THE EVOLVING USE OF CANNABIS AFTER LEGALIZATION IN

THE OLDER ADULT

Amanjot Sidhu, MD, FRCPCDivision of Geriatric MedicineMcMaster University

Disclosure

• Relationships with commercial interests:

• Grants/Research Support: none

• Speakers Bureau/Honoraria: none

• Consulting fees: none

• Other: none

Disclosure of Commercial Support

• This program has received financial support from: None

• This program has received in-kind support from: None

• No other potential for conflict(s) of interest:

Objectives

1. Describe the pathophysiology of cannabis and how strains are differentiated

2. Review the current evidence behind cannabis use in the senior population

3. Describe how cannabis is obtained and prescribed through a health care professional and how patients are monitored

4. Address the misconceptions and differences between medicinal and recreational cannabis and their potential side effects

Clinical Case – Mr. Payne87 y/o gentleman living in the community, history of chronic

back pain and moderate OA

PMHx:

• Vascular dementia/depression

• HTN

• Dyslipidemia

• CAD

Meds:

• Tylenol 3 po qid

• Escitalopram 10 mg po daily

• Perindopril 4 mg daily

• Rosuvastatin 10 mg daily

Clinical Case

• Patient’s son is concerned about low mood, amotivation, and chronic pain symptoms

• Son is inquiring about medical marijuana as they heard it can be helpful for pain and reduce Tylenol 3 intake

Pathophysiology of Cannabis

• Cannabis plant contains over 500 compounds of which 85 of those compounds act on cannabinoid receptors

• 2 notable cannabinoids in cannabis:

• Tetrahydrocannabinol (THC) – psychoactive

• Cannabidiol (CBD) – non-psychoactive

Strain Differentiation

• Subspecies of the plant

(Indica vs. Sativa)

• Chemical breakdown

• Terpene Profile

THC

• Potential therapeutic use as an: The 4 A’s

- Antiemetic

- Antispasmodic

- Analgesic

- Appetite stimulant

DON’T FORGET….

• PSYCHOACTIVE!

Cannabinoids - CBD

• CBD mechanism unclear, and has little binding affinity to receptors

• CBD can act as:Anti-inflammatoryAnti-epilepticAnxiolyticAnti-psychotic

CBD

Advantages

• Lack of psychoactivity

• Can be administered in higher doses

• Not toxic even when administered chronically

Disadvantages

• Low bioavailability

• Low solubility leading to incomplete absorption

THC vs. CBDTHC CBD

Anti-emetic ✔ ✔

Analgesic ✔ ✔

Anxiolytic ✔

Antispasmodic ✔ ✔

Anti-inflammatory ✔ ✔

Antipsychotic ✔

Appetite stimulant ✔

Appetite suppressant ✔

Bioactive terpenoids in cannabis

Compound Structure Activities

Myrcene SedativeAnti-inflammatoryAnalgesic

LimoneneAnxiolytic

D-Linalool Anxiolytic SedativeAnalgesic

B-Caryophyllene Anti-inflammatoryCB2 agonist

Entourage Effect HypothesisEffect Hypothesis35

THC

CBD

CBC

CBG

CBN

THCV

CBD

THC

Alone

OR

Alone

R

Terpenes

Flavonoids

17

Cannabis

Chronic Pain – Systematic Reviews

Year Title Conclusion

2019(CADTH)

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

Some benefit for neuropathic pain. Inconsistent effect for Fibromyalgia, MSK pain, and MS

2018(Mucke et al.)

Cannabis-based medicines for chronic neuropathic pain in adults

Cannabis achieved >pain relief compared with placebo

2018(Stockings et al.)

Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions:A systematic review and meta-analysis of controlled and observational studies

Moderate pain reduction with cannabinoid use compared with placeboSimilar NNT and NNH to opioids and other pain relievers

2015(Whiting, Wolff, Deshpande et al.)

Cannabinoids for Medical Use: A Systematic Review and Meta-analysis

Reduction in chronic pain and spasticity

Chronic pain

• 2018 Prospective, national, observational cohort of people with chronic noncancer pain prescribed opioids followed for 4 years showed NO evidence in improved outcomes like lower pain severity or exerting an opioid-sparing effect

Campbell et al. (2018). Effect of cannabis use in people with chronic non-cancer pain prescribed opioids: findings from a 4-year prospective cohort study. The Lancet, 3, 341-350.

