“Cannabis and Parkinson’s Disease” – Lecture Notes

Northwest Parkinson’s Foundation (nwpf.org) holds a Hope Conference every year. At this year’s conference (October 7, 2017, Seattle), there was a naturopathic physician, Jade Stefano, who spoke about cannabis and Parkinson’s Disease (PD). She is also a cannabis researcher and organic grower. Her talk focuses on the active compounds in cannabis, medicinal uses of those compounds, and how the compounds might be helpful in PD and might harm those with low blood pressure. She also discusses the pros and cons of different administration methods.

The 40-minute lecture was recorded and is available online:
nwpf.yourbrandlive.com/c/jade-stefano

Of course, thanks to Brain Support Network volunteer Denise Dagan, we have notes to share. See below.

Medical marijuana is legal now in California, and recreational marijuana will be legal as of January 1, 2018. It’s still a good idea to discuss the use of cannabis with a physician. This 40-minute lecture will prepare you for that discussion.

Robin

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nwpf.yourbrandlive.com/c/jade-stefano

Cannabis and Parkinson’s Disease
Speaker: Jade Stefano, naturopathic physician, cannabis researcher and organic grower
Northwest Parkinson’s Foundation Hope Conference, Seattle
October 7, 2017

The cannabis plant has over 60 cannabinoids, the most famous of which is THC.

There are over 483 identified chemical constituents in cannabis and many more unknown.

Other biologically active compounds are:
– Terpenes (essential oils)
– Flavonoids (proanthocyanins in some purple varieties – also in grapes and berries)
– Carotenoids (beta-carotene – also found in carrots)

Used in medicine for thousands of years, worldwide, even in the US into the 1930s when there were 23 pharmaceutical companies making cannabis preparations. It became illegal in the US in 1937. At the time, the AMA opposed the ban and supported cannabis as medicine. (Source: Russo and Grotenerman, 2006)

Why do people with PD use cannabis?
Pain
Tremor
Sleep
Anxiety
Depression
Dyskinesia
Dystonia
Bradykinesia
Inflammation

Different people will have varying responses. Not all people get relief from all symptoms.

For some it may help pain and sleep, but not movement at all. Ease of pain and sleep is common in all user of cannabis, not just for those with PD, so it is likely cannabis will help with these PD symptoms.

Others find relief with movement symptoms, but it is less common than relief from pain and sleep symptoms.

Bioactive Constituents Explained…

Delta-9 Tetrahydrocanabinol (THC)
– most common cannabinoid in US cannabis
– flower ranges between 10-28% THC dry weight
– causes the ‘high’
– low doses can be therapeutic, especially in conjunction with other compounds found in the plant

THC medicinal actions:
– analgesic
– antispasmodic
– appetite stimulant
– neuroprotective
– anti-inflammatory
– reduces blood pressure
– bronchodilator
– anti-neoplastic (anti-cancer)
– anti-emetic (anti-nausea)

THC adverse reactions:
– can cause drop in blood pressure in some people, resulting in fainting and dizziness
– rapid heart beat
– lethargy, especially in high doses or oral consumption
– paranoia
– hallucinations
– impaired short term memory, but not long term memory
– altered consciousness
– giddiness
– social phobia
– nausea at high oral doses

Canabidiol (CBD)
– second most common cannabinoid in medical cannabis
– does not cause euphoria or alteration of consciousness / non-intoxicating
– may cause a relaxed sensation
– patients report it helps with panic attacks, generalized anxiety, and nervousness
– synergistic with THC for some therapeutic benefits such as analgesia, anti-emetic, anti-neoplastic while simultaneously reducing undesirable effects of THC such as anxiety, tachycardia, hunger, lethargy and alteration of consciousness. (Source: Russo and Guy, 2005)
– Adverse reactions are rare and include headaches

