Parkinson's Disease is a Nightmare Full of Nightmares and One Women is Waking Up
Through unfailing commitment — and a little luck — Helen Garvy stumbled upon a possible solution buried in a particular strain of cannabis. In doing so, she very well may have found an end to the living nightmares.
[The] most important results [of cannabis] are to be found in the mental sphere; as, for instance, in Senile Insomnia with wandering. An elderly person (perhaps with brain softening), is fidgety at night, goes to bed, gets up, thinks he has some appointment to keep, that he must dress and go out. Day, with its stimuli and real occupations, finds him quite rational again. Nothing can compare in utility to a moderate dose of Indian hemp at bedtime.
— Dr. John Russell Reynolds (1890), leading neurologist and the personal physician to Queen Victoria
Imagine acting out a nightmare. You’re in the woods. You’re with your family. A wild animal appears — a wolf or a bear or a monster — and springs for you. Desperate and terrified, you’re forced to defend yourself and your loved ones with a furious violence. You fight tooth and nail and in one lucky maneuver you’re somehow able to position your hands around the beast’s throat. Then, you begin to wake up, groggy and confused, to find your hands clasped not around a wild dog but the throat of the person in bed with you.
RBD — or REM sleep behavior disorder — is a challenging and terrifying glitch in the sleep-wake system, in which sufferers act out their dreams in real life. It occurs in less than one percent of the population, but is quite common among one particular set: those suffering from Parkinson’s disease.
Much like Parkinson’s, RBD is a tricky illness to diagnose and treat. What works at one moment might lead to dangerous symptoms the next. Both disorders have troubled researchers for decades. And it can be heartbreaking: Partners and spouses must live in fear of their sleeping loved ones, concerned they might become victims of some dream brought to life.
And this makes the untold story of Helen Garvy all the more remarkable. A citizen scientist, Helen took it upon herself to search for a cure for her Parkinson’s-stricken husband’s RBD. Through unfailing commitment — and a little luck — she stumbled on a possible cure buried in a particular strain of cannabis. Sensing hope, she conducted a small observational study to learn more about how to use this old plant medicine to treat the nagging nocturnal struggles of RBD. In doing so, she very well may have found an end to one of the nightmares.
A WOMAN WITH A SANDWICH BOARD
When I first saw her at the Portland Patients Out of Time Conference on medical marijuana last year, Helen wore a sandwich board reading, “Ask me about Cannabis & Parkinson’s.” She handed out flyers filled with evidence and advice and chatted amiably with the many who approached her.
A trustworthy-looking woman from Santa Cruz, California, Helen had that particular glint of activism in her eye. Coming up through the early ranks of Students for a Democratic Society — the infamous SDS movement of the 60s New Left — she became a filmmaker producing educational films to pay the bills and fund the documentaries she made from passion.
In one coup, Helen convinced a film distributor to green-light an educational film she made on the immune system, a topic about to explode in importance as the AIDS epidemic unfolded. It became a widely shown educational film for junior high school students and she turned it into the book “The Immune System: Your Magic Doctor.”
When a mishap during her father’s open heart surgery caused Helen to spend a week in the hospital with him, she noticed that everyone on staff “looked at the machines but they never looked inside the head of the patient to see what was going on there.” This led to years of research about the correlation between emotional reactions and illness. “Coping with Illness” was the book that followed.
“I just get interested in stuff,” Helen says. “Once I learn about it, I share it with others. That’s the RBD study.”
Helen represents a type of underground researcher often seen around these heady conferences, who’s focused on the practical medical applications of cannabis in the clinic. From the nurses running dispensaries to the authoritative country doctor advising her network of elderly patients, to the grandma medicine-makers running an underground bakery for friends and neighbors, a trove of medical cannabis knowledge exists here. But the data is hard to find and disseminate, decades of anecdotes locked away in the skulls of providers or in obscure books or infrequent articles.
Cannabis, with its many strains, modes of ingestion and medical potential, is often a tricky venture through the research, scattered advice, self-experimentation, patchwork evidence and knowing thyself. These unaccredited treasure troves of anecdotal evidence rarely see publication in mainstream science. So luckily, Helen (and her sandwich board) makes it easy to find her.
