cannabidiol and Parkinson-Disease

Topics: Cannabidiol; Cannabinoids; Cannabis; Drug-Related Side Effects and Adverse Reactions; Hallucinogens; Humans; Parkinson Disease

The aberrant accumulation of disease-specific protein aggregates accompanying cognitive decline is a pathological hallmark of age-associated neurological disorders, also termed as proteinopathies, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and multiple sclerosis. Along with oxidative stress and neuroinflammation, disruption in protein homeostasis (proteostasis), a network that constitutes protein surveillance system, plays a pivotal role in the pathobiology of these dementia disorders. Cannabidiol (CBD), a non-psychotropic phytocannabinoid of Cannabis sativa, is known for its pleiotropic neuropharmacological effects on the central nervous system, including the ability to abate oxidative stress, neuroinflammation, and protein misfolding. Over the past years, compelling evidence has documented disease-modifying role of CBD in various preclinical and clinical models of neurological disorders, suggesting the potential therapeutic implications of CBD in these disorders. Because of its putative role in the proteostasis network in particular, CBD could be a potent modulator for reversing not only age-associated neurodegeneration but also other protein misfolding disorders. However, the current understanding is insufficient to underpin this proposition. In this review, we discuss the potentiality of CBD as a pharmacological modulator of the proteostasis network, highlighting its neuroprotective and aggregates clearing roles in the neurodegenerative disorders. We anticipate that the current effort will advance our knowledge on the implication of CBD in proteostasis network, opening up a new therapeutic window for aging proteinopathies.

Topics: Cannabidiol; Humans; Neurodegenerative Diseases; Parkinson Disease; Proteostasis; Proteostasis Deficiencies

Parkinson's disease (PD) is a major neurodegenerative disease (ND), presenting a progressive degeneration of the nervous system characterized by a loss of dopamine in the substantia nigra pars compacta. Recent findings have shown that oxidative stress and inflammation play key roles in the development of PD. However, therapies remain uncertain and research for new treatment is of the utmost importance. This review focuses on the potential effects of using cannabidiol (CBD) as a potential therapeutic strategy for the treatment of PD and on some of the presumed mechanisms by which CBD provides its beneficial properties. CBD medication downregulates GSK-3β, the main inhibitor of the WNT/β-catenin pathway. Activation of the WNT/β-catenin could be associated with the control of oxidative stress and inflammation. Future prospective clinical trials should focus on CBD and its multiple interactions in the treatment of PD.

Topics: Animals; Cannabidiol; Dopaminergic Neurons; Humans; Inflammation; International Cooperation; Neuroprotective Agents; Oxidative Stress; Parkinson Disease; Wnt Signaling Pathway

Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID) are motor disorders with significant impact on the patient's quality of life. Unfortunately, pharmacological treatments that improve these disorders without causing severe side effects are not yet available. Delay in initiating L-DOPA is no longer recommended as LID development is a function of disease duration rather than cumulative L-DOPA exposure. Manipulation of the endocannabinoid system could be a promising therapy to control PD and LID symptoms. In this way, phytocannabinoids and synthetic cannabinoids, such as cannabidiol (CBD), the principal non-psychotomimetic constituent of the Cannabis sativa plant, have received considerable attention in the last decade. In this review, we present clinical and preclinical evidence suggesting CBD and other cannabinoids have therapeutic effects in PD and LID. Here, we discuss CBD pharmacology, as well as its neuroprotective effects and those of other cannabinoids. Finally, we discuss the modulation of several pro- or anti-inflammatory factors as possible mechanisms responsible for the therapeutic/neuroprotective potential of Cannabis-derived/cannabinoid synthetic compounds in motor disorders.

