Cannabinoids in Parkinson's Disease

by Duncan Fisher

September 07, 2022 - 3 min read

Parkinson’s disease is aprogressive neurodegenerative disorder characterized by tremor, rigidity, and ‘bradykinesia’, or slowness of movement, and sometimes postural instability. 

The body’s endocannabinoid system, part of our onboard neural signaling network (and the reason we are sensitive to administered cannabinoids),has emerged as a potential therapeutic target forthe treatment of this disease. 

This is based on a number of lines of evidence, including the dense localization of endocannabinoid neural receptor sites in brain regions involved in the control of movement and signs of dysregulation of the endocannabinoid system in human Parkinson’s patients. Pharmacological modulation could well represent a new therapeutic tool. Studies in animal models are supportive so far, suggesting that drug development may offer benefits specifically in motor symptoms, neuroinflammation, and neuroprotection. 


Evidence implicating the endocannabinoid system

There are two known endocannabinoid receptors. They are spoken of as ‘CB1’ and ‘CB2’. It is the latter which seems of promise, the site most associated in animal models with mediation of neurodegeneration, in which dying neurons activate microglia, which in turn elicits infiltration of macrophages and generates proinflammatory factors that kill further neurons. Evidence shows that activating microglial CB2 receptors can suppress microglial activity and reduce their downstream neurotoxicity, and as well prevent BBB leakage and protect against oxidative stress.

Components of the endocannabinoid system are heavily expressed in basal ganglia in particular, where they interact with dopaminergic, glutamatergic, and GABAergic signaling systems. This can explain the motor inhibition that is typical of Parkinson’s disease. It is known that excitatory synapses onto indirect-pathway medium spiny neurons (MSNs) demonstrate higher release probability and larger N-methyl-d-aspartate receptor currents than do direct-pathway synapses, and indirect-pathway MSNs selectively express endocannabinoid-mediated long-term depression (eCB-LTD). This requires dopamine D2 receptor activation, and in models of Parkinson's disease, indirect-pathway eCB-LTD is non-existent, but is rescued by a D2 receptor agonist or inhibitors of endocannabinoid degradation. These two agents coadministered reduce parkinsonian motor deficits. This would appear to confirm that in the control of movement, endocannabinoid-mediated depression of indirect-pathway synapses has a central role. 


Toward a therapeutic strategy

There have been almost no clinical observations or trials of cannabinoid-based therapies for motor symptoms in Parkinson’s disease. Such data that exists is not yet conclusive. Preclinical experimental data continues to mount, however. 

Experimental use of the cannabinoid agonist WIN-55,212-2, a cannabinoid receptor agonist, protects against nigrostriatal cell loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine animal model, and has elsewhere demonstrated overall suppression of the excitotoxicity, glial activation, and oxidative injury that causes degeneration of dopaminergic neurons. Efficacy against bradykinesia and levodopa-induced dyskinesia in Parkinson’s disease has also been demonstrated by the cannabinoid-like compounds CE-178253, oleoylethanolamide, nabilone, and HU-210. As well, modulation of the endocannabinoid 2-arachidonoyl-glycerol by inhibiting monoacylglycerol lipase changes glial phenotypes and provides neuroprotection. Anti-cataleptic properties have also been shown byURB597, JNJ1661010, and TCF2, all fatty acid amide hydrolase inhibitors, and by two GPR55 agonists, CID1792197 and CID2440433. VCE-003.2, a cannabigerol quinone derivative, is neuroprotective against inflammation-driven neuronal damage in vivo and, in cellular models of neuroinflammation, in vitro. This probably implicates involvement of different binding sites at the PPARγ receptor. AM1241 also holds promise, ameliorating MPTP-induced Parkinson's disease and neuronal regeneration in mice. β-Caryophyllene, a phytocannabinoid, attenuates oxidative stress, neuroinflammation, and glial activation, and salvages dopaminergic neurons in a rat model of Parkinson’s disease, and in another model attenuates MPP+ induced cytotoxicity, and in yet another, guards against dopaminergic neuron injury Induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Studies that investigate the effects of cannabidiol (CBD) on movement disorders are also beginning to emerge as possible treatment or prevention of movement disorders like Parkinsonism. Abnormal-cannabidiol (Abn-CBD), a synthetic cannabidiol isomer, is a GPR55 agonist whose anti-cataleptic effect was reversed by cannabidiol and PSB1216, a newly synthesized GPR55 antagonist. 


DiolPure products contain PureForm CBD™ transformed from aromatic terpenes for pharmaceutical-grade purity. PureForm CBD™ is bioidentical to CBD extracted from hemp and cannabis, but free of any residual cannabinoids like THC or impurities or chemicals that can associate with traditional plant-derived production processes. 


The foregoing is a report on trends and developments in cannabinoid industry research. No product description herein is intended as a recommendation for diagnosis, treatment, cure or prevention of any disease or syndrome. 




Cannabigerol (CBG): Another promising cannabinoid?

Cannabigerol (CBG): Another promising cannabinoid?

For some good reasons, research and commercial attention is beginning to turn to cannabigerol, or 'CBG'. 
Read More

October 04, 2022 2 min read

Up close: Cannabinoids in Huntington's chorea

Up close: Cannabinoids in Huntington's chorea

In vitro and in vivo models of Huntington's disease, an inherited condition in which nerve cells in the brain break down over time, show disease-related alterations in the endocannabinoid system, part of the body’s neural cell-signaling network, and the dopamine regulatory system downstream. 
Read More

October 03, 2022 3 min read

Up close: Cannabinoids in neurodegenerative diseases

Up close: Cannabinoids in neurodegenerative diseases

Modulation of cannabinoid receptor signaling should represent a viable therapeutic target in neurodegenerative diseases. 
Read More

September 30, 2022 2 min read

Follow us on Instagram

Net Orders Checkout

Item Price Qty Total
Subtotal $ 0.00
Shipping
Total

Shipping Address

Shipping Methods