• CBD’s neuroprotective effects have been demonstrated in various significant clinical trials. Clinical findings indicate CBD’s pharmacological activity in managing clinical symptoms and slowing the progression of multiple neuropathological conditions(1).
  • CBD offers neuroprotective potential based on its anti-inflammatory, anxiolytic, and antioxidant properties. These properties are currently the focus of preclinical research in various neurodegenerative disorders(2).
  • Researches indicate that CBD has neuroprotective, anti-inflammatory properties. The combination of CBD and other cannabinoids may help reduce symptoms of medical conditions such as Parkinson’s and Alzheimer’s disease(3).
  • Rare disorders are diseases that affect fewer than 200,000 people in the United States(4). This definition is in the Orphan Drug Act of 1983, passed by the U.S Congress to motivate the development of drugs for rare diseases.

CBD for Rare Disorders

The neuroprotective properties of CBD (cannabidiol) are demonstrated in various clinical trials. CBD showed pharmacological activity in managing clinical symptoms and slowing the progression of different medical issues(5).

CBD offers neuroprotective potential based on its anti-inflammatory, anxiolytic, and antioxidant properties. These properties are currently the focus of preclinical research in various neurodegenerative disorders(6).

CBD, which constitutes up to 40% of the cannabis extract, may represent the most promising candidate for clinical utilization due to its remarkable lack of cognitive and psychoactive actions and its excellent tolerability profile in humans(7). 

Users may optimize the therapeutic effect of the CBD product using various delivery methods(8).

Inhalation of activated cannabinoid extracts requires producing a thick cloud of visible vapor, which allows onset of effect within 2 to 15 minutes. However, vaping raises the risk of respiratory symptoms, resulting in lung damage or lung irritation.

On the other hand, the sublingual delivery method of CBD oil is done by placing CBD oil drops under the tongue and on the cheeks. This administration takes effect after 5 to 30 minutes. The topical applications of CBD creams, oils, salves, balms, and sprays offer the same onset time.

Likewise, ingesting edibles or any CBD oil-infused food and drinks takes a more prolonged onset of action. Individuals usually feel the product’s effects after 30-90 minutes as food or beverages still have to pass through the stomach and the liver enzymes(9).

CBD offers several beneficial pharmacological effects. CBD could be used at high doses to treat psychiatric disorders such as schizophrenia, dementia, diabetes, and nausea(10). 

CBD has a broad range of biological activity, including antioxidant and anti-inflammatory properties. The compound is used in the prevention and treatment of diseases related to redox imbalance and inflammation has been examined.

Current research findings consider using CBD to treat diabetes, diabetes-related cardiomyopathy, cardiovascular diseases, cancer, arthritis, anxiety, psychosis, epilepsy, and neurodegenerative disease, including Alzheimer’s disease and skin disease(11). 

A CBD formulation is usually in oil format. CBD may also be sold as an extract, a vaporized liquid, and an oil-based capsule. 

CBD-infused products like balms, lotions, tinctures, patches, and edibles like gummies should be inspected for adverse effects on health and wellness.

CBD options are provided through the three types of CBD made available for users. 

The term full-spectrum or whole-plant often refers to a plant extract or product that contains all of the cannabinoids and other active substances contained in the plant from which it was derived(12).

This form contrasts with products containing only CBD or THC, referred to as isolates.

Cannabis or hemp flower is organically full spectrum. However, any extract-based product can be full-spectrum or whole-plant or isolate.

This product varies according to the extraction method and the amount of refinement applied to the extract(13).

The FDA (Food and Drug Administration) has only approved Epidiolex, a CBD product administered orally for rare and severe forms of epilepsy(14). 

Aside from Epidiolex, state restrictions on CBD differ, and research into the compound’s possible health benefits is ongoing.  


Benefits of CBD and What Rare Disorders CBD Can Treat

CBD, and all cannabinoids, work by interacting with the body’s endocannabinoid system (ECS). The ECS is an internal series of cannabinoid receptors located throughout the body that brings the body and its organs back into balance or homeostasis(15).

The ECS has millions of endocannabinoid receptors- CB1 receptors and CB2 receptors, located primarily within the brain cells, relay neurological signals across the body’s systems(16). 

Pharmaceutical-grade CBD compounds have demonstrated potential as anti-seizure, antipsychotic, neuroprotective, antidepressant, and anxiolytic medicines. The neuroprotective effect appears to result from the chemical compound’s purported anti-inflammatory and antioxidant properties(17). 