Topics: Animals; Cannabidiol; Cannabinoids; Dyskinesia, Drug-Induced; Humans; Levodopa; Neuroprotective Agents; Parkinson Disease

Neurodegeneration leading to Parkinson's disease (PD) and Alzheimer's disease (AD) has become a major health burden globally. Current treatments mainly target controlling symptoms and there are no therapeutics available in clinical practice to preventing the neurodegeneration or inducing neuronal repairing. Thus, the demand of novel research for the two disorders is imperative. This literature review aims to provide a collection of published work on PD and AD and current uses of endocannabinoid system (ECS) as a potential drug target for neurodegeneration. PD is frequently treated with L-DOPA and deep brain stimulation. Recent gene modification and remodelling techniques, such as CRISPR through human embryonic stem cells and induced pluripotent stem cells, have shown promising strategy for personalised medicine. AD characterised by extracellular deposits of amyloid β-senile plaques and neurofibrillary tangles of tau protein commonly uses choline acetyltransferase enhancers as therapeutics. The ECS is currently being studied as PD and AD drug targets where overexpression of ECS receptors exerted neuroprotection against PD and reduced neuroinflammation in AD. The delta-9-tetrahydrocannabinoid (Δ

Topics: Alzheimer Disease; Animals; Cannabidiol; Dronabinol; Endocannabinoids; Humans; Inflammation; Parkinson Disease

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.

Topics: Cannabidiol; Cannabinoid Receptor Modulators; Humans; Neuroprotective Agents; Parkinson Disease

Topics: Animals; Anxiety; Brazil; Cannabidiol; Cannabis; Clinical Trials as Topic; Epilepsy; Humans; Neuroprotective Agents; Parkinson Disease; Psychotic Disorders; Translational Research, Biomedical

Neurodegenerative diseases represent, nowadays, one of the main causes of death in the industrialized country. They are characterized by a loss of neurons in particular regions of the nervous system. It is believed that this nerve cell loss underlies the subsequent decline in cognitive and motor function that patients experience in these diseases. A range of mutant genes and environmental toxins have been implicated in the cause of neurodegenerative disorders but the mechanism remains largely unknown. At present, inflammation, a common denominator among the diverse list of neurodegenerative diseases, has been implicated as a critical mechanism that is responsible for the progressive nature of neurodegeneration. Since, at present, there are few therapies for the wide range of neurodegenerative diseases, scientists are still in search of new therapeutic approaches to the problem. An early contribution of neuroprotective and antiinflammatory strategies for these disorders seems particularly desirable because isolated treatments cannot be effective. In this contest, marijuana derivatives have attracted special interest, although these compounds have always raised several practical and ethical problems for their potential abuse. Nevertheless, among Cannabis compounds, cannabidiol (CBD), which lacks any unwanted psychotropic effect, may represent a very promising agent with the highest prospect for therapeutic use.

Topics: Alzheimer Disease; Animals; Cannabidiol; Cytoprotection; Disease Models, Animal; Humans; Huntington Disease; Multiple Sclerosis; Neurodegenerative Diseases; Neuroprotective Agents; Parkinson Disease; Prion Diseases

The aim of this review is to describe the historical development of research on cannabidiol.. This review was carried out on reports drawn from Medline, Web of Science and SciELO.. After the elucidation of the chemical structure of cannabidiol in 1963, the initial studies showed that cannabidiol was unable to mimic the effects of Cannabis. In the 1970's the number of publications on cannabidiol reached a first peak, having the research focused mainly on the interaction with delta9-THC and its antiepileptic and sedative effects. The following two decades showed lower degree of interest, and the potential therapeutic properties of cannabidiol investigated were mainly the anxiolytic, antipsychotic and on motor diseases effects. The last five years have shown a remarkable increase in publications on cannabidiol mainly stimulated by the discovery of its anti-inflammatory, anti-oxidative and neuroprotective effects. These studies have suggested a wide range of possible therapeutic effects of cannabidiol on several conditions, including Parkinson's disease, Alzheimer's disease, cerebral ischemia, diabetes, rheumatoid arthritis, other inflammatory diseases, nausea and cancer.. In the last 45 years it has been possible to demonstrate that CBD has a wide range of pharmacological effects, many of which being of great therapeutic interest, but still waiting to be confirmed by clinical trials.

