cbd oil dosage for dementia

Using CBD (Cannabidiol) to Treat the Symptoms of Alzheimer’s & Other Dementias

CBD (aka Cannabidiol) is a compound derived from the Cannabis plant that has positive medicinal effects but does not make people feel “high” or anxious. CBD, in various forms, is legal in 48 US States. The states where it remains illegal are Idaho, and South Dakota, though in SD it will be legal beginning in July 2021. For much more on legality, see below.

CBD should not be confused with Marijuana or the THC (Tetrahydrocannabinol) compound which is known for generating a “high” with users. CBD is derived from Cannabis plants, similar to how caffeine is derived from the coffee bean, or aspirin from the bark of a Willow tree. CBD oil is the most common form of administration of the compound, with the oil contained in a gel cap or dropper bottle.

CBD Health Benefits for Dementia

The dementia-related conditions that can be helped by CBD include: Alzheimer’s disease, Vascular Dementia, Dementia with Lewy bodies (DLB), Parkinson’s disease, Frontotemporal dementia and Huntington’s disease.

According to researchers at California’s Salk Institute, their 2016 study found evidence that cannabinoids such as CBD could help remove dementia from, and increase connections between, brain cells. Those results were validated by other laboratories. While the US Food and Drug Administration has yet to approve a CBD drug for the purposes of treating dementia, it has approved a CBD-based drug called Epidiolex for treating epilepsy.

There are several ways CBD can work to improve health outcomes for persons with dementia: by reducing inflammation, by reducing oxygen buildup, by working as a brain stimulant and neuroprotectant, and by eliminating dead brain cells and the protein tangles that are believed to cause brain ailments including dementia. From a user’s perspective, CBD may improve movement while reducing stress and anxiety in the individual with dementia, as well as reduce the decline of memory and other brain functions.

It should be noted that controversy surrounds CBD and the claims companies have made as to its positive effects. The FDA warns that CBD can cause liver injury (as shown in some animal experiments with super high doses) and affect metabolism of other drugs. The agency also says that long-term side effects remain unknown.

Alzheimer’s Disease

The topic of CBD health benefits continues to grow with new CBD and Alzheimer’s research. In recent studies, CBD has been shown to reduce or remove the impact of inflammation, oxygen buildup and brain cell decline. CBD also increases levels of proteins that eliminate dead cells and plaques in brains with Alzheimer’s, improving both memory and motor function.

When the brain’s immune cells fail to clear blockages associated with Alzheimer’s disease, the result is an inflammatory response. When inflammation happens in the brain, oxygen is released as a result. The greater the inflammation, the greater the negative impact. Important brain functions such as memory are decreased as more oxygen is released in the brain’s cells. Memory loss and other brain deterioration indirectly leads to increased oxygen in the brain. CBD is an antioxidant, which helps reduce the problems associated with oxygen stress. Brain functions negatively impacted by oxygen stress can be improved by using CBD.

Alzheimer’s patients’ brain cells often show a path of rapid decline and destruction. The potential of stimulating brain tissue was recently discovered as a potential benefit of CBD. In clinical trials, CBD has shown the ability to reverse and even prevent the development of Alzheimer’s negative impact. A 2011 study by Australian researchers Tim Karl and Carl Group found that CBD promotes the growth and development of brain cells, reducing the decline of memory and other brain functions.

More recently, in a study researchers were able to increase levels of proteins in the brain (called IL-33 and TREM2) that maintain cognitive functions by eliminating dead cells and helping clear beta-amyloid plaque tangles associated with the disease. After CBD was regularly injected into mice afflicted with Alzheimer’s disease, scientists noticed major improvements in their ability to think. Specifically, the mice could better tell the difference between old objects and new ones. The mice’s movement improved, as well. People with Alzheimer’s often develop stiffness that affects their ability to walk, and mice with these same symptoms will continuously walk in a tight circle. After CBD treatments, that behavior stopped.

Vascular Dementia

Vascular dementia is a general term describing problems with reasoning, planning, judgment, memory and other thought processes caused by brain damage from impaired blood flow to one’s brain. To effectively treat vascular dementia, a 2016 study by the US National Institute of Health (NIH) found that activating CB2 (cannabinoid) receptors in the brain helped recover better blood flow to the brain. Activating the CB2 receptors with CBD has increased brain cell activity and helped reduce brain cell damage commonly associated with vascular dementia.

Dementia with Lewy Bodies

Lewy body dementia (LBD) is a disease associated with abnormal deposits of a protein called alpha-synuclein in the brain. These deposits, called Lewy bodies, affect chemicals in the brain whose changes, in turn, can lead to problems with thinking, sleeping, movement, behavior, and mood. Unlike most pain, anxiety or behavior management drugs, CBD does not block acetylcholine, the main chemical that LBD attacks. Research has shown that CBD can be an effective anti-inflammatory agent, reduce motor symptoms (tremor, rigidity, bradykinesia) and maintain circadian (sleep) rhythms.

Parkinson’s Disease

Parkinson’s is a chronic progressive disease of the nervous system chiefly affecting middle-aged and elderly people. Parkinson’s is linked to decreased dopamine production and marked by tremor, muscular rigidity, and slow, imprecise movement. Digestive imbalance may also play a role in the progression of Parkinson’s and the severity of symptoms. Cannabinoids such as CBD have been shown to contain effective brain protectors, antioxidants and anti-inflammatory properties which can be beneficial for managing Parkinson’s disease. Read more about Parkinson’s and CBD.

Frontotemporal Dementia / Pick’s Disease

Frontotemporal dementia (FTD) or frontotemporal degenerations refers to a group of disorders caused by progressive nerve cell loss in the brain’s frontal lobes (the areas behind one’s forehead) or its temporal lobes (the regions behind one’s ears) that leads to symptoms of depression and psychosis. Unlike most antipsychotic drugs, CBD does not lead to an increased risk of death. Research has shown that CBD can be an effective anti-inflammatory agent, reduce anxiety, reduce motor symptoms (tremor, rigidity, bradykinesia) and maintain circadian (sleep) rhythms.