THE NEURAL MYSTERIES OF PARKINSON’S
It began in the early ‘90s. Robert, Helen’s husband, felt his hands begin to tremble slightly, evidence of the die-off of the neurons in his midbrain responsible for producing dopamine, the neurotransmitter essential for voluntary motion.
This telltale degeneration can first manifest as tremors, slowness of movement, gait problems and/or rigidity, but the underlying causes of cell death are poorly understood, despite the fact that descriptions of the symptoms date back to Egyptian papyrus, Ayruvedic medical treatises and the writings of Galen. Modern dopamine replacement medicine often helps extend the golden years, but the medication is nearly as poorly-understood as the disease’s origin.
Still, much knowledge has been collected since 1817, when Dr. James Parkinson published his essay on six cases of “the shaking palsy.” The motor symptoms, collectively called a “parkinsonian syndrome,” are further broken down into four subtypes.
The most common form, referred to as primary Parkinson’s, is defined as idiopathic, a disease of unknown cause and seemingly spontaneous origin. The motor symptoms mark the beginning of a constant slide into worsening motor control that robs a patient of the dignity of limbs that obey their commands. Before modern advancements of drugs and surgery, the average patient would become bedridden within a decade. On the mental side, frequent mood difficulties include depression, apathy and anxiety. As the decline progresses, cognitive problems often arise. They’re referred to as “mental fog” or “dementia,” although the technical terms include problems in executive function and working memory.
Secondary parkinsonism arises from known causes such as stroke, head trauma, brain infections and exposure to toxins. Factors associated with an increased risk of developing this subtype include farming or living in the country — perhaps because of rural exposure to pesticides in the air and well-water.
Activists for civil rights and against the Vietnam war, Helen and Robert met at the Students for Democratic Society office in 1964 but didn’t become a couple until more than 30 years later. In between, Robert dropped out of a graduate program in math to organize students against the war and then became a metal worker to earn money. He also spent some time on a commune in the ‘70s.
“Ironically, Rotenone, an ‘organic’ pesticide is probably a big culprit,” said Helen. “Robert rubbed it on the cow when he lived on the commune in the 70’s to control flies. It worked great. Only he got Parkinson’s.”
Other implicated toxins include insecticides like DDT and herbicides like Agent Orange. While Robert lived on the commune, the government sprayed the local forests with leftover defoliants from the Vietnam War to replace the woods with farmlands. Similarly, paraquat — an herbicide that quickly kills all green plant tissue on contact — became notorious for being aerially sprayed over U.S. cannabis fields by Nixon’s drug warriors and now is one of the neurotoxins used to induce parkinsonian symptoms in lab monkeys for testing new treatments
As Helen and Robert found out when they saw a doctor about his tremors, the first difficulty of the parkinsonian syndromes is that no lab tests exist to identify the disease conclusively. Brain scans appear normal. Radioactive tracers for dopamine function can be useful, but not conclusive. The existing standard of proof to confirm a Parkinson’s diagnosis comes too late because it takes an autopsy to show that midbrain neurons contain Lewy bodies, a type of misfolded protein that builds up.
This brings us to the third subset: hereditary parkinsonism. Parkinson’s is not usually considered a genetic disorder, but around 15 percent of patients have a close relative with it and roughly five percent have causes attributed to known genetic factors. Pure genetic causes can be hard to find and usually seem to have an environmental trigger.
One of the most studied genes, SNCA, concerns the synthesis of alpha-synuclein, a protein that is abundant in the brain but not well-understood. It’s suggested to be of help in gathering the vesicles of the neuron’s synapse, which contain the neurotransmitters for release, and may also be a regulator of dopamine release. Mice who’ve had this gene knocked out exhibit poorer working memory and less spatial learning. Other related genetic issues include lysosome dysfunctions, which may reduce the ability of those garbage men of the cellular city to break down the alpha-synuclein. Only in 1997 did scientists find the protein alpha-synuclein to be the main component of Lewy bodies.
