Category Archives: Parkinson’s Disease

Biological bases for a possible effect of cannabidiol in Parkinson’s disease.

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 SciELO - Scientific Electronic Library Online“Current pharmacotherapy of Parkinson’s disease (PD) is palliative and unable to modify the progression of neurodegeneration. Treatments that can improve patients’ quality of life with fewer side effects are needed, but not yet available.

Cannabidiol (CBD), the major non-psychotomimetic constituent of cannabis, has received considerable research attention in the last decade. In this context, we aimed to critically review the literature on potential therapeutic effects of CBD in PD and discuss clinical and preclinical evidence supporting the putative neuroprotective mechanisms of CBD.

RESULTS:

Few studies addressed the biological bases for the purported effects of CBD on PD. Six preclinical studies showed neuroprotective effects, while three targeted the antidyskinetic effects of CBD. Three human studies have tested CBD in patients with PD: an open-label study, a case series, and a randomized controlled trial. These studies reported therapeutic effects of CBD on non-motor symptoms.

CONCLUSIONS:

Additional research is needed to elucidate the potential effectiveness of CBD in PD and the underlying mechanisms involved.”

https://www.ncbi.nlm.nih.gov/pubmed/31314869

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462019005012104&tlng=en

Evidence for the use of cannabinoids in Parkinson’s disease.

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 “Cannabis and synthetic cannabinoid formulations have now been legally approved in several countries for treatment of patients with Parkinson’s disease (PD). Hence, PD patients consult physicians more frequently for prescription of cannabinoids to alleviate symptoms that might not respond well to dopaminergic treatment. Despite the increasing volume of research generated in the field of cannabinoids and their effect on Parkinson’s disease, there is still paucity of sufficient clinical data about the efficacy and safety in PD patients. There is increasing understanding of the endocannabinoid system, and the distribution of cannabinoid receptors in basal ganglia structures might suggest potential benefit on parkinsonian symptoms. Concerning clinical research, only one of to date four conducted randomized placebo-controlled trials showed an effect on motor symptoms with alleviation of levodopa-induced dyskinesia. There are a growing number of uncontrolled trials and case reports that suggest beneficial effects of cannabinoids in PD patients. However, the variety of substances investigated, the varying routes of intake, differing doses and time courses make it difficult to compare data. We here provide an overview of the current literature in this field and discuss a pragmatic approach for the clinical use of cannabinoids in PD.”

https://www.ncbi.nlm.nih.gov/pubmed/31131434

https://link.springer.com/article/10.1007%2Fs00702-019-02018-8

Nabilone for non-motor symptoms of Parkinson’s disease: a randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study (The NMS-Nab Study).

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 “Although open-label observations report a positive effect of cannabinoids on non-motor symptoms (NMS) in Parkinson’s disease (PD) patients, these effects remain to be investigated in a controlled trial for a broader use in NMS in PD patients. Therefore, we decided to design a proof-of-concept study to assess the synthetic cannabinoid nabilone for the treatment of NMS. We hypothesize that nabilone will improve NMS in patients with PD and have a favorable safety profile. The NMS-Nab Study is as a mono-centric phase II, randomized, placebo-controlled, double-blind, parallel-group, enriched enrollment withdrawal study. The primary efficacy criterion will be the change in Movement Disorders Society-Unified Parkinson’s Disease-Rating Scale Part I score between baseline (i.e. randomization) and week 4. A total of 38 patients will have 80% power to detect a probability of 0.231 that an observation in the treatment group is less than an observation in the placebo group using a Wilcoxon rank-sum test with a 0.050 two-sided significance level assuming a true difference of 2.5 points between nabilone and placebo in the primary outcome measure and a standard deviation of the change of 2.4 points. The reduction of harm through an ineffective treatment, the possibility of individualized dosing, the reduction of sample size, and the possible evaluation of the influence of the placebo effect on efficacy outcomes justify this design for a single-centered placebo-controlled investigator-initiated trial of nabilone. This study should be the basis for further evaluations of long-term efficacy and safety of the use of cannabinoids in PD patients.”

https://www.ncbi.nlm.nih.gov/pubmed/31129719

https://link.springer.com/article/10.1007%2Fs00702-019-02021-z

Marijuana for Parkinson’s Disease?

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“Marijuana is popular in the United States and is being widely legalized for recreational and medicinal purposes. It remains a Schedule 1 substance without fully proven risks and benefits; yet, it is increasingly available in many US states and territories.

