SweetSue's Class Notes

Study Hall organization - continuing work: through page 25 and working backwards through page 353

BASIC BIOLOGY

Post #59 - 2-minute neuroscience:The Blood Brain Barrier (BBB)

Post #39 - How Receptors Work: Agonists and Antagonists

Post #46 Fatty Acid Binding Proteins (Society of Cannabis Clinicians)

Post #4 - First Pass Metabolism

Post #17 - Bioavaibility of routes of administration (Green House Labs White Paper)


THE ENDOCANNABINOID SYSTEM

Post #40 - The Scientist (video on Raphael Mechoulam, credited as the discoverer of the ECS)

Post #2 - An introduction to the ECS

Post #15 - Pharmacological actions of non-psychotropic cannabinoids (with the indication of the proposed mechanisms of action)

Post #71 - Relative Affinities of Various Cannabinoids to Bind to CB1 and CB2 Receptor Sites

Post#74 - Minor Cannabinoids and Cannabis Terpenoids: Ethan Russo for The Society Of Cannabis Clinicians

Post #163 - Dr. Jeffrey Hergenrather on cannabinoid ratios.

Post #90 - Taming THC: Potential Cannabis Synergy - Ethan Russo (PDF file)

Post #141 - Terpene Boiling Points (link)


SUPPORTING THE ECS

Post #171 - The value of hemp seeds.



CONCERNING CANCER:

Post #5 - Competitive Inhibition

Post #3 - Demethylation

Post #50 - Demethylation: Essential (Phenolic) Oil Capsules

Post #56 - Cajun's thoughts on frequency of Demethylation

Post # 64 LCFAs can't cross the BBB? If this is the case, will this effect carrier oil choices for brain tumors?

Post #131 - Cannabinoids And Cancer: a flow chart (Journal of British Pharmacology)

Post #150 - ShiggityFlip explains the flow chart.

Post #154 - ShiggityFlip and SlowToke continue the invaluable conversation on how cells perform apoptosis (natural, safe, programmed cellular suicide).

Post #158 - ShiggityFlip explains Molarity as a concept of concentration. (In answer to a question about nano molars)

[COLOR="#000FF"]DRYING AND CURING[/COLOR]

Post # 3852 - DrZiggy's Low and Slow Drying Technique

Post # 3856 - AKgramma on curing in the refrigerator

STRAIN TEST RESULTS

Post #309 - neikodog's test results for AC/DC x Querkle #2

MAKING OILS

Decarboxylation

Post #159 - panacea's decarb method in a BBQ (reformatted version :battingeyelashes:)

Post #83 - A study showing the slow rate of cure THC to CBN (not what everyone expected).

Post #86 - More thoughts on decarbing for maximum THC and CBD.

Post #94 - More discussion on decarbing, concerning loss of THC over time

Post #117 - Decarbing in a roasting bag.

Post #118 - Rambo's decarb experiment.

Post #49 - An Overview of Methods to Produce Concentrated Cannabis Oil
- Post #207 - SCET modificationsLab Rat has abandoned the SCET method of extraction in favor of methods known to produce better purity.

Post #211 - cajuncelt on expected oil pulls.

PsyCro's Olive Oil Extraction

Post #55 - CORRECTED POST:PsyCro's corrections to his fresh-harvested oil

Post #169 - fookinel's thoughts on essential oil choices, with valuable links. The next post continues this discussion.

Post #214 - fookinel&/ continuing thoughts on PsyCro's olive oil extraction.

Post #222 - PsyCro starts playing with pressure cookers. :slide:

Post #120 - wildjim's excellent notes on reclaiming solvent using a distiller.

Post # 3851 - Fresh Harvest Oil


The Washes

Post #200 - panacea's detailing of the washes. ****Excellent Post****

POST #178 - Review of the methods used by SkunkPharm

Post #219 - Winterizing explained

Post # 314 - results from washing with Everclear 151


Choosing The Carrier Oil

Post #80 - Fookinel's excellent thoughts on choice of carrier oil when dosing for particular disease.

Post #172 - More thoughts by fookinel on choosing the carrier oil.

Post # 3833 - CannaDad's guidelines on carrier oils


First Tries

Post #183 - neikodog's first attempt. Post #201 - the wrap-up


MISC THOUGHTS ON OILS

Post #190 - An interesting supposition: could you improve oil potency with a SOG?

Post # 3797 - Steep Hill Labs Cost Sheet


ADMINISTRATION AND DOSING

Post #160 - cajuncelt explains calculating the dose

Post # 3818 - Calculating the dose: Infused oils

Post #176 - PsyCro's thoughts on dosing his oil.

Post #187 - fookinel finishing this conversation.

Post #185 - fookinel calculates the cannabinoid load in PsyCro's olive oil.

Post #218 - Links to Radic-Al Conscious's "Medicinal Cannabis Therapy" and "Medicinal Cannabis Therapies for Cancer"

Post # 364 - Why CannaBudwig works

Post 3792 - a link to the Pain Creme recipe


The conversation on suppositories

Post # 320 - Dr. Jeffrey Hergenrather, MD on the efficacy of suppositories (2015)

Post # 326 - SlowToke on the current thinking of suppositories in the clinical field

Post # 329 - CajunCelt responds on the effectiveness of suppositories made with carrier oils

Post # 346 - PsyCro joins the conversation: Rectal Absorbtion of Cannabis Revisited - Greenbridge Medical Center

Post # 352 - CajunCelt chimes in again

From Post 3809 - Božidar RadiÅ¡ič presentation — Cannabis In Medicine: Practice & Experience (PDF)

Post # 3810 - Božidar RadiÅ¡ič's recommendations for suppository treatment

Following the Regimines B]

Post #242 - fookinel updates patient info (update from Post #173)

Post #3029 - Danolo describes a regimine for RA

Post # 333 - panacea explains the gist of a patient protocol for breast cancer

BIO-BOMBS

Post #161 - cajuncelt's original instructions on the BioBomb and thoughts on initiating a protocol.

Post #95 -fookinel includes links to cajuncelt's original recipe and panacea's adaptations.

Post #121 - BioBombs (our study hall beginnings)

Post #173 - fookinel's tutorial on mixing oils for increased bioavailability. ***Excellent Post***

Post # 334 - BioBomb Smoothies

[COLOR="000FF"]EQUIPMENT[/COLOR]

Post # 3834 - Nova Home Decarboxylator

MISCELLANEOUS STUDY JOY:

Post #3038 - Dr. Courtney on Raw Cannabis

Post #28 - Crash Course Chemistry and Energy: Carbon

Post #29 -Crash Course Chemistry and Energy: Biological Molecules & Crash Course Biology - DNA Transcription and Translation

Post #30Crash Course Chemistry: The Nucleus

Post #35 - Crash Course: Chemistry and Energy -

Post #45 - Support Organization for Medical Cannabis

Pick up on page 26 and 252
 
When we evaluate medications we're looking at efficacy, safety, tolerability and cost.

The ECS is there so we can eat, sleep, rest, protect, relax, and forget.
 
2017 Green Flower Media Cannabis Health Summit - Saturday, May 6, 2017

Preliminary notes

Dr. Alan Frankel - Normalization of Cannabis: Taking a managed dose on a consistent schedule

Cannabinoids
3 forms: endocannabinoids, anandamide, 2-AG
Phytocannabinoids will help the endocannabinoids work more efficiently

CBD and THC - the longer you use them the less you'll need (is this because of the fact that the photos encourage exo?)

120 major , 80-90 minor, hundreds of terpenes, waxes, flavonoids, etc

They've found that the waxes we toss are helpful for topicals

THCa - one of his favorites molecules
- may be as beneficial as THC

Have an assortment of many different extracts for personal adjustment

THCV may be more important than CBD.
- found in African strains
- manages the metabolic system (weight and endocrine issues)

Entourage effect

P450 system - liver enzyme system
Reality is that cannabis doesn't interfere with this system because the phytocannabinoids send a message to the liver that has the liver create more enzymes for the overflow

No receptors of the brain stem so no danger of cessation of breathing or stopping the heart

Cannabinoids are essential nutrition
- it's a vegetable
- in the 1600s tomatoes were outlawed and thought to be dangerous and poisonous

Endocannabinoid deficiency is a nutritional deficiency. Cannabis is the food that fills the need

Anti-inflammatory
-THCa might be the most powerful
- CBD, CBDa also

Anti-spasmodic
- muscular, bladder, menstrual, etc.

neurological

CBD suppresses some immune t-cell function? (12:32)

- euphoria : 85% of those pooled want no euphoria, just healing

- we need consistency in dosing options and protocols


Is Cannabis Safe To Use As Medicine?

Do a keyword search for "marajuiana"You'll find over 25,000 notations for independent, peer-reviewed citations on cannabis

Tylenol will bring up 20,500 notations

We know more about cannabis than any other drug used this widely. Who's saying we need more studies on hydro codons? Less than 1000 citations pop up for that one.

What do you mean by safety? That word has many meanings.

It's not "do no harm". Safety doesn't mean "iniquitous." Clearly it's not the burden of any other drug manufacturer to say that using the substance will be completely risk-free.

Cannabis has less risk than the conventional medicines it would replace. If you judge the safety of medical cannabis in the same way we judge conventional meds it comes out looking substantially better

Criteria you will have to establish

1. Dependence liability: How addictive will this drug be?
- cannabis isn't addictive. About 1 out of 11 will meet this vague definition
- Many take issue with this. The questions are skewed to get positive responses
- The dependence liability of cannabis is only 2 points off caffeine and significantly lower than alcohol

* does cannabis meet the social standards we accept for other therapeutic and non-therapeutic substances

2. Risk of fatal overdose?
- LD50 - at what level will 50 % of the consumers die?
- a low LD50 is a safe drug
- no one has ever died from a cannabis OD

Conscious, breathing, and alive is controlled in the brain stem
- opioids are CNS agents, which is why they can kill
- cannabinoids work outside of the brain stem
- our societies are willing to accept very narrow windows of LD50


3. Side-effects profile?
- common drugs have up to 500 potential side effects listed right on the labels
- cannabis may give you periodontal disease when you're 90, will potentially give you the munchies and you might get high
- most commonly reported fall into what we call "insignificant side effects" like dizziness, dry mouth, drowsiness, euphoria
- cannabis enhances your quality of life and make you want to get out of bed in the morning
- How did we get to the point where we believe we need to feel bad? That euphoria is something to be avoided and called an "adverse side-effect.?"

Those who know cannot unknow. Cannabis won't legalize itself. It'll take our help.

3. Colton Turner - treated his Chron's disease
- swimming accident that triggered disease
- series of ineffective pharma drugs made him a cancer patient with hair
- ended up in wheelchair with no life outside home
- options for him were dangerous pharmacy, surgery, or "alternative treatments"
- alternative treatments led them to Colorado to establish residency and his dad made him "pot brownies" in their hotel room :Love:
- his dad tested potency on himself and dosed his son
- they graduated to a caregiver who supplied capsules and he got his life back
- 7 month - it only took him 7 months to get complete remission

This 17 year old young boy is a prisoner in Colorado, separated by federal laws from a loving family

Your available medicine shouldn't be determined by your zip code

He'd rather be illegally alive than legally dead.

