Effects of Cannabis in Parkinson’s Disease: A Systematic Review and Meta-Analysis

Urbi, Berzenn; Corbett, Joel; Hughes, Ian; Owusu, Maame Amma; Thorning, Sarah; Broadley, Simon; Sabet, Arman; Heshmat, Saman

doi:10.3233/jpd-212923

Cited by 30 publications

(26 citation statements)

References 57 publications

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“…Analysis of clinical meta-data offers mixed evidence in support of medical cannabis. While well tolerated, medical cannabis has been shown to have limited benefit in improving dyskinesia and motor function (Thanabalasingam et al, 2021), although patients did report improvements in sleep quality and quality of life (Urbi et al, 2022). Conversely, cannabis-derived phytocannabinoids have shown a clear neuroprotective effect in rodent models (Prakash and Carter, 2021).…”

Section: Discussionmentioning

confidence: 99%

Identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of Parkinson’s disease

et al. 2022

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Medicinal cannabis has shown promise for the symptomatic treatment of Parkinson’s disease (PD), but patient exposure to whole plant mixtures may be undesirable due to concerns around safety, consistency, regulatory issues, and psychoactivity. Identification of a subset of components responsible for the potential therapeutic effects within cannabis represents a direct path forward for the generation of anti-PD drugs. Using an in silico database, literature reviews, and cell based assays, GB Sciences previously identified and patented a subset of five cannabinoids and five terpenes that could potentially recapitulate the anti-PD attributes of cannabis. While this work represents a critical step towards harnessing the anti-PD capabilities of cannabis, polypharmaceutical drugs of this complexity may not be feasible as therapeutics. In this paper, we utilize a reductionist approach to identify minimal essential mixtures (MEMs) of these components that are amenable to pharmacological formulation. In the first phase, cell-based models revealed that the cannabinoids had the most significant positive effects on neuroprotection and dopamine secretion. We then evaluated the ability of combinations of these cannabinoids to ameliorate a 6-hydroxydopmamine (OHDA)-induced change in locomotion in larval zebrafish, which has become a well-established PD disease model. Equimolar mixtures that each contained three cannabinoids were able to significantly reverse the OHDA mediated changes in locomotion and other advanced metrics of behavior. Additional screening of sixty-three variations of the original cannabinoid mixtures identified five highly efficacious mixtures that outperformed the original equimolar cannabinoid MEMs and represent the most attractive candidates for therapeutic development. This work highlights the strength of the reductionist approach for the development of ratio-controlled, cannabis mixture-based therapeutics for the treatment of Parkinson’s disease.

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Section: Discussionmentioning

confidence: 99%

Identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of Parkinson’s disease

et al. 2022

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“…A systematic search of the literature, conducted in June 2021 [ 55 ], presented five RCT and eighteen nonrandomized studies investigating cannabis treatments in PD patients. According to the authors, although no compelling evidence was found to recommend the use of cannabis in PD patients, a potential benefit was identified with respect to alleviation of PD-related tremor, anxiety, pain, improvement of sleep quality and quality of life.…”

Section: Cbd and Parkinson's Diseasementioning

confidence: 99%

Cannabis sativa and Cannabidiol: A Therapeutic Strategy for the Treatment of Neurodegenerative Diseases?

Viana

Aquino

Estadella

et al. 2022

Med Cannabis Cannabinoids

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This work is a literature review, presenting the current state of the use of cannabinoids on neurodegenerative diseases. The emphasis is on Parkinson’s (PD) and Alzheimer’s (AD) diseases, the two most prevalent neurological diseases. The review goes from Cannabis sativa and its hundreds of bioactive compounds to Δ9-tetrahydrocannabinol (THC) and mainly cannabidiol (CBD) and their interactions with the endocannabinoid receptors (CB1 and CB2). CBD molecular targets were also focused on to explain its neuroprotective action mechanism on neurodegenerative diseases. Although THC is the main psychoactive component of C. sativa, and it may induce transient psychosis-like symptoms, growing evidence suggests that CBD may have protective effects against the psychotomimetic effects of THC and therapeutic properties. Furthermore, a great number of recent works on the neuroprotective and anti-inflammatory CBD effects and its molecular targets are also reviewed. We analyzed CBD actions in preclinical and in clinical trials, conducted with PD and AD patients. Although the data on preclinical assays are more convincing, the same is not true with the clinical data. Despite the consensus among researchers on the potential of CBD as a neuroprotective agent, larger and well-designed randomized clinical trials will be necessary to gather conclusive results concerning the use of CBD as a therapeutic strategy for the treatment of diseases such as PD and AD.

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“…There are reports of motor and non-motor benefits in PD. But natural and synthetic cannabinoids have not shown significant effects in controlled clinical trials ( Thanabalasingam et al, 2021 ; Urbi et al, 2022 ), and there is insufficient evidence for cannabis products as adjunctive dopaminergic therapy.…”

Section: Cannabinoidsmentioning

confidence: 99%

Parkinson’s disease, dopaminergic drugs and the plant world

Kempster

2022

Front. Pharmacol.

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A large proportion of drugs used for the treatment of neurological disorders relate to naturally occurring compounds, many of which are plant alkaloids. This is particularly true of Parkinson’s disease (PD). The pharmacopoeia of PD has strong botanical origins, while major discoveries about the neurochemistry of the basal ganglia came from the study of phytochemicals. This article narrates the development of pharmacotherapy for PD in terms of historically important plant-derived substances—tropane and hamala alkaloids, reserpine, levodopa, apomorphine, and ergoline dopamine receptor agonists. Alkaloids are nitrogen-containing secondary metabolic products that tend to be biologically active. They appear to be involved in plants’ adaptation to herbivorous animals, though their exact purpose and the ways in which they work are uncertain. A sizable group of alkaloids influence animal dopaminergic systems, highlighting a key biological relationship. While animals must acquire the energy that plants harness, plants need to engage with the animal attribute that they lack—movement—in order to maximize their reproductive fitness. Neuroactive flowering plant compounds have been interacting with vertebrate and invertebrate motor systems for 100 million years. A deep evolutionary connection helps to explain why the pharmacological treatment of PD is imprinted with the power of these mysterious botanical chemicals.

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Effects of Cannabis in Parkinson’s Disease: A Systematic Review and Meta-Analysis

Cited by 30 publications

References 57 publications

Identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of Parkinson’s disease

Identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of Parkinson’s disease

<b><i>Cannabis sativa</i></b> and Cannabidiol: A Therapeutic Strategy for the Treatment of Neurodegenerative Diseases?

Parkinson’s disease, dopaminergic drugs and the plant world

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