The buildup of alpha-synuclein into Lewy bodies characterizes the disorders known collectively as synucleinopathies. With significant clinical overlap in motor dysfunctions, but varied progressions and treatments, this group of neurodegenerative diseases include Parkinson’s, Lewy body dementia and multiple system atrophy — a dire name for a disease that’s similar to Parkinson’s but not helped by the dopamine medications (or anything else).
Depending on which pathologist or neurologist you ask for classification, some or all of these diseases make up the fourth and final parkinsonian category known as “Parkinson-plus syndromes” or, more ominously, “disorders of multiple system degeneration.” They share the classical signs of Parkinson’s but include an array of additional symptoms. Debate rages about whether to include an alphabet soup of other depressing diseases of neurodegeneration in this group; some would even include Alzheimer’s. These closely related disorders complicate any diagnosis.
THE TROUBLE WITH LEVODOPA
One of the most common treatments for Parkinson’s is Levodopa. Often referred to as L-DOPA, it was the medication featured in the Robert DeNiro-Robin Williams film “Awakenings,” based on Oliver Sacks’ account of “waking up” patients permanently asleep from encephalitis lethargica.
Levodopa can be produced in a lab but it already occurs widely in nature across animals, plants and humans. In our brains, it serves as the precursor for the production of adrenaline, noradrenaline and dopamine. When administering an IV drip to human patients in the early ’60s showed dramatic results, levodopa rose to become the prominent treatment of the last 30 years.
One advantage of the drug’s delivery is that, unlike dopamine, levodopa (partially) crosses the blood-brain to be converted in the midbrain. The drug’s ability to reduce early motor symptoms of the disease became one of the key tools in deciding on a diagnosis of Parkinson’s.
Robert started his treatments and responded well to the first line of levodopa.
Parkinson’s is often broken down into two stages: The first, where levodopa gives anywhere from some relief to almost complete reduction of symptoms, and a second, where the levodopa itself causes motor complications (though this itself is still controversial; perhaps the cause is actually the disease itself or even the nature of levodopa pills to deliver the drug in bursts).
Since no more than 10 percent of the drug actually crosses into the brain, the rest stays elsewhere in the body to be converted to dopamine and causes side effects like nausea, joint stiffness and, perhaps, the involuntary muscle movements. Fear of these sometimes debilitating complications, can make patients reluctant to take the treatment.
Because of this, another drug is always added to the cocktail: carbidopa. It helps to block the levodopa from getting metabolized until it reaches the brain, hence lowering dosage and lessening side effects. These lower dosages are a key target because, for half of patients, this second stage occurs within five years of starting levodopa. After that, the patient often fluctuates between the “on” phase where the medication works reasonably well and an “off” phase where it provides almost no relief.
As the medications stop working as smoothly, doctors begin to ratchet up the dosage or add other medicines, like dopamine agonists. More of the levodopa means more dopamine. Amid the daily worsening cycles of dopamine levels, it gets harder and harder to manage the dynamic tension between symptoms and medications. Thus, Helen learned the dirty secret about dopamine: It’s all about hitting the happy medium.
She didn’t want to see Robert fall prey to those side effects, so she continued to research Parkinson’s tirelessly in search of an alternative. As she did, some friends around her California town urged her and Robert to try smoking marijuana because, well, “it helps with everything.” A reasonable assumption for Parkinson’s disease, given that recent positive findings from Israel showed improvements in sleep, pain and motor control. Robert puffed and puffed but it didn’t help reduce the tremors.
More accurately, Helen later observed, the smoked cannabis didn’t seem to present any additional relief over the still reasonably effective levodopa in their early experiments.
THE RBD REARS ITS HEAD
In an effort to manage Robert’s worsening symptoms, Helen got word of a drug trial for a pharmaceutical called Rytary. Impax Laboratories wanted to test their novel formulation, the standard package of levodopa and carbidopa, but now in an extended release capsule. She and Robert hoped this would modulate the highs and lows of the instant release pills already on the market. The first two weeks went well. Then the doctor asked if he was content at his current dosage and Robert decided to try more in hopes of obtaining more relief.