4. Malik Burnett: The ECS
Maintains systemic homeostasis between nervous system and the immune system

Law of 2s

1. Endo
2. Phyto

Receptors
1. CB1 nervous system, pre synaptic
2. CB2 immune , minimizing the amount of inflammation systemically

Seizures: nervous system
- overstimulation between neurons
- cannabis modulates the neurotransmitters to create balance

Chron's disease: immune and digestive
Immune system attacks digestive system
Over activation of immune response against gut wall

Chronic Pain: immune and nervous systems are out of balance and cannabis brings it back into balance

Homeostasis is a moving target, not a static thing. So is dose. Balance is push and pull between the systems and you need to give the body the balance of cannabinoids (proper ratios) to effect the vpcellular change necessary to create balance.

Andy Williams : (Medicine Man) Moving Research Forward

He gets daily testimonies of the efficacy of cannabis as medicine

GREAT AD - FIND THIS AD

He believes we need the research the government keeps saying we need, and he's starting a company to do just that. MedPharm.

Andy encourages you speak up in support of cannabis.



Panel: How CBD can change the world

- inflammation, anxiety,
- Swiss Army knife of the cannabinoids
- multitasker, with effects beyond the ECS
- cannabis-based CBD is more effective

Hemp biosphere
- microorganisms in the environment will influence

Genotype by environment

Competition within the plant seems to favor CBD production over THC

Growing indoors you can control the environment to favor THC

Under sunlight in an outdoor environment the hemp biosphere allows the plant to express its maximum medicinal values.

Because CBD is hitting a lot of targets at once the other cannabinoids help

Whole plant extract is more powerful at lower doses than an isolate

one region of hippocampus is impacted by CBD alone. Using THC and CBD together .....ask! They lost me! Can't keep up and take notes. :laughtwo:

Sleep aids need THC

THC kills cancer cells. Trying to fight cancer without it seems a fool's folly.

We've evolved with cannabis and our bodies can understand how to use the medicine from a whole plant extraction. Those molecules create the dance we call synergy, and they balance each other out in the body, making them more usable for homeostasis.

Cannabis is a bioaccumulator. You have to be careful about the soil you plant in

One of the panelists believes the most efficient extractions are infused oils. :cheesygrinsmiley: His point, and I agree with it, is that with an infusion you get 100% of the medicine.

We're finding that the hemp plant has the same kind of variety the cannabis strains have. The "minor" components turn out to be important molecules.

Dosing CBD
Typically start with 200 mg, sublingual doses to avoid first pass through the liver

Understanding the particular form of CBD you have can make a difference.

Values of CBD:

Anxiety - most common use of CBD
- can be caused by a number of different conditions 2-5 up to 10-15 mg

Sleep - CBD will help you sleep if you're exhausted you'll fall asleep
- if you're not tired and take CBD you'll wake up

Herbal medicines balance the system

Pain -
- patients have used CBD to get away from opioids
- chronic pain is based in inflammation, and CBD modulates inflammation
- CBD appears to reduce some of the reward opioids that come with the meds so they can stop the path of addiction

You need to know what receptor system is functioning in the cancer you're treating because some CBD applications can accelerate tumor growth

It all depends on the level of stress being expressed by this system and the level of deficiency in the ECS

The idea is a light touch. The dispensary system exists to sell cannabinoids. Michael believes you want low doses to gently encourage the ECS, rather than the push of a dagger of cannabinoid overload

On a blood thinner? Take low doses and watch for effect. The CBD will allow the blood thinner meds to build up in your system to dangerous levels.

How long will you need to take CBD to see positive effect?
- how are you taking it
- what carrier did you use?
- what dose are you taking?
- what are you treating?
- how out of whack is your ECS?

The questions continue. :laughtwo:

The general population is cannabinoid deficient. Phytocannabinoids allow us to increase cannabinoid levels in the body without being concerned of side effects

Athletes can definitely benefit from cannabinoid therapies rich in CBD. It's a neuroprotector.

Elderly and those challenged with dementia have much to gain from CBD.

Lunch break - need to stretch :battingeyelashes:


Ron Smith : National Cannabis Indusrty Association

National trade organization

Lobbyists for end to cannabis prohibition

It's not just an industry, it's a movement. When you come into the market you need to keep this in mind

We're lucky to be alive today. Let's not squander it. Let's take lessons from the cannabis plant. Let our industry stand for transparency, safety, education, social justice, and open business community, to continue to raise

Robyn: cooking

Controlling the dose

1 gram eaten = 5 grams smoked

2 TBS infused oil = 4-5 joints

Edibles need time to metabolize

Council on Responsible Cannabis ???? says start at 5 mg THC

Colorado regulation starts at 10 mg THC

Set and setting have to do with dosing

"Don't be stoned when you have to pretend you're not." - Melissa Etheridge


Dr. Silver and Dr. : Using Cannabis to treat animals
- pain - arthritis, mobility, lameness, Appetite

Cancer - reduce tumor size, post-surgical pain, quality of life

Glaucoma and inflammatory disease like iBS

Restlessness at night (CBD)

Anxiety in general
- sensitivity to noise
- abandonment issues
- CBD is helpful for all of the above

All mammals and fish have an ECS

Properly administered cannabinoid therapies can positively effect pain, seizures, GI distress, anxiety, etc

Particularly in dogs there's a greater concentration of CB1 receptors in the brain. Dosing THC needs to take into consideration the dog's heightened sensitivity to THC.
- Dr. Silver recommends to begin with a hemp-based oil for its low THC count
- in cases of cancer or high pain you'll need THC but you need to be concerned about the quality and cannabinoid count in medical cannabis

Don't feed your pets your edibles

Available medications for pets:
- Dried herb materials
-Liquid tinctures allow careful dosing *preferred method*
- Edibles: biscuits, chews, etc

Case study of dog
- 0.05 mg/pound (2 drops!) CBD twice daily
- In 5 days he improved so well that they were able to reduce the steroid dose the dog was getting.

Be open and honest with your vet about what you're using for your pet

When dosing you need to know:
THC:CBD ratios?
How many mg of the cannabinoids available in the product?

Dogs and cats aren't smaller people. Don't attempt to scale down your meds for them.

The big takeaways:
Cannabis can be highly effective
Educate yourself
Know what's in the medication
Start low and work up slowly
Avoid edibles for people
Share this information with your vet

Medical Marijuana and Your Pets - good book
nurseyourpet.com

Dr. David Bearman (AACM): History of cannabis

Didn't take any notes here today. I'll get them next week when the videos are posted.


Panel: Growing

Seed vs clone
- clone will always be inferior, in immune function, over time
- seeded plants have more vigor and more potential

If planting outside and using clones from a dispensary you need to be alert about photo period change. In greenhouses they're going from 18/6 to colder to 12/12.

Clones let you maintain genetic consistency

Enforce isolation when bringing in new plants

Use beneficial biologicals for pest control
- nature sticks a balance in a happy world, for every pest there's a biological counter

The Cure
You can't cure dry cannabis, you age it. You can't cure properly without a decent dry.
When you fall below a certain level of humidity you begin to degrade
Temps between low 60s to 70 degrees
67 degrees and 67% humidity for the cure
Constantly moving air that doesn't blow over the drying material
Keep fan leaves on the plant to slow the drying process
When the bud is dry to the touch but the stem still has some flexibility jar it up
Use Bovedas
Burp daily for a time

Wisdom:
Kyle Kushman* Patience
* Do not grow more than you have the ability to dry. (don't go faster than you have the infrastructure to support)
Mel Frank * Spend time with your plants

Panel: Terpenes, the building blocks of essential oils
Terpenes are hydrocarbons found in cannabis responsible for the smells of cannabis.
For Communication of the plant for pest repelling

How many? Well over 200, 266 is the largest list from an analysis

Right now we're making inaccurate assumptions about terpenes in cannabis
- the research was done with olfactory, not conbusted or vaped

Terpenes will allow us to personalize the medication
- they determine the experience of the cannabinoids

Most frequent
Myrcene
Beta-caroyophyllene
Limonene
Alpha- Humaline

Limonene and Pinene in the OG is what makes it so attractive

Linalool is present in almost every strain

Camphor is the cheese smell

Nerualadol - GG

Diesel: no way to tell what mix of components create this smell

We need to look at terpenes in a more holistic way. Find the balance in the plant.

User needs to discriminate between mono and sesqui terpenes
- mono drive the sale (smell)
- sesqui drive the repeat sale (taste)

Limonene, pinene and neuralodol are often found in the fuel strains

find a strain that smells good to you. If it works for you get a lab report. Now you know what the terpene profile is and you can find others that are a close match

Record the smell and taste in your own words. What were your perceptions?
- if you have profile data to accompany this keep it together

The typical range is 1% to 4% terpene content by weight
Above 2% increases value and medicine

How to grow for more terpenes
- you can't get both bulk and terpenes at the same time
- stress increases terpene production
- you see higher levels in rough environments

- processing can destroy many terpenes

When you step outside the natural balance of component relationships you start walking in places no one understands. "Danger Will Robinson!"

A lot of people's experience with terpenes is dose dependent. Nature had created balance. More is not necessarily better.

Trust your senses. Let the nose direct you. Let the taste be something you find desirable.


The Knox Family : Cannabis Doctors (mother and two doctors)

Expectation training

THC without getting euphoria
- topical
- suppositories
-

Mom's list of administration preference runs
Sublingual,
vaping for breakthrough,
suppositories (anal or vaginal)

Dr. Wilson King: Victory Rejuvination Center - cannabis and aging

In 2015 6 mil people over 55 use medical cannabis

Over five generations of cannabis use

What I'd aging?
- start in late initiated by hormone changes
- loss of muscle function and mass
- muscle loss is replaced by far
- loss of bone density ( first 7 years of menopause women lose bone mass faster than the standard 1%)
- polypharmacy : on multiple drugs
- memory issues
- hair loss
- disease

You also learn acceptance and how wonderful life can be without judgement
You gain confidence in your decisions
You lose the need to make everyone bend to your will

Cannabis as a potent anti-oxidant

CBD Is 30-50 % more effective as an anti-oxidant than vitamins

Inflammation is caused by damage to the system
- acute inflammation is helpful
- chronic inflammation isn't helpful
- aging diseases are likely caused by chronic inflammation
- cannabis is effective as an anti-oxidant

CBD indirectly stimulates the CB2 receptor to effect inflammation

Pain is the most common complaint of the elderly population
- neuropathic pain is the most common cause of pain
- cannabis is safer than anything now being prescribed

Depression and anxiety
- effect social life, motivation, productivity, overall health
Cannabis benefits by balancing the emotion tone
- CBD inhibits FAAH and thereby increases presence of anandamide
- inflammation may contribute to depression and anxiety

Sleep disorders are one of biggest elderly populations
- THC in low doses will increase the duration of sleep
- can be used for sleep apnea

Bone cells express CB1 and CB2 receptors as well as GPR55
- GPR55 signaling causes production of osteoclasts, which degrade bone tissue

Wellness is a global initiative
Nutrition - go for a whole plant diet, rich in unprocessed foods
Exercise can prevent bone and muscle loss
Self Care is the VIP of pain management
- laugh as often as possible, end the day with a chuckle or an orgasm (that last part was my idea :laughtwo:)
Proper supplements : omega-3, Vit D, C, E B vitamins, hormone balance
Consider cannabis as a supplement to improve the quality of your aging.