Huntington’s Disease

Huntington’s disease (HD), also known as Huntington’s chorea, is an inherited disorder that results in death of brain cells. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unsteady gait often follow. According to 2016 research from the University of Madrid, due to CBD’s effectiveness as antioxidants and its anti-inflammatory properties, CBD can be beneficial for managing Huntington’s disease. Experiments with mice have shown that another chemical called cannabigerol, or CBG, in marijuana plants can help maintain brain health for people with Huntington’s (see next section).

What is CBG? (CBG vs. CBD)

Another cannabinoid (compound in cannabis) that has shown health benefits is cannabigerol, also known as CBG. Often taken as an oil, like CBD, CBG is rarer than CBD and THC because there is much less of it in a plant. Whereas cannabis strains usually contain about 25% THC and 20% CBD, the compound CBG makes up only about 1% of most plants. CBG can, however, be extracted at higher volumes if the plants are harvested at the right age, meaning younger. CBG turns into CBD and THC as the plant gets older.

CBG binds to cannabinoid receptors in the body, strengthening neurotransmitters (brain cells) that specifically function to do things like motivate us and regulate our appetites and sleeping patterns. Studies have even shown that CBG protects nerve cells in the brain.

Unfortunately, those studies were done on the brains of mice, not humans (specifically, mice with an experimental model of Huntington’s disease). There are actually fewer studies on CGB in humans than the other cannabinoids, so while there is a strong case to be made that CGB works as a neuroprotectant that preserves nerve cells in the brain, the evidence is slimmer.

Like CBD, CGB is non-psychotropic and won’t get you high. A key difference between CBD and CBG is that CBG is harder to extract and therefore more expensive.

Risks & Side Effects

The World Health Organization (WHO) stated that “no public health problems… have been associated with the use of pure CBD,” and there has been no known association with potential for dependence or abuse, unlike most pharma alternatives. The most commonly reported potential side effects of CBD usage were diarrhea and bloating, with some also reporting nausea. About 3% of patients in studies reported liver problems and had to discontinue CBD use. Specifically, in dementia, some patients reported increased tremor with high doses of CBD. As with any new treatment, patients and caregivers should monitor effects and outcomes closely.

Misperceptions & Myths

1) CBD is non-psychoactive and medicinal while THC is recreational, not medicinal
CBD (cannabidiol) has been shown to have antipsychotic and anti-anxiety effects in humans. This does not mean it is non-psychoactive, but rather that the psychoactive effects are often beneficial and non-intoxicating vs. the “high” feelings of the THC (aka Tetrahydrocannabinol) compound. THC has also shown medicinal benefits for patients, particularly those suffering from pain or inflammation, especially when combined with CBD for consumption by patients.

2) CBD is a sedative and reduces awareness or alertness
Even in high doses (600mg), CBD has not produced sedating effects in healthy humans. CBD usually makes humans feel more awake and alert without negative impact on sleeping patterns. What is more likely happening is that cannabis strains being used by a patient that have high levels of CBD also contain a potentially sedating natural oil (terpene) such as myrcene.

3) All CBD sources are the same
There are multiple sources of CBD such as hemp, medical cannabis and isolate. Hemp-based CBD is plagued by mislabeling and recent studies have found that only 31% of 84 tested hemp-based CBD products were accurately labeled. Medical, locally sourced cannabis has consistently produced the best CBD source as it is held to stricter laboratory testing for potency and contaminants. If you’re ordering CBD online, know that mislabeling is common, and look for products that have been third-party tested, meaning independent testing has shown the stated percentages are correct.

4) CBD is legal in all 50 States
Despite CBD being sold in health food stores, tobacco shops, on Amazon, etc., and legalization by many US States, the Federal government has not legalized CBD-rich medical cannabis, even when there is little or no THC included. Hemp-based CBD (with less than 0.3% THC) would not technically have this restriction, but the sourcing and labeling risks are many. Officials in Idaho and South Dakota have said they still consider hemp-based CBD illegal, though South Dakota voters recently voted to change the law and cannabis will become legal for personal use there beginning in July 2021.Medical-based CBD has been legalized in more than 30 states and is recreationally legal in a growing number of US locations. The US Federal Drug Administration recently has approved one CBD medication, Epidiolex, to treat rare forms of epilepsy in patients 2 years and older.

Forms of CBD Administration

CBD comes in many forms. It can be inhaled or taken in pill format as an oil, to name just a few options. Most CBD patients prefer non-inhalable options, such as CBD-rich cannabis oil products that can be consumed orally (such as gel caps), squeezed under the tongue (with liquid dropper) or delivered via patches on the skin (like Band-Aids). Inhalters, like those used by people with asthma, that deliver CBD are also available. The effects of orally administered CBD can last for up to 4 hours, and the onset of effects has shown to take between 30-90 minutes.

In cases of acute symptoms that require immediate attention, inhalation of concentrated CBD-rich cannabis effects can be felt within 2-3 minutes and last up to 1 or 2 hours. Inhalation can be achieved either through smoking of CBD-rich cannabis flower, or through increasingly popular vaporizer ‘pens’. Both forms are widely available at medical marijuana dispensaries.

Legal Status of CBD in the U.S. (as of May 2021)

Despite CBD being sold in health food stores, tobacco shops, on Amazon, etc., its legal status remains convoluted. The federal government has said since 2018 that CBD with less than 0.3%THC is federally legal. Individual states, however, have their own rules.

Laws by State
CBD and medical cannabis is legally available to all adult users (21+) in Alaska, Arizona, California, Colorado, District of Columbia, Illinois, Maine, Massachusetts, Michigan, Nevada, New Jersey, Oregon, Vermont, and Washington. Legally recognized state ID is required for purchase.

