Cannabis

The first recorded medical use of cannabis was to treat pain, inflammation, _____________ and nausea in China 5,000 years ago. But it was also used recreationally and it was this use which resulted in its bad reputation especially in the West over the last 60 years.

seizures

Legal medical use is now allowed in _________ states and Cannabidiol (CBD) preparations can be sold legally in _________ states as long as the Tetrahydrocannabinol (THC; psychoactive molecule) is equal or less than _________%.

24

all

0.3

CBD and THC act on specific cannabinoid receptors (__________ and ____________) which define the neuromodulatory endocannabinoid system.

CB1R

CB2R

In the _______ nervous system the endocannabinoid system is known to affect appetite, learning and memory, anxiety, depression, schizophrenia, stroke, MS, neurodegeneration, epilepsy and addiction.

central

In the __________ nervous system and other tissues, the endocannabinoid system is known to affect nociception, metabolism, cardiovascular and reproductive function, inflammation, glaucoma, cancer, liver and musculoskeletal disorders.

periphreal

The endogenous ___________ for these receptors are the arachidonic acid derivatives N-arachidonoylethanolamine (AEA/anandamide) and 2-arachidonoylglycerol (2-AG)

ligands

Cloning of the first endogenous cannabinoid receptor CB1R which is a ___________ coupled receptor (GPCR).

g-protein

THC is a ___________ agonist of both cannabinoid receptors and its psychoactive and nociceptive actions are via CB1R activation.

partial

CBD appears to have little direct effect on either receptor and may even _____________ THC binding.

antagonize

True or False?

It is thought that CBD can interact with other receptors apart from CB1R and CB2R.

True

Both CB1R and CB2R act predominantly via the heterotrimeric G-protein Gi/o to inhibit adenylate cyclase and reduce ____________ levels.

cAMP

CB2R, in addition to inhibiting adenylate cyclase and decreasing cAMP levels, also appears to activate ____________ and affect gene expression.

MAPK

_____________ promotes neuronal survival by activating PI3K/AKT and JNK pathways.

CB2R

Brain __________ activation can affect neuronal excitability. For example, __________ agonists can inhibit the ventral tegmental area dopaminergic neurons which are involved in reward-related behavior, motivation, addiction and motor functioning.

CB2R

CB2R

THC is a very ____________ compound.

It has a rapid peak in the brain and eventual distribution into fat tissue

hydrophobic

Does CBD or THC have a faster time course of the plasma concentration?

THC

THC and CBD are principally metabolized (oxidized) by the cytochrome __________ system to decrease hydrophobicity (Phase 1 Metabolism) and are then typically conjugated with ____________ for excretion (Phase 2 Metabolism).

P450

glucuronide

Marijuana is a Schedule ____ substance under the Controlled Substances Act (DEA status as of 4/2020), meaning that it has a ________ potential for abuse, no currently accepted medical use in treatment in the United States, and a lack of accepted safety for use under medical supervision.

This of course contradicts the fact that currently 24 states have allowed its medical use!

1

high

Sativa contains greater amounts of __________ than __________.

THC > CBD

Indica contains greater amounts of __________ than __________.

CBD > THC

CBD stands for

cannabidiol

THC stands for

tetrahydrocannabinol

Marijuana is derived from __________

sativa

Hemp is derived from ___________ and has low to no ___________. It is a fibrous product from the stem of the plant and from the seeds of the sativa plant.

sativa

THC

Hemp and marijuana come from the _________ plant

cannabis

CBD oil is oil extracted from the _____________ and ___________ of the sativa plant

flowers

leaves

CBD oil hemp variety must contain no more than _________% THC

0.3

Is CBD oil associated with psychotropic effects?

No

In what 4 states must pharmacist dispense marijuana

Connecticut

Minnesota

New York

Oklahoma

What other 4 states pharmacists can dispense marijuana but are not required to?