End of Day 1

Well, that was fun. :cheesygrinsmiley:
- CBD blocks GOR55 signaling, protecting the bones from degradation
 
Hahaha! Last comment on the previous notes, and I misspell it. Lol!

CBD blocks GPR55 receptors :cheesygrinsmiley:

Day 2: Green Flower Media

1. Steve DiAngelo : modern cannabis

We've come so far in the field with controlled dosing and the advent of capsules means you can now travel with your meds with limited concern.

More socially acceptable cannabis product formats have allowed people to consume in public without fear.

We've decreased the anxiety level over use. It's now consumed everywhere.

The largest neurotransmitter system in the body wasn't identified until the 1990s and then it took 15 years for Steep Hill Labs to get established

Now science meet cannabis

Most of the cannabis out there only tell us the ratios of two of the cannabinoids. We're beginning to find out more about cannabinoids

THCV suppresses appetite

CBN, THC, and CBD in combination are being called the "ambien" mix

CBN shows potential to treat resistant bacteria.

Cannabinoids and terpenes interject with each other in synergistic ways, and now terpenes are gaining traction in the market

Pinene- promote alertness, focus, concentration

Myrcene- crosses the BBB
Calming, relaxing, pain-killing

Limonene- stress reducer, mood elevator (Tangie)

Now they're breeding to combine the components to achieve therapeutic goals

The foundation is increased activism. The fences are finally coming down.

We're beginning to see trusted brands, and now we're gearing into particular populations, athletes, women, children, etc,

Prices are beginning to drop. The biggest problem people complain about, after illegality, is cost.

Legalization and regulation raise costs through fees and taxes. If we can't reduce production costs the prices stay high.
let's drop the taxes and fees instead. Why do the producers have to be the ones who take the hit?

In all legal markets opioid deaths are down, domestic violence is down, suicide is down, alcohol binge-drinking is down, alcohol sales, opioid use, use of antidepressants and anti-anxiety meds are down.

In all measurable ways cannabis legalization has created a better world.

Our hope is that as cannabis use spreads we can continue to evolve in ways that offer more acceptance and tolerance for all.


2. Gay Hendricks : Using cannabis for creative writing

Being in an altered state of mind helped him discover things he might have never found.

The altered state of consciousness allows you to go deeper into yourself and shift to a broader perspective.

Creativity, assisted by cannabis can bring you to points of insight to deal with situations you found difficult to handle.

Personal growth modalities: ask yourself

Does it put you in touch with who you really are?
Does it have the power to shift your perspective away from your narrow view?
Does it make you feel good?

Unless we can speak to the fears shared by our lawmakers and regulators we'll be continually bumping heads about cannabis

He started using cannabis therapeutically ten years ago for arthritis. Today he has no joint pain to speak of.

3. Mara Gordon: self-dosing guidelines

Mechanisms of action - dig deeper into this concept Susan

Strategies for dosing

Seizure disorders

Epilepsy - if you've treated one epilepsy patient what you learned is you treated one epileptic patient. It's that individual an expression with cannabis.

- dosing is the most frustrating part of the treatment
- starting dose is 1/3 a mg and titrate up until you feel the psychoactivity
- you won't get same results with hemp-based CBD

THCa will relieve gastro-intestinal disorders

Pain
- Chronic pain is the disease itself
- micro dosing: the amount of medicine you have to take to achieve therapeutic goals without feeling it euphorically, beyond what they're comfortable with
- on days when you're having a bad time you'll need more
- 25 mg twice a day THC
- topicals are soooo helpful and can be used whenever

Immune disorders
- inflammation is the real disorder
- CBD doesn't depress the immune system, it modulates it
-
Cancer
-

Steph Sherer : Americans for Safe Access

Over 70% of the planet lives with pain

We're in this position because modern medicine has let most of us down. They're not looking for solutions for this maladies that aren't profitable from a medicine perspective.

If treating ourselves and our loved ones means breaking federal law, then so be it.

Safe Access means (photo)

Wellness and medicine keep getting blurred. Wellness means it enhances your life. Medicine, poorly prepared or in the wrong formulation can cost you your life.

There's a responsibility to those in the industry to uphold standards that keep the momentum going. Tread carefully and thoughtfully. Be responsible in packaging and production.

The industry isn't big enough to keep from being taken down by just one billionaire who gets pissed off and finances the propaganda war that would bury it.

Don't think it could happen? Ha!

Cannabis access is a matter of social justice. It should be possible to make it accessible to the masses and paid for by the insurance companies.
- in order for this to happen it'll have to be tracked and traced professionally

patients use much more cannabis than recreational users. Steph uses four pounds a year for her medical care. I could have cured Dale.

ASA has resources online to assist patients and activists

Josh Werzer: SCLabs - Terpenes

Terpene categories
- high in Myrcene
Sedative, bitter citric you, fresh green taste
Blueberry, Tangie, fruity strains are likely high in Myrcene
Almost all purples fit into Myrcene dominate

God!!!! He moves too fast!!! Haha!

Hybrids: mix of Myrcene and others
Standard OG Kush: equal amounts of Beta-caryophyllene, myrcene, and limonene

Classic sativa strains are high in terpinoline

This was the best talk so far, aside from Mara. I'll do this talk for posting first.

Such a great talk!

Panel: Topicals

Cannabinoids don't get into the bloodstream, they interact with the peripheral nervous system to give relief

The ECS might not be strong enough to get out to the edges of the skin for healing purposes

Pain relief, muscle soreness, anxiety or depression (medicated bath), invaders to the skin
Arthritis, pain of the lower back, muscle tension, swelling, bruising, skin conditions, psoriasis, shingles, nerve issues

Topicals help the body heal itself

Nerve issues are commonly healed with topicals. The cannabinoids repair nerves and will regenerate

MAKE A TOPICAL FOR THE BIL TO USE DAILY

Topicals contain cannabinoids that attach to the CB2 receptors
- all of your nerve endings in the skin are found in the areas of the CB2 receptors

Interesting testimonials

The entourage effect is what you're seeking. Full spectrum topicals
Be aware of the terpenes

THC, THCa, CBD, CBG, CBN,

Adding other essential oils can enhance the effects

THC for pain
THCa for inflammation
CBD for entourage and anti-inflammatory
More cannabinoids for greater effect

More THC, THCa to CBD about 60/40 THC/THCa blend with a little CBD thrown in

You're using a small amount of cannabinoids but applied right at the receptors

25 ml in the baths

1000 mg in a 4 oz topicals

Sweet Creme (?) has a line of extra strength with double the cannabinoid dose.

Make a simple infused coconut oil and apply it head to toe

Medical baths an exciting possibility for psoriasis. One panelist has seen healing with psoriasis with topicals. I'm thinking a medicated bath where I could soak my head. This way the entire system gets a therapeutic hit. Maya and Whoopie have seen amazing results with the baths.

I'd like to start doing this. I need to harvest more cannabis. :cheesygrinsmiley:


AFTERNOON SESSION

Jeff the 420 Chef

3 Day process

Distilled water
French Press
Cannabis 7 grams)

Place cannabis (pulled apart) into French press, add distilled water to just over the plant, but enough to pull the impurities out.

Leave for 12 hours and change water. Do this for two days

Blanching
Pour cannabis into tea strainer, close it up (do over bowl to catch any loose pieces)
Place into boiling water for 5 minutes.
Shock it in ice water
Squeeze out excess water
Break apart on a tray and decarb 240 F for 1 hour
When dry weigh it (this is what you're infusing; his 7 grams ended up as 4.5

After decarb put back into French press and cover with your measured oil or butter. Place in a pot of boiling water, gently boiling for four hours.

Strain and use.

Martha Montemayor : Dosing and titration

THCa and CBDa
make raw cannabis juice
Chlorophyll is a blood booster ( akin to hemoglobin)

1 mg for every 20 pounds of body weight every 8 hours for Type 2 diabetics

Jeffrey Raber: Molecular Cannabis

Follow your nose

There is no longer any molecular determinate between sativa and indica

Names mean nothing anymore. The breeding market is out of hand.

You'll need lab results.

* GROW YOUR OWN *

Find the compositions that work for you, cannabinoids and the combinations of terpenes that work with those cannabinoids to get the effect you desire.

Cannabis impacts a great number of diseases. It's an individual medication, safe to experiment with and free of catastrophic side effects the doctors seem to have no problem at all writing prescriptions for. :straightface:

Panel: Cannabis for athletes

Bas says eat the edible, wait 10 minutes and eat the meal. The edible hits within 15 minutes
- he uses CBD pre workout to help working harder and post to help with recovery

Diversity of administrative choices can enhance health better than one method.

Panel: extractions

Allison Ettel: Ethanol
- safe, effective, versatile
- uses alcohol to extract what you want, from what you don't
- benefits:
- full plant medicine


Mike Clemmons: Hydrocompounds
- solvent can be purged
- higher terpene counts
- diversity of extraction techniques is good, know that it's clean

David Hargett: CO2
- when you use CO2 there is no solvent to remove
- only one step
- negatives: machines have to be at high pressure
- temperature can be controlled to determine the cannabinoid count (conversion rates)

Allison speculated that the breaking of bonds may effect response, and ethanol doesn't do that. She stated they've noticed that the breaking of the bonds makes for less effective medicine.

Difference in effect by extraction method is most likely caused by residual solvents or from the loss of terpenes

Go for products that have lab testing

Experiment to find out what works with your own personal biosphere.

Rosin
- mechanical separation using heat and pressure (essentially steam distillation)
- make a sublime product on a small scale

Live Resin
- hydrocarbon extraction done on fresh plant material
- preserves the terpenes
- frozen at sub-freezing
- extraction gets the full terpene profile

Consumer choice is all about esthetics
- clear is being interpreted as more pure, and so shatter sells better than wax
- people are becoming more educated about the value of content

Know the company and their practices
- ask for lab tests and hold them accountable

Input matter is the most important
- what part of the plant are you using?


Panel: Hemp




This was a good day to listen. Didn't take many notes. I'll be watching them again and get more out.
 
Partial notes: to be continued. :cheesygrinsmiley:

Josh Werzer: SC Labs - Why the Same Strain Can Impact People Differently

What tools do you have at your disposal to help you pick out the strain for you?

Use your senses.
- Look at it
- Smell it; the nose is one of the most sophisticated sensory devices on the planet.
- Look at test results

What makes cannabis samples distinctive? Terpenes. 100% terpenes.