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CBD and medical cannabis is legally available by prescription only in Alabama,, Arkansas, Connecticut, Delaware, Florida, Georgia, Hawaii, Iowa, Louisiana, Maryland, Minnesota, Missouri, Montana, New Hampshire, New Mexico, New York, North Dakota, Ohio, Oklahoma, Pennsylvania, Rhode Island, Utah, Virginia, West Virginia, Wisconsin and Wyoming.

CBD is also available with limited THC content in states such as Indiana, Kansas, Kentucky, Louisiana, Mississippi, Nebraska, South Carolina, North Carolina, Tennessee, and Texas.

CBD in all forms is prohibited in Idaho and South Dakota. After July 1, 2021, however, CBD and other cannabinoids will be legal for personal use in South Dakota. Idaho will be the only state where possession of cannabis remains illegal for all residents.

CBD can also be used legally in most states by residents of assisted living and memory care communities. Read more.

Obtaining CBD

The most common means to obtain CBD rich medical marijuana is from a state licensed dispensary. These dispensaries can be found by searching on any number of dispensary directories (Leafly, Yelp, etc.) or Google Maps.

For those that have trouble with transportation, another increasingly available option would include delivery-based options. However, while convenient for senior patients, these options are not available in every city or town.

Finally, CBD can be purchased over the Internet and delivered to all 50 states. One reputable seller is CBDPure. One can visit their website here.

Dosage Information

Given the lack of regulation in the CBD marketplace and given the challenges of self-reporting of the benefits with persons with dementia, getting the CBD dosage correct is especially challenging. Even though no prescription is required to purchase CBD, many doctors are still knowledgeable about the product and can provide dosage recommendations. Furthermore, given many persons with dementia take multiple medications, it is worth researching drug-drug interactions when considering CBD. CBD dosage consultations can be arranged online with a doctor for about $60. This is a preferable approach to proceeding without professional medical input. However, it is unlikely one’s insurance would pay for these online dosage consultations.

Should one proceed in testing CBD’s impact on a loved one’s dementia, it’s best to start with the gel cap form of administration as the levels of CBD are consistent (when compared to a dropper) and the act of swallowing a pill is familiar. A further benefit is the once-daily scheduling. While many of CBD’s hypothetical benefits cannot be easily observed, loved ones should pay careful attention for behavior changes. Persons with dementia who appear calmer or experience less severe sundowning symptoms may be benefitting from CBD. Another area in which CBD’s impact may be observed is in reducing sleeplessness.

Finding the Right Dose

It’s a good idea to start small and slowly increase the dosage. Begin with between 1 and 2 milligrams per day for one week, and increase by 2 to 3 milligrams weekly until you notice improvements in symptoms. Base the dosage on body weight: go smaller if your loved one is particularly light, and give a slightly larger dose for a heavier person. A normal dose for an average adult is around 5 milligrams. You may not want to exceed that number. Again, consult a doctor as you would with any other new supplement or medication.

Insurance Coverage of CBD

At this early stage of development, there are few options covered by insurance. The Food and Drug Administration would need to sign off, and as of now there is only one CBD drug (Epidiolex, for epilepsy) with FDA approval. However, when compared to the prices of alternative pharmaceuticals, patients and caregivers may still find that CBD-based medical marijuana is a more cost effective and safer option.

Medicare’s Policy

Does Medicare cover CBD? Because of the federal prohibitions on prescribing Schedule 1 substances, there is no Medicare coverage for the purchase of medical marijuana or CBD derivatives. Any out-of-pocket costs one would incur purchasing marijuana for medical use will not count toward any deductibles under Part B or a Medicare Prescription Drug Plan.

Medicaid Policy

Medicinal cannabis is not covered by Medicaid, private plans, group plans, the Veterans Administration (VA) or Obamacare plans.

Bookshelf

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Medical Cannabis for the Treatment of Dementia: A Review of Clinical Effectiveness and Guidelines

CADTH Rapid Response Report: Summary with Critical Appraisal

Kwakye Peprah and Suzanne McCormack .

Abbreviations

adverse drug events

Clinical Global Impression (-S, severity)

Cohen–Mansfield Agitation Inventory

gamma amino butyric acid

Mini-Mental State Examination

Neuropsychiatric Inventory Index

Pittsburg Agitation Scale

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

randomized controlled trial

Unified Parkinson Disease Rating Scale

visual analog scale

Context and Policy Issues

Dementia refers to a set of symptoms and signs associated with a progressive deterioration of cognitive functions that affects daily activities. 1 Symptoms may include memory loss and difficulties with thinking, problem-solving or language, as well as changes in mood, perception, personality, or behaviour. 2 , 3

According to the World Alzheimer Report 2018, about 50 million people worldwide lived with dementia in 2018, with the number projected to increase to 152 million by 2050. 4 In Canada, the estimated number of people living with dementia in 2016 was 564,000, and this is expected to increase to 937,000 by 2031. 5 The total health care system costs and out of pocket costs of caring for people with dementia were $10.4 billion in 2016, and are projected to double by 2031. 5

Alzheimer’s disease is the most common type of dementia, accounting for about two thirds of all dementia. 4 Other types of dementia that occur less frequently include vascular dementia, mixed dementia, Lewy body dementia, frontotemporal dementia, and young-onset dementia. 1 , 3 Neuropsychiatric symptoms (NPS) are common to all dementia types and may manifest as agitation, aggression, wandering, apathy, sleep disorders, depression, anxiety, psychosis, and eating disorders. 3 These behavioral symptoms of dementia present significant risks of injury to the patients and caregivers, reduce quality of life, and may cause distress or depression.