CBD received the unique designation as an orphan drug to treat autoimmune hepatitis, a rare disease that can cause liver fibrosis or cirrhosis, and even liver failure(18). 

Rare disorders are diseases or conditions afflicting less than 200,000 people in the United States(19). 

Clinical findings in neurology suggest that cannabidiol may be a viable therapeutic option as it inhibits hyperphosphorylation or signaling mechanisms used by the cell to regulate mitosis in the human chromosomes(20). 

When these mechanisms fail, developmental problems or cancer of tau protein in Abeta-stimulated PC12 neuronal cells may exist. Tau is connected with several neurodegenerative illnesses.

There is particularly compelling evidence in medical reviews to support CBD’s pro-cognitive effects in pathological conditions(21). 

Moreover, there is evidence that various therapeutic levels of beneficial terpenes and cannabinoids, such as pinene, linalool, and CBD, could present a unique opportunity to discover novel medicines that may offer potential benefits in psychiatric and neurological illnesses(22).

The entourage effect may imply that synergistic interactions with other phytochemicals may enhance CBD’s medicinal potential(23). As a result, various cannabis strains may provide better benefits for specific clinical conditions, opening up additional avenues for discovering novel individualized therapeutics for neurodegenerative disorders.

In Tauopathies

Tauopathies are neurodegenerative conditions that are identified pathologically by the presence of intracellular tau-positive inclusions and clinically by dementia and parkinsonism(24).

Alzheimer’s disease, Pick’s disease, dementia with Lewy bodies (DLB), Parkinson’s disease, frontotemporal dementia and its specific type, primary progressive aphasia (PPA), and Huntington’s disease are just a few of the dementia-related illnesses that CBD may help with(25).

Clinical studies indicated that the administration of cannabinoids such as CBD may help improve brain cell connections and modulate the expression of Alzheimer’s disease-related genes by regulating the actions of the tau gene(26). 

CBD may enhance health outcomes for people with neurodegenerative diseases, such as dementia, by potentially reducing neuroiflammation, protectant against neurotoxicity and slow down the neurodegenerative process(27). 

The U.S. Food and Drug Administration has not yet approved a CBD drug for the treatment of dementia. However, the agency has approved Epidiolex, a CBD-based drug for the treatment of epilepsy(28).

Alzheimer’s disease, vascular dementia, dementia with Lewy bodies (DLB), Parkinson’s disease, frontotemporal dementia, and Huntington’s disease are just a few of the dementia-related illnesses that CBD can aid with(29).

According to experts, cannabinoids such as CBD may help clear dementia from brain cells and strengthen neural connections(30).

CBD can enhance health outcomes for people with dementia in various ways: by reducing inflammation, decreasing oxygen accumulation, acting as a brain stimulant and neuroprotectant, and removing dead brain cells and protein tangles known to cause brain diseases such as dementia(31). 

CBD may increase movement and reduce tension and anxiety in those with dementia, and slow the decline of memory and other cognitive abilities(32).

In Multiple System Atrophy

MSA is a rare degenerative neurological condition that affects the body’s involuntary (autonomic) blood pressure, respiration, bladder function, and motor coordination(33). This rare nervous system disorder gradually destroys nerve cells in the brain.

This condition affects balance, movement, and the autonomic nerve system, regulating several fundamental activities, including breathing, digestion, and bladder control.

MSA symptoms typically begin between 50 and 60(34). However, MSA can develop at any age after 30. The symptoms may vary and include difficulties with muscle control, comparable to Parkinson’s disease.

Numerous bodily functions, including the urinary system, blood pressure management, and muscle movement, may also be impacted by this disorder. 

CBD possesses neuroprotective and neuroinflammatory properties(35). These benefits may potentially boost brain health and cognitive function. 

In Corticobasal Ganglionic Degeneration

According to the NINDS (National Institute of Neurological Disorders and Stroke) of the NIH (National Institutes of Health), corticobasal degeneration or cortical-basal ganglionic degeneration is a degenerative neurological condition marked by nerve cell death and atrophy (brain shrinkage) in several parts of the brain, including the cerebral cortex and basal ganglia(36). Corticobasal degeneration is progressive.