Topics: Anti-Anxiety Agents; Anti-Inflammatory Agents; Antiemetics; Antineoplastic Agents; Antioxidants; Antipsychotic Agents; Biomedical Research; Cannabidiol; Cannabis; Diabetes Mellitus; Humans; Mental Disorders; Neuroprotective Agents; Parkinson Disease; Schizophrenia

Cannabis is increasingly available worldwide but its impact on cognition in Parkinson's disease (PD) is unknown.. Present cognitive safety data from study of an oral high-dose cannabidiol (CBD; 100 mg) and low-dose Δ9-tetrahydocannabinol (THC; 3.3 mg) drug in PD.. Randomized, double-blind, parallel-group, placebo-controlled study of a CBD/THC drug administered for 16.3 (SD: 4.2) days, with dosage escalating to twice per day. Neuropsychological tests were administered at baseline and 1-1½ hours after final dose; scores were analyzed with longitudinal regression models (alpha = 0.05). Cognitive adverse events were collected.. When adjusted for age and education, the CBD/THC group (n = 29) performed worse than the placebo group (n = 29) on Animal Verbal Fluency. Adverse cognitive events were reported at least twice as often by the CBD/THC than the placebo group.. Data suggest this CBD/THC drug has a small detrimental effect on cognition following acute/short-term use in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Topics: Cannabidiol; Cannabis; Cognition; Double-Blind Method; Dronabinol; Parkinson Disease

REM sleep behaviour disorder (RBD) is a common non-motor feature of Parkinson's disease (PD). Cannabidiol (CBD) is one of the main non-psychoactive components of Cannabis sativa and may represent an alternative route for treating RBD.. This study assessed the efficacy and safety of CBD for RBD in PD.. We conducted a phase II/III, double-blind, placebo-controlled clinical trial in 33 patients with RBD and PD. Patients were randomized 1:1 to CBD in doses of 75 to 300mg or matched capsules placebo and were followed up for 14 weeks. The primary outcomes were the frequency of nights with RBD, CGI-I, and CGI-S.. CBD showed no difference to placebo for primary outcomes. Regarding secondary outcomes, we observed a significant improvement in average sleep satisfaction from the 4th to 8th week in the CBD versus placebo group with P = 0.049 and P = 0.038, respectively.. CBD, as an adjunct therapy, showed no reduction in RBD manifestations in PD patients. A transient improvement in sleep satisfaction with a dose of 300mg has been noted. © 2021 International Parkinson and Movement Disorder Society.

Topics: Cannabidiol; Humans; Parkinson Disease; REM Sleep Behavior Disorder

Cannabidiol (CBD) is one of the main components of. A randomised, double-blinded, placebo-controlled, crossover clinical trial was conducted. A total of 24 individuals with PD were included and underwent two experimental sessions within a 15-day interval. After taking CBD or a placebo, participants underwent the SPST. During the test, the following data were collected: heart rate, systemic blood pressure and tremor frequency and amplitude. In addition, the Visual Analog Mood Scales (VAMS) and Self-Statements during Public Speaking Scale were applied. Statistical analysis was performed by repeated-measures analysis of variance (ANOVA) while considering the drug, SPST phase and interactions between these variables.. There were statistically significant differences in the VAMS anxiety factor for the drug; CBD attenuated the anxiety experimentally induced by the SPST. Repeated-measures ANOVA showed significant differences in the drug for the variable related to tremor amplitude as recorded by the accelerometer.. Acute CBD administration at a dose of 300 mg decreased anxiety in patients with PD, and there was also decreased tremor amplitude in an anxiogenic situation.

Topics: Aged; Anxiety; Blood Pressure; Cannabidiol; Cross-Over Studies; Double-Blind Method; Female; Heart Rate; Humans; Male; Middle Aged; Parkinson Disease; Self Report; Speech; Treatment Outcome; Tremor

Parkinson's disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no neuroprotective treatments for PD have been found to date, the endocannabinoid system has emerged as a promising target.. From a sample of 119 patients consecutively evaluated in a specialized movement disorders outpatient clinic, we selected 21 PD patients without dementia or comorbid psychiatric conditions. Participants were assigned to three groups of seven subjects each who were treated with placebo, cannabidiol (CBD) 75 mg/day or CBD 300 mg/day. One week before the trial and in the last week of treatment participants were assessed in respect to (i) motor and general symptoms score (UPDRS); (ii) well-being and quality of life (PDQ-39); and (iii) possible neuroprotective effects (BDNF and H(1)-MRS).. We found no statistically significant differences in UPDRS scores, plasma BDNF levels or H(1)-MRS measures. However, the groups treated with placebo and CBD 300 mg/day had significantly different mean total scores in the PDQ-39 (p = 0.05).. Our findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities; however, studies with larger samples and specific objectives are required before definitive conclusions can be drawn.