The progressive course of dementia cannot be altered since there is no known cure or disease-modifying therapy. 6 However, there are interventions to manage NPS, although they are based on limited and disparate evidence. 3 The first-line treatment of NPS comprises a range of nonpharmacological interventions based on identifying unmet physical and emotional needs, such as inadequately treated pain and unpleasant environmental factors, which may trigger the symptoms. Pharmacological therapies are the second-line treatment in patients for whom nonpharmacological interventions were unsuccessful and who present a potential risk of injury to either themselves or others. Pharmacological interventions commonly involve off-label use of atypical antipsychotics or second-generation antidepressants, usually in combination the nonpharmacological strategies. 3

Given the limited currently available therapeutic options, their side-effect profiles, and inconsistent evidence base, there is a need for alternate therapies in the growing population of dementia patients. 7 – 9 Medical cannabis has been investigated as one the potential alternative treatments for dementia. 10 , 11 Cannabis (also known as marijuana) is a plant that contains over 70 different chemical compounds called cannabinoids. 2 Although their mechanism of action in dementia is not well elucidated, they have been shown to interact with neurotransmitter systems that have been implicated in the manifestations of NPS. 11 Currently, patients living in Canada who have a prescription from an authorized health care professional can legally use cannabis for medical purposes, if they are registered with a licensed producer or Health Canada. 12 , 13

The objective of this report is to summarize the evidence regarding the clinical effectiveness of medical cannabis for the treatment of dementia and the evidence-based guidelines for its use in this condition.

Research Questions

Key Findings

Limited evidence from one systematic review 3 and one uncontrolled before-and-after study 10 suggested that medical cannabis may be effective for treating agitation, disinhibition, irritability, aberrant motor behaviour, and nocturnal behaviour disorders as well as aberrant vocalization and resting care, which are neuropsychiatric symptoms associated with dementia. There was also limited evidence of improvement in rigidity and cognitive scores as assessed by Mini-Mental State Examination. The evidence from the systematic review came from four of its primary studies, whereas its remaining eight included studies did not find favourable or unfavourable evidence regarding the effectiveness of cannabinoids in the treatment of dementia. Sources of uncertainty included the low quality of evidence in the primary studies of the systematic review 3 and the fact that the uncontrolled before-and-after study 10 was a nonrandomized pilot study in 10 dementia patients that reported descriptive outcomes without statistical analysis. No relevant evidence-based clinical guidelines regarding the use of medical cannabis for treating dementia were identified.

Methods

Literature Search Methods

A limited literature search was conducted by an information specialist on key resources including PubMed, the Cochrane Library, the University of York Centre for Reviews and Dissemination (CRD) databases, the websites of Canadian and major international health technology agencies, as well as a focused Internet search. The search strategy was comprised of both controlled vocabulary, such as the National Library of Medicine’s MeSH (Medical Subject Headings), and keywords. The main search concepts were cannabis and dementia. No filters were applied to limit the retrieval by study type. The search was also limited to English language documents published between January 1, 2009, and June 18, 2019.

Selection Criteria and Methods

One reviewer screened citations and selected studies. In the first level of screening, titles and abstracts were reviewed and potentially relevant articles were retrieved and assessed for inclusion. The final selection of full-text articles was based on the inclusion criteria presented in Table 1.

Table 1

Exclusion Criteria

Articles were excluded if they did not meet the selection criteria outlined in Table 1; they were duplicate publications or were published before 2009. Systematic reviews 11 , 14 – 18 with relevant included studies fully captured in an already selected systematic review (i.e., complete overlap), and primary studies 19 – 24 that were included in an already selected systematic review, were also excluded.

Critical Appraisal of Individual Studies

The included systematic review 3 was critically appraised using A Measurement Tool to Assess Systematic Reviews (AMSTAR 2), 25 while the prospective before-and-after study 10 was critically appraised using the Risk of Bias for Nonrandomized Studies (RoBANS) 26 tool. Summary scores were not calculated for the included studies; instead, a review of the strengths and limitations of each included study were described.

Summary of Evidence

Quantity of Research Available

A total of 570 citations were identified in the literature search. Following screening of titles and abstracts, 544 citations were excluded, and 26 potentially relevant reports from the electronic search were retrieved for full-text review. The grey literature search identified one additional relevant publication. Of the 27 potentially relevant articles, 25 papers were excluded for various reasons, and two reports that met the inclusion criteria were included in this review. These comprised one systematic review 3 and one uncontrolled before-and-after study. 10 Appendix 1 presents the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 27 flowchart of the study selection process. Additional references of potential interest are provided in Appendix 5.

Summary of Study Characteristics

Additional details regarding the characteristics of included publications are provided in Appendix 2.

Study Design

One systematic review 3 and one uncontrolled before-and-after prospective pilot study, 10 both published in 2019, were included in this report. The primary studies in the systematic review 3 were identified through a comprehensive literature search involving 27 online resources, including Medline, PsycINFO, and Embase. The databases were searched from inception (where possible) to January 1 st , 2018. A total of 12 studies published from 1997 to 2017 were included in the systematic review. 3 They comprised six randomized controlled trials (RCTs), two cohort studies, and four case series or case studies.

Country of Origin

Reviewers from Australia authored the systematic review. 3 Four primary studies of the systematic review 3 were from the Netherlands, two each from the United Kingdom and United States of America, and one each from Germany, Israel, Switzerland, and Canada. The uncontrolled before-and-after prospective pilot study 10 was conducted in Switzerland.

Patient Population

The systematic review 3 involved a total of 178 patients, aged 65 years or older, across 12 included studies. The mean age ranged from 72.7 to 81.5 years. Five primary studies of the systematic review 3 included patients with any type of dementia, whereas four studies included participants with Alzheimer’s disease only and three studies included one or two dementia types (Alzheimer’s disease, vascular, mixed and frontotemporal). Seven primary studies in the systematic review 3 were undertaken in psychogeriatric units of hospitals. Two studies were conducted in the community. Another two studies took place in both the community and hospital, while one study was undertaken in the community and nursing home settings.

