Elizabeth Plant Chief Medical Officer RegPharmNZ FPS ...

An Overview of Medical CannabisAugust 2019

Elizabeth PlantChief Medical Officer

RegPharmNZ FPS MRPharmS MHSc(Distn) PGDipClinPharm(Distn)

+64 27 244 [email protected]

Endocannabinoid system

E N D O C A N N A B I N O I D S

• Found throughout the body (brain, organs, connective tissue, glands, immune cells

• Goal of homeostasis—maintenance of stable internal environment

An Overview of Medical CannabisAugust 2019Copyright Eqalis Group NZ Ltd 2019


Endocannabinoid system

A S U M M A R Y

• Natural endocannabinoid receptors (CB1 and CB2 and GPR55-CB3)

• CB1: Highly concentrated in brain/executive function

• CB2: Emphasis on immune system

• Two major endocannabinoid ligands:

• Anandamide• 2AG

• Act by reducing the pre-synaptic transmitter (negative feedback system)

• Phyto-cannabinoids mimic the action of the natural endocannabinoids


The goal is homeostasis…

• Immune Functions• Reproductive System• Pleasure/pain perception• Mood elevating/antidepressant/

anxiolytic effects• Appetite• Memory/Cognition/

Neuroprotection• Body movement and sensory

processing (taste, touch, smell, hearing and sight)

• Sleep• GI tract• Cell signaling/inflammation/

immune function


What’s in a cannabis plant?

Two main cannabinoids



Cannabinoids impacting wellness


Terpenes: More than 200 in cannabis



All cannabinoids, terpenes (smell) and flavonoids (colour) have therapeutic potential…

F U L L S P E C T R U M V S . I S O L A T E S

• All cannabinoids, terpenes (smell) and flavonoids (colour) have therapeutic potential

• Different strains produce different profiles

• All forms of the raw, decarboxylated and aged components have therapeutic potential

• Isolates: Just one or two cannabinoids (THC and CBD)

• Entourage Effect: Where using full spectrum or a selected range of components to achieve better effect than isolates alone.



Understanding medical cannabis



Indica vs. Sativa

Indica

• Short bushy, wide leaves, grows fast, higher yields

• Higher CBD/lower THC• Increases dopamine • Provides sense of deep body

relaxation

Sativa

• Tall, thin with narrow leaves

• Take longer to grow, requires more light

• Provides a more energizing experience

Evidence


Report: The Health Effects of Cannabis and Cannabinoids www.nap.edu/catalog/24625/the-health-effects-of-

cannabis-and-cannabinoids-the-current-state

https://www.drugsandalcohol.ie/26086/1/Cannabis_medical_use_evidence.pdf

Professor Michael and Dr. Jennifer BarnesCannabis: The Evidence for Use

Handouts at EQALIS Stand with useful references and summary documents


Evidence

http://www.nap.edu/catalog/24625/the-health-effects-of-cannabis-and-cannabinoids-the-current-state

https://www.drugsandalcohol.ie/26086/1/Cannabis_medical_use_evidence.pdf


Good evidence

• Chronic Pain• Spasticity with MS (other

spasticity cause)• Epilepsy• Antiemetics for treatment of

chemotherapy-induced nausea


Moderate evidence

• Fibromyalgia• Sleep disorders• Appetite stimulation (HIV)• PTSD


Some evidence

• Agitation in dementia• Glaucoma• Bladder dysfunction• Tourette’s syndrome• Aspects of Parkinson’s disease

“Cannabis is the only thing that gives me relief, it lets me sleep all night.” —Helen Kelly


Side effects are mild and well-tolerated

S I D E E F F E C T S

• Mild and well tolerated• Most SE due to THC-psychoactive

component, drowsiness, dry mouth, disorientation, confusion

• Can cause high heart rate• Smoking can cause worsening

respiratory symptoms/increased chronic bronchitis (no smoking allowed-only vaping)

• Cannabis Use Disorder: Dependency (9% chronic users)-mainly high THC/low CBD

• Cannabis Hyperemesis Syndrome:Severe vomiting. Rare

• Allergy to cannabis or carrier oils

Contraindications


• Children except for CBD/low THC products for intractable epilepsy

• Adolescents (<20years and <25 in young males)

• Pregnancy and breast-feeding Mothers • Those with unstable psychiatric conditions and

where high risk of psychosis or schizophrenia (family history)

• History of suicide attempt or suicide ideation• Severe cardiovascular disease (arrhythmia/post

MI)• Post stroke• Immunological conditions (especially

liver related) • Cirrhosis-Hep C Related• Kidney Disease • Cannabis Use Disorder (THC)


Cannabis naïve vs. non-naïve

Daytime vs. nighttime

Oral oils vs. inhaled short term relief

Full spectrum (extracts) vs. isolates

Indica vs. Sativa profile

Terpene profile

Dosing considerations


Routes of administration Route Smoking Vaping Oral

Oral Mucosal

Topical

Onset 5–10mins 5–10mins 1–3 hours 15–45 mins Variable

Duration 2–4 hours 2–4 hours 6–8 hours 6–8 hours Variable

Bioavailability 2–56% 40%6–20%(1st Pass)

20% 5% systemic

• Recommended that a symptom chart is kept to record dosing and symptom control.

