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hi there.

I hope you're excited to learn something new today.

In the landscape of medical cannabis for chronic pain, GPS

have reported a more than 65% increase in chronic pain

presentations in the past decade.

Given the health concerns and addiction risks associated with common

only prescribed pharmaceuticals for pain like nonsteroidal anti inflammatories and

opioids, medical professionals and patients are looking to cannabinoids to

manage chronic pain.

As of October 2020 the TJ is approved more than

72,000 medical cannabis applications.

Private sector data suggests that up to 80% of that

could relate to pain presentations.

So let's jump into this topic starting with the Indo

cannabinoid system.

We'll look at this integral body system before we assess

how we can target it to optimize chronic pain management.

Cannabinoid receptor Canavan Hide researcher Professor Vince Enzo de Marzo

summarizes the Indo cannabinoid system in five words.

Eat, sleep, relax, forget and protect.

The end of cannabinoid system, or CCS, is present in

all vertebrate animals and is an integral regulator in home

yo Stasis throughout the body.

The CS begins establishing from 14 weeks gestation in humans

and is essential in the initial formation of neuronal connectivity.

In general, it has influence over the activity of digestive

and endocrine hormones, the immune and nervous systems the body

produces. Endogenous cannabinoids that interact with this system and exogenous

cannabinoids from cannabis also have potent actions.

Yet it might surprise you to know there are a

number of other herbs that have Canada Memet IQ qualities

or otherwise interact with the E.

C s al calamities in the echinacea species interact directly

with the E.

C s fire cannabinoid receptors one and two, which may

have implications for inflammatory conditions and immune function by mediating

actions of intelligence and Truman of courses Factor Alfa.

There are a number of other plants that are agonist

for PCs, receptors or impact enzymatic processes in the system.

But for now, let's move on to components of the

entire cannabinoid system.

I won't spend long here, but I felt this is

a great example of the complexities of the under cannabinoid

system. This image shows the reactions between cannabinoids, receptors, enzymes

and a whole range of other processes in a single

cell. While this is an artist interpretation, it's largely biologically

accurate and gives an understanding of the huge influence of

the CS and its components.

Given I've already mentioned receptors, let's stop there.

The two key ones in the E.

C s a G protein coupled receptors, namely cannabinoid receptors,

C B one and C B two.

There are a number of other part G protein receptors

that play a role, but that's outside of today's scope.

Both receptors have found systemically in the body.

They have different areas of density if you like.

CB one receptors are abundant in the brain and nervous

system, and ah, primarily famous for their interactions with Delta.

Nine th see Facilitating the intoxicating effects of cannabis CB

one receptors contribute to maintaining home your Stasis via processes

in the nervous and endocrine system.

In influencing serotonin, dopamine and HP a access pathways, they

have both the direct and indirect role in mood, sleep,

stress, pain and more.

CB one receptors are found in the cardiovascular and digestive

systems in the heart.

CB one receptors more moderate dilation and contraction and vessels

thereby maintaining blood pressure.

And in the gastrointestinal tract, they have influence over appetite

hormones, motility and digestive secretions.

CB two receptors do not market modulate You forgot intoxicating

effects. But they do have a strong presence in the

immune and reproductive systems, their key mediators in the regulation

of inflammation, pain and the integrity nervous system, while in

the skeletal system they modulate bone density through supporting osteoblasts

and osteoclasts.

O Genesis.

There are a number of other receptors that act in

this CCS symphony.

Get only a few more.

Get our honorary mention here and that it's serotonin receptors.

Tr P V s and P p a r S

T L P V one receptor accounts for the mechanistic

action of Indo Cannabinoids and CBD and pain presentations in

part and P P.

A. Receptors are thought to play roles in both inflammation

Neuro protection whilst five ht three receptor activation by Ananda

Meid results in analgesia, the next component of the Indo

cannabinoids, the two most abundant and well researched and oh

cannabinoids are Ananda Mydd and to a rack.

O'Donnell, Glycerol or to a G to E.

J. Has a high affinity for both receptors, with basil

levels approximately 1000 times higher than Ananta Mind, which has

a lower affinity for CB one receptors in an even

lower affinity for C B two to age is thought

to have rain over the brain and nervous system while

in an demise influences spread more systemically.

There are a number of other inter cannabinoids, such as

P E A and N a d A, both of

which have relevance to pain processes and inflammation.

The final component of the CS for today.

The enzymes involved in regulating its function n a p

e is the synthesizing enzyme.

Fernanda Mydd and P I.

P two enzymes build to a G fatty acid, amino

hydrolyzed and moderate pays of the primary Who were the

primary? Oh fatty acid and Maynor Hydra lays and monitor

Astle glycerol lie pays at the primary enzymes in the

breakdown of an anti mine into a G respectively.

Though there are other metabolic pathways in which they integrated

Now that we have a bit of an understanding of

the E.

C s.

Let's look at cannabinoids seen here in light green is

Delta nine th see the most commonly talked about cannabinoid,

preclinical and animal trials show it to have analgesic, anti

inflammatory and anti a medic action on top of its

infamous youf orient or intoxicating effects, CBD is most well

known for its anti left, anti epileptic and anti convulsant

action. However, it's also known to have an algae sick

politic antipsychotic, antioxidant, anti spasmodic, important anti inflammatory actions.

I'd like to make it an important right here on

psycho activity.

I find this time is often mislabeled in the academic

and medical community alike, with most sources stating CBT to

be non psychoactive.

This is, in fact, a misrepresentation.

Psycho activity determines the substance has an action on hormones

or nervous system, signaling that influences cognition, mood or behaviors.

Given CBD has an excellent qualities attributed in part to

its influence over serotonin pathways.