Topics: Aged; Aged, 80 and over; Aspartic Acid; Brain-Derived Neurotrophic Factor; Cannabidiol; Creatine; Double-Blind Method; Female; Humans; Male; Middle Aged; Neuroprotective Agents; Parkinson Disease; Proton Magnetic Resonance Spectroscopy; Putamen; Quality of Life; Severity of Illness Index; Treatment Outcome

Progressive neurodegenerative disorders such as Parkinson Disease (PD) lack curative or long-term treatments. At the same time, the increase of the worldwide elderly population and, consequently, the extension in the prevalence of age-related diseases have promoted research interest in neurodegenerative disorders. Caenorhabditis elegans is a free-living nematode widely used as an animal model in studies of human diseases. Here we evaluated cannabidiol (CBD) as a possible neuroprotective compound in PD using the C. elegans models exposed to reserpine. Our results demonstrated that CBD reversed the reserpine-induced locomotor alterations and this response was independent of the NPR-19 receptors, an orthologous receptor for central cannabinoid receptor type 1. Morphological alterations of cephalic sensilla (CEP) dopaminergic neurons indicated that CBD also protects neurons from reserpine-induced degeneration. That is, CBD attenuates the reserpine-induced increase of worms with shrunken soma and dendrites loss, increasing the number of worms with intact CEP neurons. Finally, we found that CBD also reduced ROS formation and α-syn protein accumulation in mutant worms. Our findings collectively provide new evidence that CBD acts as neuroprotector in dopaminergic neurons, reducing neurotoxicity and α-syn accumulation highlighting its potential in the treatment of PD.

Topics: Aged; alpha-Synuclein; Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cannabidiol; Disease Models, Animal; Dopaminergic Neurons; Humans; Neurodegenerative Diseases; Neuroprotective Agents; Parkinson Disease; Receptors, G-Protein-Coupled; Reserpine

Parkinson's disease (PD) is a complex and multifactorial neurodegenerative disease. The main pathological feature of PD is the loss or apoptosis of dopaminergic neurons in the substantia nigra (SN). This study aimed to investigate the protective effect of cannabidiol (CBD) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal dopamine injury by inhibiting neuroinflammation, which was one of the factors that cause neuronal apoptosis. Male SPF C57BL/6 mice were used to create a PD model by administering MPTP intraperitoneally for seven days and treated by oral administration of CBD for 14 days. Behaviorally, CBD improved cognitive dysfunction and increased the number of spontaneous locomotion in PD mice. Biochemically, CBD increased the levels of 5-HT, DA and IL-10, and decreased the contents of TNF-α, IL-1β and IL-6. Pathologically, CBD increased the expression of tyrosine hydroxylase (TH). Mechanistically, CBD up-regulated the expression of Bcl-2, down-regulated the levels of Bax and Caspase-3, and repressed the expression of NLRP3/caspase-1/IL-1β inflammasome pathway. In summary, CBD has a therapeutic effect on MPTP-induced PD mice by inhibiting the apoptosis of dopaminergic neurons and neuroinflammation. Therefore, CBD is a potential candidate for PD therapy.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Apoptosis; Cannabidiol; Disease Models, Animal; Dopaminergic Neurons; Male; Mice; Mice, Inbred C57BL; Neurodegenerative Diseases; Neuroinflammatory Diseases; Neuroprotective Agents; Parkinson Disease; Pyrrolidines; Substantia Nigra