This condition is a pathologically defined entity associated with various clinical phenotypes(37). The most prevalent phenotype—corticobasal syndrome (CBS)—is marked by progressive dementia and often asymmetric parkinsonism. This condition is resistant to dopaminergic therapy, dystonia, limb apraxia, and myoclonus. 

However, these may occur due to a variety of other pathologic entities. The most characteristic is in frontotemporal degeneration spectrum disorders. Alzheimer’s disease and rare conditions such as CNS Whipple disease, Creutzfeldt–Jakob disease, and Niemann–Pick disease type C can also be associated.  

CBD combined with other cannabinoids, offers potential help with its neuroprotective, anti-inflammatory properties to reduce symptoms of this rare condition(38).

In Pyoderma Gangrenosum

PG (Pyoderma gangrenosum) is an inflammatory skin condition that manifests as small, red bumps or blisters (papules or nodules) that eventually disintegrate to produce swelling lesions and open sores (ulcerations)(39). 

These ulcerations vary significantly in size and depth and can develop, widen, and deepen, becoming extremely painful. Around 50% of the time, PG develops due to another ailment, such as inflammatory bowel disease(40).

CBD is being investigated as a novel analgesic strategy for wound-related pain. Topical medical cannabis has been shown to have the ability to enhance pain management in patients with all types of wounds(41). 

Clinical findings show a case series of individuals with pyoderma gangrenosum. Treatment with topical medical cannabis combined with nongenetically modified organic sunflower oil showed the potential to enhance pain management in individuals suffering from wounds of all classes(42).

Progressive Supranuclear Palsy

Progressive supranuclear palsy (PSP) is a rare disorder in the brain that causes problems with speech, swallowing, eye movements, behavior, and thinking(43). This condition results from damage to the nerve cells in the brain that control thinking, body movement, and other essential functions. 

Progressive supranuclear palsy is also called Steele-Richardson-Olszewski syndrome.

The most prevalent initial symptom of PSP is losing balance while walking. Individuals may have abrupt and unexplained falls without loss of consciousness, a stiff and awkward gait, or slow movement(44). As the disease progresses, most people will begin to develop a blurring of vision and problems controlling eye movement. 

Clinical findings showed how CBD/THC combination improved severely demented individuals regarding rigidity and behavioral problems(45). This new treatment might give hope to patients suffering from diseases with no available treatment, such as the coronavirus disease (COVID-19). Research on medical cannabis is still beginning but should be encouraged.

Alien Hand Syndrome

Alien hand syndrome is a neurological condition in which one hand is uncontrolled by the brain(46). The individual loses control of the hand, acting as if it has its mind. 

Neurosurgery, tumors, aneurysms, and stroke are all possible causes of this disorder. The term alien limb phenomenon refers to the involuntary motor activity associated with a sense of estrangement from that limb. The syndrome has been associated with corpus callosum surgery, brain tumors, aneurysms, degenerative brain illnesses, and, more rarely, stroke(47). 

Published findings from the Journal of Neurology (sometimes abbreviated as J.Neurol) show CBD benefits for movement disorders(48). CBD’s antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects are associated with CBD’s improvement of motor disorders. 

The beneficial neuroprotective profile of CBD is encouraging, and future investigations are needed to endorse these initial data and elucidate the mechanisms involved in the preventive and therapeutic potential of CBD in these rare conditions(49).

Risks and Side Effects of CBD for Rare Disorders

Drug metabolism via the CYP450 system (a group of isozymes that are involved in the biotransformation of various medicines) has been identified as a critical factor in the occurrence of a variety of drug interactions that can result in drug toxicity, decreased pharmacological impact, and adverse drug reactions(50). 

CBD tests demonstrate that the primary phytocannabinoids mostly inhibit CYPs, with cannabidiol as the most powerful inhibitor of many CYPs. The drug-drug interactions of cannabinoids with a variety of medicines at the CYP level are described, but their clinical significance remains unclear(51).  

The WHO (World Health Organization) indicated that CBD is generally well tolerated with a good safety profile(52). Adverse side effects of CBD may result from drug-drug interactions between CBD use and the individual’s existing medications.

Research has limited findings regarding the use, risks, and adverse effects of CBD in various medical conditions. Hence medical advice from a healthcare professional is recommended.

The Legality of CBD

CBD found in all cannabis plants is derived from either hemp or marijuana. However, CBD products are only federally legal if derived from hemp and contain less than 0.3 percent THC(53).

