain . . . . . . . . . . 266
Around the edges of fibromyalgia . . . . 269
Enhancing the eCB system . . . . . . . 270
Other approaches . . . . . . . . . . . . 272
Conclusions . . . . . . . . . . . . . . . 274


Fibromyalgia has been characterized as an ‘endocannabinoid (eCB) deficiency syndrome’, along with other refractory maladies such as irritable bowel syndrome, migraine, premenstrual syndrome and other painprocessing disorders (Russo 2004). This syndrome may arise from diminished receptor expression,
inadequate ligand biosynthesis or gain-of-function mutations in ligand-catabolizing enzymes. Helping
you to understand these basic science concepts (and applying them) will be the goal of this chapter. Our
trawl through basic science begins with definitions :

• Ligands are natural or synthetic compounds that bind to receptors.
• Ligands may activate receptors (‘agonists’) or deactivate receptors (‘inverse agonists’).
• Endogenous ligands (ligands produced by our own bodies) are synthesized by anabolic enzymes.
• To serve in self-regulatory roles, ligands must be broken down by catabolic enzymes.

Clinicians with a biomechanical or structural orientation may better understand the chemical concepts
underlying eCB research by realizing that chemistry is structure (Ingber 1998). For example, the pharmacological principle of structure–activity relationships (SAR) is analogous to the anatomical concept of structure–function relationships.

On a molecular level, the eCB system resembles the better-known endorphin system. The endorphin
system was indirectly discovered in 1801, when morphine was isolated from opium. The mechanism
of action of morphine remained a mystery until the m-opioid receptor was discovered by Candice Pert in
1973. That discovery begged the question: Why do humans have a receptor for an opium plant compound? Shortly thereafter, scientists discovered the enkephalins and endorphins, endogenous compounds that are mimicked by the plant compound (reviewed by Pert 1997).

According to Dr Andrew Taylor Still, the founder of osteopathic medicine, ‘Man should study and use the drugs compounded in his own body’ (Still 1897). Still hypothesized that osteopathic manipulative treatment (OMT) stimulated the production of endogenous compounds that promoted homeostasis and healing. Soon after enkephalins and endorphins were discovered, researchers at schools of osteopathy, chiropractic, physical therapy, massage therapy and acupuncture carried out endorphin research. The initial wave of enthusiasm dampened after studies produced conflicting evidence. In fact, endorphins and enkephalins may not be modulated by OMT, chiropractic manipulation, massage therapy, acupuncture or even ‘runner’s high’ (reviewed in Dietrick & McDaniel 2004, Harbach et al 2007, McPartland et al 2005, Schultz et al 2000). In the past few years, research has swung from endorphins to the eCB system. In 1992, the year eCBs were discovered, an internet query using the PubMed search engine ( with the term ‘endorphin’ returned 596 hits, and ‘endocannabinoid’ returned only two hits. In a search limited to 2008, ‘endorphin’ returned 141 hits whereas ‘endocannabinoid’ returned 565 hits.

The eCB system embodies our holistic concept that the body possesses self-regulatory mechanisms
that are self-healing in nature. The eCB system has emerged as an important regulator of mind–body
structure and function. This self-regulatory capacity can be rephrased as the maintenance of homeostasis. The eCB system’s capacity to maintain homeostasis will be cited many times in this chapter. As Dr Still emphasized: ‘To find health should be the object of the doctor. Anyone can find disease’ (Still 1897).