Parkinson disease (PD) is the second most progressive neurodegenerative disorder of the central nervous system (CNS) in the elderly, causing motor impediments and cognitive dysfunctions. Dopaminergic (DA) neuron degeneration and α-synuclein (α-Syn) accumulation in substantia nigra pars compacta (SNPc) are the major contributor to this disease. At present, the disease has no effective treatment. Many recent studies focus on identifying novel therapeutics that provide benefits to stop disease advancement in PD patients. Cannabidiol (CBD) is a cannabinoid derived from the Cannabis sativa plant and possesses anti-depressive, anti-inflammatory, and antioxidative effects. The present study aims to evaluate the neuroprotective effect of CBD in transgenic C. elegans PD models. We observed that CBD at 0.025 mM (24.66 %), 0.05 mM (52.41 %) and 0.1 mM (71.36 %) diminished DA neuron degenerations induced by 6-hydroxydopamine (6-OHDA), reduced (0.025, 27.1 %), (0.05, 38.9 %), (0.1, 51.3 %) food-sensing behavioural disabilities in BZ555, reduced 40.6 %, 56.3 %, 70.2 % the aggregative toxicity of α-Syn and expanded the nematodes' lifespan up to 11.5 %, 23.1 %, 28.8 %, dose-dependently. Moreover, CBD augmented the ubiquitin-like proteasomes 28.11 %, 43.27, 61.33 % and SOD-3 expressions by about 16.4 %, 21.2 %, 44.8 % in transgenic models. Further, we observed the antioxidative role of CBD by reducing 33.2 %, 41.4 %, 56.7 % reactive oxygen species in 6-OHDA intoxicated worms. Together, these findings supported CBD as an anti-parkinsonian drug and may exert its effects by raising lipid depositions to enhance proteasome activity and reduce oxidative stress via the antioxidative pathway.

Topics: alpha-Synuclein; Animals; Antioxidants; Caenorhabditis elegans; Cannabidiol; Disease Models, Animal; Dopamine; Dopaminergic Neurons; Neuroprotective Agents; Oxidopamine; Parkinson Disease

Little is known about the patients' view on treatment with medical cannabis (MC) for Parkinson's disease (PD).. To assess the PD community's perception of MC and patients' experience with MC.. Applying a questionnaire-based survey, we evaluated general knowledge and interest in MC as well as the frequency, modalities, efficacy, and tolerability of application. Questionnaires were distributed nationwide via the membership journal of the German Parkinson Association and locally in our clinic to control for report bias.. Overall, 1.348 questionnaires (1.123 nationwide, 225 local) were analysed. 51% of participants were aware of the legality of MC application, 28% of various routes of administration (ROA) and 9% of the difference between delta9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). PD-related cannabis use was reported by 8.4% of patients and associated with younger age, living in large cities and better knowledge about the legal and clinical aspects of MC. Reduction of pain and muscle cramps was reported by more than 40% of cannabis users. Stiffness/akinesia, freezing, tremor, depression, anxiety and restless legs syndrome subjectively improved for more than 20% and overall tolerability was good. Improvement of symptoms was reported by 54% of users applying oral CBD and 68% inhaling THC-containing cannabis. Compared to CBD intake, inhalation of THC was more frequently reported to reduce akinesia and stiffness (50.0% vs. 35.4%; p < 0.05). Interest in using MC was reported by 65% of non-users.. MC is considered as a therapeutic option by many PD patients. Nevertheless, efficacy and different ROA should further be investigated.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Cannabidiol; Cannabinoid Receptor Modulators; Dronabinol; Female; Health Knowledge, Attitudes, Practice; Health Surveys; Humans; Male; Medical Marijuana; Middle Aged; Outcome Assessment, Health Care; Parkinson Disease; Patient Acceptance of Health Care; Patient Preference; Urban Population

The 3-hydroxyquinone derivative of the non-psychotrophic phytocannabinoid cannabigerol, so-called VCE-003.2, and some other derivatives have been recently investigated for neuroprotective properties in experimental models of Parkinson's disease (PD) in mice. The pharmacological effects in those models were related to the activity on the peroxisome proliferator-activated receptor-γ (PPAR-γ) and possibly other pathways. In the present study, we investigated VCE-004.8 (formulated as EHP-101 for oral administration), the 3-hydroxyquinone derivative of cannabidiol (CBD), with agonist activity at the cannabinoid receptor type-2 (CB

Topics: Administration, Oral; Animals; Benzamides; Camphanes; Cannabidiol; Cannabinoids; Cell Line, Tumor; Cell Survival; Disease Models, Animal; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Neurons; Neuroprotection; Oxidopamine; Parkinson Disease; PPAR gamma; Pyrazoles; Pyridines; Quinones; Tyrosine 3-Monooxygenase