CBD actions:
– analgesic (especially for neuropathic pain)
– anti-inflammatory
– anxiolytic (anti-anxiety)
– anticonvulsant (seisure disorders)
– neuroprotective
– anti-oxidant
– antipsychotic
– anti-neoplastic (anti-cancer)
– modulates THC metabolism (taken with THC reduces THC effects of euphoria/high)
– immune modulating
(Source: Russo and Guy 2005, Fernandex-Ruiz et al. 2013, Zuardi et al 2001, Lee 2011)

CBD from Hemp
– Hemp is an agricultural form of cannabis use to produce fiber, oil, and seed.
– Contains high amounts of CBD and less than .3% THC.
– It is available online, at farmers markets, etc. as nutritional supplements and medicine.
– Hemp derived CBD is often of dubious origin, unregulated, and may be contaminated with heavy metals and pesticides.
– Because Hemp is a bio-accumulator (absorbs toxins from soil), it is used in bio-remediation projects to ‘clean’ soils from heavy metals and pesticides.
– Devoid of terpenes and other beneficial constituents
– Use caution when buying these products!
– Some ‘clean’ hemp CBD is available on market from Kentucky and Colorado, but do your research if considering these products.

Which THC:CBD ratio is best?
– it depends…
– every person varies in their THC:CBD needs
– some cannot tolerate significant THC and respond well to CBD dominant strains 20:1 CBD:THC
– some need a strong analgesic effect and have a high tolerance to THC so prefer a THC dominant strain 20:1 THC:CBD
– some need some THC for symptoms, but cannot tolerate the a THC only strain. These people do well on a 1:1, 2:1, or 3:1 THC:CBD ratio
– CBD acts at the same receptors as THC so ingesting CBD and THC together helps to moderate the effect of THC by antagonizing the THC at the cannabinoid receptors.
– By adjusting the THC: CBD ratio, a person can customize e medicine to fill their needs.
– high CBD ratios can be used during the day when a person may have tasks to accomplish that would be hindered by high THC intake. Then at night they can switch to a higher THC variety that may be more effective for pain or sleep.

A 1:1 CBD:THC medicine is a great place to start: Harder to find, but available in WA.
– 1:1 ratios have been very effective in trials conducted on the drug Sativex (a whole plant nasal spray pharmaceutical, available in the UK and currently in US trials)
– They proved effective in double-blind trials for neuropathic pain, intractable pain due to cancer unresponsive to opiates and a various MS symptoms in severals studies.
– MS patients experienced reduced spasms, pain, bladder problems and tremor.
(Source: Russo and Guy, 2005)

CBG, CBC, THCV, CBN, CBDV, delta-8-THC
– These are some of the other cannabinoids fund in cannabis, present in very small amounts
– They are important components in creating a whole plant medicine and synergies with the other constituents.

Terpenes
– Essential oils found in all plants and used in body care products and foods, as fragrances and flavors
– Cannabis is high in these
– They create unique flavors and contribute to effects of different strains
– Contains hundreds of different terpenes and profile varies by cultivar
– Common terpenes found in cannabis: Myrcene, Pinene, Linalool, etc.
– Synergistic effect with cannabinoids
– provides aromatherapy benefit
– provides significant medical benefits

Terpenes take away…
– look for cannabis that is high in terpenes
– will have better flavor and is better medicine
– some companies test their flower and concentrates for terpenes so look for tested products
– flower should test over .8% terpenes, Concentrates over 5% (maybe higher depending on product)
– untested flower should be fragrant when squeezed between fingers It should not smell like hay.

The Entourage Effect
– the collective action of all the active constituents
– involving both synergy and antagonism
– the whole medicine is greater than its parts
– a review by McPartland and Russo in 2011 cite research that whole plant cannabis extracts produce an effect 2-4 times greater than expected based on its THC content alone.

