Neuroprotection

Neuroprotection is the mechanisms and strategies used to protect against neuronal injury or degeneration in the Central Nervous System (CNS) following acute disorders (e.g. stroke or nervous system injury/trauma) or as a result of chronic neurodegenerative diseases (e.g. Parkinson’s, Alzheimer’s, Multiple Sclerosis)

Chronic Traumatic Encephalopathy

By Boston University Center for the Study of Traumatic Encephalopathy – http://www-tc.pbs.org/wgbh/pages/frontline/art/progs/concussions-cte/h.png, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=37222621

Chronic traumatic encephalopathy (CTE) is a progressive degenerative disease found in people who have had a severe blow or repeated blows to the head. A subtype of this is dementia pugilistica (DP), i.e. “punch-drunk,” as it was initially found in those with a history of boxing. CTE has been most commonly found in professional athletes participating in American football, rugby, ice hockey, boxing, professional wrestling, stunt performing, bull riding, rodeo, Association football and other contact sports who have experienced repeated concussions or other brain trauma. Its presence in domestic violence is also being investigated. It can affect high school athletes, especially American football players, following few years of activity. It is a form of tauopathy.

Chronic traumatic encephalopathy. (2017, February 24). In Wikipedia, The Free Encyclopedia. Retrieved 21:27, February 24, 2017, from https://en.wikipedia.org/w/index.php?title=Chronic_traumatic_encephalopathy&oldid=767152871

Hepatic Encephalopathy

CBD for Hepatic encephalopathy

By Nephron – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=10756384

Hepatic encephalopathy (HE) is the occurrence of confusion, altered level of consciousness, and coma as a result of liver failure. In the advanced stages it is called hepatic coma or coma hepaticum. It may ultimately lead to death.

It is caused by accumulation in the bloodstream of toxic substances that are normally removed by the liver. The diagnosis of hepatic encephalopathy requires the presence of impaired liver function and the exclusion of an alternative explanation for the symptoms. Blood tests (ammonia levels) may assist in the diagnosis. Attacks are often caused by another problem, such as infection or constipation.

Hepatic encephalopathy is reversible with treatment. This relies on suppressing the production of the toxic substances in the intestine and is most commonly done with the laxative lactulose or with non-absorbable antibiotics. In addition, the treatment of any underlying condition may improve the symptoms. In particular settings, such as acute liver failure, the onset of encephalopathy may indicate the need for a liver transplant.

Source: Hepatic encephalopathy, https://en.wikipedia.org/w/index.php?title=Hepatic_encephalopathy&oldid=766939259

By Jftrempe – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=33335899

Parkinson’s Disease

PD is one of the most progressive neurological disorders today. It results from the loss of dopaminergic neurons in the basal ganglia, a region of the brain. The loss of dopamine attributes to the motor disabilities in patients with PD; without this neurotransmitter, the brain has a harder time regulating smooth movement within the limbs. The connection between the substantia nigra and the striatum is responsible for this motor control.

It was estimated in 2015 that 1-2% of the worldwide population older than 65 have the disease. Its prevalence in the U.S. has increased over the last decade in males and females of all races, although males are 1.5-2 times more likely to get the disease. Of the one million Americans living with PD, only 5-10% stem from familial-inheritance.The rest of the cases, 90-95%, have an unknown cause of origin.

The most common symptoms and side effects of PD are tremors, bradykinesia, rigidity, dyskinesia, slurring words and inflammation. Currently, treatments for PD include deep brain stimulation and a variety of drugs featuring levodopa, the most effective medication for PD on the market. However, chronic use of levodopa can lead to dyskinesia (involuntary movements) or resistance to the drug. Because of this discouraging reality, scientists and doctors started looking into medical marijuana and cannabinoids as a potential treatment.

CBD for Picks Disease

Brain MRI in Pick’s disease
By Jftrempe – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=33335899

Alzheimer’s/Dementia

Alzheimer’s Disease (AD) and dementia are debilitating neurodegenerative diseases characterized by progressive cognitive decline. AD is the most common form of dementia, accounting for over 60% of cases and affecting over 33 million people worldwide (Alzheimer’s Association, 2015). Due to the boom in the aging population, this number is expected to reach 115 million by the year 2050 (Wisniewski and Goni, 2014). AD typically begins with deficits in short-term memory, learning, communication and ability to navigate the world. In the subsequent stages of the disease, the deficits begin to impact eating, dressing and emotional control. In the late stages of the disease there is catastrophic disruption which renders the patients in need of 24-hr care.

Cannabinoids have demonstrated neuroprotective, anti-inflammatory and antioxidant properties in vitro, and has thus been investigated as a potential multifunctional treatment option for Alzheimer’s Disease (AD) and dementia. AD is characterized by the accumulation of protein plaques in the brain, as well as neuro-inflammation and oxidative stress.

CBD reverses and prevents the development of cognitive deficits in preclinical models. Much of the data supports combination therapies of CBD and ∆9-tetrahydrocannabinol (THC), the main active ingredient of cannabis sativa, show that CBD can stop the psychoactive (i.e. high-inducing) effects associated with THC and possibly contribute greater therapeutic benefits than either phytocannabinoid alone.