“If I knew then what I know now, I would have hit him over the head,” says Helen sharply.
In healthy sleepers, a physical paralysis takes place during the REM stage of sleep when most vivid dreams occur. This failsafe prevents us from physically acting out our reveries. For reasons unknown, this necessary sleep paralysis breaks down in RBD patients. They respond to their dreams or nightmares with violent motions and loud vocalizations including yelling, swearing, crying and laughter. They imagine attacks by wild animals or evil humans and will violently defend themselves or their partner against these phantasmal assaults. In reality, they can harm themselves, their partners or anyone trying to subdue them.
Some patients run into walls, knock themselves unconscious and break bones in crazed defense. If awakened in the middle of the episode or asked about it the next day, the patient usually remembers little. But their partners surely do. Helen knew two wives who had gotten choked and several more who were forced to move into another bedroom for their safety. Partners protect themselves by removing sharp objects and even tying down their loved one before sleep. Sometimes, out of fear for their wellbeing, partners are forced to send husbands and wives into nursing homes.
In first discussing the disease that bears his name, Dr. Parkinson mentioned something like REM Behavior Disorder. The onset of RBD and its relation to Parkinson’s, however, is anything but linear. Some patients never develop it all while others experience RBD for a decade prior to the onset of Parkinson’s motor symptoms.
After taking the higher doses of Rytary, Robert’s RBD began. He’d lash out with punches in his sleep, sometimes wild enough to wake himself up. If Robert woke up, he would just assume he did so needing a glass of water.
The higher dose of levodopa seemed to coincide with Robert’s bouts, but Helen knew there was no definitive finger of causation here.
“Did it cause the RBD to emerge three months earlier than it would have anyway? Or would it never have happened at all? There’s no way to know,” she says.
Despite the emergence of RBD, Robert continued with the Rytary study. When the trial finally ended, they immediately lowered the dosage. His RBD lessened but did not go away.
“I do think higher levels of levodopa are related to RBD,” says Helen. “The RBD literature, limited as it is so far, does not reflect this but I’m convinced.”
There are treatments for RBD. Clonazepam (the benzodiazepine branded as Klonopin) helps control symptoms for many, but the dulling side effects of benzos — not to mention their notoriously addictive nature and increasing likelihood of being linked to dementia — are distasteful to many elderly patients. Some find melatonin to be an effective, more natural alternative, but this hormone can cause it’s own problems.
Helen and Robert didn’t want to resort to these options; thus the matter was more complicated. Additional complications, however, provide different angles to solutions.
THE CANNABINOIDS COME INTO VIEW
There’s a lot of gray area in the uses of THC for sleep. And this contradictory data is what made marijuana an alternative medicine of interest to Helen. However, it seems that THC boosts the effects of levodopa and makes it unhelpful for Parkinson’s sufferers. What’s more, sleep and THC have a complicated relationship.
The neurologist Dr. Ethan Russo collected early experiments showing THC’s ability to reduce sleep latency (the time it takes to fall sleep) and, most importantly for RBD, the ability to decrease the length and density of REM sleep, an effect well-known to heavy stoners, who often experience little to no dreaming. In addition, a little-known fact about THC is the tremendous surge of melatonin it causes in the brain, a 4000x increase of the very molecule often used as a natural RBD treatment.
After more research, Helen learned about another cannabinoid: CBD. This non-psychoactive molecule contains much of the anti-anxiety effects of good pot and seems to do a lot of the heavy lifting when it comes to healing, immune system modulation and maintaining homeostasis for health.
In fact, in one of the strangest scientific twists in the century-long federal war on weed, the U.S. Department of Health received a patent in 1999 for “cannabinoids as antioxidants and neuroprotectants” on the strength of their ability to protect the brain from an array of injuries, finding the drug “useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases… [with] particular application as neuroprotectants, for example in limiting neurological damage … such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and HIV dementia.”
