“Marijuana and PD: What Do We Really Know?” – Webinar Notes

The Parkinson’s Foundation (parkinson.org) conducts occasional webinars on Parkinson’s Disease (PD).  Recently, it hosted a very thorough webinar on marijuana and PD.  The speaker was Dr. Benzi Kluger, a movement disorder specialist in Colorado, which legalized recreational marijuana a couple of years ago.

You can download the speaker’s slides here:


And you can watch the hour-long recording of the webinar here: (requires registration)


Brain Support Network uber-volunteer Denise Dagan listened to the webinar and took excellent notes.  See below.



Notes by Denise Dagan, Brain Support Network Volunteer

Marijuana and PD: What Do We Really Know?
Parkinson’s Foundation Expert Briefing Webinar
April 17, 2018

Speaker: Benzi M. Kluger, M.D., M.S, movement disorder specialist, University of Colorado Hospital

Learning Objectives:
* Define cannabis, cannabinoids and endocannabinoids
* Review the basic science of the potential of cannabinoids to affect Parkinson’s and other movement disorders
* Understand the current state of the evidence of cannabinoids as a treatment for Parkinson’s
* Know the most common side effects of cannabinoid-based therapies
* How he works with patients in using cannabinoid products for medical use.

What is cannabis, cannabinoids and endocannabinoids?
How does cannabis effect the nervous system?
Do cannabinoids improve motor or nonmotor symptoms in PD?
Can cannabinoids slow down the progression of PD?

What is cannabis, cannaboinoids and endocannabinoids?
* Cannabis is a genus of flowering plants including sativa (higher THC), indica and ruderalis (higher CBD).
* Cannabinoids are chemicals that act on cannabinoid receptors in the nervous system and other tissues.
* Synthetic cannabinoids are man-made and very targeted, phytocannabinoids (now over 100) come from the cannabis plant. Endocannabinoids are produced by neurons and other tissues – analogous to the endorphins system in the body.

Phytocannabinoids:  D9-tetrahydrocannabinol (THC)
– Primary psychoactive component of cannabis
– Higher concentration in Sativa strains

cannabidiol (CBD)
– May have more calming effects on the nervous system
– Significant interest in medical research (particularly epilepsy)
– Higher concentration in indica and ruderalis strains

– name means ‘bliss’
– Discovered in 1992
– May play a role in pain, sleep, stress response and other behaviors as well as development.  Most research done on adolescents and young animals so we don’t know much about its effects on adults, especially older adults.
– Also found in chocolate (why we crave chocolate?)

Synthetic Cannabinoids
* Marinol (dronabinol): THC developed to treat nausea and appetite in cancer
* Nabilone: Cannabinoid Receptor 1 and 2 agonist
* K2 and Spice
– legal alternatives to cannabis
– have been associated with adverse health effects and hospitalizations (avoid these!)

How does cannabis effect the nervous system?
* It slows response and reaction time.
* It reduces dopamine reception.

The Endocannabinoid System
* Cannabinoid Receptor 1 (CB1) and 2 (CB2)
* CB1 primarily in the central nervous system and CB2 in immune system
* Endocannabinoids act on the presynaptic neuron to decrease neurotransmitter release at CB1 receptors
* Tend to increase GABA and decrease Glutamate and Dopamine release in the basal ganglia

Action of Cannabinoids
* Agonist, antagonist and partial agonist at CB1 receptors
* Antioxidant and anti-inflammatory effects
* CB2 on microglia (the primary immune cells in the brain)  Research into slowing progression of PD in the brain.
* CB independent effects. Other receptors (adenosine A2A is acted on by caffeine)

Do cannabinoids improve motor symptoms in PD?  No.

Animal Models
* Published studies generally support motor improvement but effects are mixed as are mechanisms.  Cannabinoids have actually induced PD symptoms in animals.
* CB1 antagonists (blocking CB1 receptors) are most consistently helpful probably through non-dopaminergic mechanisms.
* Both CB1 agonists and antagonists have been reported to improve dyskinesias.

Clinical Reports and Trials
A survey of 339 PD patients : 25% reported using cannabis, 46% described some benefit, 31% reported improvement of rest tremor, 45% of bradykinesia, and 14% of LID
* In US, 207 PD patients:  only 5% reported using, and most reported benefit only for non-motor Sx (pain, sleep, appetite, anxiety, muscle stiffness)
* All randomized controlled trials to date have been negative (inconclusive).  There are 100 phytocannabinoids, but these trials picked only 4.  Small number of participants so harder to see trends and rule out placebo effect.
* Recent Israeli study showed benefit, but also flawed study.
* Current study has worked out some of the study flaws so may show good results on effect of CBD in PD.

Do cannabinoids improve nonmotor symptoms in PD?  Yes.

Clinical Reports
* No randomized controlled trials
* Some case series report benefit for REM Behavior disorder and psychosis
* Colorado experience suggests benefit for appetite, nausea, pain, anxiety and sleep, muscle spasms & spasticity, depression (chronic cannabis use increases risk for depression)
* Web based survey made associations between cannabis and better memory, although all participants were young.

Most Common Side Effects
Cognitive (dopey), depression, apathy
Low Blood Pressure
Smoking may increase risk for cancer or other pulmonary issues so use vaping, edibles to avoid this
Edibles may have less predictable absorption and dosing, eating too much because effects kick in later through digestion
Risks – children and animals getting into cannabis products.

Can cannabinoids slow down the progression of PD?  No.