In 2018, the Farm Bill made hemp legal in the United States, removing all hemp-derived products from the Controlled Substances Act, including CBD. Cannabidiol from hemp is lawful, but not from cannabis, per this bill(54). 

The FDA has approved only one cannabis-derived product and three cannabis-related products. These FDA-approved medications are available only with a prescription from a licensed healthcare professional(55). 

What are Rare Disorders?

A rare disorder is defined as a disease that affects fewer than 200,000 people in the United States(56). This definition is indicated in the Orphan Drug Act of 1983, passed by the United States Congress to encourage entities to develop drugs for rare diseases. 

Rare diseases became known as orphan diseases due to drug companies’ lack of interest in developing treatments. The Orphan Drug Act established financial incentives to spur the development of new drugs for rare diseases(57).

Published reviews indicated that there could be up to 7,000 rare diseases in the United States. While these diseases may be rare, the total number of people who suffer from these diseases is estimated to be extensive(58).

What is Corticobasal Degeneration?

This condition is a rare progressive neurological disorder characterized by cell loss and deterioration of specific areas of the brain(59). Motor deficits begin in one limb which progressively spreads to all arms and legs. This disorder causes motor impairment and abnormalities such as muscle rigidity and the inability to perform deliberate or voluntary actions(60).

Corticobasal degeneration (CBD) is also known as corticobasal syndrome (CBS). This condition affects people between the ages 50 and 70. CBD, also known as CBS, is a rare disorder that causes progressive issues with movement, speech, memory, and swallowing(61).

A progressive abnormal buildup of tau protein in neurons and glia causes this syndrome. This action causes a rare neurodegenerative disease characterized by cell loss and degradation in specific brain lobes.

CBD’s symptoms progressively worsen over time and may include:

  • Muscle stiffness
  • Difficulty swallowing
  • Difficulty controlling the limbs on one side of the body 
  • Shaking (tremors), jerky movements, and spasms (dystonia)
  • Problems with balance and coordination
  • Slurred speech
  • Symptoms of dementia, such as memory and visual problems(62)