The uncontrolled before-and-after prospective pilot study 10 enrolled 10 female patients with dementia from different causes with persisting behavior problems, notwithstanding optimal conventional treatment. Patients had to have a neuropsychiatric inventory index (NPI) score higher than 10 to be eligible for inclusion. The average age of the patients was 79.5 years. The study was conducted at a nursing home specialized in the care of elderly with severe dementia.

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Interventions and Comparators

Studies included in the systematic review 3 evaluated three different orally administered cannabinoids – dronabinol, delta-9 tetrahydrocannabinol (THC), and nabilone. The medications were given at daily dose ranges of 2.5 to 7.03 mg, 1.5 to 15 mg, and 0.5 to 2.0 mg, respectively. In all comparative studies, placebo was given to patients in the control arm. Overall, reporting of prior treatment for NPS was limited and varied across the included studies. Reported concomitant medications included antipsychotics, antidepressants, and neuromodulators. However, it was unclear if these drugs were indicated for treating NPS of dementia or co-morbid conditions.

Cannabis oil containing THC and cannabidiol (CBD) combination (THC/CBD) was the intervention in the uncontrolled before-and-after prospective pilot study. 10 The medication was given with a small piece of chocolate cake to facilitate intake. The average doses were titrated over the study period as follows: up to 7.6 mg THC/13.2 mg CBD daily over two weeks, 8.8 mg THC/17.6 mg CBD by one month, and 9.0 mg THC/18.0 mg CBD by two months. No information was provided about previous treatments or concomitant therapy during the study.

Outcomes

Six of the primary studies included in the systematic review 3 evaluated the effectiveness of cannabinoid therapy for treating NPS of dementia using more than one set of criteria. The most common assessment tool was the NPI, which was used in five primary studies. The NPI is a validated tool developed to assess dementia-related behavioral symptoms, and it is routinely used to evaluate the effects of treatment on these symptoms. 28 The instrument is administrated to caregivers of dementia patients, who assess 12 behavioral areas commonly affected in such patients. The 12 behavioral domains are: delusions, hallucinations, agitation/aggression, depression, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor activity, night-time behaviors, and appetite and eating disorders. 28 For each domain, there are four scores: frequency, severity, total (frequency × severity), and caregiver distress. The total possible score is 144, with higher scores denoting greater severity. 28 The Cohen–Mansfield Agitation Inventory (CMAI) was used in three included RCTs. The CMAI is a validated 29-item tool intended to assess the frequency of manifestations of agitated behaviors in elderly persons in the long-term care setting. 29 Each item is rated on a 7-point scale of frequency (i.e., from 1 = never to 7 = several times an hour). 29 A primary caregiver rates the elderly patients regarding the frequency with which they manifest physically aggressive, physically non-aggressive, and verbally agitated behaviors. Changes in cognition following cannabinoid treatment were reported by one study out of nine studies included in the systematic review 3 that assessed baseline cognition using the Mini-Mental State Examination (MMSE).

The NPI and CMAI were also used in the uncontrolled before-and-after prospective pilot study. 10 In addition, item 22 of the Unified Parkinson Disease Rating Scale (UPDRS), a widely-used clinical rating scale consisting of a 31-item questionnaire for Parkinson’s disease, 30 was used to assess the degree of rigidity with passive movements, on a scale of 0 (absent) to 4 (severe, range of motion achieved with difficulty). 31 Lastly, a 0 to 10 visual analog scale (VAS) was used to evaluate the most “invalidating daily activity” or “disturbing behavior” (as determined by staff; however these were not defined).

Summary of Critical Appraisal

Additional details regarding the strengths and limitations of included publications are provided in Appendix 3.

Systematic Review

The systematic review 3 followed the PRISMA guidelines, and it was registered with International Prospective Register of Systematic Reviews (PROSPERO). The research objective was stated clearly, and inclusion and exclusion criteria were specified. The population, intervention, and control (comparator) of interest, as well as the outcome measures, were defined. The review authors searched multiple databases, with search dates ranging from inception to January 1 st , 2018. Also, the reference lists of relevant studies were hand-searched to identify additional studies. However, the search was limited to studies published in English and older patients (≥65 years old). Studies undertaken in younger populations (<65 years) were excluded. Study selection and data extraction were performed in duplicate by two review authors, with disagreements between them resolved by a third reviewer. The review authors did not explain their selection of the study designs for inclusion in the review. However, given the limited number of high-quality RCTs on the subject, it seems reasonable to include peer-reviewed studies regardless of the study design, as they did. The included primary studies were listed in tabular form, with the relevant characteristics of each study. A list of excluded studies was not provided; however, the number of studies excluded and the reasons for exclusion were specified in the PRISMA flow chart illustrating the study selection process. The risk of bias and methodological quality of the studies were evaluated using the Johanna Briggs Institute and Cochrane Collaboration critical appraisal tools (i.e., for observation studies and RCTs, respectively). Disagreements were resolved with a third reviewer. Overall, the included studies were of low quality with a high risk of bias, except for one RCT and one cohort study that were rated as having moderate risk of bias by the authors. The systematic review 3 considered the risk of bias in individual studies in the discussions of the results and conclusions, and stated that they had no conflicts of interest to disclose. However, they also acknowledged funding support from a cannabis manufacturing firm, although they noted that the firm and its employees were not involved in undertaking the systematic review 3 or interpreting its results.