Arkansas

Ohio

Pennsylvania

Utah

Requirements for obtaining marijuana at a pharmacy include:

i. Closed distribution

ii. Certain dosage _________

iii. Patients and providers ______________

iv. Qualifying medical __________

v. Required _______________________

forms

registered

condition

continuing education

Conditions that medical marijuana is used for

AIDs

Cancer/Nausea

Hep C

Pain

Alzheimer's disease

Crohn's disease

Migraines

Tourettes

Arthritis

Epilepsy

MS

Terminal illness

Asthma

Glaucome

Opioid treatment

Is recreation cannabis legal in NC

No

Is medical cannabis legal in NC

No

NC is dispensing synthetic _______

THC

Dronabinol (Marinol) is often used for anorexia with _______ and chemo-induced ____________

AIDS

N/V

Nabilone (Casamet) is often used for N/V associated with __________

cancer

K2, Spice, Kush, Kronic acts on ____________________ receptors. They are not marijuana or ______________-derived.

cannabinoid

cannabis

Pros for legalization of marijuana include

evidence of efficacy

ample supply

more research opportunities

quality, consistent products

decreased stigma

Cons for legalization of marijuana include

gateway drug

public health concerns

adverse effects

increased adolescence access

THC in the literature states its _________ effective for:

i. chemo-induced N/V

ii. MS

iii. Neuropathic pain reduced by 30%

possibly

based on the literature, it is unsure is THC is effective for what?

Anorexia

Crohn's Disease

Dementia

Fibromyalgia

Glaucoma

Migraines

Parkinson Disease

Rheumatoid Arthritis

THC Dosing:

Smoking = __________

2mg

THC Dosing:

Retail edible = __________

10mg

THC Dosing:

Medical edible = __________

100mg

THC Dosing:

Retail tincture = __________

1000mg/container

THC Dosing:

Medical tincture = __________

4000mg/container

What is the onset of THC is smoked vs. edible consumption?

10 minutes

1-3 hours

What is the peak effect of THC when smoked vs. edible consumption?

30-50 minutes

3 hours

What is the duration effect of THC when smoked vs. edible consumption?

4-6 hours

Up to 24 hours

THC safety includes _________ impairment, weight gain, __________ (reported 10% of uses have a sign of dependence, greater in adolescence population)

driving

addiction

The Farm Bill is updated every ____ years, with the most recent update in 2018. It discusses expansion of previous hemp-related policies. It allows the transfer of hemp products across _______ lines. No restriction on sale, transport, or ___________ of hemp. Section 12619 removes hemp-derived products from its schedule _____ status under the Controlled-Substance Act, but the legislation does not legalize CBD generally.

5

state

possession

1

CBD in the literature

Epidiolex is commonly used for ____________. Lennox-Gastaut syndrome, Dravet syndrome in children ≥ ____ years of age

It is a strawberry flavored solution

Epilepsy

2

CBD in the literature

Sativex is commonly used in _______. Not available in the US. Comes as an oral spray with CBD and THC.

MS

Other disease states CBD is used in and their effect:

Alzheimer's disease: prevent _______ plaque development

amyloid

Other disease states CBD is used in and their effect:

Anxiety and Depression: conflicting results in social ______ and public speaking

anxiety

Other disease states CBD is used in and their effect:

Cancer pain: ____________ pain improvement

modest

Other disease states CBD is used in and their effect:

Insomnia: increased sleep ___________ in higher doses

duration

Other disease states CBD is used in and their effect:

Neuropathic pain: ____________ pain improvement

modest

Other disease states CBD is used in and their effect:

Parkinson's disease: no difference control of motor effects, ___________ QoL

improved

Other disease states CBD is used in and their effect:

Schizophrenia: no difference in cognitive impairment or neurological complications. Mood and suicidality not ______________.

worsened

Other disease states CBD is used in and their effect:

Bipolar diorder: manic episodes ______ improved

not

Other disease states CBD is used in and their effect:

Crohn's Disease: _______ disease improvement

no

Other disease states CBD is used in and their effect:

Diabetes: ________ glucose improvement

no

Other disease states CBD is used in and their effect:

Tobacco dependance: _____________ less

smoked

Other disease states CBD is used in and their effect:

Substance use disorder: reduced cannabis use, but not ___________ symptoms

withdrawal

Cannabis drug interactions:

i. _________ depressants

ii. THC CYP1A2 inducer

iii. CBD CYP3A4 inhibitor

iv. CBD CYP2D6 inhibitor

CNS

Cannabis drug interactions:

THC _________ concentrations of:

i. Clozapine

ii. Duloxetine

iii. Naproxen

iv. Cyclobenzaprine

v. 2nd gen. antipsychotics

decreases

Cannabis drug interactions:

CBD _____________ concentrations of:

i. CCB

ii. Benzodiazepines

iii. PDE5 inhibitors

iv. Tricyclic antidepressants

v. Beta-blockers

vi. Opioids

increases

_________ has evidence to support MS, neuropathic pain, anorexia (AIDs), N/V in cancer/chemo

THC

__________ has evidence to support epilepsy, MS

CBD

_________ is a crop from the Pacific Islands. It is brewed or chewed. Often enjoyed socially.

Kava

Kava mechanism:

Potentiates GABA2 receptor, _________ antagonist, binds to CB1 receptor, ___________ monomine oxidase B

dopamine

inhibits

Kava in the literature:

Anxiety: comparable to ____________10mg.

Effects are seen after _________ of use, not a one-time event.

Dose: _______-________mg daily

buspirone

weeks

100-300mg

Kava in the literature:

Does is cause benzodiazepine withdrawl?

No

Kava in the literature:

Insomnia: ______mg daily for ____ weeks

200mg

4

Kava Kinetics and Dynamics:

Absorption: ______-_____ hour peak

Metabolism: _________ hydroxylated metabolites (rats)

Excretion: _________ and ________

Half life: _____ hours

1-8

2/3

urine, feces

9

Kava safety:

-Extrapyramidal side effects, hepatotoxicity, ________ failure (100 cases over one month)

-Kava-induced dermopathy

_____% in regular users

______% in heavy users

-GI ARDS

-Dizziness, drowsiness

-Oculomotor equilibrium disturbance

liver

45

78

Kava drug interactions:

Inhibitor of CYP2C9, CYP2C19, CYP3A4, CYP2D6, CYP1A2

________ depressant

______________ medications

CNS

Hepatoxic (chemical driven liver damage)

Kava take home points:

-Used for stress relief, social beverage. _____________ efficacious for anxiety but evidence-based therapies should be utilized first in mental-health conditions.

-Should be avoided in ________ impaired, patients with _________, patients on drugs with hepatic metabolism

somewhat

hepatically

alcoholism

Kratom is derived from the leaves of southeast asian evergreen tree and used as a _________ or stimulant

sedative

Kratom is an opioid _________. It should not be used for substance use disorder.

agonist

Kratom

Using less than 5g gives what effect?

Using more than 5g gives what effect?

sedative (narcotic-like effect)

stimulant

How is kratom supplied or prepared?

The leaves are _______, then grinded up into a powder or extract form. It can also be used as ______.

dried

tea

What is the evidence for using kratom for medication conditions?

No proven evidence but often seen used for pain relief, mental health, coping mechanism of drug withdrawl.

Safety consideration of kratom:

Large doses can cause nausea, dizziness, aggression, __________, overdose potential, trouble breathing, and possibly death. Linked to dependance and withdrawal symptoms similar to those of common __________.

hallucinations

opioids

Safety consideration of kratom:

Not regulated, risk of ____________. Case of cross-contamination with salmonella years ago that caused 90 people to become sick.

contamination

What 3 cannabis species are there?

cannabis sativa

cannabis indica

cannabis ruderalis