Emerging Role of (Endo)Cannabinoids in Treating Migraines. In-Depth Look at (Endo)Cannabinoids and the Human Brain

Cannabinoid Products as Natural Aids to Existing Processes in the Body’s Endocannabinoid System

Throughout the body, a relatively (until recently) unexplored system of receptors has been providing diverse benefits from regulating digestive system motility to managing pain signalling within the brain and outwards to the extremities. Research into the effects of phytocompounds found in varieties of the cannabis plant has been uncovering these receptors, currently referred to as CB1 and CB2. These receptors are present throughout the body, but in the case of migraine patients they are especially important in the brain, reducing the symptoms conditions involving neurological overstimulation.

Cannabis gets the Naming Credit for an Important Biological System

Since cannabis provided the initial pointer towards this powerful body-wide regulation system, the endocannabinoid or ECS system has been named for the endogenous cannabinoid molecules, or eCBs, that first prompted this discovery. Much of recent cannabis research has been directed towards understanding both the roles of the CB1 and CB2 receptors in the body, and the effects of plant-based cannabinoid compounds such as CBD and CBG introduced to supplement eCB in its work throughout the body, especially with neurological conditions.

Current ECS Knowledge and where the System ties into Migraine-Related Structures

Both major cannabinoid receptors, CB1 and CB2, are currently under extensive study for pain issues. The CB1 receptor is one of the most abundant G-protein coupled receptors in the brain, and the CB2 receptor is involved with peripheral nerve function. G-protein coupled receptors are essential for both the function and plasticity of neurons, providing a pathway through the otherwise protective cell membrane. This means that the availability of cannabinoids to the CB1 receptor can have a substantial effect on the operation of the brain. THC, the powerful psychoactive component of cannabis, has strong effects on both CB1 and CB2, while other products such as CBD have little or no psychoactive effect, but beneficial influence via either CB1 or CB2 in a more specific manner.

Migraine as an Excellent Demonstration of ECS Function

The pervasive effects of migraines have helped reveal a number of eCB mechanisms throughout the body. In addition to effects in the brain and surrounding meninges, eCBs work in the central nervous system (CNS) and peripheral nervous system help to mitigate pain, reducing inflammation and neurodegeneration. Current theory suggests that stress-responsive production of eCB provides active assistance to the body, reducing pain and overactivation of nociceptive (pain) systems.

Migraine research also points to prolonged activation of the brain’s trigeminal vascular system (TGVS), a network of blood vessels and nerves in the cranium. TGVS is suspected of being involved in several types of headaches such as migraines. This extended activation is also believed to have a sensitizing effect on neurons in the central nervous system or CNS. This in turn leads to persistent nociceptive signaling, in other words — persistent pain without an external stimulus.

When the ECS System is Poorly Regulated, Widespread Problems Occur

The enzymes monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase play essential roles in controlling the body’s levels of internally generated eCBs. These levels rise and decay quickly in the process of managing numerous processes including pain sensations, appetite regulation, and cognition and mood. In vivo animal experiments have shown that genetically disrupting the availability of MAGL in mice leads to dysfunction of CB1 receptors in the brain and elsewhere, and a reduction in the beneficial effects of the eCB system as a whole.

Self-Medication as a Result of MAGL Deficiency

This evidence suggests that migraine patients who have MAGL deficiencies may benefit from either addressing this issue as methods become available, or supplementing the eCB system with phytocannabinoids to address internal deficiencies. It also explains why some patients may find that external sources of cannabinoids have helped normalize their systems and reduce conditions such as migraine.

The Clinical Endocannabinoid Deficiency (CECD) Hypothesis

Research has demonstrated the role of endocannabinoids in overall body homeostasis. It has also established endocannabinoids’ role in balancing and preserving positive mental states and conversely, how the disruption of eCB availability is connected with mental state disturbances, especially migraine. The abnormally high levels of pain experienced in connection with migraine, fibromyalgia, and IBS are tending to support a hypothesis called CECD, or Clinical Endocannabinoid Deficiency. This hypothesis holds that, since the beneficial support of endocannabinoids is lacking, these treatment-resistant pain conditions including migraine arise. Research into CECD conducted in laboratory-bred mice has suggested that eCB deficiencies may be treatable with a modest amount of additional external cannabinoid.

The Migraine Aura Phenomenon and Cortical Spreading Depression (CSD)

Migraine auras, experienced by 20-30 percent of migraine patients, is thought to be a phenomenon brought on by waves of excitation and inhibition rippling through the cortical neurons. This electrophysiological phenomenon, called cortical spreading depression or CSD, is suspected as a direct cause of auras, which precede migraine pain by about twenty minutes. They manifest as visual phenomena such as flashing lights, wavy lines, blurry vision, or blind spots. The activation of CB1 receptors by cannabinoids has mitigated CSD, leading to the expectation that further research will increasingly support the treatment of migraine symptoms from aura onset to pain manifestation.

Cannabis-Derived Benefits Which May Help Treat Migraines

The introduction of plant-derived phytocannabinoids or synthesized versions to supplement the existing endogenous cannabinoids produced by the body can provide a broad-spectrum approach to migraine treatment via the ECS. The range of benefits provided by cannabinoids covers a number of typical treatment approaches for migraines. Specific effects include:

• Anticonvulsive — Reduction of seizure-like activity in the brain
• Analgesic — Pain management benefits both within the brain and at extremities
• Antiemetic — Help with the urge to vomit common with migraines
• Antiemetic — Help with the urge to vomit common with migraines

Further research into the CECD hypothesis may provide benefits for other treatment-resistant conditions in addition to migraine including fibromyalgia and IBS. Where patients once received a variety of targeted medications for specific symptoms, treatment with cannabinoids may provide a big-picture approach to these frustrating and debilitating conditions.

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