Primary Study

On account of its non-randomized design, the included uncontrolled before-and-after study 10 was inherently likely to have more systemic biases as it lacked the risk-diminishing property of randomization. It was unknown if all consecutive eligible patients were considered for inclusion or if the study participants were intentionally targeted. Thus, the risk of bias due to inappropriate selection was unclear. Data for the study 10 were collected prospectively, which minimized risk of bias. Selection bias due to an inappropriate comparison group was low because data were available for all the same study participants both before and after the intervention. Although there was no reference to a pre-specified protocol for the study, the expected main outcomes were included, and results were measured with validated scales, suggesting a reduced risk of bias due to selective outcome reporting. However, it was unknown if the outcome assessors were blinded to the study hypothesis or exposure to the medication. Thus, the risk of confirmation bias due to inappropriate blinding of assessors was unclear. Also, it was not reported how the cannabis oil was standardized or how the stated doses were determined. Therefore, there was uncertainty about the level of risk of performance bias that could arise from variability in the intended doses the patients received. The severity of dementia among the patients precluded patient-reported feedback. Therefore, the assessments were based on the perception of third parties (i.e., family members and caregivers).

There was no indication that the uncontrolled before-and-after study 10 or any of the primary studies of the systematic review, 3 had any mechanism to identify and adjust for potential confounding factors that could affect the observed outcomes beyond the cannabinoids medication. Overall, the quality of evidence from the systematic review 3 and the uncontrolled before-and-after study 10 included in this report was limited.

Summary of Findings

Appendix 4 presents a table of the main study findings and authors’ conclusions.

Clinical Effectiveness of Medical Cannabis for the Treatment of Dementia

The included systematic review 3 reported study-level findings without meta-analysis. Four of the 12 primary studies in the systematic review 3 found that treatment of patients with dementia with medical cannabis resulted in significant improvements in a range of neuropsychiatric symptoms associated with dementia. The remaining eight primary studies did not find evidence to support the efficacy of cannabinoids in the treatment of dementia. They comprised five placebo-controlled RCTs, and one case series and two case studies without controls. Three of the RCTs evaluated THC (two studies) or dronabinol (one study) for agitation and behavior changes. Another RCT evaluated THC for static and dynamic balance as well as gait, and one RCT assessed safety. Doses of THC used varied between 0.75 mg twice daily to 1.5 mg three times daily, with follow-up varying from 14 to 84 days across the studies. Dronabinol was dosed at 2.5 mg twice daily for 84 days. The case series evaluated nabilone for NPS titrating doses from 0.5 mg twice to thrice daily for 78 days. The period of dose titration was not mentioned. The two case studies also assessed nabilone, with change in behaviours as outcome for one and observed response to nabilone outcome for the other. None of these two case studies provided quantifiable results, and it was not possible to determine significant effect.

The following paragraphs summarize the findings from the four primary studies of the included systematic review 3 and the uncontrolled before-and-after study. 10

Effectiveness
Changes in overall symptoms score

One RCT with a crossover design included in the systematic review 3 compared dronabinol 2.5 mg at night to placebo in two patients and found that after 28 days of treatment with dronabinol the overall NPI score was reduced by 10 points in patient and 11 points in the other. The significance of this reduction was not clear. One open-label prospective cohort study with 11 patients included in the systematic review 3 found that the overall NPI was reduced by 31.6 points (P < 0.001) after 28 days of treatment with up to 7.5 mg/day of THC. Also, one uncontrolled before-and-after study 10 found that the overall NPI was reduced by 32.9 points (P-value not reported) after two months of treatment with up 9.0/18 mg/day of THC/CBD. One case series included in the systematic review 3 reported that, in comparison to before treatment, a significantly lower total NPI (P < 0.05) was observed after 14 days of treatment with 2.5 mg oral dronabinol at night (the score values were not reported).

One cohort study included in the systematic review, 3 which assessed patient outcomes using the Pittsburg Agitation Scale (PAS), found significant improvements (P < 0.05) in the overall mean PAS among 40 patients after treatment with dronabinol at a mean dose of 7.3 mg/day for a mean duration of 16.88 days.

Changes in specific symptoms

One open-label prospective cohort study included in the systematic review 3 found statistically significant improvements (P < 0.05) in the NPI subscales agitation, disinhibition, irritability, aberrant motor behaviour, and nocturnal behaviour disorders among 11 patients, following 28 days treatment with medical cannabis oil containing THC given orally at doses up to 7.5 mg twice daily. Caregiver burden was also reduced significantly (P < 0.05). One case series included in the systematic review 3 also reported significantly lower (P < 0.05) NPI sub-scores in six patients for aberrant motor behavior, agitation and night-time behaviors, after 14 days of treatment with 2.5 mg oral dronabinol at night. However, the study did not report the actual score values.

One cohort study included in the systematic review 3 found significant improvements (P < 0.05) in aberrant vocalization, motor agitation, aggressiveness and resting care as assessed on PAS among 40 patients, after treatment with dronabinol at a mean dose of dose of 7.3 mg/day for a mean duration of use of 16.88 days.

One RCT with a crossover design (involving two patients) included in the systematic review 3 found a 67% reduction in nightly movement counts by the third week of treatment with dronabinol. It was unclear if this symptom referred to nocturnal behavior disorders. However, in the fourth week, nocturnal activity returned to baseline in one patient and increased in the other patient. One case series included in the systematic review 3 involving six patients found that nocturnal activity significantly decreased (P < 0.05) after 14 days of treatment with 2.5 mg oral dronabinol at night. It was unclear whether this symptom referred to nocturnal behavior disorders or aberrant motor behavior.

One uncontrolled before-and-after study 10 found that baseline agitation as measured by CMAI, and rigidity scores on UPDRS, decreased from 74.5 to 47.5, and 3.4 to 1.7, respectively, in 10 patients with severe dementia after two months follow-up. Statistical significance was not assessed.

One uncontrolled before-and-after study 10 involving 10 patients with severe dementia who were treated with THC/CBD (at doses up to 9.0/18.0 mg daily), found that persistent screaming stopped almost entirely in two women (20%) and frequent vomiting stopped in one patient (10%) after two months. Also, two patients (20%) stopped all morphine within three months, one patient (10%) decreased morphine by two-thirds in two months, and one patient (10%) stopped two antipsychotic medications after one month.