Alcohol-Related Neurotoxicity

Approximately 8.5% of the U.S. population currently meets the diagnostic criteria for an alcohol use disorder (AUD) (Hasin, Stinson, Ogburn, & Grant, 2007). Although four pharmacotherapy based interventions are approved in the U.S. for the treatment of AUDs, these drugs have had limited efficacy in the patient population (Litten et al., 2012). Additionally, these medications primarily target the motivational properties of alcohol, while the neurodegenerative effects of alcohol that are hypothesized to impair behavioral control and decision making, are not managed by these specific treatments. Therefore, identification of novel targets and development of new therapeutic agents is critical to improve pharmacotherapy based treatment strategies for AUDs (Liput, Hammell, Stinchcomb, & Nixon, 2013).

Neuroprotective agents are hypothesized to have high therapeutic utility for the treatment of AUDs (Crews, 1999). Excessive alcohol intake, characteristic of AUDs, results in neurodegeneration and cognitive and behavioral impairment, effects which are hypothesized to influence the transition to addiction (Crews, 1999; Koob, 1997; Liput et al., 2013). CBD has shown particular promise in attenuating the neurodegeneration associated with binge drinking and other AUDs.

CBD for Picks Disease

Epilepsy

Over the past several years, medical marijuana use has become a controversial topic not only within the medical community but also at state and national legislative levels. Many of the misconceptions regarding medical marijuana in the pediatric population stem from negative connotations associated with the term marijuana owing to its psychoactive effects. Therefore, it is important to define the various terms associated with products that are currently being used by the public as well as by pediatric researchers (Campbell, Phillips, & Manasco, 2017).

The data in pediatric epilepsy have been surrounding the use of CBD products as well as unregulated THC/CBD products from private dispensaries. A Cochrane review (Gloss & Vickrey, 2014) was conducted in 2012 to assess the safety and efficacy of cannabinoid use in patients with epilepsy. The authors included blinded and unblinded randomized controlled trials. The authors summarized the finding that a CBD dose of 200 mg to 300 mg daily was safely administered over a short period, and the rate of adverse reactions in each of the studies was low over a short period. The American Academy of Neurology conducted a systematic review in 2014 which included 34 studies that used medical marijuana to treat MS, epilepsy, and movement disorders (Koppel, Brust, & Fife, 2014). Two studies were included to assess the role of cannabinoids in decreasing seizure frequency (Ames, Cridland, & Med, 1985; Campbell et al., 2017; Cunha, Carlini, & Pereira, 1980).

Many parents and patients are making the decision to use CBD for 3 reasons according to Cilio et al (Cilio, Thiele, & Devinsky, 2014):

1) prominent Internet and nation media attention; 2) reports of cases of children successfully treated with CBD products; and 3) the belief that treatments derived from natural products are safer or more effective (Campbell et al., 2017; Cilio et al., 2014).

National attention has been on those patients who have moved to states where CBD use is legal and researchers have sought to gather data from parental observations. The most famous case was presented on a CNN special, “Weed.” Charlotte is a little girl from Colorado who was diagnosed with Dravet syndrome at the age of 3 months. She suffered from frequent status epilepticus. Charlotte failed multiple medications, and at 5 years of age, she had significant cognitive delay and required help with all of her activities of daily living (Maa & Figi, 2014). Her parents sought out a group in Colorado that created an oral, liquid, high-concentration CBD-to-THC strain of cannabis. Once her parents started giving her this strain, dubbed “Charlotte’s Web”, within 3 months Charlotte had a 90% reduction in her seizure frequency and by month 20, Charlotte was able to perform most of her daily activities independently with only 2 to 3 nocturnal tonic-clonic seizures per month.

Stories like Charlotte’s have prompted parents across the country in similar situations to move their families across the country to gain access to these products. In a retrospective chart review of 75 children and adolescents younger than 18 years who were given oral cannabis extracts for treatment of their epilepsy, 57% of parents reported some improvement in seizure frequency with 33% reporting a 50% reduction in seizures (Press, Knupp, & Chapman, 2015). Dosage information was not reported and parents used various formulations and concentrations of CBD and THC. Parents also described improvements in behavior and alertness (33%), language (11%), and motor skills (11%). Major adverse effects noted were somnolence (12%) and gastrointestinal symptoms (11%) (Campbell et al., 2017; Press et al., 2015).

Investigators at Stanford University administered a survey to 150 parents on Facebook to identify parentally reported effects of CBD on their child’s seizures (Porter & Jacobson, 2013). Of 19 respondents aged 2 to 16 years, 18 had treatment-resistant epilepsy for more than 3 years before CBD use. Based on parental response, 84% reported a reduction in child’s seizure frequency with 50% having a greater than 80% reduction in seizure frequency. Twelve of these 19 patients were also able to be weaned from another antiepileptic drug. In addition, parents reported overall better mood, increased alertness, and better sleep. Parents reported oral CBD dosages of 0.5 mg/kg/ day to 28.6 mg/kg/day and THC of 0 to 0.8 mg/kg/day. In a similar Facebook survey administered by researchers at the University of California, Los Angeles, the authors (Hussain, Zhou, & Jacobson, 2015) similarly reported an 85% reduction in seizure frequency among 117 respondents, with an average age of 6 years. Most patients (86%) conveyed that changes in frequency occurred within 14 days. As with previous surveys, dosage and formulations were varied but based on parental report of formulation used. Overall, most parents (83.5%) reported using an oral CBD product with at least a 15:1 ratio of CBD to THC.