Alzheimer’s Disease

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

Breastfeeding.

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)

– Cimetidine

– Macrolides (Clarithromycin, Erythromycin)

– Antimycotics (e.g. Itraconazole, Fluconazole, Ketoconazole, Miconazole)

– Calcium Antagonists (e.g. Diltiazem, Verapamil)

– HIV protease inhibitors (e.g. Ritonavir)

– Amiodarone

– Isoniazid

– 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:

– Rifampicin

– Primidone

– Carbamazepine

– Phenobarbital

– Phenytoin

– Rifabutin

– 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,

Clopidogrel (Plavix)

• 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.