• Genetic variation regarding effect and DNA profiling is useful to identify optimal treatment.


• For Cannabis naïve:• Start with CBD and add in THC at

night only initially • Non Cannabis naïve:

• Can start with CDB and THC mix• CBD should always be given with THC

as can balance out side effects• Aim for higher CBD and low THC• Very personalised response—

significant variability• Full extract (spectrum) products need

much lower dosing than isolates• Use oral oils as base of therapy with

vaporised products for rescue/breakthrough

Key principles:Start low, go slow, stay slow


CBD dosing:Start low, go slow, stay low

S T A R T W I T H 5 – 1 0 M G I N D I V I D E D D O S E S ( B D T O T D S )

• Increase by 5–15mg every 3–5 days up to 100/200mg daily in divided doses

• Try to take consistently with/without food.

Exceptions to max dose:• Psychosis: Max daily CBD dose is

800mg• Seizure disorders: CBD

20–50mg/kg (or 2,500mg max daily dose)


THC dosing:Start low, go slow, stay low

S T A R T A T 1 – 2 . 5 M G T H C D A I L Y ( B E D T I M E T O L I M I T A D E )

• Increase slowly (every 3 days) in 1–2mg increments and increase as needed and as tolerated to 10mg THC - equivalent dose BID-TID

• NB: Professor Barnes recommended 15–20mg maximum daily dose.

Recommended maximum total daily dose equivalent of THC is 30mg/day. (Russo)


Inhalation: Vaping oil or dried flower • Start with 1 inhalation and

wait 15min. • Then increase by 1

inhalation every 15–30 min until desired symptom control has been achieved.


Tolerance

• Average about 10-12 months• Try increasing dose• Try reducing dose (biphasic

effect-ID the optimal dose)• Drug holiday• Strain swop• Try THCA or CBDA


Cease medical cannabis if desired effect not apparent after 4–12 weeks, or

psychoactive effects/SE prohibitive

Ceasing cannabis


Drug interactions

P H A R M A C O D Y N A M I C I N T E R A C T I O N S

• Additive sedation effect with alcohol/barbiturates/benzodiazepines and possibly opioids

• Drugs with sympathomimetic activity (tachycardia, hypertension)

• CNS depressants (drowsiness, ataxia)• Drugs with anticholinergic effects

(tachycardia, drowsiness)


Drug interactions

C Y T O C H R O M E P - 4 5 0 I S O E N Z Y M E S

• THC induces CYP-1A2 and can reduce levels of drugs metabolized by CYP-1A2

• THC is metabolised by CYP-2C9 and CYP-3A4—watch patients who are poor metabolisers of CYP2C9—3x levels THC

• Inhibitors of CYP2C9—will result in increase THC levels

• Ketoconazole (inhibitor of CYP-3A4) shown to increase THC levels by 1.2–1.8 (as likely with other 3A4 inhibitors)

• Rifampicin (a CYP3A4 inducer) reduce THC levels by 20–40%


Drug interactions

• CBD is a potent inhibitor of CYP-2D6 and CYP-3A4 thus can increase levels of drugs metabolised by these isoenzymes

• Substrate of CYP 3A4 and CYP2C19• Ketoconazole shown to increase

CBD levels by about 2- fold• Rifampicin reduces CBD levels by

50–60%• Other CYP3A4/CYP 2C19 inhibitors

and inducers could effect CBD levels.


C A U T I O N S

• High dose CBD with clobazam, where high levels of a sedating metabolite, N-desmethyl clobazam will require a dose reduction for that drug

• Warfarin: THC and CBD increase warfarin levels -in patients taking warfarin, INR monitoring is suggested during initiation and up-titration of cannabinoids.

Drug interactions:Alert

Summary


Complex plant with therapeutic potential

All cannabinoids, terpenes(smell) and flavonoids (colour) have therapeutic potential-family of medicines

Different strains provide different effects

Evidence is increasing (isolates vs full spectrum)

Improve QALY but rarely cure for conditions

Dosing-start low, go slow and stay low (THC=SE)

Always give CBD with THC to moderate psychoactive SE

Monitor if concomitant with clobazam or warfarin

Wide interpersonal variation

Summary

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