Medical Cannabis and Alzheimer’s Disease

Alzheimer’s disease (AD, Alzheimer’s) is a progressive neurodegenerative disease that starts slowly and worsens over time. The most common cause of dementia is an impaired ability to remember, think and make decisions. Medical cannabis may improve the quality of life (QoL) for those with Alzheimer’s due to phytocannabinoids’ potential neuroprotective properties.

What is Alzheimer’s Disease?

Alzheimer’s disease is a type of dementia where an ongoing decline of brain function affects the sufferer’s memory, thinking skills, care for themselves, and other mental abilities. Mood swings and difficulty processing language are other symptoms. Age and genetics are the most significant risk factors in developing Alzheimer’s, but depression, hypertension, and head injuries are also contributing factors. Those with Alzheimer’s may also develop optic neuropathy (nerve pain in the eye or eyes). Over 55 million people worldwide have Alzheimer’s disease.

Alzheimer’s is the cause of between 60%-80% of cases of dementia. Although Alzheimer’s is not necessarily life-threatening, it can significantly diminish the quality of life. The average life expectancy after diagnosing of Alzheimer’s, which usually presents itself after age 65, is four to eight years. However, depending on many variables, some people may live as long as 20 years after initial diagnosis.

Although the precise cause of Alzheimer’s is unknown, environmental and genetic risk factors play a role in the development of the disease. A buildup of proteins called beta-amyloid peptides is thought to form a neurotoxic plaque in and around brain cells. It differs from another type of dementia called Lewy body dementia (LBD), which involves a protein called “alpha-synuclein” and targets a different set of cognitive functions. LBD targets problem-solving and reasoning, whereas Alzheimer’s predominantly targets memory.

grayed closeup photo of old woman's hand and baby's hand

Brief Summary of Current Treatments

The only disease-modifying medication approved for the treatment of Alzheimer’s is aducanumab (Aduhelm). Aducanumab is an amyloid beta-directed monoclonal antibody (laboratory-produced molecules engineered to serve as substitute antibodies) that targets amyloid-beta buildup. It is a form of immunotherapy. Other drugs that may be prescribed include donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon). These drugs are prescribed to improve mental function. Antipsychotics may also be prescribed.

Non-drug interventions include gaming (puzzles, card, and board games are popular), memory and orientation exercises, art therapy, music therapy, aromatherapy, and contact with animals. Caregivers may also be given support and training.

How Might Medical Cannabis Help?

There is a lot of debate surrounding the use of cannabis for Alzheimer’s. Cannabinoids can promote neurogenesis, and some believe they can potentially be used to delay the onset of Alzheimer’s. Alzheimer’s is also characterized by plaque formation caused by the clumping together of the amino acid amyloid-beta. Evidence shows that a low dose of tetrahydrocannabinol (THC) “directly interacts with Aβ peptide, thereby inhibiting aggregation.”

Cannabidiol (CBD) may help promote neurogenesis, which can help prevent or even “resuscitate” dead or malfunctioning receptors and help prevent anxiety. Small doses of THC may help remove amyloid-beta, preventing it from clumping together and forming plaque. However, most of the experiments on using cannabis for Alzheimer’s have been carried out on animals and extracted tissues rather than on living humans.

THC’s effects on short-term memory may also be of concern for Alzheimer’s patients, and it could be the case that low or moderate amounts of THC may be helpful, while high doses of THC should be avoided. Neuropathic (nerve) pain may also be managed by medical cannabis.

Yet, medications based on synthetic versions of THC, such as Marinol and dronabinol, are being tested to treat agitation in those with Alzheimer’s. However, more research is needed to determine whether synthetic versions of THC are as effective or safe for Alzheimer’s disease or other conditions.

Current medications for Alzheimer’s can have moderate to severe adverse side effects. These include sleepiness, dizziness, mood swings, confusion, and an increased risk of death in older patients. Medical cannabis and cannabinoids could provide an alternative or adjunct, helping reduce the need for some types of medication.

Cannabinoids

THC could be beneficial for removing beta-amyloid, the plaque-causing protein.
CBD may help reduce inflammation.
Cannabichromene (CBC) also has many neuroprotective properties.
Cannabigerol (CBG) also has antioxidative and neuroprotective properties.
The acidic cannabinoids tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA) have anti-inflammatory properties that could help manage Alzheimer’s.

Cannabinoid Ratios

THC:CBD 1:20
THC:CBD 1:3
THC:CBD 1:1
- THC may be helpful for dementia, although care must be taken regarding the dosage of THC to prevent adverse effects.
THC:CBD 2:1

Terpenes and Terpenoids

Terpenes such as limonene and pinene may help alleviate “brain fog” and memory loss.
Beta-caryophyllene has anti-inflammatory properties that could help reduce neuroinflammation and manage nerve pain.
Linalool may help restore emotional and cognitive function.

