Seriousness of medical condition(s)
Alzheimer’s disease is the most common type of dementia and symptoms of Alzheimer’s can be detrimental to a person’s final years of life and can require 24-hour care. Alzheimer’s causes problems with memory, thinking and behaviour. In the early stages, dementia symptoms may be minimal, but as the disease causes more damage to the brain, symptoms worsen. The rate at which the disease progresses is different for everyone, but on average, people with Alzheimer’s live for eight years after symptoms begin. Alzheimer’s has no current cure, but treatments for symptoms are available and research continues.
Who could benefit from this treatment?
Clinical justification for using Medicinal Cannabis
Alzheimer’s Disease symptoms that may respond to cannabis include sleep problems, paranoia, anxiety, dysphoria, pain, poor appetite, and weight loss. Low-dose cannabinoid therapy appears to be effective and well-tolerated for treatment of behavioural disturbances (Backes, 2017).
Concentrations of the endocannabinoids, anandamide and 2-AG, plus their metabolizing enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), are generally increased in areas of brain damage in humans and in animals with AD. Microglia, like systemic inflammatory cells, have both CB1 and CB2 receptors. When activated, these receptors can downregulate the CB receptors on microglia (Maroof et al, 2013).
Inflammation plays a critical role in the progression of AD (Ferrer, 2016). Targeting the body’s own endocannabinoid system may offer the potential to stimulate neuroprotective mechanisms while dampening neuro-inflammation by the build-up of amyloid proteins in the brain. It may be that plant cannabinoids, including THC and CBD, may slow the build-up of plaques and tangles, or reduce the inflammatory response to their build up (Campbell & Gowran, 2007).
According to Michael Backes (Cannabis Pharmacy), high-THC varieties are indicated for the treatment of AD symptoms, while high-CBD varieties also have neuro-protective effects (Backes, 2017).
Unknown or expected adverse effects, risks and safety issues & related toxicology:
A systematic review by Whiting et al. (2015) stated in their conclusions that “Cannabinoids were associated with an increased risk of short-term adverse effects”.
According to the Guidance for the Use of Medicinal Cannabis in Australia: Overview, Therapeutics Good Administration
(2017): Cannabis is not appropriate for patients who:
- Are under the age of 25 (with the exception of intractable epilepsy or severe pain syndrome)
- Have a personal history or strong family history of psychosis
- Have a current or past cannabis use disorder, or active substance use disorder
- Have unstable respiratory or cardiovascular disease (including angina, peripheral vascular disease, cerebrovascular disease, arrhythmias)
- Are pregnant, planning to become pregnant, or
Cannabis should be authorized with caution in patients who:
- Smoke tobacco
- Have risk factors for cardiovascular disease
- Are heavy users of alcohol
- Are taking sedating medications or any other medication metabolized by the CYP450 pathway
- At risk or have liver disease
Potential drug interactions
Increasing THC concentration:
Examples of inhibitors:
– Antidepressants (e.g. Fluoxetine, Fluvoxamine)
– Proton Pump Inhibitors (e.g. Omeprazole)
– Macrolides (Clarithromycin, Erythromycin)
– Antimycotics (e.g. Itraconazole, Fluconazole, Ketoconazole, Miconazole)
– Calcium Antagonists (e.g. Diltiazem, Verapamil)
– HIV protease inhibitors (e.g. Ritonavir)
– Grapefruit juice
Increasing CBD concentration:
– Metabolized by CYP 2C19 and CYP 3A4
– Bioavailability could be increased by many of the same substances as for THC
Decreasing THC and CBD concentration:
- CYP 2C9 and 3A4 Inducers accelerate THC and CBD metabolism
- Examples of inducers:
– Saint John’s Wort
Significantly changed serum levels of clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine were seen in the study by Gaston et al (2017) on interactions between cannabidiol (Epidiolex.) and commonly used antiepileptic
drugs. Abnormal liver function test results were noted in participants taking concomitant valproate. This study emphasizes the importance of monitoring serum AED levels and LFTs during treatment with supraphysiological doses of CBD (e.g. 1000mg/kg).
- Caution with blood thinners like Warfarin, Heparin,
- Additionally, pharmacodynamic interactions should be expected between cannabis and drugs with sympathomimetic activity (tachycardia,
hypertension), central nervous system depressants (drowsiness, ataxia), and drugs with anticholinergic effects (tachycardia, drowsiness).
Many of these drug interactions can be mitigated in complex patients with polypharmacy by slowly titrating cannabis.
Approved treatments for this medical condition
There are different medications and treatment regimes for dementia. The main types of medication that can be used are:
- Cholinesterase Inhibitors
Why is medicinal cannabis appropriate for use?
Medicinal cannabis products will be considered for treatment when:
- standard of care medications have been trialed to maximally tolerated dose without acceptable symptom relief or functional improvements.
- Patient is unable to tolerate standard of care medications
- Standard of care medications are contraindicated.
The medicinal cannabis will not be used as sole treatment of condition. Alzheimer’s often requires other therapies to manage. In this way, the medicinal cannabis can act as an adjuvant. Tolerability and efficacy of adjuvants must be trialed in individual patients.
- org/au/dementia-alzheimers australia.asp#about
- Backes, M., n.d. Cannabis Pharmacy. 1st ed. London: Elephant Book Company Limited, pp.178, 180.
- Aso, I. Ferrer. “CB2 Cannabinoid Receptor as Potential Target Against Alzeimer’s Disease,” Frontiers in Neuroscience 2016;10:243)
- N Maroof, M.C. Pardon, D.A. Kendall, “Endocannabinoid Signalling in Alzheimer’s Disease,” Biochemical Society Transactions 2013;41:1583-7.
- A. Campbell and A. Gowran, “Alzheimer’s Disease; Taking the edge off with cannaibinoids?,” british Journal of Pharmacology 152, no.5 (November 2007): 655-62, doi:10.1038/sj.bjp.0707446
- Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA 2015;313(24):2456-73. Errata in: JAMA 2016;315(14):1522, JAMA 2015;314(21):2308, JAMA 2015;314(5):520, JAMA 2015;314(8):837.