Active ingredients in cannabis:
- cannabinoids
- terpenes: linked isoprene units (Josh likens them to small Lego blocks)

Most plants produce terpenes in one form or another.
- the essential oil of the plant, what you smell
- some animals also produce terpenes
- analogous to our hormones
- cannabinoids are terpenes too, terpenoids
* they're specialized terpenes only cannabis produces

Cannabis can produce the terpenes found in other plants. This is unique. Most plants have a few terpenes or one terpene. Cannabis has hundreds.

Terpenes are biologically active. They interact with your body at a cellular level.
 
Study Hall organization - continuing work: through page 26, page 253 and pages 280-291, post #4353

BASIC BIOLOGY

Post #59 - 2-minute neuroscience:The Blood Brain Barrier (BBB)

Post #39 - How Receptors Work: Agonists and Antagonists

Post #46 Fatty Acid Binding Proteins (Society of Cannabis Clinicians)

Post #4 - First Pass Metabolism

Post #17 - Bioavaibility of routes of administration (Green House Labs White Paper)



THE ENDOCANNABINOID SYSTEM

Post #40 - The Scientist (video on Raphael Mechoulam, credited as the discoverer of the ECS)

Post #2 - An introduction to the ECS

Post #15 - Pharmacological actions of non-psychotropic cannabinoids (with the indication of the proposed mechanisms of action)

Post #71 - Relative Affinities of Various Cannabinoids to Bind to CB1 and CB2 Receptor Sites

Post#74 - Minor Cannabinoids and Cannabis Terpenoids: Ethan Russo for The Society Of Cannabis Clinicians

Post #163 - Dr. Jeffrey Hergenrather on cannabinoid ratios.

Post #90 - Taming THC: Potential Cannabis Synergy - Ethan Russo (PDF file)

Post #141 - Terpene Boiling Points (link)

Post #4326 - Dr. Christina Sanchez on cannabinoid therapies

SUPPORTING THE ECS

Post #171 - The value of hemp seeds.


The Cannabinoids

Post #4234 - Benefits of CBD

Post #4191 - 9 remarkable healing properties of CBD

Post #4196 - Cannabinoid Synthesis

Post #4195 - link to Leafly's Cannabinoid Crash Course - CBGa

Post #4200 - They found anandamide in chocolate! :yahoo:


CONCERNING CANCER:

Post #5 - Competitive Inhibition

Post #3 - Demethylation

Post #50 - Demethylation: Essential (Phenolic) Oil Capsules

Post #56 - Cajun's thoughts on frequency of Demethylation

Post # 64 LCFAs can't cross the BBB? If this is the case, will this effect carrier oil choices for brain tumors?

Post #131 - Cannabinoids And Cancer: a flow chart (Journal of British Pharmacology)

Post #150 - ShiggityFlip explains the flow chart.

Post #154 - ShiggityFlip and SlowToke continue the invaluable conversation on how cells perform apoptosis (natural, safe, programmed cellular suicide).

Post #158 - ShiggityFlip explains Molarity as a concept of concentration. (In answer to a question about nano molars)


[COLOR="#000FF"]DRYING AND CURING[/COLOR]

Post # 3852 - DrZiggy's Low and Slow Drying Technique

Post # 3856 - AKgramma on curing in the refrigerator


STRAIN TEST RESULTS

Post #309 - neikodog's test results for AC/DC x Querkle #2


MAKING OILS

Decarboxylation

Post #159 - panacea's decarb method in a BBQ (reformatted version :battingeyelashes:)

Post #83 - A study showing the slow rate of cure THC to CBN (not what everyone expected).

Post #86 - More thoughts on decarbing for maximum THC and CBD.

Post #94 - More discussion on decarbing, concerning loss of THC over time

Post #117 - Decarbing in a roasting bag.

Post #118 - Rambo's decarb experiment.

Post #4260 - ShiggityFlip shares a table on decarboxylation & Post #4264 - Link to the article Shiggity pulled table from

Post #49 - An Overview of Methods to Produce Concentrated Cannabis Oil
- Post #207 - SCET modificationsLab Rat has abandoned the SCET method of extraction in favor of methods known to produce better purity.

Post #211 - cajuncelt on expected oil pulls.


PsyCro's Olive Oil Extraction

Post #55 - CORRECTED POST:PsyCro's corrections to his fresh-harvested oil

Post #169 - fookinel's thoughts on essential oil choices, with valuable links. The next post continues this discussion.

Post #214 - fookinel&/ continuing thoughts on PsyCro's olive oil extraction.

Post #222 - PsyCro starts playing with pressure cookers. :slide:

Post #120 - wildjim's excellent notes on reclaiming solvent using a distiller.

Post # 3851 - Fresh Harvest Oil

Post #4314 - Link to Fresh Harvest Infused Oil thread


Grow Goddess's Naturally Decarbed Sap Oil

Link to Grow Goddess blogs

Post #4349 - SweetSue's Cannabis Oil Study HallKingston Rabbi's thoughts on his first attempt.

Post #4344 - Chew's first attempt at ND Sap oil

Post #4352 - Chew's first attempt at ND Sap oil, cont.


The Washes

Post #200 - panacea's detailing of the washes. ****Excellent Post****

POST #178 - Review of the methods used by SkunkPharm

Post #219 - Winterizing explained

Post # 314 - results from washing with Everclear 151


Choosing The Carrier Oil

Post #80 - Fookinel's excellent thoughts on choice of carrier oil when dosing for particular disease.

Post #172 - More thoughts by fookinel on choosing the carrier oil.

Post # 3833 - CannaDad's guidelines on carrier oils


First Tries: CCO

Post #183 - neikodog's first attempt. Post #201 - the wrap-up


MISC THOUGHTS ON OILS

Post #190 - An interesting supposition: could you improve oil potency with a SOG?

Post # 3797 - Steep Hill Labs Cost Sheet


ADMINISTRATION AND DOSING

Post #160 - CajunCelt explains calculating the dose

Post # 3818 - Calculating the dose: Infused oils

Post #4213 - Calculating the cannabinoid load in infused oils (SweetSue's in-depth explanation)

Post #4229 - Kingston Rabbi on calculating the cannabinoid values in infused oils

Post #176 - PsyCro's thoughts on dosing his oil.

Post #187 - fookinel finishing this conversation.

Post #185 - fookinel calculates the cannabinoid load in PsyCro's olive oil.

Post #218 - Links to Radic-Al Conscious's "Medicinal Cannabis Therapy" and "Medicinal Cannabis Therapies for Cancer"

Post # 364 - Why CannaBudwig works

Post 3792 - a link to the Pain Creme recipe

Post #4295 - Canna Bath Salts


THE CONVERSATION ON SUPPOSITORIES

Post # 320 - Dr. Jeffrey Hergenrather, MD on the efficacy of suppositories (2015)

Post # 326 - SlowToke on the current thinking of suppositories in the clinical field

Post # 329 - CajunCelt responds on the effectiveness of suppositories made with carrier oils

Post # 346 - PsyCro joins the conversation: Rectal Absorbtion of Cannabis Revisited - Greenbridge Medical Center

Post # 352 - CajunCelt chimes in again

From Post 3809 - Božidar RadiÅ¡ič presentation — Cannabis In Medicine: Practice & Experience (PDF)

Post # 3810 - Božidar RadiÅ¡ič's recommendations for suppository treatment

FOLLOWING THE REGIMENS B]

Post #242 - fookinel updates patient info (update from Post #173)

Post #3029 - Danolo describes a regimine for RA

Post # 333 - panacea explains the gist of a patient protocol for breast cancer

Post #4205 - Update: Diabetes

Post # 4353 - SweetSue's patients; update of June 3, 2017


BIO-BOMBS

Post #161 - cajuncelt's original instructions on the BioBomb and thoughts on initiating a protocol.

Post #95 -fookinel includes links to cajuncelt's original recipe and panacea's adaptations.

Post #121 - BioBombs (our study hall beginnings)

Post #173 - fookinel's tutorial on mixing oils for increased bioavailability. ***Excellent Post***

Post # 334 - BioBomb Smoothies

[COLOR="000FF"]EQUIPMENT[/COLOR]

Post # 3834 - Nova Home Decarboxylator

Post #4305 - The brew bag: for straining the oil

Post #4308 - The capsule machine illustrated

MISCELLANEOUS STUDY JOY:

Post # 4353 - Cannabis Stops The Worst Pain In The World

Post #3038 - Dr. Courtney on Raw Cannabis

Post #28 - Crash Course Chemistry and Energy: Carbon

Post #29 -Crash Course Chemistry and Energy: Biological Molecules & Crash Course Biology - DNA Transcription and Translation

Post #30Crash Course Chemistry: The Nucleus

Post #35 - Crash Course: Chemistry and Energy -

Post #45 - Support Organization for Medical Cannabis


Begin at page 26 and work ahead or 279 and work backwards
 
Outstanding "again" Sue! Lot of info at a quick glance.
:bravo::cco::welldone:
 
That's a very useful post Sue. I didn't realise how much i have missed...
 
Outstanding "again" Sue! Lot of info at a quick glance.
:bravo::cco::welldone:

That's a very useful post Sue. I didn't realise how much i have missed...

Thank you both. :hugs::hugs: I'm going to make an effort to put in time every day catching up the Study Hall so I can start on Cajun's thread. There's so much info in that one that needs organized I may start it as a side project.

Once I catch up I'll post it as its own thread and begin updating monthly from then on.
 
Wow just finished reading from start to now. I love the spacing so I can read without overwhelming blocks of text.

Really amazing work SS! Thank you for posting all these links, my brain loves it.

You are helping me so much, super hugs! This thread will be my new home come harvest time. .❤️.

You're very welcome dear. I have a massive job ahead cataloging that thread. We're creeping up on 300 pages and no signs of slowing down.

I'm glad the format helps you. It was my intent to make it easy to access.
 
You're very welcome dear. I have a massive job ahead cataloging that thread. We're creeping up on 300 pages and no signs of slowing down.

I'm glad the format helps you. It was my intent to make it easy to access.

We wrote each other at the same time...I love when that happens. This thread is officially accessible! ;) Brain approved .

Now to catch up on your others threads. .
 
Wow just finished reading from start to now. I love the spacing so I can read without overwhelming blocks of text.

Really amazing work SS! Thank you for posting all these links, my brain loves it.

You are helping me so much, super hugs! This thread will be my new home come harvest time. .❤️.

When it's finished being catalogued it'll have its own thread. We have a while until then. This is my playground where I pull threads together.
 
Study Hall organization - continuing work: through page 26, page 253 and pages 270-291, post #4353

BASIC BIOLOGY

Post #59 - 2-minute neuroscience:The Blood Brain Barrier (BBB)

Post #39 - How Receptors Work: Agonists and Antagonists

Post #46 Fatty Acid Binding Proteins (Society of Cannabis Clinicians)

Post #4 - First Pass Metabolism

Post #17 - Bioavaibility of routes of administration (Green House Labs White Paper)



THE ENDOCANNABINOID SYSTEM

Post #40 - The Scientist (video on Raphael Mechoulam, credited as the discoverer of the ECS)

Post #2 - An introduction to the ECS

Post #15 - Pharmacological actions of non-psychotropic cannabinoids (with the indication of the proposed mechanisms of action)

Post #71 - Relative Affinities of Various Cannabinoids to Bind to CB1 and CB2 Receptor Sites

Post#74 - Minor Cannabinoids and Cannabis Terpenoids: Ethan Russo for The Society Of Cannabis Clinicians

Post #163 - Dr. Jeffrey Hergenrather on cannabinoid ratios.