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia Nigra pars compacta, leading to classical PD motor symptoms. Current therapies are purely symptomatic and do not modify disease progression. Cannabidiol (CBD), one of the main phytocannabinoids identified in Cannabis Sativa, which exhibits a large spectrum of therapeutic properties, including anti-inflammatory and antioxidant effects, suggesting its potential as disease-modifying agent for PD. The aim of this study was to evaluate the effects of chronic treatment with CBD (10 mg/kg, i.p.) on PD-associated neurodegenerative and neuroinflammatory processes, and motor deficits in the 6-hydroxydopamine model. Moreover, we investigated the potential mechanisms by which CBD exerted its effects in this model. CBD-treated animals showed a reduction of nigrostriatal degeneration accompanied by a damping of the neuroinflammatory response and an improvement of motor performance. In particular, CBD exhibits a preferential action on astrocytes and activates the astrocytic transient receptor potential vanilloid 1 (TRPV1), thus, enhancing the endogenous neuroprotective response of ciliary neurotrophic factor (CNTF). These results overall support the potential therapeutic utility of CBD in PD, as both neuroprotective and symptomatic agent.

Topics: Animals; Anticonvulsants; Behavior, Animal; Cannabidiol; Ciliary Neurotrophic Factor; Disease Models, Animal; Dopaminergic Neurons; Male; Neuroprotective Agents; Parkinson Disease; Rats; Rats, Sprague-Dawley; TRPV Cation Channels

Medications that improve pain threshold can be useful in the pharmacotherapy of Parkinson's disease (PD). Pain is a prevalent PD's non-motor symptom with a higher prevalence of analgesic drugs prescription for patients. However, specific therapy for PD-related pain are not available. Since the endocannabinoid system is expressed extensively in different levels of pain pathway, drugs designed to target this system have promising therapeutic potential in the modulation of pain. Thus, we examined the effects of the 6-hydroxydopamine- induced PD on nociceptive responses of mice and the influence of cannabidiol (CBD) on 6-hydroxydopamine-induced nociception. Further, we investigated the pathway involved in the analgesic effect of the CBD through the co-administration with a fatty acid amide hydrolase (FAAH) inhibitor, increasing the endogenous anandamide levels, and possible targets from anandamide, i.e., the cannabinoid receptors subtype 1 and 2 (CB1 and CB2) and the transient receptor potential vanilloid type 1 (TRPV1). We report that 6-hydroxydopamine- induced parkinsonism decreases the thermal and mechanical nociceptive threshold, whereas CBD (acute and chronic treatment) reduces this hyperalgesia and allodynia evoked by 6-hydroxydopamine. Moreover, ineffective doses of either FAAH inhibitor or TRPV1 receptor antagonist potentialized the CBD-evoked antinociception while an inverse agonist of the CB1 and CB2 receptor prevented the antinociceptive effect of the CBD. Altogether, these results indicate that CBD can be a useful drug to prevent the parkinsonism-induced nociceptive threshold reduction. They also suggest that CB1 and TRPV1 receptors are important for CBD-induced analgesia and that CBD could produce these analgesic effects increasing endogenous anandamide levels.

Topics: Amidohydrolases; Analgesics; Animals; Benzamides; Brain; Cannabidiol; Capsaicin; Carbamates; Celecoxib; Hyperalgesia; Male; Mice; Mice, Inbred C57BL; Morphine; Nociception; Oxidopamine; Pain; Parkinson Disease; Piperidines; Pyrazoles; Thienamycins

Topics: Antiparkinson Agents; Cannabidiol; Humans; Parkinson Disease; Treatment Outcome

Topics: Apathy; Autonomic Nervous System Diseases; Cannabidiol; Cannabinoid Receptor Modulators; Humans; Mood Disorders; Parkinson Disease; Sleep Wake Disorders

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. We searched MEDLINE (via PubMed) for indexed articles published in English from inception to 2019. The following keywords were used: cannabis; cannabidiol and neuroprotection; endocannabinoids and basal ganglia; Parkinson's animal models; Parkinson's history; Parkinson's and cannabidiol. 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. Additional research is needed to elucidate the potential effectiveness of CBD in PD and the underlying mechanisms involved.

