Alzheimer and Parkinson

Would you consider CBD for neurodegenerative diseases?
Introduction and Statistics of each disease
•Both Alzheimers (AD) and Parkinsons (PD) are Neurodegenerative diseases
•Cognitive decline is common in both AD and PD
Behavioral Symptoms of both diseases include: Depression, Anxiety, Psychotic events, and sleep disturbances
•Cannabis contains antioxidants, vitamins, neuroprotectants,, minerals, ligands, terpenes
•Both diseases decrease the quality of life
Cannabinoid receptors( CB1 and CB2) react with endogenous receptors in the body to create homeostasis (balance)
•Cannabis can help benefit the ECS, AD and PD
•Cannabis can relieve symptoms of AD and PD
•There are minimal risks associated with cannabis
•Cannabis can work in the body to protect the brain, fight cancer, slow aging, reduce pain and inflammation
•Modern scientific research supports the robust antioxidant and neuroprotective properties of CBD and THC in the treatment of neurodegenerative diseases, such as Alzheimers disease, Parkinsons disease, and dementia
•Various combinations of CBD, THC, and THCV may provide relief for Parkinsons
  • Both CBD and THC are nature’s alternatives to traditional medications
  • Traditional medications may become less effective over time or stop working altogether
  • Studies show that CBD, a Cannabidiol, also referred to as ”CBD-rich cannabis”, may relieve debilitating symptoms of Parkinsons
  • CBD is a natural compound found in cannabis Sativa plants, with very few of the adverse side effects of prescription medications
  • CBD will not give you a high
  • THC will give you a ”high” effect
  • Natural medications are becoming more and more accessible for persons suffering from the effects of Parkinsons disease
  • While traditional medications may become less effective over time, or stop working altogether, CBD users are noting long-term benefits as opposed to prescription meds
  • Both have been shown in clinical studies to protect from:•
  • neurotoxic events in cell culture, and cognitive neurodegeneration
  • 1998, the U.S.government obtained a patent on cannabinoids
  • Cannabis -has many Intake (delivery) methods
  • There is no cure for AD or PD
  • there is an urgent, unmet need for innovative approaches to treating these degenerative neurological illnesses
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WHAT IS CANNABIS?
What are the Components of cannabis and how do they address various symptoms?
 
Cannabis is a Phytocannabinoid plant-based medicine from the Cannabis Sativa plant
 
•Cannabis Sativa, has two major molecules; (cannabinoids), CBD and THC
The major cannabinoids are THC and CBD; but there are many minor Cannabinoids
•CBD (Cannabidiol), is non-psychoactive
  • THC is psychoactive
  • The key difference between the types of cannabis is the ratio of the two chemicals found in all strains.
  • •Tetrahydrocannabinol (THC) is the primary active ingredient and is responsible for the effects associated with the classic “high,” including euphoria and giddiness but also anxiety and paranoia.
  • The second chemical, cannabidiol, (CBD) has more calming effects, and brain-imaging studies have shown that it can block the psychosis-inducing effects of THC
  • CBD is gaining momentum as a treatment for health-related conditions including Alzheimers disease, epilepsy, anxiety, and chronic pain, Parkinsons
  • There are many different Intake/delivery methods
  • Both have cannabinoid receptors (C1) and C2
  • The cannabinoids receptors become dysregulated during Alzheimer’s disease neurodegeneration
CBD
•The second major chemical or molecule is, cannabidiol,
•CBD has more calming effects, and brain-imaging studies have shown that it can block the psychosis-inducing effects of THC2
  • Cannabis can work in the body to protect the brain, fight cancer, slow aging, reduce pain and inflammation
  • Cannabis can help benefit PD and AD
  • CBD is a natural compound found in cannabis Sativa plants, with none of the adverse side effects of prescription medications and without the “high” effect from THC in marijuana.
  • CBD is a healthy, natural alternative to traditional medications
  • CBD is non-psychoactive and does not give a “high” effect
  • CBD has few if any, adverse side-effects
  • CBD is an anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent,
  • Studies show that CBD, a Cannabidiol also referred to as CBD-rich cannabis, may relieve debilitating symptoms of Parkinsons
  • CBD is becoming more and more accessible for persons suffering from the effects of Parkinsons disease.
  • And while traditional medications may become less effective over time, or stop working completely, CBD users are reporting long-lasting benefits, with many giving up their pharmaceuticals for good
  • CBD is under current evaluation for Huntington’s disease receptors for serotonin or adenosine
  • Studies show that CBD, a Cannabidiol also referred to as CBD-rich cannabis, may relieve debilitating symptoms of Parkinsons 
  • THC
  • THC, or Δ9-THC, is psychoactive
  • THC can:
•Mitigate pain, Muscle spasticity, Glaucoma and Insomnia
Help with appetitesleep, and pain
  • THC is psychoactive and can get you high effect
  • Skunk-type strains of cannabis contain a high
  • •Both have been shown in clinical studies to protect from:
  • •neurotoxic events in cell culture and cognitive neurodegeneration
  • Patients taking between 0.75 mg and 1.5 mg of THC twice daily saw improvements in many
 