Post #90 - Taming THC: Potential Cannabis Synergy - Ethan Russo (PDF file)

Post #141 - Terpene Boiling Points (link)

Post #4326 - Dr. Christina Sanchez on cannabinoid therapies

SUPPORTING THE ECS

Post #171 - The value of hemp seeds.


The Cannabinoids

Post #4234 - Benefits of CBD

Post #4191 - 9 remarkable healing properties of CBD

Post #4196 - Cannabinoid Synthesis

Post #4195 - link to Leafly's Cannabinoid Crash Course - CBGa

Post #4200 - They found anandamide in chocolate! :yahoo:

Post #4162 - Why choose THCa? The real reason you should be eating raw cannabis

CONCERNING CANCER:

Post #5 - Competitive Inhibition

Post #3 - Demethylation

Post #50 - Demethylation: Essential (Phenolic) Oil Capsules

Post #56 - Cajun's thoughts on frequency of Demethylation

Post # 64 LCFAs can't cross the BBB? If this is the case, will this effect carrier oil choices for brain tumors?

Post #131 - Cannabinoids And Cancer: a flow chart (Journal of British Pharmacology)

Post #150 - ShiggityFlip explains the flow chart.

Post #154 - ShiggityFlip and SlowToke continue the invaluable conversation on how cells perform apoptosis (natural, safe, programmed cellular suicide).

Post #158 - ShiggityFlip explains Molarity as a concept of concentration. (In answer to a question about nano molars)


[COLOR=#000FF]DRYING AND CURING[/COLOR]

Post # 3852 - DrZiggy's Low and Slow Drying Technique

Post # 3856 - AKgramma on curing in the refrigerator

Post #4058 - Low and Slow drying: Results


STRAIN TEST RESULTS

Post #309 - neikodog's test results for AC/DC x Querkle #2


MAKING OILS

Decarboxylation

Post #159 - panacea's decarb method in a BBQ (reformatted version :battingeyelashes:)

Post #83 - A study showing the slow rate of cure THC to CBN (not what everyone expected).

Post #86 - More thoughts on decarbing for maximum THC and CBD.

Post #94 - More discussion on decarbing, concerning loss of THC over time

Post #117 - Decarbing in a roasting bag.

Post #118 - Rambo's decarb experiment.

Post #4260 - ShiggityFlip shares a table on decarboxylation & Post #4264 - Link to the article Shiggity pulled table from

Post #49 - An Overview of Methods to Produce Concentrated Cannabis Oil
- Post #207 - SCET modificationsLab Rat has abandoned the SCET method of extraction in favor of methods known to produce better purity.

Post #211 - CajunCelt on expected oil pulls.


PsyCro's Olive Oil Extraction

Post #55 - CORRECTED POST:PsyCro's corrections to his fresh-harvested oil

Post #169 - fookinel's thoughts on essential oil choices, with valuable links. The next post continues this discussion.

Post #214 - fookinel&/ continuing thoughts on PsyCro's olive oil extraction.

Post #222 - PsyCro starts playing with pressure cookers. :slide:

Post #120 - wildjim's excellent notes on reclaiming solvent using a distiller.

Post # 3851 - Fresh Harvest Oil

Post #4314 - Link to Fresh Harvest Infused Oil thread


Grow Goddess's Naturally Decarbed Sap Oil

Link to Grow Goddess blogs

Post #4349 - SweetSue's Cannabis Oil Study HallKingston Rabbi's thoughts on his first attempt.

Post #4344 - Chew's first attempt at ND Sap oil

Post #4352 - Chew's first attempt at ND Sap oil, cont.


The Washes

Post #200 - panacea's detailing of the washes. ****Excellent Post****

POST #178 - Review of the methods used by SkunkPharm

Post #219 - Winterizing explained

Post # 314 - results from washing with Everclear 151


Choosing The Carrier Oil

Post #80 - Fookinel's excellent thoughts on choice of carrier oil when dosing for particular disease.

Post #172 - More thoughts by fookinel on choosing the carrier oil.

Post # 3833 - CannaDad's guidelines on carrier oils

Post #4077 - Storing CCO and BioBombs

First Tries: CCO

Post #183 - neikodog's first attempt. Post #201 - the wrap-up


MISC THOUGHTS ON OILS

Post #4143 - Oldbear and medmanmike on the practicalities of using oils
Post #4116 - Continuing the conversation
Post #4119 - More thoughts

Post #190 - An interesting supposition: could you improve oil potency with a SOG?

Post # 3797 - Steep Hill Labs Cost Sheet


ADMINISTRATION AND DOSING

Post #4184 - Kingston Rabbi on the courage to choose cannabinoid therapies over chemotherapy

Post #160 - CajunCelt explains calculating the dose

Post #4154 - Link to BioBombs thread

Post # 3818 - Calculating the dose: Infused oils

Post #4213 - Calculating the cannabinoid load in infused oils (SweetSue's in-depth explanation)

Post #4229 - Kingston Rabbi on calculating the cannabinoid values in infused oils

Post #176 - PsyCro's thoughts on dosing his oil.

Post #187 - fookinel finishing this conversation.

Post #185 - fookinel calculates the cannabinoid load in PsyCro's olive oil.

Post #4063 - Danolo on "that loaded feeling"

Post #4181 - A conversation on the "loaded" feeling one gets from intense cannabinoid therapies


Post #218 - Links to Radic-Al Conscious's "Medicinal Cannabis Therapy" and "Medicinal Cannabis Therapies for Cancer"

Post # 364 - Why CannaBudwig works

Post #4068 - Oldbear's breakfast smoothie

Post 3792 - a link to the original Pain Creme recipe & the revised and improved recipe by Dave Groomer

Post #4054 - Canna Bath Salts (from Cannabis Cheri

Post #4295 - Canna Bath Salts: SweetSue's scaled down version


THE CONVERSATION ON SUPPOSITORIES

Post # 320 - Dr. Jeffrey Hergenrather, MD on the efficacy of suppositories (2015)

Post # 326 - SlowToke on the current thinking of suppositories in the clinical field

Post # 329 - CajunCelt responds on the effectiveness of suppositories made with carrier oils

Post # 346 - PsyCro joins the conversation: Rectal Absorbtion of Cannabis Revisited - Greenbridge Medical Center

Post # 352 - CajunCelt chimes in again

From Post 3809 - Božidar RadiÅ¡ič presentation — Cannabis In Medicine: Practice & Experience (PDF)

Post # 3810 - Božidar RadiÅ¡ič's recommendations for suppository treatment

FOLLOWING THE REGIMENS B]

Post #242 - fookinel updates patient info (update from Post #173)

Post #3029 - Danolo describes a regimine for RA

Post # 333 - panacea explains the gist of a patient protocol for breast cancer

Post #4205 - Update: Diabetes

Post # 4353 - SweetSue's patients; update of June 3, 2017


BIO-BOMBS

Post #161 - CajunCelt's original instructions on the BioBomb and thoughts on initiating a protocol.

Post #95 -fookinel includes links to cajuncelt's original recipe and panacea's adaptations.

Post #121 - BioBombs (our study hall beginnings)

Post #173 - fookinel's tutorial on mixing oils for increased bioavailability. ***Excellent Post***

Post # 334 - BioBomb Smoothies

[COLOR=000FF]EQUIPMENT[/COLOR]

Post # 3834 - Nova Home Decarboxylator

Post #4305 - The brew bag: for straining the oil

Post #4308 - The capsule machine illustrated

MISCELLANEOUS STUDY JOY:

Post # 4353 - Cannabis Stops The Worst Pain In The World

Post #3038 - Dr. Courtney on Raw Cannabis

Post #28 - Crash Course Chemistry and Energy: Carbon

Post #29 -Crash Course Chemistry and Energy: Biological Molecules & Crash Course Biology - DNA Transcription and Translation

Post #30Crash Course Chemistry: The Nucleus

Post #35 - Crash Course: Chemistry and Energy -

Post #45 - Support Organization for Medical Cannabis


Begin at page 26 and work ahead or 269 and work backwards
 
Cannabidiol (CBD) fighting inflammation & aggressive forms of cancer

Inflammation Triggers the Symptoms of Disease

The presence of inflammation is what makes most disease perceptible to an individual. It can and often does occur for years before it exists at levels sufficient to be apparent or clinically significant. How long it has been smoldering really determines the degree of severity of a disease and often the prognosis assuming the inflammation can be controlled. One could also argue that without inflammation most disease would not even exist. Take a look at this list of diseases and their relationship with inflammation:

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5 Reasons To Add Astaxanthin to Your Skincare Routine - Maya Chia

If you need a quick refresher, Astaxanthin is one of nature’s most potent antioxidants, it is what is classified as a caretenoid. It is primarily found in marine life including micro algae, wild salmon, red trout, krill, shrimp, crabs, and lobsters. It gives flamingos and salmon their brilliant pink hue – and in the case of salmon gives them the ability to swim upstream.

So what can Astaxanthin do for your skin?

Astaxanthin is particularly impressive for your skin due to the fact that it never becomes a pro-oxidant, meaning that it protects our cells against oxidation. And, what is oxidation? Technically speaking, oxidation means the loss of electrons. In simpler terms, oxidation is decay or decomposition.

Maya Chia Beauty was at the vanguard of introducing the powerhouse antioxidant, astaxanthin, into beauty care. It can be found in the Maya Chia Beauty’s “Super Couple” face oil, which features Astaxanthin’s signature coral hue that imparts a beautiful radiant glow to the skin – one that appears as if you are glowing from within.

With that said, here are 5 fun facts about Astaxanthin, showing why it is a game changer in the world of high-performance, natural skincare.

1. Astaxanthin has been shown in clinical studies to increase skin moisture, moisture retention, elasticity, as well as promote skin smoothness, decreasing fine lines and wrinkles.

2. Astaxanthin has incredible UV-blocking properties, which helps to assist the skin in protecting itself against sun-related damage. So long dark spots! Please note: our oil does note have SPF in it – which means you will need to use an SPF in addition to the application of this face oil.

3. While we err on the side of quoting a more conservative study which found Astaxanthin 65 times stronger than Vitamin C in combating free radicals. Another reputable clinical study, has shown “Natural astaxanthin is exceptionally powerful in singlet-oxygen quenching. A 2007 study analyzed several popular antioxidants and their antioxidant power. This study found astaxanthin was 6,000 times stronger than vitamin C, 800 times stronger than CoQ10, 550 times stronger than green tea catechins and 75 times stronger than alpha lipoic acid.”

4. Astaxanthin can neutralize multiple free radicals at once, protecting your skin and body from oxidation, damage, and inflammation.