Sativa vs Indica
– Different cultivars based on their genetic origin, growth patterns and perceived effects
– Little scientific backing for this distinction, but a commonly used marketing strategy by dispensers and growers
– Does not often correlate with chemical composition
– The variation in effects is now known to be a result of terrine and cannabinoid profiles
– Dispensaries often ask if you want saliva or indica, BUT the CBD:THC ratio and terpene profile are much more relevant

Suggestions Specific to PD Symptoms:
Cannabis Actions that may be of benefit in PD
– analgesic
– soporific (sleep inducing)
– neuroprotective (Hampson et all 2000, and Kluger et all 2015)
– anti-oxidant
– anti-inflammatory
– stimulate neurogenesis (test-tube evidence)
– anti-depressant
– antiolytic (anti-anxiety) [Approved for PTSD treatment]
– anti-spasmotic: CBD can reduce dyskinesia

Insomnia
– some people find THC heavy strains to be best, but others find THC stimulating. Try different THC:CBD ratios, as well as different cultivars with varying terpene profiles.
– Myrcene is a terpene that is very common in cannabis and known to have a soporific opiate like effect. A good choice for sleep. (Source: Russo 2017)
– Pinene is a terpene known to be stimulating so avoid it for sleep, but use during the day.

Tremor
– Dr. Mischley study at Bastyr Univ. on tremor and cannabis using a gyroscope sensor to monitor tremor.
– Only 4/10 had tremor substantial enough to be picked up with the sensor; of those, it decreased tremor.
– During interviews, 9/10 said it helped PD symptoms, 1 said it made tremor worse initially then better, 6/10 said it improved sleep.

REM Sleep Behavior Disorder (RBD)
– A study found cannabis CBD can control symptoms of RBD in those with PD (Source: Chagas et all 2014)

Dystonia (Muscle Cramping)
– e.g. curled toes in the morning when you wake up.
– cannabis works very well for all sorts of muscle cramping (intestinal, menstrual, etc.)

Pain (Myalgia)
– THC and CBD are both analgesics
– higher doses = more analgesia
– some terpenes are also analgesics: Myrcene (also good for sleep), Pinene (also good for daytime alertness) and Linalool ( also good for anxiety)
– good for musculoskeletal pain, GI pain, headaches, Nerve pain…
– CBD may be especially good for nerve pain
– THC better for cramping
– direct analgesic effect as well as indirect effect by taking one’s focus off pain
– can help get off opiates after injury

Dyskinesia
– due to too much supplemental dopamine
– multiple studies show benefit and some show no effect
– possible differences in formulations used in studies so experiment. Possibly higher ratio of THC as it helps cramping.

Anxiety
– common in PD
– cannabis can cause anxiety as a side effect. This is caused by THC and certain terpenes. To avoid anxiety, add CBD to your formula. Increase ratio of CBD until anxiety symptoms subside.
– cannabis can also treat anxiety, especially CBD chemovars
– if you have tried one strain and it makes you anxious it does not mean other strains will do the same
– adding CBD to your formula can modulate the THC and reduce or eliminate anxiety
– research: Cannabis users experience less stress. Cortisol levels do not rise as easily (Cuttler, C. 2017)

Depression
– epidemiological studies have shown cannabis users are less depressed
– other studies have shown an association with cannabis use and depression but it is not clear if the depression is due to the cannabis or other factors.
– moderate use in PD patients has potential to improve symptoms of depression by alleviating pain, anxiety and other symptoms that exacerbate depression. (Source: Babayeva et al 2016)

Euphoria as a Side Effect:
– caused by THC
– frequent use creates a tolerance to this effect
– some find this to be pleasant, others do not
– can be reduced by increasing CBD content/ratio

Choosing/Sourcing Quality Medicine:
Avoiding contamination (pesticides and molds) and understanding test results
– grown your own
– buy at retail in legal states
– buy via medical cannabis programs
– purchase on the black or gray market

Organic/Pesticide Free Cannabis Products
– pesticides are lipophilic, meaning they bind to lipids (oils and waxes) which cannabis is high in
– pesticides will concentrate to very high levels in hash oil and cannabis extracts
– extracts are often produced by third party processors buying input material from many sources using unknown pesticides
– products are rarely feted for pesticides
Jade knows growers who label their product as pesticide free and knows they use pesticides, so don’t trust the claim “Pesticide Free” on the label. Nobody is verifying, so it can’t be trusted in many cases.