Cannabis might have medicinal efficacy in Parkinson’s disease as a form of medical marijuana. Endocannabinoid receptors exist throughout the nervous system and are documented to influence receptors affecting a wide variety of areas. Neuroprotective aspects might be induced by cannabis exposure that might yield benefit against the nigrostriatal degeneration of patients with Parkinson’s disease.

Animal investigations support suggestions of improvement in bradykinesia and/or tremors, but this is unsubstantiated in human studies. However, some patient surveys and anecdotal or case reports indicate that marijuana attenuates some motor manifestations of parkinsonism and also of non-motor, mood and/or cognitive symptoms. Medical marijuana might benefit motor and nonmotor aspects of Parkinson’s disease patients. Currently, these assertions are not substantiated in human investigations and cannabis can also induce side effects. Until studies clarify the safety and efficacy of pharmacotherapy with cannabis products, medical marijuana remains largely without scientific endorsement. Research has yet to document the full benefits, risks, and clinical applications of marijuana as a treatment for patients with Parkinson’s disease.”

https://www.ncbi.nlm.nih.gov/pubmed/31037227

Medicinal Cannabis for Parkinson’s Disease: Practices, Beliefs, and Attitudes Among Providers at National Parkinson Foundation Centers of Excellence.

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Movement Disorders Clinical Practice banner

“Legalization of the medical use of cannabis for Parkinson’s disease (PD) has bypassed the traditional drug-approval process, leaving physicians with little evidence with which to guide patients.

OBJECTIVE:

The goal of this study was to gather data on the cannabis-related prescribing practices and views regarding potential risks and benefits of cannabis among experts caring for patients with PD.

METHODS:

An anonymous, 73-item online survey was conducted through an online service (SurveyMonkey) and included neurologists at all National Parkinson Foundation Centers of Excellence.

RESULTS:

Fifty-six responders represented centers across 5 countries and 14 states. 23% reported some formal education on cannabis. Eighty percent of responders had patients with PD who used cannabis, and 95% were asked to prescribe it. Fifty-two percent took a neutral position on cannabis use with their patients, 9% discouraged use, and 39% encouraged it. Most believed that the literature supported use of cannabis for nausea (87%; n = 48), anxiety (60%; n = 33), and pain (86%; n = 47), but responses were divided with regard to motor symptoms. Most respondents expected that cannabis would worsen motivation (59%; n = 32), sleepiness (60%; n = 31), and hallucinations (69%; n = 37). In addition, most feared negative effects on short-term memory (75%; n = 42), long-term memory (55%; n = 31), executive functioning (79%; n = 44), and driving (96%; n = 54). Although many did not believe that cannabis should be recreational (50%; n = 28), most believed that it should be legalized for medicinal purposes (69.6%; n = 39).

CONCLUSIONS:

This study provides data on the cannabis-related practices, beliefs, and attitudes of expert PD physicians. There is a lack of consensus that likely reflects a general knowledge gap and paucity of data to guide clinical practice.”

https://www.ncbi.nlm.nih.gov/pubmed/30713951

https://onlinelibrary.wiley.com/doi/full/10.1002/mdc3.12359

Is cannabidiol the ideal drug to treat non-motor Parkinson’s disease symptoms?

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 “Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by motor symptoms such as bradykinesia, rest tremor, postural disturbances, and rigidity. PD is also characterized by non-motor symptoms such as sleep disturbances, cognitive deficits, and psychiatric disorders such as psychosis, depression, and anxiety. The pharmacological treatment for these symptoms is limited in efficacy and induce significant adverse reactions, highlighting the need for better treatment options.

Cannabidiol (CBD) is a phytocannabinoid devoid of the euphoriant and cognitive effects of tetrahydrocannabinol, and preclinical and preliminary clinical studies suggest that this compound has therapeutic effect in non-motor symptoms of PD.

In the present text, we review the clinical studies of cannabinoids in PD and the preclinical and clinical studies specifically on CBD.

We found four randomized controlled trials (RCTs) involving the administration of agonists/antagonists of the cannabinoid 1 receptor, showing that these compounds were well tolerated, but only one study found positive results (reductions on levodopa-induced dyskinesia).

We found seven preclinical models of PD using CBD, with six studies showing a neuroprotective effect of CBD.