Flavonoids

The flavonoids found in fruit, vegetables, tea, coffee, chocolate, and wine may help reduce the risk of Alzheimer’s disease due to their antioxidative properties. Of particular interest are the flavonoids:

Cannflavin A, B, and C
Quercetin
Apigenin
Catechin
Epigallocatechin-3-gallate
Epigallocatechin
Epicatechin-3-O-gallate
Icariin
Procyanidin
Silibinin

Effective Ways of Taking Medical Cannabis for Alzheimer’s Disease

Routes of Administration

Inhalation
Ingestion
Sublingual

Special Formulations

A formulation with a well-balanced and roughly equal ratio of THC:CBD may be helpful. CBC and CBG could also be useful for their potential to boost brain cell growth.

A formulation or cannabis cultivar rich in linalool, limonene, pinene, and beta-caryophyllene may be helpful.

Dosing Methods

Vaporization
Inhaler
Oil-based tincture
Edible

What are the Pros and Cons of Taking Medical Cannabis for Alzheimer’s Disease?

Potential Pros

Small doses of THC may help remove or prevent the clumping of the plaque-causing beta-amyloid from brain cells.
Cannabidiol (CBD) may help prevent Beta-Amyloid-induced toxicity in PC12 cells and act as an anxiolytic.
Cannabinoids, particularly CBD, may help promote neurogenesis (the growth of new neural pathways).

Potential Cons

THC, particularly in high doses, can cause problems and difficulties with memory, problem-solving, balance, and hand-eye coordination, which is not ideal for those with Alzheimer’s.
Cannabinoids may alter the senses to some degree.

Useful Anecdotal Information

“Can Cannabis Help Alzheimer’s Patients?” Connecting Point, New England Public Media. Apr. 22, 2019.

Presentation by Dr. Walter J. Nieri. “Dementia and Cannabis.” Tempe 11 Video, Jun. 20 2019.

Scientific Data Overview and Studies

Total Studies = 97
Positive Studies = 89
Inconclusive Studies = 8
Negative Studies = 0
53 Meta-Analyses (49 positive, 4 inconclusive); 18 Animal Studies (15 positive, 3 inconclusive); 2 Double-Blind Human Trials (both positive); 2 Human Trials (both positive); 22 Lab Studies (21 positive, 1 inconclusive)
31 studies include CBD (29 positive, 2 inconclusive); 25 studies include THC (23 positive, 2 inconclusive); 1 study includes CBC (positive); 2 studies include CBG(both positive); 1 study includes CBDA (positive); 1 study includes THCA (positive)
Possible Overall Efficacy: Moderate

Quotes from Studies

“Several neurobiological effects of cannabinoids have been demonstrated, which could be relevant in treating dementia. The main function of the endogenous cannabinoid system (ECS) is thought to be the regulation of synaptic transmission (Baker 2003), and this process can be disordered in many neurological conditions, including dementia.”

Source: Markovic, Domagoj et al. “Cannabinoids for the treatment of dementia.” The Cochrane Database of Systematic Reviews vol. 2017,10 CD012820. 4 Oct. 2017, doi:10.1002/14651858.CD012820

“CBD components of cannabis might be useful to treat and prevent AD because CBD components could suppress the main causal factors of AD. Moreover, it was suggested that using CBD and THC together could be more useful than using CBD or THC alone.”

Source: Kim SH, Yang JW, Kim KH, Kim JU, Yook TH. “A Review on Studies of Marijuana for Alzheimer’s Disease – Focusing on CBD, THC.” J Pharmacopuncture. 2019;22(4):225-230. doi:10.3831/KPI.2019.22.030

“Limited evidence from one systematic review3 and one uncontrolled before-and-after study10 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.”

Source: Peprah, Kwakye and McCormack, Suzanne. “Medical Cannabis for the Treatment of Dementia: A Review of Clinical Effectiveness and Guidelines.” Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Jul 17.

“A substance called A-beta [amyloid-beta] — strongly suspected to play a key role in Alzheimer’s because it’s the chief constituent of the hallmark clumps dotting the brains of people with Alzheimer’s — may, in the disease’s earliest stages, impair learning and memory by blocking the natural, beneficial action of endocannabinoids in the brain, the study demonstrates. The Stanford group is now trying to figure out the molecular details of how and where this interference occurs. Pinning down those details could pave the path to new drugs to stave off the defects in learning ability and memory that characterize Alzheimer’s.

In the study, published June 18 in Neuron, researchers analyzed A-beta’s effects on a brain structure known as the hippocampus. In all mammals, this midbrain structure serves as a combination GPS system and memory-filing assistant, along with other duties.”

Source: Goldman, Bruce. “Blocking brain’s ‘internal marijuana’ may trigger early Alzheimer’s deficits, study shows.” Stanford Medicine. Jun. 18 2014.

Conclusion

There is moderate evidence that medical cannabis can help manage neuropsychiatric symptoms associated with Alzheimer’s-related dementia, including agitation, disinhibition, irritability, aberrant motor behavior, and nocturnal behavior disorders. Phytocannabinoids like THC may remove beta-amyloid peptides, whereas CBD, CBC, and CBG may provide neuroprotective and anti-inflammatory benefits.

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Lewy Body Dementia and Medical Cannabis

Using Cannabis for FNDs (Functional Neurological Disorders)

Rare Neurological Disorders and Medical Cannabis

Can Cannabis Boost Brain Cell Growth?

Please note: the information in this article does not constitute medical advice