How to find pesticide free cannabis:
– if buying on black/gray market, know and trust your grower. Ask for a list of pesticides they use.
– if buying at retail in legal states:
— Look for a Third Party Certification that inspects growers and is on the label as having tested soils, etc at the grower.
1. Clean Green Certified
2. Certified Kind
3. Certified Sun Grown

Department of Health (DOH) Certified Complaint Cannabis
– WA state
– tested for heavy metals, mycotoxins and pesticides
– hard to source
– expensive
– poor product selection
– availability improving as testing requirements will change
– www.doh.wa.gov/Portals./1/Documents/Pubs/608011.pdf

Sungrown vs. Indoor Grown (uses a TON of electricity, has less pesticides)
– Good quality Sungrown is:
— Ecologically sustainable
— Less pesticides
— more vital and patent than herbs grown under artificial lights
— terpenes are produced by plants as a defense mechanism against pests and stressors which only exist outdoors
— more flavor/higher terpene content
— more complex phytoconstituent profile due to full spectrum sunlight.
— better medicine

Understanding test results – required by WA law (* only these are required on the package. Total testing by request in store)
– THC*
– THCA
– CBD*
– CBDA
– CBG
– CBGA
– others, CBC, THCV
– Total cannabinoids*
– terpenes
– microbial: E. Coli and salmonella
– mycotoxins
– residual solvents
– moisture content

Many products and consumption methods currently available:
Products:
– Flower (smokable)
– Edibles
– Capsules
– Tinctures, glycerites, syrups
– Concentrates: Hash, hash oil
– Creams, oils, salves (good for muscloskeletal pain and sore joints)
– Sublingual sprays and drops
– Suppositories (vaginal or rectal)
– Pharmaceuticals

Consumption methods:
– vaporizing or vaping (pre-rolls and infused pre-rolls are available at retail stores)
– dabbing
– smoking
– oral ingestion
– mucousal applications
– topical absorption

Inhalation, including vaporization (with no combustion products into the lungs, so safer)
– inhalation goes directly from the lungs into the bloodstream and then to the brain and other tissues where it binds with CB1 and CB2 receptors. It acts quickly (5 minutes) and wears off quickly (within 2 hrs.) (Source: Huestic et al 1992 a,b)
– fast acting, easy to control dose
— pre-rolls and infused pre-rolls are available at retail stores
— portable flower vaporizers vaporizes off cannabinoids and leaves carbon behind
— vape pens
—— avoid cartridges made of plastic (hormone mimicking compounds)
—— glass and metal are better. Look for 100% certified pesticide free CO2 oil.
—— discrete
—— effective way to get moderate doses with minimal smoke
—— easy to calibrate dosing. Start with 1 puff and increase until relief is noted
—— available in refillable and disposable models
—— cautions: (a) components made in China and there are many low quality on the market that may contain heavy metals and plastic residues. (b) in many products the concentrate in cart is diluted with PEG or another carrier oil such as MCFAs. These have not been tested for safety and PEG creates formaldehyde as a byproduct when vaporized.

Oral consumption
– enters the bloodstream through the gut where it is sent to the liver before entering other tissues. It takes up to 2 hrs. to act and can last 8-12 hrs.
– easy to over consume. Doses must be titrated
– over consumption can be uncomfortable but is not toxic. Symptoms can include nausea, panic attack, rapid heart rate and hallucinations.
– some cannot tolerate oral consumption of THC-containing products at all.

Tinctures (drops)
– traditional herbal preparation are ethanol based, but not available in WA state. You can make your own by soaking flowers in Ever Clear.
– glycerin and water based are available and very palatable
– WA state has very low limits on amount of THC allowed in edible/oral products – 10mg/serving. Good for many, but some find them too weak. Experiment to find what works.