  1. Cannabidiol: A Promising Drug for Neurodegenerative Disorders? https://onlinelibrary.wiley.com/doi/10.1111/j.1755-5949.2008.00065.x
  2. Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579248/
  3. Current Aspects of the Endocannabinoid System and Targeted THC and CBD Phytocannabinoids as Potential Therapeutics for Parkinson’s and Alzheimer’s Diseases: a Review https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515854/
  4. Rare Diseases at FDA https://www.fda.gov/patients/rare-diseases-fda#whatisraredis
  5. Cannabidiol: A Promising Drug for Neurodegenerative Disorders? https://onlinelibrary.wiley.com/doi/10.1111/j.1755-5949.2008.00065.x
  6. Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579248/
  7. ibid
  8. Healing with CBD page 190 https://drive.google.com/file/d/1AGlxnhS2SoFeOXEuysv75bd_C9pEnwsU/view
  9. ibid p 191
  10. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. https://www.ncbi.nlm.nih.gov/books/NBK425767/
  11. Antioxidative and Anti-Inflammatory Properties of Cannabidiol https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023045/#
  12. Healing with CBD page 80 https://drive.google.com/file/d/1AGlxnhS2SoFeOXEuysv75bd_C9pEnwsU/view
  13. ibid
  14. What are the benefits of CBD — and is it safe to use?
    https://www.mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/is-cbd-safe-and-effective/faq-20446700#
  15. The Endocannabinoid System, Our Universal Regulator https://www.jyi.org/2018-june/2018/6/1/the-endocannabinoid-system-our-universal-regulator#:
  16. ibid
  17. Use of Cannabidiol in the Treatment of Epilepsy: Efficacy and Security in Clinical Trials
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514832/
  18. Research leads to potential treatment for rare disease https://www.sc.edu/uofsc/posts/2018/07/nagarkattis_research_autoimmune_hepatitis.php#.YnNaBtpBzIU
  19. Rare Diseases at FDA https://www.fda.gov/patients/rare-diseases-fda#whatisraredis
  20. The marijuana component cannabidiol inhibits beta-amyloid-induced tau protein hyperphosphorylation through Wnt/beta-catenin pathway rescue in PC12 cells https://pubmed.ncbi.nlm.nih.gov/16389547/
  21. The United Chemicals of Cannabis: Beneficial Effects of Cannabis Phytochemicals on the Brain and Cognition https://www.intechopen.com/chapters/62431
  22. A Review of the Potential Use of Pinene and Linalool as Terpene-Based Medicines for Brain Health: Discovering Novel Therapeutics in the Flavours and Fragrances of Cannabis
    https://pubmed.ncbi.nlm.nih.gov/34512404/
  23. ibid
  24. Tauopathies
    https://pubmed.ncbi.nlm.nih.gov/28987182/# :
  25. Using CBD (Cannabidiol) to Treat the Symptoms of Alzheimer’s & Other Dementias
    https://www.dementiacarecentral.com/aboutdementia/treating/cbd/
  26. Cannabidiol Modulates the Expression of Alzheimer’s Disease-Related Genes in Mesenchymal Stem Cells https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297661/
  27. Cannabinoids and Dementia: A Review of Clinical and Preclinical Data
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033945/
  28. FDA Approves New Indication for Drug Containing an Active Ingredient Derived from Cannabis to Treat Seizures in Rare Genetic Disease https://www.fda.gov/news-events/press-announcements/fda-approves-new-indication-drug-containing-active-ingredient-derived-cannabis-treat-seizures-rare
  29. Using CBD (Cannabidiol) to Treat the Symptoms of Alzheimer’s & Other Dementias https://www.dementiacarecentral.com/aboutdementia/treating/cbd/
  30. ibid
  31. ibid
  32. ibid
  33. Multiple system atrophy
    https://www.nhs.uk/conditions/multiple-system-atrophy/#
  34. ibid
  35. The United Chemicals of Cannabis: Beneficial Effects of Cannabis Phytochemicals on the Brain and Cognition
    https://www.intechopen.com/chapters/62431
  36. Corticobasal Degeneration Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Corticobasal-Degeneration-Information-Page#
  37. Corticobasal Syndrome and Corticobasal Degeneration https://emedicine.medscape.com/article/1150039-overview
  38. Current Aspects of the Endocannabinoid System and Targeted THC and CBD Phytocannabinoids as Potential Therapeutics for Parkinson’s and Alzheimer’s Diseases: a Review
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515854/
  39. Pyoderma gangrenosum https://www.mayoclinic.org/diseases-conditions/pyoderma-gangrenosum/symptoms-causes/syc-20350386#
  40. Pyoderma Gangrenosum https://rarediseases.org/rare-diseases/pyoderma-gangrenosum/#:
  41. Topical Medical Cannabis: A New Treatment for Wound Pain-Three Cases of Pyoderma Gangrenosum
    https://pubmed.ncbi.nlm.nih.gov/28818631/
  42. ibid
  43. Progressive supranuclear palsy https://www.mayoclinic.org/diseases-conditions/progressive-supranuclear-palsy/symptoms-causes/syc-20355659
  44. Progressive Supranuclear Palsy Fact Sheet https://www.ninds.nih.gov/health-information/patient-caregiver-education/fact-sheets/progressive-supranuclear-palsy-fact-sheet#:
  45. Neurological Improvement with Medical Cannabis in a Progressive Supranuclear Palsy Patient: A Case Report https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489313/
  46. The alien limb phenomenon https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059570/
  47. The alien hand syndrome https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059570/
  48. Cannabidiol as a Promising Strategy to Treat and Prevent Movement Disorders? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958190/
  49. ibid
  50. Drug interactions due to cytochrome P450 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1312247/
  51. Cannabinoids and Cytochrome P450 Interactions https://pubmed.ncbi.nlm.nih.gov/26651971/
  52. World Health Organization Reports CBD Oil Is Generally Safe https://www.rtor.org/2019/07/05/who-report-on-cbd-oil/#
  53. Cannabidiol (CBD)-what we know and what we don’t https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-we-dont-2018082414476
  54. ibid
  55. What are the benefits of CBD — and is it safe to use?
    https://www.mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/is-cbd-safe-and-effective/faq-20446700#
  56. Rare Diseases at FDA https://www.fda.gov/patients/rare-diseases-fda#whatisraredis
  57. FAQs About Rare Diseases https://rarediseases.info.nih.gov/diseases/pages/31/faqs-about-rare-diseases
  58. ibid
  59. Corticobasal Degeneration https://rarediseases.org/rare-diseases/corticobasal-degeneration/
  60. Corticobasal degeneration https://www.nhs.uk/conditions/corticobasal-degeneration/
  61. ibid
  62. ibid
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