Studies have demonstrated the neuroprotective effect of cannabidiol (CBD) and other Cannabis sativa L. derivatives on diseases of the central nervous system caused by their direct or indirect interaction with endocannabinoid system-related receptors and other molecular targets, such as the 5-HT1A receptor, which is a potential pharmacological target of CBD. Interestingly, CBD binding with the 5-HT1A receptor may be suitable for the treatment of epilepsies, parkinsonian syndromes and amyotrophic lateral sclerosis, in which the 5-HT1A serotonergic receptor plays a key role. The aim of this review was to provide an overview of cannabinoid effects on neurological disorders, such as epilepsy, multiple sclerosis and Parkinson's diseases, and discuss their possible mechanism of action, highlighting interactions with molecular targets and the potential neuroprotective effects of phytocannabinoids. CBD has been shown to have significant therapeutic effects on epilepsy and Parkinson's disease, while nabiximols contribute to a reduction in spasticity and are a frequent option for the treatment of multiple sclerosis. Although there are multiple theories on the therapeutic potential of cannabinoids for neurological disorders, substantially greater progress in the search for strong scientific evidence of their pharmacological effectiveness is needed.

Therapeutic applicability of cannabidiol and other phytocannabinoids in epilepsy, multiple sclerosis and Parkinson's disease and in comorbidity with psychiatric disorders.

Background While cannabis-based medicine is being commonly used in patients with movement disorders, there is a scarcity of publications regarding the effect of cannabis on dystonia. We aimed to describe medical cannabis use in patients with dystonia and related pain. Methods We employed a structured interview to obtain data on the cannabis treatment regimen, perception of effectiveness and side effect profile. Eligible participants were patients diagnosed with dystonia from the movement disorders unit at the Tel-Aviv Medical Center who had used licensed medical cannabis between January 2019 and January 2021. Results Twenty-three subjects were interviewed (11 women, mean age 52.7). The most common way of administration was smoking (n = 11). Following an average of 2.5 ± 2.9 years of use, those with widespread dystonia (generalized, hemi and multifocal, n = 11) self-reported on a numeric rating scale an average 63% (range 0%–100%) reduction in symptoms of dystonia, while those with more focal dystonia patterns reported a significantly lower treatment effect of 32%. Participants reported a positive impact in related pain and quality of life, with an average rating of 3.8 out of 5 (SD = 1.2, median = 4) and 3.6 out of 5 (SD = 1.15, median = 4), respectively. Most common side effects were dry mouth (65%), sedation (43%), dizziness (39%) and psychiatric disorders (26%). Three patients (13%) discontinued therapy. Conclusion A subset of dystonia patients who use medical cannabis under clinical observation reported significant subjective improvement during 30 months of use in average. Further prospective randomized controlled trials are required to examine the effectiveness of cannabis in dystonia.

/pdf/a-single-center-real-life-study-on-the-use-of-medical-tqpt27jv.pdf

A single-center real-life study on the use of medical cannabis in patients with dystonia

Dystonia is characterised as uncontrolled, often painful involuntary muscle contractions that cause abnormal postures and repetitive or twisting movements. These movements can be continuous or sporadic and affect different parts of the body and range in severity. Dystonia and its related conditions present a huge cause of neurological morbidity worldwide. Although therapies are available, achieving optimal symptom control without major unwanted effects remains a challenge. Most pharmacological treatments for dystonia aim to modulate the effects of one or more neurotransmitters in the central nervous system, but doing so effectively and with precision is far from straightforward. In this chapter we discuss the physiology of key neurotransmitters, including dopamine, noradrenaline, serotonin (5-hydroxytryptamine), acetylcholine, GABA, glutamate, adenosine and cannabinoids, and their role in dystonia. We explore the ways in which existing pharmaceuticals as well as novel agents, currently in clinical trial or preclinical development, target dystonia, and their respective advantages and disadvantages. Finally, we discuss current and emerging genetic therapies which may be used to treat genetic forms of dystonia. 

Advances in targeting neurotransmitter systems in dystonia

Neurodegenerative diseases have complex etiologies, however, neuroinflammation and oxidative stress are important markers in this pathogenesis and, in this sense, cannabinoids, especially CBD, have been identified as potential therapeutics for playing a neuroprotective role. Studies have demonstrated the neuroprotective effect of cannabinoids and derivatives of Cannabis sativa L in diseases of the central nervous system due to their interaction with the endocannabinoid system through receptors and other molecular targets. The aim of this review was to provide an overview of the endocannabinoid system and a summary of the clinical and preclinical findings of the therapeutic use of cannabinoids in epilepsy, multiple sclerosis and Parkinson’s disease, pointing out interactions with molecular targets and the potential for neuroprotection of CBD. Electronic searches were carried out in international databases, including studies that presented consistent data on this subject. Significant therapeutic effects of CBD were shown for epilepsy and Parkinson’s disease, while nabiximols contributed to the reduction of spasticity, being a frequent option for the treatment of multiple sclerosis. Although much has been projected on the therapeutic potential of cannabinoids for neurological disorders, there is a long way to go in the search for strong scientific evidence of their pharmacological effectiveness. 

A literature review on the therapeutic applicability of cannabidiol in epilepsy, multiple sclerosis and Parkinson's disease

Purpose The purpose of this study was to evaluate the safety and efficacy of low dose cannabidiol (CBD; Epidiolex) as adjunctive therapy for idiopathic adult-onset blepharospasm (BPS), as well as develop a novel objective assessment methodology to gauge response. Methods Prospective, randomized, double-masked, placebo-controlled crossover design of 6 months duration of 12 patients with BPS undergoing routine maximal botulinum toxin (BTX) therapy and experiencing breakthrough symptoms. Participants received their standard BTX every 3 months and were randomized to group A = CBD daily in cycle 1, followed by placebo in cycle 2 or group B = placebo followed by CBD. Videos recorded at days 0, 45, and 90 of each cycle were analyzed to quantify eyelid kinematics. The Jankovic Rating Scale (JRS) was used to provide a clinical rating. Results All 12 patients completed the study without adverse events. CBD decreased median eyelid closure amplitude by 19.1% (−1.66 mm, confidence interval [CI] = −3.19 to −0.14 mm, P = 0.03), decreased median eyelid closure duration by 15.8% (−18.35 ms, CI = −29.37 to −7.32 ms, P = 0.001), and increased the maximum eyelid closure velocity by 34.8% (−13.26 mm/ms, CI = −20.93 to −5.58 mm/ms, P = 0.001). The JRS showed a 0.5 reduction in severity and frequency, which was not statistically significant. Conclusions Low dose CBD was safely tolerated and improved several BPS kinematic parameters. The clinical scale suggested a direction of effect but may have been underpowered. Further studies are needed to better quantify the clinical relevance. Translational Relevance This work describes a novel assessment methodology and therapeutic approach to bBPS.

Cannabidiol as an Adjunct to Botulinum Toxin in Blepharospasm – A Randomized Pilot Study

Medical cannabis oil for benign essential blepharospasm: a prospective, randomized controlled pilot study

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Medical cannabis oil for benign essential blepharospasm: a prospective, randomized controlled pilot study