Preclinical Models
Most published studies suggest neuroprotective effect in toxin-based models
Mechanisms may include anti-inflammatory and microglia effects
Most studies suggest cannabinoid receptors are not involved
No data in people

Speaker works with patients using cannabis for medical purposes.  He does not write a prescriptions.  He fills out paperwork so patients can get a license to buy marijuana.  In other states it may work differently.  There is no regulatory body saying 10% CBD will be the same across dispensaries.  You should stay with the same dispensary for the maximum consistency.  Most patients start w/CBD (cannabidiol) although THC may help more with pain, dyskinesias and motor functioning.  Avoid smoking due to cancer risk.  Use creams, patches, edibles, vaping in that order.  Start low and increase slowly.  There are side effects.  Tell your doctor about your use.

Take-Home messages
* There are many different (100+) psychoactive chemicals in cannabis and products derived from cannabis may vary widely in terms of their benefits and side effects.  Some are stimulants, others will help you sleep.
* There is currently no conclusive evidence supporting the benefits of cannabis for any aspect of PD.
* Anecdotal evidence suggests cannabis may help pain, sleep, appetite, nausea and anxiety.
* Research to date on motor symptoms and dyskinesias in people have been either negative or inconclusive to date.
* Potential side effects include confusion, low blood pressure, falls and pulmonary issues if smoked.

Question and Answer:

There’s no evidence to suggest people with PD will experience benefits from medical marijuana?
There’s evidence from other diseases that symptoms like nausea, appetite, anxiety, sleep will also help in PD.

THC most helps pain.  Would you recommend creams for that?  How do you go about acquiring that?
Where it’s legal if you have a medical license you go to a dispensary and ask for the creams or patches.  Where it is not legal, pure CBD (cannabidiol) products can be shipped across state lines, although it may not be as efficacious without a small amount of THC for pain.  There is still a legal risk.

The negative interactions of these drugs include hallucinogenic effects so what is the risk for people with psychosis?
The literature provides guidance.  For people with dementia or advanced PD you must be more cautious.  The potential for developing side effects is higher.  Paranoia, hallucinations, and delusions risk is higher.  For those with Lewy Body Dementia CBD has been useful as a calming influence.

What is the difference between recreational and medical marijuana?
In Colorado there are both types of dispensaries.  The products are similar although the recreational dispensaries focus on higher THC. The reason to get a medical license is to have more access to more CBD (cannabidiol) products, creams and patches that are not usually used for recreational purposes.  It also gives you a tax break.

Is it covered by insurance?
Not yet.

People with PD are resigned to the need to increase dose as disease progresses.  Same with marijuana?
No long term studies to show this.  The doses he’s worked with patients seem to be stable.  Other medications, like opioids, benzodiazepines can be replaced with cannabis in lower doses, less cloudy cognition to get off opioids.

Should you worry about getting addicted to cannabis?
It does not appear using cannabis creates a physical dependency like opioids and benzodiazepines, although they can develop a psychological dependence.  If you are younger and considering cannabis for sleep or pain he would say to give it a try.  There is no downside to using it long term.

Hemp is related to cannabis.  What is the relationship between them?
They are the same genus but it does not include the psychoactive chemicals.  Hemp products will be legal, but he doesn’t know if they would be effective to treat what they claim to, or not.

People with pain muscle cramping find the calming effect of marijuana relieve dystonia symptoms?  Do you think that’s what’s happening?
Muscle cramping or dystonic pain shows benefit by using CBD (cannabidiol) with a bit of THC to relieve muscle cramping.  It could be the relaxation effect that relieves the pain.  The cannabinoid system is also involved in pain perception.  A recent study (last year) tested people with PD pain perception 1/2 hour after cannabis use.  Their pain threshold increased. After 12 weeks of use the thresholds were even higher.  Cannabis use quiets the nervous system and increases pain tolerance.  It can be particularly useful, especially creams, for pain control by both peripheral and central mechanisms.

Do the cannabinoids go right into the skin through the skin?
Yes, predominantly that is a local effectiveness similar to lidocaine cream.  With the patches it is a combination of local and periphery effect.

Does cannabis help with tremor?
That is being studied now by using CBD (cannabidiol).  There are reports of cannabis effectiveness on tremor, but they are just reports, not studies.

For a person with Parkinson’s who wants to try cannabis, how do they approach their doctor?
Even in Colorado, neurologist responses are mixed.  Some are still not comfortable in writing the paperwork to get a license.  There is some talk about teaching and training in medical school to accommodate this need by patients.  You should talk about cannabis as complementary medicine.  If your doctor is not cooperative you should not proceed on your own or you may experience detrimental side effects without medical support.  You should get a referral to a cooperative doctor before proceeding.  Ask for a 2nd opinion. Insurance pays for 2nd opinions.

Any concern about cannabis and DBS (deep brain stimulation)?
Same cautions apply.  Speech, balance, cognition challenges can be magnified by cannabis.  There should be not any particular benefit or detriment due to the presence of a DBS unit.

Impulse control disorder magnification by cannabis use?
No studies on this.  There should be no relationship excepting if the individual becomes obsessed with using cannabis just as they could become obsessed with anything else (sex, food, gambling, etc.)

Atypical parkinsonisms advice?
One study suggested CBD (cannabidiol) can be helpful in Lewy Body Dementia (LBD) by calming reaction to hallucinations.  Be aware of low blood pressure, falling risk, etc. as for regular PD.

How can you get involved in research studies for cannabis?
Clinicaltrials.gov has all the clinical trials in the world.  Search Parkinson’s and cannabis.
Look at Fox Trial Finder.  Use the PubMed search engine.  Search for research studies on topics of interest to you and contact those researchers.  You can make financial donations to those researchers and/or their research organizations.