The times Robert tried marijuana, the only strain available was very THC-heavy and it never seemed to temper his RBD. However, after he had spent more than a decade on levodopa, and he was fully into the “on” and “off” phases of the meds, Robert recreationally took a puff of a CBD-heavy joint and his tremors lessened. The levodopa had kicked in.
With help from their new secret weapon to activate the levodopa, Helen could lessen her husband’s need for ever-increasing doses and therefore reduce the risk of overmedication and such side effects as RBD.
With these tantalizing descriptions of neuroprotection and positive reports from the underground, Helen decided to start experimenting. She obtained high-CBD capsules and immediately found incredible results. With his nightly dose of high-CBD, Robert experienced an almost complete elimination of the strange nightmares and dangerous violent movements of the REM behavior disorder.
HELEN PROVES HER THEORY
It took some fiddling for Helen find the best dosage, cannabinoid ratio and timing to help control her husband’s RBD. She eventually settled on a nightly capsule of 1 mg of THC to 10 mg of CBD. It’s intriguing that CBD helped calm down his sleep because single-molecule experiments have generally found that THC and CBD act as yin-and-yang counterbalances to each other.
In one of the best designed studies in the rather uneven field of sleep and cannabis, British sleep researchers found that 15mg of THC had a sedative effect while 15 mg of CBD increased wakefulness. When administered together, it seemed that CBD overpowered the sedation from the THC while also protecting against THC’s tendency to result in memory loss and a fuzzy hangover the next morning. Depending on the patients, these dose ratios can have a potent impact. With such powerful results, Helen knew she needed to answer her own call for more data.
Through the local Parkinson’s groups in her area, she started soliciting for RBD patients to join her observational study. She hoped to find better answers for the individualistic details of pairing cannabis with the host of Parkinson’s medications and symptoms. She found a source of assistance in Dr. Andy Hospodor, an engineer that she met at the Society of Cannabis Clinicians (SCC) while sharing her findings. He offered to provide the calibrated-dose cannabis capsules free of charge. She eventually enrolled nine patients and their care partners. The patients begin with two weeks of pre-study to calibrate, four weeks with a nightly dose and then an additional daytime dose.
In the study, every RBD patient reacted uniquely, but all nine found relief. Spouses gushed that their husbands and wives “never slept so well.” Partners fearful of RBD-related injury returned to the bedroom. Quality of life improved in many directions. Helen’s study also confirmed the often-reported ability of cannabis to facilitate a lower dosage of pharmaceutical drugs or even quit them all together. One patient reported the CBD capsules worked equally as well as his Klonopin without having the obvious downsides of benzos.
Another patient took daily doses of clozapine — an antipsychotic so powerful that the FDA required five “black box warnings” and a regular blood-testing regimen because of its dangerous tendency to lower white blood cell counts. With the CBD capsules, he found he could halve the dosage of the unpleasant drug.
It should be noted that this same patient also became a cautionary tale for a common danger when introducing elderly patients to cannabis: the risk of getting too high and having a trip unpleasant enough to make them never touch the medicine again. This, however, simply proves that every patient is different. For some, getting high is a benefit; for others, it’s a drawback.
The results of the study led Helen to new questions: Do we want to get rid of RBD all together or just lower it to a tolerable level? Because people need the neural reset of REM sleep, waking someone from their dream of movement pulls them out of their most restful stage of sleep. She wished that she could have afforded the rigorous data from a sleep lab, but the facilities are expensive for a small open-label study.
In any case, Helen is overjoyed: “The results speak for themselves. Even though my study was small and had its flaws, it was careful enough that people should be willing to give this a try,” she says. What’s more, a small study in Brazil recently confirmed her results by using a synthetic single molecule at a different dosage.
Now Helen collects more data using a survey for Parkinson’s patients who use cannabis. She’s trying to learn what works for them and what doesn’t and identify the specifics of helpful strains, mixtures and ingestion methods. She wants to learn about the nuts and bolts of treatment, how it differs from patient to patient so she can help other people find the same relief she found for her husband.
If you’re interested in Helen’s research, or know someone who may be, please contact Helen Garvy (email@example.com) for a copy of the survey or for more advice from her on Parkinson’s, pot and RBD.