SleepYear Title Conclusion

2017(Babson, K., Sottile, J. & Morabito, D.)

Cannabis, Cannabinoids, and Sleep: a Review of the Literature

Mixed results. CBD may be helpful for REM sleep disorder, Nabilonedecreases nightmares associated with PTSD, THC may decrease sleep latency but impair sleep quality in the long run

2014(Chagas et al.)

Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleepbehaviour disorder in Parkinson's disease patients: a case series

Case series of 4 patients with Parkinson’s disease with REM sleep behavior disorder – use of CBD had prompt, substantial and persistent reduction in the frequency of RBD-related events.

2014(Gates, P., Albertella, L. & Copeland, J.)

The effects of cannabinoid administration on sleep: a systematicreview of human studies

Cannabis may be thought to improve sleep via the mediating improvement of confounding symptoms like pain and spasticity

Cannabis and Dementia

Year Title Conclusion

2018(Lanctot et al.)

Nabilone significantly improves agitation/ aggression in patients with moderate-to-severe AD: Preliminary results of a placebo-controlled, double-blind, cross-over trial

14 week trial comparing 6 weeks of Nabilone (dose 1-2 mg) compared to 6 weeks of Placebo. Improved agitation, NPS, cognition and nutrition

2015(van den Elsen et al.)

Tetrahydrocannabinol for neuropsychiatricsymptoms in dementia: a randomized controlled trial.

THC did not reduce NPI scores compared to placebo, but well tolerated and did not produce more or different adverse events than placebo

2016(Barak et al.)

Safety and Efficacy of Medical Cannabis Oil for Behavioral and Psychological Symptoms of Dementia: An-Open Label, Add-On, Pilot Study.

Use of THC oil reduced CGI and NPI scores

Common Misconceptions

• Hemp CBD vs CBD from Cannabis

• Indica vs Sativa

• Nabiximols (Sativex) Spray

• Nabilone use as an alternative

• Cannabis dependence and withdrawal

Strain Breakdown

Indica vs Sativa

Nabiximols (Sativex)

• Cannabis-based oral spray - approved for MS

• Ingredients are extracted from cannabis plant concentrate

• Each spray (100 µL) contains 2.7 mg delta-9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD). Nonmedicinal ingredients: ethanol, propylene glycol, and peppermint oil

• Also contains terpenes and other cannabinoid compounds

Nabilone Alternative

• Nabilone is a synthetic isomer of THC

• Off label use is often for chronic pain

• Side effects: drowsiness, euphoria, anxiety, paranoia, palpitations, dry mouth, insomnia, lightheadedness, headache

Dependence and Withdrawal

• Tolerance and dependence can occur with cannabis use

• Heavy cannabis use follows a similar path to other drugs of abuse that cause a blunting of dopamine release

• Withdrawal

• Dependence often occurs after taking chronically or in higher amounts

• Average ½ life of THC-based strain is 3-4 days, and can take up to 3-4 weeks in chronic users

Most common reasons for use among older adults • Pain management

• Sleep

• Dementia with neuropsychiatric symptoms/responsive behaviors

• Polypharmacy

• Anxiety/Depression/Appetite

Routes of Administration

Cannabis oils

• Convenient

• Start low at 0.1-0.2 ml and place directly on tongue or in fatty substance like pudding

• Recommend initial use to be in the evening

• Increase dose by 0.05-0.1 ml on scheduled basis

Cannabis capsules

• Cannabis oils in capsule and soft gel form

• Strains available similar to oil selection

• Can be expensive if patient requiring multiple doses throughout the day (60 caps = $75-200)

Cannabis Spray

• LPs are introducing oral sprays that are similar to the oil selection currently available

• 1 spray = 0.1 ml

• Onset of action 15-30 minutes

• Duration of action less than oil

• Breakthrough pain

Topical

• Purchase oil and cream base separately from LP and mix the oil into the cream as instructed

• Apply to affected area 1-2 times daily

• Does not penetrate systemically

• Indicated for localized pain

• Numerous N of 1 studies looking at topical cannabis for would healing with promising results

Special Consideration in LTC patients • Cognitive impairment

• Swallowing difficulties

• Falls risk

• Potential for enhanced side effects of cannabis to be felt

• Therefore, oil, capsules and sprays generally more convenient and safer route of administration in LTC patients

Contraindications:

• Contraindicated in: active ischemic heart disease and psychosis (except CBD-predominant strains)

• Systolic blood pressure <100 as cannabis may lower blood pressure by as much as 40 points

• Atrial fibrillation with unstable INR and rapid heart rate as cannabis can worsen

Adverse Effects

• 3 D’s - dry mouth, dizziness, drowsiness

• Change in appetite, weight loss is possible!