5. Astaxanthin has been proven to increase blood flow, meaning that it will help your skin to have better circulation. Increased circulation has various benefits, including increased cell turnover, amplified elasticity, and increased water retention.
 
The Endocannabinoid System 101 - with Samantha Miller and Green Flower

Cannabinoids are a class of substances in cannabis that are responsible for some of the effects you feel in your body.

THC and CBD pretty much drive the experience for the patient.

THC (tetrahydrocannaboid)
- comes in different forms; THC converts to THC with time or heat, or both
- good for pain, inflammation, nausea, as a sleep aid, and can completely alleviate the symptoms of depression
- It's important to distinguish between depression and anxiety; depression used THC, anxiety uses CBD

CBD (cannabidiol)
- also comes in 2 forms, CBDa and CBD
- both are non psychoactive, non-euphoric, which many find attractive
- it's an easy entry for new patients
- inflammation, particularly pain due to spasticity, making it a good choice for disease with this expression (i.e. Fibromyalgia, MS, ALS, and Parkinson's)
- CBD is doing miraculous things to control symptoms in this patient population and to improve the quality of their lives.

The experience of cannabis is that increased cannabinoid loads translate not into increased euphoria but rather to increased therapeutic benefit. Increased cannabinoid levels correlate with increased therapeutic effect.
- people begin to think that if it doesn't get me high it won't have the effect on my pain.

When talking about the effects of cannabis we need to separate the ideas of therapy and intoxication.
- An increase in THC won't necessarily get you higher, but it will give you a greater therapeutic effect.
- Understanding these things allows us to focus more precisely on creating therapy and wellness regimens that are truly effective and are based upon the factors that are actually influencing our outcome.
- Cannabinoid content will correlate to the level of relief that you perceive from most THC or CBD treatable ailments. The amount of symptom relief from pain, depression, anxiety, and nausea, among others will have a direct correlation to your cannabinoid load.

The designations of indica and sativa are ways we use to give the patient a general overview of the anticipated effect, mood elevating, sedating, euphoric.
- Indicas are associated with sedation and couch lock, sativas with alertness and upbeat moods.
- These reactions are caused by the flavonoid and terpene profiles.

Terpenes and flavonoids are responsible for a variety of nuanced effects in the cannabis consumption experience.
- euphoria, flavor, smell, feelings of sedation, the amount of psychoactivity you feel
- Terpenes can drive the experience of cannabis use, from sedating to energized and more euphoric

When choosing a new strain you want to determine
- indica, sativa or hybrid?
- cannabinoid loads (potency) and ratios
- keep tasting notes to track your experience with pertinent information from labs included, if you have access
- make notes thorough enough to guide you if you need to find a match for a strain that becomes unavailable
- Document the information that gives you the desired effects, including taste, smell and your reactions to both, cannabinoid and terpene profiles.
- Doing this allows you to have a more consistent experience with flower.

Within your body, inhaled cannabinoids are absorbed within seconds.
- oral will take longer
- inhalation has shown itself to be the best way to get a repeatably consistent experience with flower-based cannabis.
- One of the goals of cannabinoid therapies is self-titration, the ability of the patient to independently get a repeatable therapeutic dose.

Smoking a joint you lose over 65% to smoke that wafts away into the room. You can't measure a dose.

A vapor bag inhalation system is the best way to get the entire dose from your flower.

How Cannabinoids Produce Effects in the Body

Ingestion
- with a vapor bag all vaporized cannabinoids are captured and inhaled completely
- vaporizing allows a therapy regimen based on specific dose levels

Calculating milligrams of THC or CBD in cannabis based on potency %

1 gram of 15% THC yields 150 mg of THC

(1gram) x (0.15) = 0.150 g or 150 mg

Oral ingestion is loaded with variables that can skew dosage numbers
- both with patient and producer
- this can make it difficult to get a repeatable response through the gut
- the secret to success is consistency in your usage
- products can be inconsistent if producer isn't knowledgable or careful with processes
- if cannabinoids aren't decarbed you won't get any euphoria or pain relief anticipated.

Magnification of effects of activation
- THCa doesn't interface with the CB1 receptors, the most abundant one in the brain, and the one THC interfaces with

- the liver enzymes convert cannabinoids to 11-hydroxy THC, which is 4-10 times stronger in euphoric effect than delta-9 THC
- you can eat much less than you need to smoke for the same effect
- some of the products on the market make it difficult to cut down to a consistent dose
- a standard dose of THC is 15 mg, so how does one effectively dose a candy bar with a total of 1000 mg?
- it's important for the patient to know your threshold

If you go too far CBD can help reign in a THC overdose
- keep some CBD on hand, just in case your new edible turns out to be too intense

Eating one milligram is equivalent to smoking a gram
Eating 2 mg is equivalent to smoking a 2 gram joint

*caution when entering the world of edibles for the first time*
- have a rescue plan just in case
- remember to go with smaller doses and wait for the delayed onset (step wise)

There are ECS receptors everywhere except the brain stem

The experience through the gut is determined by a myriad of variables
Did you eat? Was it an empty stomach? Was the meal fatty? (This will effect euphoria, more fat = more pronounced high) Are you dosing on schedule?
- stomach acids can degrade cannabinoids
- stick to a consistent schedule with oral meds

Cannabis doesn't come with instructions
- if you take with food, be consistent with that, if you don't, don't
- be consistent in content and in the way you dose and you'll have more consistent response
- a more consistent approach leads to repeatable successful therapeutic results

Cannabinoids bond to fats and proteins pretty quickly
- they attach to receptor sites, docking sites that cannabinoids can communicate with
- the ECS is a key and lock system (receptor is the lock, cannabinoids the key)
- there's a specific fit between the cannabinoids and the receptors, keeping other molecules from also attaching

The specific fit is determined by the shape of the receptor
- more than one component can fit the receptor

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The receptors are embedded to pass through the cell membrane. Below them are the G-proteins.
- When a cannabinoid attaches to the receptor it cause the G-protein to change shape and move.
- When the G-protein changes shape this causes it to kick off a different ligand (a neurotransmitter) to start a cascade of events
- You'll have a binding of the THC molecule to the receptor, a change in shape that stimulates the g-protein to move and release of a new neurotransmitter


The primary receptors THC binds to are CB1 and CB2. There are other receptors that THC binds to, these are simply the primary ones.

* CB1
- central nervous system (brain and spinal cord)
- in cases of brain injury CB2 receptors will arise spontaneously in the brain to get to work reducing inflammation
- the most abundant cannabinoid receptor. Makes sense, considering the number of brain cells in the average human.
- thought to effect memory and adverse memories (think PTSD), appetite, response to rewards, our propensity to addiction, how we deal with stress, how we experience pain and how that can be managed.
- These are big quality of life issues. Create balance and you improve the patient's life, and enhance the journey to homeostasis.

* CB2
- peripheral nervous system, including immune system tissue (spleen, tonsils, white blood cells, etc)
- thought to effect inflammation, pain, especially inflammatory GI response, and immune response
- in some cases it's thought that activation of the CB2 receptor can induce immune suppression


The primary receptors CBD binds to are A2A, VR1, GPR55, and 5HT

* GPR55
- generating excitement in cancer treatment
- Different cancers respond to different cannabinoids in different ways. Some respond well to THC and don't respond well to CBD. In some cases CBD seems to be the wisest choice. We need more studies.
- When GPR55 is active it promotes tumor cell proliferation. More cancer cells are being made.
- It's believed that CBD can inhibit the activity of this receptor.
- Researches are looking into whether this pathway can be used to treat gliomas

* A2A Adenosine receptor
- Thought to influence anti-anxiety properties of CBD, to give broad anti-inflammatory effects, and regulate cardiovascular function, from blood flow to oxygen levels.
- will down-regulate certain neurotransmitters like glutamate
- Certain diseases are caused by imbalance of neurotransmitters causing over activity in the system. Excess glutamate, for example, is responsible for certain seizure conditions.


* VR1 Vanilloid receptor
- Has a role in our perception of pain, the regulation of body temperature, inflammation, and may be why CBD works as a pain medication for neuropathy.
- Plays a role in sexual arosal, and has a dose-dependent response.
- At high doses other parts of the receptor are activated, which explains why some benefits of cannabis are dose-dependant. The receptors sometimes react differently to lower doses than higher doses. More isn't necessarily better. Find the sweet spot for you.

* 5HT Seratonin receptor
- the same one that SSRI drugs target (Wellbutrin, Prozac, Lexapro, etc)
- CBD can be a safe alternative to these anti-anxiety drugs, without the significant side effects they present.
- SSRIs interrupt REM sleep. Disrupt it for years and you end up with things like fibromyalgia, IBS, anxiety, etc.
- Sometimes when these drugs stop working they can create anxiety response.
- CBD has anti-anxiety properties
- The receptor is also involved in addiction,appetite, sleep, pain, nausea, and vomiting.
- An important receptor to keep in balance. Witness the number of humans on anti-anxiety drugs.

The reasons cannabinoids offer the relief they due is based on biochemistry and the architecture of the ECS

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Alpha helix proteins form the receptors. They pass through the cell membrane to form a link to the interior. Below the receptor is a G-protein sub unit. When a neurotransmitter drops into the receptor it changes the shape of the receptor. This change causes a corresponding change in the shape of the G-protein that initiates a chemical event that creates a new sub unit that goes on to become a neurotransmitter. This new neurotransmitter then goes on to activate another receptor, starting the sequence all over again and extending the reach of the neurotransmitters. The resultant sequence of new neurotransmitters being created is called a cascade event. A cascade of signal events.

This is the way all neurotransmitters work in your body.

More receptors are being discovered all the time.

CBD can act as a regulatory molecule as well as the main receptor activator.
- There are auxiliary attachments on the cell and CBD can activate them, changing the affinity of that receptor for that molecule. and thereby the function of the CB receptor.
- CBD can interact with the CB1 receptors and down-regulate the sensitivity of the receptor. This is how CBD modifies the euphoric experience of THC.

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Metabolism of cannabinoids

Enzymes essentially do a shape change of the cannabinoids by binding to the molecule and then splitting the components apart for elimination from the system.
- Sometimes there will be a sugar molecule added to hasten elimination
- Most cannabinoids (about 80%) are excreted in feces.
- Your urine is what's tested because the labs don't want to be testing feces. Heavy users can hold onto detectable cannabinoids for up to 80 days.
- Cannabinoids hide out in fat cells. If you have excess fat you have a plethora of binding spots. It can take up to 80 days to clear THC from the system of a heavy user.

There are receptors in placenta tissue. Cannabinoids are found in breast milk. Just worth knowing. No studies have linked cannabinoids in an infant that caused detrimental effects. Consider the potential effects and make your own decisions.

Q&A

How do you tell if your ECS is out of balance?

- look for problem areas: skin breakout? Can't sleep? Digestive issues? Pain that won't go away? Emotional wreck he out of whack?
- By stimulating the ECS with phytocannabinoids you can support balance.
- you can't potentially eliminate a lot of drugs with side effects by choosing cannabis

Most doctors are totally uninformed about cannabis or the ECS

What will make the biggest difference with doctors, beyond education and a broader knowledge base, is an administration method that allows control of the dose and consistent repeatability.

