All 21 states that have approval for medical marijuana have listed multiple sclerosis (MS) as an appropriate diagnosis for the use of medical marijuana. The issue has been finding the appropriate method to deliver the active ingredient tetrahydrocannabinol (THC) to treat spasticity, tremor and balance in those with MS.

Studies investigating the use of marijuana with traditional smoking as a means to deliver THC were inconclusive, and the patients reported uncomfortable side effects. There is further concern that smoking marijuana presents similar significant health risks as tobacco.

Pharmaceutical-grade marijuana products hope to eliminate many of the drawbacks of marijuana inhaled in smoke or ingested from the plant. Some of the major issues of smoking or ingestion are a lack of consistent dosage, low bioavailability, variations in the quality due to variability of the plants, purity of extracts and limited shelf life at room temperatures. Furthermore, the use of marijuana — even with medical approval — is considered illegal by the federal government.

But there is hope in a new drug currently in Phase II of clinical development. Namisol, taken orally, contains a 98 percent pure form of natural THC — in contrast to the synthetic form, dronabinol, found in Marinol. Once approved, Namisol is expected to have other uses in addition to MS, targeting the behavioral disturbances in Alzheimer's disease and chronic pain. Early studies show that the oral delivery of THC in Namisol provides more predictable and consistent levels in the blood plasma.

There is indication that certain cannabinoids may have neuroprotective properties, and the hope is that this natural form will be more successful in treatment of MS than the synthetic dronabinol.

Dronabinol was studied in 2013 to determine if its use would slow the progression of MS, but the research under the direction of Dr. John Zajicek demonstrated did not show a positive effect on MS disease progression. A separate study also under the direction of Zajicek using an extraction of the botanical marijuana plant containing THC in capsule form demonstrated a significant improvement in muscle stiffness in those with MS.

Cannabidiol (CBD), a compound found in the marijuana plant that does not produce any psychotopric effects has been shown to have anti-inflammatory and immunosuppressive properties. An animal virus model of MS was used to demonstrate that CBD helped prevent motor deficits in the disease.

Marijuana plants grown under a rigidly-controlled environment are used to produce a the botanical medicine Sativex, which contains THC and CBD as well as other ingredients. Sativex in the form of an oral mucus sparay has received approval in the United Kingdom for the treatment of MS. In a multicenter randomized, double-blind, placebo-controlled, parallel-group study of Sativex, researchers found that for a group of MS patients with severe spasticity that there was an improvement in over 50 percent of those enrolled.

The use of marijuana or marijuana ingredients is not without a toll. Studies of patients with MS using either inhaled or ingested nonpharmaceutical marijuana compared to those with MS not using any marijuana, found that those using marijuana had significantly poorer performance on measures of information processing speed, working memory, executive functions and visuospatial perception.

Cannabinoids such as THC are known to affect cognitive function and have been implicated in the negative effect of marijuana on learning and memory. THC has been shown to have a substantial effect on visuomotor skills, especially with chronic use. The use of marijuana has been shown to result in impairments to safe driving, and this is exacerbated by other factors contributing to slower reaction times.

While a small study of those with MS using the oral Sativex spray demonstrated little impact on tests of visual function related to driving, there were no control groups nor was the study controlled for learning effects with repeated measurements.

What is allowed related to marijuana plants and marijuana compound varies from state to state, as well as country to country, making treatment decisions complex. In order to effectively treat and manage debilitating illnesses such as MS, it is appropriate to consider all options, and marijuana in botanical form is an option allowed in 21 states.