CBD with THC (Δ9-tetrahydrocannabinol together can:
•Enhance the endocannabinoid system to:
•regulate cellular repair and renewal,
•regenerate and replace at the cellular level to
achieve homeostasis.
In times of illness, CBD and THC can:
•regenerate dysfunction and degradation
  • CBD and THC studies in trials for spasticity
  • Neutral cannabinoids through a process of decarboxylation, lose their carboxyl group through aging or heat.
  • The neuroprotective potential of CBD and THC based on the combination of its anti-inflammatory and anti-oxidant properties is presently under intense clinical research
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ALZHEIMERS and PARKINSONS DISEASE
 
Alzheimers AD (AD)
  • Alzheimers Disease is a progressive mental deterioration that is characterized by memory loss, confusion, and problems communicating.
  • Alzheimers disease (AD) results in a devastating decline in cognitive ability
  • The incidence of AD is increasing due to improved longevity, causing a major socio-economic burden
  • •Alterations of ECS have been found in AD patients suggesting that the ECS plays a role in the development of Alzheimer’s disease
  • Cannabinoids may support intrinsic neurological repair mechanisms by increasing neurotrophin expression and neurogenesis.
  • Certain cannabinoids, such as CBD, may be able to protect against induced neurotoxicity via the antioxidant and anti-inflammatory effects found in AD
  • Cannabinoid receptors become dysregulated during Alzheimers disease neurodegeneration Oo
  • Patients taking between 0.75 mg and 1.5 mg of THC twice daily saw improvements in many cases
 
STATISTICS
•5 million Americans have Alzheimers
•35 million diagnose with Alzheimer’s worldwide
  • •5.8 million Americans age 65 and older are living with Alzheimers dementia in 2020.
  • •Between 2000 and 2018 deaths from heart disease have decreased 7. 8 %; death from AD have increased1 4 6 %
  • •Eighty percent are age 75 or older.
  • •One in 10 people age 65 and older (10%) has Alzheimer’s dementia.
  • •AD is the 6th disease leading to death
  • •cost the nation $305 billion—By 2050, these costs could rise as high as in 1.1 trillion
  • •In 2020, Alzheimer’s and other dementias will cost the nation $305 billion—By 2050, these costs could rise as high as in 1.1 trillion
  • there is an urgent, unmet need for innovative approaches to treating this degenerative neurological disease
 
MECHANISM
 
AD is a chronic neurodegenerative disorder that leads to progressive symptoms including dementia, memory loss, emotional issues, and speech problems and others
•Few treatments exist and therapies address only some symptoms but not the progression of the disease itself
•Unwanted central effects that result from activation of cannabinoid receptor 1 (CB1) has
limited the therapeutic use of drugs
•The discovery of CB2 and endogenous cannabinoid receptor ligands in Alzheimers
disease led the way for new therapeutic options •Significant interest in cannabis-based treatments, e.g., due to Endocannabinoids, raise the safe targeting of this endocannabinoid system
•Researchers are currently working to advance roles medical cannabis could play in the future of Alzheimers treatment and possible roles medical cannabis could play in the future of Alzheimers treatment
•Clinical success has been limited and complicated by the discovery of an expanded
endocannabinoid system – known as the “endocannabinoidome” system“
This extended system includes several mediators that are biochemically related to endocannabinoids, their receptors, and metabolic enzyme; including
  • Cannabinoid receptors 1 and 2 (CB1 and CB2), the two endocannabinoids, anandamide and 2-arachidonoylglycerol, and endocannabinoid anabolic and catabolic enzymes form the endocannabinoid system
  • Endocannabinoids can activate different receptors and their biosynthetic and catabolic pathways are often shared with other mediators.
  • The endocannabinoidome hinders therapeutic targeting of endocannabinoid anabolic or catabolic enzymes but inhibitors of endocannabinoid inactivation and allosteric modulators of CB1 and CB2 are being actively investigated in neurological conditions and disorders
    • The existence of the endocannabinoidome explains in part why some non-euphoric cannabinoids affect several endocannabinoidome proteins that are useful for the treatment of neurological disorders, such as multiple sclerosis and epilepsy
  • Endocannabinoid signaling is involved in the regulation of cell, tissue, organism homeostasis, brain development, neurotransmitter release and synaptic plasticity and cytokine release from microglia implicated in multiple neurological disorders
  • Endocannabinoid signaling is altered in most neurological disorders; enhancers and
  • inhibitors of endocannabinoid signaling can have therapeutic effects in preclinical models depending on the disease
  • CBD also reverses and prevents the development of cognitive deficits in AD rodent models.
  • Combination therapies of CBD and Δ9-tetrahydrocannabinol (THC), the main active ingredient of cannabis Sativa, show that CBD can antagonize the psychoactive effects associated with THC and possibly mediate greater therapeutic benefits than either phytocannabinoid alone.
  • The studies provide “proof of principle” that CBD and possibly CBD-THC combinations are valid candidates for novel AD therapies Further investigations should address the long-term potential of CBD and evaluate mechanisms involved in the therapeutic effects described
 