It's important for the patient to learn where the sweet spot for therapeutic effect is and how to repeat that effect successfully.

Start sub-therapeutically and titrate up slowly.

Can you damage the ECS with too much saturation?
- there's always a concern of tolerance buildup
- tolerance is determined by daily use and amount
- interrupt the schedule and the system will reset (as little as a couple days will reset the tolerance levels)
- this doesn't qualify as damage

Cannabinoids hide in the fat cells
- they stay there until saturation levels drop and they can be expelled

Everyone's level of usage is individually determined, both frequency and dose

When using medicinally the consistent scheduling of dosing is a necessity

People who use daily tend to have heartier immune systems.

Cannabis is becoming a wellness medication.

The receptors of the ECS are linked into the rest of the system in ways that support sleeping
- stimulation of CB1 receptors by THC disrupts short-term memory allowing the mind to stop looping through the day and concerns
- pain is shorted out by THC
- restless leg is a result of muscle spasticity, so CBD will slow it down

If CBD does so many things to positively impact disease states, is there a danger of CBD being embraced while tossing THC aside as a medicine?
- THC hits pain in a way nothing else does
- THC initiates apoptosis
- the major cannabinoids potentiated each other to become a power couple of healing

Pay attention to your body and listen to it it. Pay attention to the way cannabis effects your body. Separate the ideas of therapy and intoxication.

Samantha shared that it took her a concerted three weeks to make the shift to a vaporizer before she got high from the vaporizer.



Pain, sleep, appetite, addiction, sexual expression, etc, etc are all monitored by the ECS
 
messenger RNA / mRNA

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Messenger RNA (mRNA) is a subtype of RNA. An mRNA molecule carries a portion of the DNA code to other parts of the cell for processing. mRNA is created during transcription. During the transcription process, a single strand of DNA is decoded by RNA polymerase, and mRNA is synthesized. Physically, mRNA is a strand of nucleotides known as ribonucleic acid, and is single-stranded


exon / exons
Exons are coding sections of an RNA transcript, or the DNA encoding it, that are translated into protein. Exons can be separated by intervening sections of DNA that do not code for proteins, known as introns. Following transcription, new, immature strands of messenger RNA, called pre-mRNA, may contain both introns and exons. These pre-mRNA molecules go through a modification process in the nucleus called splicing during which the noncoding introns are cut out and only the coding exons remain. Splicing produces a mature messenger RNA molecule that is then translated into a protein.


ribonucleic acid / RNA

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Ribonucleic acid (RNA) is a linear molecule composed of four types of smaller molecules called ribonucleotide bases: adenine (A), cytosine (C), guanine (G), and uracil (U). RNA is often compared to a copy from a reference book, or a template, because it carries the same information as its DNA template but is not used for long-term storage.

Each ribonucleotide base consists of a ribose sugar, a phosphate group, and a nitrogenous base. Adjacent ribose nucleotide bases are chemically attached to one another in a chain via chemical bonds called phosphodiester bonds. Unlike DNA, RNA is usually single-stranded. Additionally, RNA contains ribose sugars rather than deoxyribose sugars, which makes RNA more unstable and more prone to degradation.

RNA is synthesized from DNA by an enzyme known as RNA polymerase during a process called transcription. The new RNA sequences are complementary to their DNA template, rather than being identical copies of the template. RNA is then translated into proteins by structures called ribosomes. There are three types of RNA involved in the translation process: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA).

Although some RNA molecules are passive copies of DNA, many play crucial, active roles in the cell. For example, some RNA molecules are involved in switching genes on and off, and other RNA molecules make up the critical protein synthesis machinery in ribosomes.

RNA polymerase

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RNA polymerase is an enzyme that is responsible for copying a DNA sequence into an RNA sequence, duyring the process of transcription. As complex molecule composed of protein subunits, RNA polymerase controls the process of transcription, during which the information stored in a molecule of DNA is copied into a new molecule of messenger RNA.

RNA polymerases have been found in all species, but the number and composition of these proteins vary across taxa. For instance, bacteria contain a single type of RNA polymerase, while eukaryotes (multicellular organisms and yeasts) contain three distinct types. In spite of these differences, there are striking similarities among transcriptional mechanisms. For example, all species require a mechanism by which transcription can be regulated in order to achieve spatial and temporal changes in gene expression.


deoxyribonucleic acid / DNA

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Deoxyribonucleic acid (DNA) is a molecule that encodes an organism's genetic blueprint. In other words, DNA contains all of the information required to build and maintain an organism. DNA was discovered in 1868, when twenty-four-year-old Swiss physician Friedrich Miescher isolated a compound from the nuclei of white blood cells. This compound was neither a protein nor a lipid nor a carbohydrate, so it was therefore a novel type of biological molecule. Miescher named his discovery "nuclein," because he had isolated it from the nuclei of cells. Today, this molecule is called DNA. Nearly all of the cells within a single organism include exactly the same DNA.

DNA is a linear molecule composed of four types of smaller chemical molecules called nucleotide bases: adenine (A), cytosine (C), guanine (G), and thymine (T). The order of these bases is called the DNA sequence. Segments of DNA that carry genetic information are called genes, and they are inherited by offspring from their parents during reproduction.

In 1953, Francis Crick and James Watson described the molecular shape of DNA as a "double helix." Double-stranded DNA is composed of two linear strands that run opposite to each other, known as anti-parallel strands; these strands twist together to form a double helix. The structure of DNA can also be described as a ladder. The chemical backbones of the ladder are made up of sugar and phosphate molecules that are connected by chemical bonds. The rungs of the ladder are pairs of units between A and T or between C and G. These pairs are called base pairs and they connect the two sugar-phosphate backbones through interactions called hydrogen bonds. In cells, the DNA helix is often overwound, causing a phenomenon known as supercoiling.

In the nucleus, DNA forms a complex with proteins. This complex is called chromatin and is formed when the DNA wraps around nuclear proteins and then wraps around itself multiple times to condense the DNA into a smaller volume. Additionally, DNA chromosomes are often recognized and depicted as X-shaped structures. DNA takes this form following DNA replication during the process of cell division, when replicated chromosomes are highly condensed and appear in an X shape.

transcription / DNA transcription

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Transcription is the process by which the information in a strand of DNA is copied into a new molecule of messenger RNA (mRNA). DNA safely and stably stores genetic material in the nuclei of cells as a reference, or template. Meanwhile, mRNA is comparable to a copy from a reference book because it carries the same information as DNA but is not used for long-term storage and can freely exit the nucleus. Although the mRNA contains the same information, it is not an identical copy of the DNA segment, because its sequence is complementary to the DNA template.

Transcription is carried out by an enzyme called RNA polymerase and a number of accessory proteins called transcription factors. Transcription factors can bind to specific DNA sequences called enhancer and promoter sequences in order to recruit RNA polymerase to an appropriate transcription site. Together, the transcription factors and RNA polymerase form a complex called the transcription initiation complex. This complex initiates transcription, and the RNA polymerase begins mRNA synthesis by matching complementary bases to the original DNA strand. The mRNA molecule is elongated and, once the strand is completely synthesized, transcription is terminated. The newly formed mRNA copies of the gene then serve as blueprints for protein synthesis during the process of translation.

helicase

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Helicases are enzymes that bind and may even remodel nucleic acid or nucleic acid protein complexes. There are DNA and RNA helicases. DNA helicases are essential during DNA replication because they separate double-stranded DNA into single strands allowing each strand to be copied. During DNA replication, DNA helicases unwind DNA at positions called origins where synthesis will be initiated. DNA helicase continues to unwind the DNA forming a structure called the replication fork, which is named for the forked appearance of the two strands of DNA as they are unzipped apart. The process of breaking the hydrogen bonds between the nucleotide base pairs in double-stranded DNA requires energy. To break the bonds, helicases use the energy stored in a molecule called ATP, which serves as the energy currency of cells. DNA helicases also function in other cellular processes where double-stranded DNA must be separated, including DNA repair and transcription. RNA helicases are involved in shaping the form of RNA molecules, during all processes involving RNA, such as transcription, splicing, and translation.

splicing
Removal of introns and connecting of exons in eukaryotic pre-mRNAs.
© 2008 by Sinauer Associates, Inc. All rights reserved. Sadava, D. Life: the science of biology. 8th Edition.

codon
A codon is a sequence of three DNA or RNA nucleotides that corresponds with a specific amino acid or stop signal during protein synthesis. DNA and RNA molecules are written in a language of four nucleotides; meanwhile, the language of proteins includes 20 amino acids. Codons provide the key that allows these two languages to be translated into each other. Each codon corresponds to a single amino acid (or stop signal), and the full set of codons is called the genetic code. The genetic code includes 64 possible permutations, or combinations, of three-letter nucleotide sequences that can be made from the four nucleotides. Of the 64 codons, 61 represent amino acids, and three are stop signals. For example, the codon CAG represents the amino acid glutamine, and TAA is a stop codon. The genetic code is described as degenerate, or redundant, because a single amino acid may be coded for by more than one codon. When codons are read from the nucleotide sequence, they are read in succession and do not overlap with one another.

 
Cannabis vs Pancreatic Cancer

Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress—Related Genes | Cancer Research

Experimental Therapeutics, Molecular Targets, and Chemical Biology
Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress—Related Genes


Arkaitz Carracedo, Meritxell Gironella, Mar Lorente, Stephane Garcia, Manuel Guzmán, Guillermo Velasco and Juan L. Iovanna
DOI: 10.1158/0008-5472.CAN-06-0169 Published July 2006
ArticleFigures & DataInfo & Metrics
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Abstract

Pancreatic adenocarcinomas are among the most malignant forms of cancer and, therefore, it is of especial interest to set new strategies aimed at improving the prognostic of this deadly disease. The present study was undertaken to investigate the action of cannabinoids, a new family of potential antitumoral agents, in pancreatic cancer. We show that cannabinoid receptors are expressed in human pancreatic tumor cell lines and tumor biopsies at much higher levels than in normal pancreatic tissue. Studies conducted with MiaPaCa2 and Panc1 cell lines showed that cannabinoid administration (a) induced apoptosis, (b) increased ceramide levels, and (c) up-regulated mRNA levels of the stress protein p8. These effects were prevented by blockade of the CB2 cannabinoid receptor or by pharmacologic inhibition of ceramide synthesis de novo. Knockdown experiments using selective small interfering RNAs showed the involvement of p8 via its downstream endoplasmic reticulum stress—related targets activating transcription factor 4 (ATF-4) and TRB3 in Δ9-tetrahydrocannabinol—induced apoptosis. Cannabinoids also reduced the growth of tumor cells in two animal models of pancreatic cancer. In addition, cannabinoid treatment inhibited the spreading of pancreatic tumor cells. Moreover, cannabinoid administration selectively increased apoptosis and TRB3 expression in pancreatic tumor cells but not in normal tissue. In conclusion, results presented here show that cannabinoids lead to apoptosis of pancreatic tumor cells via a CB2 receptor and de novo synthesized ceramide-dependent up-regulation of p8 and the endoplasmic reticulum stress—related genes ATF-4 and TRB3. These findings may contribute to set the basis for a new therapeutic approach for the treatment of pancreatic cancer. (Cancer Res 2006; 66(13): 6748-55)

Introduction

Pancreatic cancer is one of the most malignant and aggressive forms of cancer ( 1). With an incidence of 10/10,000 for men and 7/10,000 for women, it represents the fourth most common death-causing cancer in the United States ( 2) and the fifth in the Western world overall ( 3). About 95% of pancreatic cancers cases are ductal adenocarcinomas. The anatomic localization of the pancreas and the nonspecific nature of the symptoms result in a complex and delayed diagnosis. Therefore, at the time of detection, 85% of patients show metastasic infiltrations in proximal lymphatic nodes, liver, or lungs, and only 15% to 20% of the tumors are typically found resectable ( 1). In addition, <20% of the operated patients survive up to 5 years. Treatment of unresectable tumors is currently based on administration of fluorouracil chemoradiation for locally advanced tumors and gemcitabine chemotherapy for metastatic disease ( 1). However, despite maximal optimization of these therapies, the median survival for the affected patients remains ∼1 year. It is therefore of especial interest to set new therapeutic strategies aimed at improving the prognostic of this deadly disease.