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Cognitive changes

One open-label prospective cohort study included in the systematic review 3 found that among 11 patients, there were statistically significant improvements in the MMSE scores from baseline (10.0) to following 28 days of treatment (11.0) with oral medical cannabis oil containing THC given at an initial dose of 2.5 mg twice daily and titrated up to 7.5 mg twice daily (P < 0.05).

Safety

Adverse events (AEs) were reported in 10 included studies in the systematic review, 3 whereas one case series and one case study did not report AEs. Overall, the most common AE reported was sedation, observed in 10 (24.4%) out of a total of 41 patients from two studies. The AEs were described as mostly mild. The exact numbers of patients involved were not clearly reported. Serious AEs (SAEs) were observed in three primary studies in the systematic review. 3 One RCT reported one seizure (7%) and two serious infections (13.4%). Another included RCT found SAEs in the form of gastroenteritis, worsening of NPS, and exacerbation of vestibular disorder and malignancy. One included cohort study reported three SAEs (dysphagia, fall, and confusion). No values were specified in either study.

One uncontrolled before-and-after study 10 reported that no patient stopped the cannabinoids for reasons of side effects; however, one patient died after one month for reasons unrelated to the cannabinoid medication.

Evidence-Based Guidelines Associated with the Use of Medical Cannabis for the Treatment of Dementia

The literature search for this review did not identify any clinical guidelines associated with the use of medical cannabis for the treatment of dementia; therefore, no summary can be provided.

Limitations

The systematic review 3 included primary studies of generally low quality and high risk of bias, except two studies with moderate risk of bias. The primary studies evaluated three isolated orally administered cannabinoids, with no study examining botanical cannabis or its crude extract. Also, no other route of administering cannabis was explored apart from the oral route. Thus, it is unknown if the finding will be generalizable to patients who used different medical cannabis preparations (i.e., not ingested orally). The authors of the systematic review 3 did not calculate effect estimates from the multiple studies due to the scarcity and heterogeneity of identified studies. Therefore, it was difficult to draw a generally representative conclusion on the effectiveness of the interventions.

Further, the systematic review 3 was limited to dementia patients 65 years or older, and studies undertaken in patients less than 65 years were excluded. Thus, it is unclear if the reported findings will be generalizable in younger populations. Patients in the uncontrolled before-and-after study were all female. Therefore, the generalizability of the results to male patients is unknown. Apart from one case study conducted in Canada, which was included in the systematic review, 3 all other studies, including the uncontrolled before-and-after study, 10 were undertaken outside Canada. Therefore, the generalizability of the findings to the Canadian context is unclear, given the potential for differences in practice patterns that might impact the interpretation of the results or the resources used to achieve them.

Although the uncontrolled before-and-after study 10 was conducted in patients with dementia with persisting severe behavior problems, notwithstanding optimal conventional treatment, medical cannabis was not compared with any active intervention in any of the studies 3 , 10 included in this report. Thus, the comparative effectiveness of medical cannabis to standard care for dementia could not be determined conclusively. Also, none of the included studies 3 , 10 had long-term effectiveness and safety data. However, in both the systematic review 3 and the uncontrolled before-and-after study 10 patients with dementia of all origins were eligibility for inclusion, which implies a good generalizability across patients with various kinds of dementia.

The literature search for this report did not identify any clinical guidelines regarding the use of medical cannabis for the treatment of dementia. However, the search was limited to English-language documents, and it is unknown if potentially relevant guidelines in other languages were missed. Given these limitations, there is a need for further studies to evaluate the use of medical cannabis in dementia, and establish clear guidelines for its use, if proven safe and effective.

Conclusions and Implications for Decision or Policy Making

One systematic review 3 of 12 primary studies and one uncontrolled before-and-after prospective pilot study 10 provided the information in this report. No relevant evidence-based clinical guidelines regarding the use of medical cannabis for treating dementia were identified. The primary studies of the systematic review 3 assessed the safety and efficacy of three isolated cannabinoids (dronabinol, THC, and nabilone) that were orally administered to patients with dementia at various doses. In the uncontrolled before-and-after prospective pilot study, 10 patients were given cannabis oil containing THC/CBD given with small pieces of chocolate cake to facilitate intake at doses from an initial dose of 7.6 mg THC/13.2 mg CBD titrated up to 9.0 mg THC/18.0 mg CBD daily over two months. None of the studies examined raw botanical cannabis or explored another route of administration apart from oral.

Overall, limited evidence from the studies 3 , 10 included this report suggested that medical cannabis may be effective for treating neuropsychiatric symptoms associated with dementia (i.e., agitation, disinhibition, irritability, aberrant motor behaviour, nocturnal behaviour disorders, and aberrant vocalization and resting care). There was also limited evidence of improvement in rigidity and cognitive scores as assessed by MMSE.

However, the data were inconclusive, given the limitations previously discussed. Key sources of uncertainty included the low quality of evidence in the primary studies of the systematic review 3 and the fact that the uncontrolled before-and-after study 10 was a nonrandomized pilot study in 10 dementia patients that reported descriptive outcomes without statistical analysis. Given these limitations, there is a need for a well-designed randomized controlled trial to confirm the effectiveness of medical cannabis for the treatment of dementia using different formulations that explore varieties of routes of administration.

Treating Alzheimer’s With CBD Oil

With an estimated 47 million seniors living with dementia worldwide and no cure or effective treatment, many people are looking for alternative modalities. Here are the basics of treating Alzheimer’s with CBD Oil.

The Problem

Increasingly, elderly folks suffer from neurodegenerative diseases such as Alzheimer’s disease and dementia. Unfortunately, the standard treatment is limited to pharmaceuticals that provide only poor to moderate improvement in managing confusion, agitation and difficult behaviors and are plagued with undesirable side effects, some of them significant.