  • Cannabis preparations have medical benefits together
  • The discovery of the psychotropic plant, cannabinoid Δ9-tetrahydrocannabinol, (THC), initiated efforts to develop cannabinoid-based therapeutics
  • These efforts were
  • Not always been successful; especially, in relation to unwanted central effects that result from activation of cannabinoid receptor 1 (CB1), (CB1 has limited the therapeutic use of drugs that activate or inactivate this receptor.)
  • The discovery of CB2 and endogenous cannabinoid receptor ligands endocannabinoids) raised new possibilities for safe targeting of this endocannabinoid system. Again,clinical success has been limited, complicated by the discovery of an expanded endocannabinoid system – known as the “endocannabinoidome”– that includes several mediators that are last biochemically related to the endocannabinoids, their receptors and metabolic enzymes.
  • Recent success with a combination of THC and a non-psychotropic, cannabinoid, cannabidiol, has helped with spasticity. This brought the therapeutic use of cannabinoids and endocannabinoids in neurological diseases into the limelight For multiple neurological diseases.
  • Other Non-typical Cannabinoid type 1 (CB1) receptors that lack psychoactivity may have therapeutic potential for the treatment of AD models of neurodegeneration.
  • Hippocampal long-term potentiation (LTP) is an activity-dependent increase in synaptic efficacy often used to study cellular mechanisms related to memory.
  • The application of CBD in hippocampal slices alone did not alter in all AD.
  • LTP, with pre-treatment of slices with CBD rescued the Aβ1–42 mediated deficit in LTP. data suggests that this major component of Cannabis sativa, which lacks psychoactivity may have therapeutic potential for the treatment of AD
  • mechanism of action of CBD, antagonists were added
  • •acute application of a peptide (Aβ1-42) associated with AD lessens LTP, but CBD rescues that deficit in LTP
  • •neuroprotective effects of CBD were not reversed.
  • Cannabinoid type 1 (CB1) receptors which lack psychoactivity may have therapeutic potential for the treatment of AD.
  • Patients taking between 0.75 mg and 1.5 mg of THC twice daily saw improvements
 
STUDIES
 
Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has demonstrated neuroprotective, anti-inflammatory, and antioxidant properties in vitro. Thus, it is being investigated as a potential multifunctional treatment option for AD.
CBD promotes neuroprotection through different signal transduction pathways mediated indirectly by cannabinoid receptors.(Han, 2020)
In regard to CBD and other neuroprotective effects in Alzheimer’s disease are detailed by Hughes, 2019. demonstrates the ability of CBD to reduce the change caused by damage to neural cells and reduce the pro-inflammatory response. CBD was found to promote neurogenesis. Importantly, CBD reverses and prevents the development of cognitive deficits in Alzheimer’s rodent models.
Hughes found cannabidiol (CBD) acts to protect synaptic plasticity in an in vitro model of Alzheimer’s disease (AD). The non-psychoactive component of Cannabis sativa, CBD has previously been shown to protect against the neurotoxic effects of beta amyloid peptide (Aβ) in cell culture and cognitive behavioural models of neurodegeneration (Hughes, Neurochem Res
. 2019 Mar;44(3):703-713. 2019)
Studies by Kant demonstrate the ability of CBD to reduce reactive gliosis and the neuroinflammatory response as well as to promote neurogenesis. Importantly, CBD also reverses and prevents the development of cognitive deficits in AD rodent models
In addition, Hippocampal long-term potentiation (LTP), is an increase in synaptic efficacy, that is used to study cellular mechanisms related to memory, and to protect synaptic plasticity in an in-vitro model of Alzheimer’s disease (AD) and the non-psychoactive component of m Cannabis sativa, CBD. (Hughes,2019)
  • LTP is shown to protect against the neuro-toxic effects of beta-amyloid peptide Aβ) in cell culture and cognitive behavior
  • The neuroprotective effects of CBD were not reversed.
  • combination therapies of CBD and Δ9-tetrahydrocannabinol (THC), the main active ingredient of cannabis Sativa, show that CBD can antagonize the psychoactive effects associated with THC and possibly mediate greater therapeutic benefits than either phytocannabinoid alone. (Watt, 2017)
The studies provide “proof of principle” that CBD and possibly CBD-THC combinations are valid candidates for novel AD therapies. Further investigations should address the long-term potential of CBD and evaluate mechanisms involved in the therapeutic effects described. (Watt,
 
PARKINSONS DISEASE (PD)
 
 
Parkinson’s disease is a progressive nervous system disorder that affects movement.
 
  • Parkinson’s affects an estimated 10 million people worldwide including 1 million Americans
  • Uncontrolled PD significantly reduces the patient’s quality of life and can render a person unable to care for themselves, trapped in a body they cannot control
  • PD results when depletion of dopamine, a neurotransmitter, does not allow messages to be sent to regions of the brain responsible for coordinating movement
  • With dopaminergic cell death, a loss of conscious control of movement occurs, and.
  • loss of control over several other bodily functions.
  • Cannabidiol, also referred to as CBD-rich cannabis, may relieve debilitating symptoms of Parkinson’s
Alzheimer and Parkinson