Topics: Animals; Cannabidiol; Clinical Studies as Topic; Disease Models, Animal; Humans; Neuroprotective Agents; Parkinson Disease

Consumer demand for cannabidiol (CBD) oil has increased, with growing sales from dispensaries because of the alleged medicinal benefits. Although studies examining the specific therapeutic effects of CBD are increasing, clinical data do not support the popular uses of CBD for Parkinson disease, schizophrenia, cancer palliation and treatment, chronic pain and spasticity, depression, anxiety disorder, insomnia, and inflammation.

Topics: Anxiety; Cannabidiol; Depression; Humans; Information Services; Pain Management; Parkinson Disease; Sleep Initiation and Maintenance Disorders

Cannabidiol (CBD) is a non-psychoactive constituent of Cannabis sativa with potential to treat neurodegenerative diseases. Its neuroprotection has been mainly associated with anti-inflammatory and antioxidant events; however, other mechanisms might be involved. We investigated the involvement of neuritogenesis, NGF receptors (trkA), NGF, and neuronal proteins in the mechanism of neuroprotection of CBD against MPP(+) toxicity in PC12 cells. CBD increased cell viability, differentiation, and the expression of axonal (GAP-43) and synaptic (synaptophysin and synapsin I) proteins. Its neuritogenic effect was not dependent or additive to NGF, but it was inhibited by K252a (trkA inhibitor). CBD did not increase the expression of NGF, but protected against its decrease induced by MPP(+), probably by an indirect mechanism. We also evaluated the neuritogenesis in SH-SY5Y cells, which do not express trkA receptors. CBD did not induce neuritogenesis in this cellular model, which supports the involvement of trkA receptors. This is the first study to report the involvement of neuronal proteins and trkA in the neuroprotection of CBD. Our findings suggest that CBD has a neurorestorative potential independent of NGF that might contribute to its neuroprotection against MPP(+), a neurotoxin relevant to Parkinson's disease.

Topics: 1-Methyl-4-phenylpyridinium; Animals; Axons; Cannabidiol; Humans; Nerve Growth Factor; Nerve Tissue Proteins; Neurites; Neuroblastoma; Neuroprotective Agents; Parkinson Disease; PC12 Cells; Rats; Receptor, trkA; Synapses; Up-Regulation

Cannabidiol (CBD) is the main non-psychotropic component of the Cannabis sativa plant. REM sleep behaviour disorder (RBD) is a parasomnia characterized by the loss of muscle atonia during REM sleep associated with nightmares and active behaviour during dreaming. We have described the effects of CBD in RBD symptoms in patients with Parkinson's disease.. Four patients treated with CBD had prompt and substantial reduction in the frequency of RBD-related events without side effects.. This case series indicates that CBD is able to control the symptoms of RBD.

Topics: Aged; Cannabidiol; Cannabis; Humans; Male; Middle Aged; Parkinson Disease; Phytotherapy; REM Sleep Behavior Disorder

The management of psychosis in Parkinson's disease (PD) has been considered a great challenge for clinicians and there is a need for new pharmacological intervention. Previously an antipsychotic and neuroprotective effect of Cannabidiol (CBD) has been suggested. Therefore, the aim of the present study was to directly evaluate for the first time, the efficacy, tolerability and safety of CBD on PD patients with psychotic symptoms. This was an open-label pilot study. Six consecutive outpatients (four men and two women) with the diagnosis of PD and who had psychosis for at least 3 months were selected for the study. All patients received CBD in flexible dose (started with an oral dose of 150 mg/day) for 4 weeks, in addition to their usual therapy. The psychotic symptoms evaluated by the Brief Psychiatric Rating Scale and the Parkinson Psychosis Questionnaire showed a significant decrease under CBD treatment. CBD did not worsen the motor function and decreased the total scores of the Unified Parkinson's Disease Rating Scale. No adverse effect was observed during the treatment. These preliminary data suggest that CBD may be effective, safe and well tolerated for the treatment of the psychosis in PD.

Topics: Adult; Aged; Cannabidiol; Female; Humans; Male; Middle Aged; Parkinson Disease; Pilot Projects; Psychotic Disorders