We found three trials involving CBD and PD: an open-label study, a case series, and an RCT. CBD was well tolerated, and all three studies reported significant therapeutic effects in non-motor symptoms (psychosis, rapid eye movement sleep behaviour disorder, daily activities, and stigma). However, sample sizes were small and CBD treatment was short (up to 6 weeks). Large-scale RCTs are needed to try to replicate these results and to assess the long-term safety of CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/30706171

https://link.springer.com/article/10.1007%2Fs00406-019-00982-6

[Endogenous Cannabinoid System of the Brain as the Target for Influences at Neurodegenerate Diseases]

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“The review represents the analysis of works about role of endogenous cannabinoid (EC) system in the neuro- degenerate diseases (ND), in which the cellular death and disturbances of neuronal functions of the hippo- campus, neocortex and striatum are observed. Here, the diseases.ofAlzheimer, of Parkinson, of Hangtington, and the temporal lobe epilepsy are considered. In recent years the fundamental role of EC system in regu- lation of neuroexcitability, energy metabolism, inflammatory and many other processes has been opened in ND pathogenesis. It points to possibility of development of therapeutic approaches which use the prepara- tions for activation of EC system. In the review various mechanisms of cellular survival and their reparations provided to EC system during action of pathological factors are stated.”

https://www.ncbi.nlm.nih.gov/pubmed/30695519

Targeting CB1 and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease.

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 “Cannabinoid CB1 receptors (CB1R) and the GPR55 receptor are expressed in striatum and are potential targets in the therapy of Parkinson’s disease (PD), one of the most prevalent neurodegenerative diseases in developed countries.

The aim of this paper was to address the potential of ligands acting on those receptors to prevent the action of a neurotoxic agent, MPP+, that specifically affects neurons of the substantia nigra due to uptake via the dopamine DAT transporter.

These results show that neurons expressing heteromers are more resistant to cell death but question the real usefulness of CB1R, GPR55, and their heteromers as targets to afford PD-related neuroprotection.”

https://www.ncbi.nlm.nih.gov/pubmed/30687889

https://link.springer.com/article/10.1007%2Fs12035-019-1495-4

Cannabis, cannabinoid receptors, and endocannabinoid system: yesterday, today, and tomorrow

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“Cannabis sativa, is also popularly known as marijuana, has been cultivated and used for recreational and medicinal purposes for many centuries.

The main psychoactive content in cannabis is Δ9-tetrahydrocannabinol (THC). In addition to plant cannabis sativa, there are two classes of cannabinoids—the synthetic cannabinoids (e.g., WIN55212–2) and the endogenous cannabinoids (eCB), anandamide (ANA) and 2-arachidonoylglycerol (2-AG).

The biological effects of cannabinoids are mainly mediated by two members of the G-protein-coupled receptor family, cannabinoid receptors 1 (CB1R) and 2 (CB2R). The endocannabinoids, cannabinoid receptors, and the enzymes/proteins responsible for their biosynthesis, degradation, and re-updating constitute the endocannabinoid system.

In recent decades, the endocannabinoid system has attracted considerable attention as a potential therapeutic target in numerous physiological conditions, such as in energy balance, appetite stimulation, blood pressure, pain modulation, embryogenesis, nausea and vomiting control, memory, learning and immune response, as well as in pathological conditions such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and multiple sclerosis.

The major goal of this Special Issue is to discuss and evaluate the current progress in cannabis and cannabinoid research in order to increase our understanding about cannabinoid action and the underlying biological mechanisms and promote the development cannabinoid-based pharmacotherapies.

 Overall, the present special issue provides an overview and insight on pharmacological mechanisms and therapeutic potentials of cannabis, cannabinoid receptors, and eCB system. I believe that this special issue will promote further efforts to apply cannabinoid ligands as the therapeutic strategies for treating a variety of diseases.”
https://www.ncbi.nlm.nih.gov/pubmed/30670816
https://www.nature.com/articles/s41401-019-0210-3

Cannabinoid Receptor as a potential therapeutic target for Parkinson’s Disease.

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Brain Research Bulletin

“Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, characterized by the loss of dopaminergic neurons from substantia nigra pars compacta of basal ganglia caused due to gene mutation, misfolded protein aggregation, reactive oxygen species generation and inflammatory stress. Degeneration of dopaminergic neurons results in muscle stiffness, uncoordinated body movements, sleep disturbance, fatigue, amnesia and impaired voice.

Currently, levodopa (L-DOPA) administration is the most widely used therapy for PD. But prolonged administration of L-DOPA is associated with the symptoms of dyskinesia.

However, emerging evidences suggest the role of cannabinoid receptors (CBRs) in curtailing the progression of PD by activating neuroprotective pathways. Hence, cannabinoid therapy could be a promising alternative to combat PD in future.

In the present review we have discussed the potential role of CBRs in attenuating the key mechanisms of PD and how the existing research gaps needs to be bridged in order to understand the molecular mechanism of CBRs in detail.”

https://www.ncbi.nlm.nih.gov/pubmed/30664919

https://www.sciencedirect.com/science/article/abs/pii/S0361923018306208?via%3Dihub