Edibles are often loaded with sugar, so be careful of your diet/calories

Topicals (massage oils, creams, etc.)
– used for muscoskeletal pain
– best preparations often contain other herbal medicines such as cayenne, menthol, arnica, calendula and other plant essential oils.

Juicing fresh cannabis leaves and sometimes flowers works well. Add to other fruit and/or veg.
– no peer reviewed research but reports from patients claim it helps with autoimmune conditions such as rheumatoid arthritis and lupus.
– juice contains all the cannabinoids in the acid form (THCA, CBDA, etc.) and the carotenoids and flavonoids which would not survive vaporization
– juice will not cause intoxication

Concentrates (smoke this)
– resin glands which contain cannabinoids and terpenes are isolated from plant material using various methods and turned into an oil or hash product
– high potency
– good for symptoms that are not responding to flower
– small amounts can be highly effective
– can use vape pen

Look for:
– CO2 oil: extracted with carbon dioxide
– Bubble hash: extractd with ice and water
– Ethanol hash oil (RSO or EHO): extracted with water and alcohol (eat or smoke this)
– Kief: isolated resin glands (trichomes) extracted by sifting through fine mesh screen
– Rosin: extracted with heat and pressure

Avoid:
– BHO / Butane hash oil – AVOID THIS PRODUCT. It is extracted with butane and contains residue
– may be sold as crumble, sugar, shatter, wax
– hydrocarbon extracted products:
— Distillates: super refined distilled hash oil or BHO, 90-98% THC and/or CBD.
— Has all other plant constituents removed
— Will concentrate any pesticides that may have been used on the plants
— No longer an herbal whole plant medicine, closer to a pharmaceutical but not tested or purity
— Devoid of natural terpenes. May have un natural terpenes added back to create ‘flavor’

Dabbing
– cannabis concentrate is placed on a hot surface and inhales through a ‘dab rig’
– efficient and effective way to ingest high doses in small quantities
– good for 10/10 pain not responding to lower doses
– not for beginners

Dabbing cautions:
– can irritate lungs if too hot or too large a dose. Use low temperature to achieve vaporization (under 580F)
– BHO (Butane) dabs are the most common and should be avoided
– dabbing THC heavy products will cause a high level of intoxication quickly so it is unsafe to drive or operate machinery
– avoid if you have low blood pressure as it can cause a rapid drop (THC mostly)
– safest product to dab are: Bubble hash, CO2 oil, Rosin

Oral ingestion of concentrates:
– concentrates can be put into capsules, cooked in food, or taken directly by mouth
– EHO and CO2 oil are commonly taken orally
– dosing can be easily calibrated if the product has been tested. 1g oil tested at 65% THC contains 650mg of THC. If desired dose is 100mg, take 153mg per dose.
– oral dosing should be titrated over 1-2 weeks starting with a dose 1/4 size of a grain of rice.

DUIC = Driving Under the Influence of Cannabis
– Illegal everywhere
– OR and WA have blood test to determine if you are DUIC

Resources:
www.beyondthc.com
www.projectcbd.org
www.cleangreencert.com has clean, green growers/suppliers

Book
Chronic Relief: A Guide to Cannabis for the Terminally and Chronically Ill, by Nishi Whiteley

Questions and Answers:

What is the shelf life of cannabis?
Cool, dark place can be years. Sunny, warm places will be really short. No need to refrigerate or freeze.

Where to buy?
DOH certified medical grade cannabis is expensive and hard to find. She likes these stores: Dockside Cannabis (2 locations in WA + online sales), Novel Tree (Bellevue, WA) has a medical section. Medical grade cannabis has been tested for pesticides and micotoxins.

Dabbing compared to morphine?
You don’t need to go straight to dabbing to wean yourself off morphine, but yes. Cannabis can be a good way to wean off morphine.