It and other cannabinoids should truly be labeled psychoactive.

However, unlike Delta nine th c and a few others,

they are non intoxicating.

Moving on there are over 100 cannabinoids.

Some others include T H C A and C B

D A.

The Pacific precursors, for which all others T H C

and C B D type compounds are derived.

Minor cannabinoids with potential energetic action include C B D,

A, C B, C, C, B G, Delta 80 HC,

Delta, T, H, C V and the recently discovered T

H C P.

You'll also see Turpin's here.

Turbines are important features in medical cannabis formulations, so it

means like Huma Lane beta carry off.

Elaine MasseyEn have analgesic and anti inflammatory actions that can

contribute to pain relief.

Together, Cannabinoids, Turpin's and other photo chemicals engage in a

phenomenon known as the entourage effect, whereby cannabinoids accent logistically

with one another to create greater or different effects than

they would in isolation.

For Marco Kinetics of cannabinoids air vary depending on the

route of administration.

Medical cannabis can come in capsules, oils, sublingual, sprays, patches,

dissolvable wafers, rectal suppositories and more.

The traditional inhalation offers the most optimal.

Bio availability, however, comes with obvious risks.

Thus Orel and sublingual applications of the most commonly utilized

in practice, Orel and Sublingual bio availability ranges from 2

to 14%.

Mucosal absorption in the mouth limits.

First possible metabolism in this case and therefore improved by

availability compared to gastrointestinal absorption inhalation by smoking and vaporization

offers 10 to 35% of our availability.

Transdermal applications are difficult to measure, but CBD seems to

have a tenfold high absorption through the skin.

The th see off the Malik administration between four and

60% and rectal, approximately 13% in general, with cannabinoids by

availability, can be quite erratic and subject to into individual

variations, especially when comparing cannabis naive individuals to experience users.

The lipo flicked nature of cannabinoids mobile why they distributed,

and vascular rised tissue, including the heart, lungs, spleen, kidney

muscles and at a post tissue onset of action, peak

plasma levels and duration of therapeutic effect differ greatly depending

on the route of administration.

Cannabinoids metabolized primarily by C Y P 4 50 enzymes

for T H C.

That is predominantly C Y P tune C nine to

C 19 and 384 for C B D.

C Y P three a four to C 19 of

the main ones and in terms of elimination, cannabinoids of

primarily excreted through the feces but also, uh, a smaller

met through the urine.

So what does the research say about medical cannabis for

pain? The evidence is promising.

All those still mixed enoughto warrant further investigations.

This is attributed to varied photochemical profiles endorsing of formulations,

a ZX well as differences in types of pain that

have been investigated in the 2018 try, A 177 patients

with treatment resistant cancer pain, 43% showed a 30% reduction

in pain scores, while 30% may not seem large in

terms of chronic pain management, it is clinically significant value.

A small study of fibromyalgia patients reported 50% to be

able to cease their pain medications.

And there's plenty of supporting evidence for medical cannabis in

pain and inflammation that's associated with arthritic conditions.

In terms of CBD, solid amounts of human clinical data

is still lacking, although it seems to be effective, especially

neuropathic pain.

UH, numerous examples for CBD to be more effective and

algae sick when combined with even small amounts of th

C or other cannabinoids.

There are also a number of systematic reviews and meta

analysis concluding, uh, cannabinoids may provide effective pain relief, especially

in difficult to treat instances.

There are dozens of farmer co dynamic mechanisms can happen

whites, but specifically in relation to pain.

The analgesic action of th C is attributed to it

binding with CB one receptors prevalent along pain pathways in

the CNS, where it has an inhibitory effect on calcium

ion channels and therefore neurotransmitter availability.

CBD has an algae zik action being associated with its

agonists. Agon is, um of T R P v 15

ht three and five ht.

One A.

Receptors. It's acidic form CBD a selectively inhibits cox two

and therefore inflammatory prostaglandin production in a similar fashion thio

nonsteroidal anti inflammatories, which give it a huge potential for

replacing or augmenting other pain medications as within any drug

or medicine, there are potential side effects.

T H C is well known.

Side effects that include euphoria and paranoia are the so

called side effects that can also be used to therapeutic

benefit. Include appetite, stimulation, sedation on increased memory loss.

The letter has a huge relevance for PTSD sufferers re

experiencing traumatic events.

Side effects of CBD include drowsiness, gastrointestinal upset and nausea.

While patients report these generally to be tolerable, a personalized

medicine approach with slow tied direction generally mitigates the manifestation

of most side effects in terms of interactions, drugs or

substances that are processed by C Y.

P. 4 50 enzymes.

Uh uh, In terms of interactions, drugs or substances that

are processed by C Y P for 50 enzymes have

the potential to interact with cannabinoid medicines, especially given the

involvement of C Y P three a four.

In more than 60% of pharmaceutical drug metabolism, cannabinoids, especially

CBD, have the potential to enhance or inhibit their metabolism.

C Y p 4 50 Cautions of general in relation

to medical cannabis and have yet to be correlated in

human trials.

Cannabinoids have the ability to both enhance and synergistically act

with opioid medications.

Teetsi particularly has the potential Azan opioid sparing action.

They have bean proven interactions with one epilepsy drug clubbers

um, and some research showing liver enzyme changes in Children

administered CBD again.

Careful tight rationing, ongoing monitoring as with any drug to

avoid negative interactions on dhe adverse effects moving forward.

Prominent cannabinoid researcher Ethan Russo and other thought leaders in

the scientific community theorized that many difficult to treat and

otherwise idiopathic conditions may be related to deficiency or dysfunction.

In the e.

C. S in Dimitrios is fibromyalgia multiple sclerosis, PB, Parkinson's

disease. You're gonna make me do it again

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