Since there is no cure and almost no one talks about prevention, patients, and caregivers have little choice but to struggle and endure for years, as best they can, in managing the difficult symptoms and challenging behaviors.

Ancient Remedies in New Times

For thousands of years, marijuana was not only legal, but an important crop among cultures throughout history, and held commercial, medicinal, and spiritual value.

In 1997, a hemp rope dating back to 26,900 BC was found in Czechoslovakia (yes, 26,900 is not a typo), making it the oldest known artifact associated with cannabis.

Cannabis use in ancient Egypt has been recorded as far back as 2,000 B.C., found on scrolls depicting medicinal plants. It was initially documented in Kemet (ancient Egypt) to treat sore eyes and cataracts.

Here are 8 of the most common uses of medicinal cannabis in ancient times:

  1. As an anesthetic.
  2. To treat insomnia.
  3. As suppositories for the treatment of hemorrhoids.
  4. In India, cannabis was extensively used for spiritual purposes, to treat nausea, diarrhea, headaches, and insomnia. It was also used it to control pain during childbirth.
  5. The Greeks found Cannabis seeds to be particularly effective in treating people suffering from tapeworms.
  6. Seizures and epilepsy. The effectiveness of CBD and cannabis together for the treatment of epilepsy and seizures is very well-documented as highly effective in controlling seizures.
  7. To treat inflammation, both internal and external.
  8. Chinese doctors used cannabis to treat a variety of poisonings, including poisoning from Vermilion, sulfur poisoning, and scorpions stings.

More recently, a growing number of medical professionals started to recommend CBD oil and/or marijuana. Both help reduce inflammation and neuronal cell death. This solution is also shown to improve mood and behavior. In fact, some residents in my care homes are currently utilizing the healing effects of CBD oil with noticeable positive results.

While this treatment may seem new and Western countries, Eastern medicine has actively used marijuana for over 4,000 years. While Europe has utilized marijuana since the 19th century.

Questions and Answers – Treating Alzheimer’s With CBD Oil

Will CBD oil or extract make me high?

No. THC is the psychoactive cannabinoid in cannabis. On the other hand, CBD extract only contains trace amounts of THC, if any at all. There are a number of excellent CBD products containing <0.3% THC, which means there is no way of getting high on CBD!

Is CBD Oil Legal?

Yes. CBD oil is legal in all 50 states and classified as a nutritional supplement.

Is hemp oil the same as medicinal cannabis oil?

Many manufacturers label their CBD products as hemp oil. Moreover, a lot of CBD products have hemp oil as the carrier base oil (some use coconut or MCT oil) which is what creates some of the confusion.

Hemp oil does contain trace amounts of CBD, normally less than 25 parts per million (ppm). Medicinal cannabis oil extracts typically contain between 3% and 30% CBD (30,000ppm – 300,000 ppm)

What’s important is the mg (milligrams) of CBD contained in the product. If the label doesn’t say how much CBD is in it, then assume that you are simply buying plain old hemp oil and not medicinal cannabis oil or CBD extract.

How Does CBD Help Alzheimer’s Patients?

Available scientific research indicates that endocannabinoids play a role similar to that of other neurodegenerative diseases. That is, they evoke an endogenous adaptive response that counteracts both the neurochemical and inflammatory consequences of beta-amyloid protein formation, possibly the most important underlying cause of AD.

Beta-amyloid (Aβ) plaques – or clumps of protein in the brain – are a hallmark of Alzheimer’s disease. In a healthy brain, Aβ breaks down and eliminated. In an Alzheimer’s brain, these Aβ plaques interfere with memory and cognition. Research also suggests that Aβ plaques inhibit normal cannabinoid activity in folk’s brains.

What Is The Best Dosage For Treating Alzheimer’s With CBD Oil?

This is meant to be a general guide. Since every person’s physiology and illness is unique, the response to treatment will be unique as well. I recommend that you start low and go slow, carefully evaluating any changes or improvements. CBD is widely considered safe and is virtually side effects-free, therefore you should be safe to increase your CBD dosage if you find it necessary or helpful.

To increase appetite: 2.5 milligrams of THC by mouth with 1 to 5 mg of CBD daily, preferably in the morning.

To treat chronic pain: 2.5 to 20 mg of CBD twice daily.

To treat inflammation: 30 to 200 mg CBD daily.

To treat confusion and difficult behavior: 50 to 400 mg CBD daily.

To treat epilepsy: 50 to 150 mg of CBD twice daily.

To treat movement problems (Huntington’s disease, Parkinson’s, dementia): 3 to 5 mg of CBD oil per pounds of body weight daily. If you weigh 150 lbs, that would be 450 to 750 mg daily.

To treat sleep disorders and insomnia: 50 to 150 mg CBD at bedtime.

What is the Endocannabinoid System?

Cannabinoid receptors are prevalent in the brain and throughout the central and peripheral nervous system – we call it the Endocannabinoid system. So what, you ask? The significance of this is that the human body produces cannabinoid compounds just like those in the cannabis plant, that’s why we have receptors for those compounds!

Two specific receptors are identified in the brain: CB1 and CB2. The endocannabinoid system impacts mood, appetite, pain, inflammation, and memory.

How Are the CB1 and CB2 Receptors Connected to Neurodegenerative Diseases?

Cannabidiol or CBD, a compound found in cannabis, activate folk’s CB1 and CB2 receptors. When activated CB1 reduces neuronal cell death, and CB2 lessens inflammation in the brain.

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About The Author
Joseph Spada

Joseph Spada is a geriatric nurse of 33 years with extensive experience in long-term care and adult family homes. He is the Founder of Spada Care Homes and author of a #2 Bestseller, “How To Find The Best Adult Family Home Care for Your Elderly Parent” (Amazon). Joseph is also a Faculty instructor at North Seattle College, teaching the 52-hour AFH Administrator Certification.