• Psychoactivity (THC)

• Perceptual alternations (eg. Depth)

• Headache, and changes in bowel habits

• Short-term memory and attention impairment (high THC)

• Palpitations and increase in heart rate by 20-50%

• Postural hypotension

Drug Interactions• CBD is a potent inhibitor of CYP3A4 and CYP2D6 and

thereby may increase serum concentrations of the following:

• Macrolides

• Calcium channel blockers

• Benzodiazepines,

• Antihistamines,

• Anti-psychotics such as haloperidol

• Some statins (atorvastatin and simvastatin)

• SSRIs

• Tricyclic antidepressants

• Beta blockers

• Opioids

The Medical Document

• Medical document = prescription

• Components:

• Quantity of cannabis in grams used per day

**~0.25-0.3 g = 1 ml**

• Duration of use, cannot exceed 12 months

• THC/CBD percentages and indication are optional but recommended to guide dosing

• Recommend to specify oil vs dried product

Oil Prescription – Dosing Instructions CBD oil prescribed

1. 0.2 ml po in the evening – hs

2. Can be mixed with high fat/protein substance

3. Continue 0.2 ml for 2-7 days and then increase to 0.3 ml if initial dose not effective

4. Continue to increase by 0.1 ml until effective dose reached

5. Do not exceed 1 ml

6. Dose can be divided such that maximum effective dose can be taken twice daily, at least 6-8 hours apart. For example 0.3 ml in am, and 0.5 ml po qhs

Adding/Switching Strains

• Keep the dosing regimen simple (i.e. 0.1 ml starting dose whether it is CBD or Hybrid (THC/CBD))

• CBD predominant strain may take weeks to months to take effect and offering PRN Hybrid dose may help

• Caution with adding capsules to oil formulation

Cost

Dry Product Oil Capsules

$5-15/g $50-200 per bottle

$75-150 for 60 capsules

Using 1g/day x30 days = $150-450

1 Bottle can last 1-3 months

Use 1-3 capsules/day1 month supply= $75-300

Monitoring • Days to weeks to obtain cannabis product

• First follow-up – after 6-8 weeks of use

• Monitor for adverse effects

• Ask patient to take a picture or bring product to appt

• Follow-up questions:

• Dose schedule

• Therapeutic benefit

• Adverse effects (falls?)

• Cost – do the benefits outweigh the costs?

• Effects on cognition/behaviours

Clinical Case

Mr. Payne - Follow-up

• Mr. Payne returns for follow-up 6 weeks later and reports taking 1 CBD capsule daily

• Mr. Payne reports improvement in pain symptoms and is more engaged in conversation

• No recent falls or effects on cognition noted

• No adverse effects reported by patient or family

Mr. Payne’s Med List at 1st F/U

Before1. Tylenol 3 po bid

2. Escitalopram 10 mg po daily

3. Perindopril 4 mg daily

4. Rosuvastatin 10 mg daily

5. CBD capsule daily

3rd Follow-up: Off Tylenol 3 all together

After1. Tylenol 3 po qid

2. Escitalopram 10 mg po daily

3. Perindopril 4 mg daily

4. Rosuvastatin 10 mg daily

Knowledge Translation

https://ccsmh.ca/wp-content/uploads/2020/01/Cannabis_Use_Disorder_ENG_WEB_Jan-21.pdf

Knowledge Translation

Take home points

• Several strain types with variable percentages of THC, CBD and terpenes

• Dosing is individualized and patients/caregivers must be educated to self-titrate to find the lowest effective dose

• Cannabis is offered through Licensed Producers as dried product, ingestible oils, sprays, capsules and topical ointments

Take home points

• A medical document (prescription) is completed and sent to the Licensed Producer

• Most of the evidence surrounding cannabis for ‘geriatric issues’ is considered low quality but research in this area is growing

• Vast amount of case study and anecdotal evidence to support its use

• One person’s side-effects may be someone else’s benefits