Can Cannabis Prevent Dyskinesia in Long-Term Treatment of Parkinson’s Disease ?
In 1970, Oliver Sacks wrote five letters to various medical journals in the U.S. expressing his concern about the prescription drug levodopa, which had been developed just a year earlier. As a practicing neurologist, he had used levodopa (L-Dopa) to treat Parkinson’s and encephalitis lethargica (or “sleepy-sickness”) in his patients—both neurological disorders that arise from a deficiency of dopamine—and found it to have serious adverse effects. As he described in his 1985 book The Man Who Mistook His Wife for a Hat, treating people with sleepy-sickness with L-Dopa resulted in an over-correction of motor function: “First they were ‘awakened’ from stupor to health: then they were driven towards the other pole—of tics and frenzy.”
This phenomenon would come to be known as levodopa-induced dyskinesia—an increase in involuntary muscle movements or spasms that results from too much dopamine flooding your brain. It’s one of the most common side effects of conventional treatment of Parkinson’s Disease (PD) and one of the most devastating: some PD patients describe their dyskinesia as worse than the disease itself, causing many to decrease or put off treatment altogether to stave off the inevitable side effects.
The search for a better treatment has pointed more and more researchers toward cannabis because it naturally targets multiple points in the endocannabinoid system, the brain’s neurological center for motor function, mood, and pleasure. Marijuana has been shown to have impressive results in the short term treatment of PD symptoms, like tremors and rigidity, and it also has supplemental therapeutic effects—like easing depression and improving sleep. But perhaps most importantly, cannabis has shown promising results in preventing dyskinesia.
What Is Levodopa-Induced Dyskinesia?
Because Parkinson’s is classically defined as a dopamine deficiency—caused by the death of dopamine-producing cells in a part of the brain called the substantia nigra—it’s most commonly treated with a dopamine precursor like levodopa, which then converts to dopamine in the brain. The effects from initial doses of levodopa are quite immediate—people’s motor functions are restored almost miraculously in some cases—but experience shows that long-term dopamine-based treatment can actually cause an increase in dyskinesia.
The problem arises from dopamine’s role as a neurotransmitter and the tricky balance of the neurons in your brain. In a healthy brain, dopamine transmits signals between brain cells about motor function, mood, and behavior, among other things. But in the Parkinsonian brain, low levels of dopamine mean two parts of the brain related to motor function—the endocannabinoid system and basal signia—are not signaling correctly. This is what causes the most well-known symptoms of Parkinson’s: body rigidity, tremors, and involuntary muscle contractions.
Supplementing dopamine with a drug like levodopa attempts to restore the neurological balance, but history shows the solution isn’t perfect because long-term treatment often results in dopamine hyperactivity, which manifests as dyskinesia. This most often affects younger people with PD, which is particularly disconcerting because they have longer to live with the disease and the side effects of treatment.