Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It's Been …

Abstract

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.

Cannabinoids in Pediatrics

“…In 1851, the United States Pharmacopeia (USP) classified marijuana as a legitimate medical compound and many physicians supported its use for conditions such as epilepsy, chronic migraines, and pain. 5 Reports of Victorian-era neurologists using Indian hemp to treat epilepsy were also promising. 6 However, when phenobarbital and phenytoin came to the market in the early 1900s, the use of marijuana-based products declined.…”

“…Many believe this was influenced by several prominent businessmen in competing synthetic fiber industries in attempts to reduce the size of the growing hemp industry. 5 Marijuana soon became labeled as a drug of abuse and to discourage its use, Congress passed the Marijuana Tax Act of 1937 placing a heavy tax on cannabis and hemp use for both medicinal and industrial purposes. Despite opposition from the American Medical Association (AMA) and physicians who believed in the medical efficacy of marijuana, by 1941, all cannabis preparations were removed from the USP and National Formulary.…”

“…Since that time, there have been repeated unsuccessful attempts to reconsider its Schedule 1 status to allow for easier investigation. 5 The AMA and the American Academy of Pediatrics (AAP) have reaffirmed their opposition to the legalization of medical and recreational marijuana use outside of any US Food and Drug Administration (FDA) regulatory process. 7 The AAP also supports further research into the indications and correct dosage for cannabinoids in addition to developing policy around how to verify purity and formulations.…”

The Pharmacological Basis of Cannabis Therapy for Epilepsy

“…CB 1 receptors are densely located on the glutamatereleasing pyramidal cells of the cornu ammonis within the hippocampus, one of the major regions of the brain affected by epilepsy. By inhibiting the release of glutamate, these receptors indirectly block NMDA-modulated excitatory currents, and therefore suppress the initiation of the learningmemory-related phenomenon of long-term potentiation and long-term depression (Baron, 2015;Goodman and Packard, 2015). The expression of CB 1 receptors in the rat hippocampus underwent a strong, plastic response following status epilepticus (Falenski et al, 2009).…”

“…Marijuana is a colloquial term given to the dried flowers, stems, and leaves of a 1-5 m weed that originated in Asia. Cannabis belongs to the plant family Cannabaceae, of which there are three main species that can differ in biochemical components: Cannabis sativa, Cannabis indica, and the lesser known Cannabis ruderalis (Baron, 2015). The cannabis plant contains over 200 compounds referred to as cannabinoids (ElSohly and Gul, 2014).…”