The hemp plant Cannabis sativa produces ∼70 unique compounds known as cannabinoids, of which Δ9-tetrahydrocannabinol (THC) is the most important owing to its high potency and abundance in cannabis ( 4). THC exerts a wide variety of biological effects by mimicking endogenous substances, the endocannabinoids anandamide ( 5) and 2-arachidonoylglycerol ( 6), which bind to and activate specific cannabinoid receptors. Thus far, two cannabinoid-specific Gi/o protein-coupled receptors have been cloned and characterized from mammalian tissues ( 7): The CB1 receptor is particularly abundant in discrete areas of the brain but is also expressed in peripheral nerve terminals and various extraneural sites. In contrast, the CB2 receptor was initially described to be present in the immune system ( 8) although, recently, it has been shown that expression of this receptor also occurs in cells from other origins ( 9— 11).

One of the most exciting areas of research in the cannabinoid field is the study of the potential application of cannabinoids as antitumoral agents ( 12). Thus, cannabinoid administration has been shown to curb the growth of several models of tumor xenografts in rats and mice ( 12). This antitumoral action of cannabinoids relies, at least in part, on the ability of these compounds to directly affect the viability, via induction of apoptosis or cell cycle arrest, of a wide spectrum of tumor cells in culture ( 12). In addition, cannabinoid treatment inhibits tumor angiogenesis ( 13— 15). Both CB1 ( 9, 11, 16, 17) and CB2 receptors ( 11, 18, 19) have been shown to mediate the growth-inhibiting action of THC and related cannabinoids on tumor cells ( 12). The present study was therefore undertaken to investigate (a) the antitumoral action of cannabinoids in pancreatic cancer and (b) the molecular mechanisms involved in that effect.



Results are too complex to transfer. Review and translate.



Discussion

Despite many years of intensive research, pancreatic cancer remains as the fourth leading cause of cancer death in the United States ( 1, 2) and the fifth in the Western world overall ( 3). Current approved therapies based on the administration of fluorouracil chemoradiation for locally advanced tumors and gemcitabine chemotherapy for metastatic disease have only slightly increased the median survival of affected patients ( 1). In the present report, we show that cannabinoids induce apoptosis of pancreatic tumor cell lines in vitro and exert a remarkable growth-inhibiting effect in models of pancreatic cancer in vivo. The latter effect is evident under various experimental settings (cells inoculated at different sites and cannabinoids administered by different routes). Moreover, our results also show that cannabinoids exert a strong inhibitory effect on the spreading of pancreatic tumor cells not only to adjacent locations such as spleen but also to distal tissues such as liver, diaphragm, stomach, and intestine, thus suggesting that these agents may also decrease the propagation of pancreatic tumor cells.

Although the pancreatic tumor biopsies and cell lines analyzed expressed both CB1 and CB2 cannabinoid receptors, our findings indicate that the CB2receptor is the one that plays a major role in the proapoptotic effect of cannabinoids in these cells. Previous observations had shown that the CB2receptor is involved in the antitumoral effect of cannabinoids in gliomas ( 9, 19), skin carcinomas ( 11), lymphomas ( 18), and prostate carcinomas ( 30), which may be clinically relevant as CB2-selective activation is not linked to the typical marijuana-like psychoactive effects of CB1 activation ( 7). However, the molecular mechanisms involved in those CB2-mediated actions are only partially understood. Results presented here, together with data obtained in rat glioma and human astrocytoma cells ( 25), show that p8 and ATF-4 up-regulation mediates cannabinoid-induced apoptosis via induction of the proapoptotic protein TRB3 ( 29, 31). Of interest, it has been recently shown that ATF-4 regulates TRB3 expression to induce apoptosis of human transformed cells ( 29). This pathway is triggered by endoplasmic reticulum stress ( 29), and our results support that it is also involved in cannabinoid-induced apoptosis of human pancreatic tumor cells in vitro and in vivo. Of potential interest for future cannabinoid-based therapies, cannabinoid treatment does not seem to activate this pathway in normal pancreas or spleen, suggesting that these agents may activate the endoplasmic reticulum stress proapoptotic pathway selectively in tumor cells.

On the other hand, our data also implicate de novo synthesized ceramide in the proapoptotic effect of THC. Many chemotherapeutic agents have been shown to mediate their antiproliferative effects via regulation of ceramide production ( 32). In line with these observations, we had previously shown that this proapoptotic sphingolipid participates in the antitumoral action of cannabinoids in glioma cells ( 9, 13, 20). Here we show that de novosynthesized ceramide is involved in THC-induced up-regulation of p8, ATF-4, and TRB3 in pancreatic tumor cells. Interestingly, p8 had been shown to be regulated by ceramide ( 24, 25) and we have also observed that pharmacologic inhibition of ceramide synthesis de novo decreases basal p8 expression (data not shown). Thus, our findings indicate that the mechanism of cannabinoid-induced apoptosis of human pancreatic tumor cells involves a CB2 receptor—dependent accumulation of de novo synthesized ceramide that leads to p8, ATF-4, and TRB3 up-regulation ( Fig. 6D).

One of the major problems that face cancer therapies is the resistance to chemotherapy. It is worth noting that low doses of THC (but not of WIN 55,212-2) slightly induced proliferation of Panc1 and Capan2, but not of MiaPaca2 and BxPc3 cells, an effect that does not depend on cannabinoid receptors (data not shown). A similar growth-promoting effect of cannabinoids at submicromolar concentrations has previously been described by us ( 33) and others ( 34) for several transformed cells. Interestingly, our observations suggest that this behavior may be related with a lower sensitivity to THC proapoptotic action, as higher doses of this compound (although still within the low micromolar range) are necessary to induce CB receptor—dependent apoptosis of the human pancreatic (present study) and astrocytoma 3 cell lines that exhibit this proliferative response. Thus, the potential development of future cannabinoid-based therapies for this or other types of tumors should ideally evaluate the sensitivity of each particular tumor to these compounds. In our laboratories, we are currently investigating the gene expression profile associated with a higher sensitivity/resistance of tumor cells to cannabinoid treatment to improve the selectivity and efficiency of a potential cannabinoid-based therapy.

In conclusion, results presented here show that cannabinoids exert a remarkable antitumoral effect on pancreatic cancer cells in vitro and in vivodue to their ability to selectively induce apoptosis of these cells via activation of the p8-ATF-4-TRB3 proapoptotic pathway. These findings may help to set the basis for a new therapeutic approach for the treatment of this deadly disease.
 
I'm Believed Power Super Antioxidant Astaxanthin

5 reasons to add astaxanthin to your skincare routine by Susanne Norwitz

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5 reasons astaxanthin is amazing for your skin (1)
Does the word Astaxanthin sound familiar? For most of you, this may sound like a really odd word. I know the first time I heard it, I said, "Asta-what?" Although if you have been following our blog, then you most likely noticed our post from a few months ago regarding this new powerhouse antioxidant. However, this blog post is going to be a bit more in-depth with regard to the numerous benefits of Astaxanthin.

If you need a quick refresher, Astaxanthin is one of nature's most potent antioxidants, it is what is classified as a caretenoid. It is primarily found in marine life including micro algae, wild salmon, red trout, krill, shrimp, crabs, and lobsters. It gives flamingos and salmon their brilliant pink hue — and in the case of salmon gives them the ability to swim upstream.

So what can Astaxanthin do for your skin?

Astaxanthin is particularly impressive for your skin due to the fact that it never becomes a pro-oxidant, meaning that it protects our cells against oxidation. And, what is oxidation? Technically speaking, oxidation means the loss of electrons. In simpler terms, oxidation is decay or decomposition.

Maya Chia Beauty was at the vanguard of introducing the powerhouse antioxidant, astaxanthin, into beauty care. It can be found in the Maya Chia Beauty's "Super Couple" face oil, which features Astaxanthin's signature coral hue that imparts a beautiful radiant glow to the skin — one that appears as if you are glowing from within.

With that said, here are 5 fun facts about Astaxanthin, showing why it is a game changer in the world of high-performance, natural skincare.

1. Astaxanthin has been shown in clinical studies to increase skin moisture, moisture retention, elasticity, as well as promote skin smoothness, decreasing fine lines and wrinkles.

2. Astaxanthin has incredible UV-blocking properties, which helps to assist the skin in protecting itself against sun-related damage. So long dark spots! Please note: our oil does note have SPF in it — which means you will need to use an SPF in addition to the application of this face oil.

3. While we err on the side of quoting a more conservative study which found Astaxanthin 65 times stronger than Vitamin C in combating free radicals. Another reputable clinical study, has shown "Natural astaxanthin is exceptionally powerful in singlet-oxygen quenching. A 2007 study analyzed several popular antioxidants and their antioxidant power. This study found astaxanthin was 6,000 times stronger than vitamin C, 800 times stronger than CoQ10, 550 times stronger than green tea catechins and 75 times stronger than alpha lipoic acid."

4. Astaxanthin can neutralize multiple free radicals at once, protecting your skin and body from oxidation, damage, and inflammation.

5. Astaxanthin has been proven to increase blood flow, meaning that it will help your skin to have better circulation. Increased circulation has various benefits, including increased cell turnover, amplified elasticity, and increased water retention.

In addition to all these amazing skin-related benefits, Astaxanthin can be taken as a supplement. There are a spate of clinical studies which demonstrates how it can increase energy, strength, eye health, and brain health, to name a few.(note: we (at Maya Chia Beauty) do not claim our products will lead to any of these benefits, but it's interesting to read about) Needless to say, we can't get enough of this transformative antioxidant!

__________________________________

Nishida Y. et. al, Quenching Activities of Common Hydrophilic and Lipophilic Antioxidants against Singlet Oxygen Using Chemiluminescence Detection System.
 
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