Clinical Applications of Cannabinoids and terpenes
Mara Gordon - Cannafest 2015, Prague
Some basic Terpenes
* Pinene - Elevates the mind, sharpens focus (can cause anxiousness if sensitive)
* Linalool- analgesic, anti-anxiety (found in lavender)
* B- Caryophyllene - most abundant in Ashanti peppers
- Look for it in purple chemovars.
- On its own this terpene will activate CB2 receptor sites
without interfering with THC uptake the way CBD will.
- Look for chemovars high in b-caryophyllene when treating diseases with lots of CB2 receptor sites.
Myrcene - found in mangos and hops
- improves bioavailability by helping Cannabinoids pass more efficiently through the BBB
- has sedative effect
- found in higher concentrations in plants we think of as indicas
- helpful when dealing with a number of chronic diseases (chronic disease typically has lots of inflammation)
Limonene - found in lemons and other citrus fruits
- good for acid reflux
- effective anti-anxiety choice
- can be used to treat depression with good effect
- On some airlines first-class passengers are offered cloths soaked in lemon water to wipe the face and hands.
Cannabis is such effective medicine in part because of the entourage effect, that synergistic dance of cannabinoids and the terpenes that direct their action creating a medicine that's more potent together than any of the components would be if used alone.
Random cannabinoid info
*
CBG is the mother compound, eventually becoming all the other cannabinoids.
- good for pain relief, best if paired with THC
CBN - sedative and pain relief
CBD is an antagonist of both CB1 and CB2 receptor sites, though not a primary antagonist
- it works more as an allosteric modulator of other eCB receptor sites
- when combined with THC both become potentiated
THCa - anti-inflammatory
- can be substituted for CBD with seizure patients if they don't respond to CBD treatment
- will work as anti-inflammatory in topicals
- imparts a sense of wellbeing instead of overwhelming euphoria
Misc. facts
Most high CBD chemovars started out as sativas.
Granddaddy Purple is an excellent indica for cancer patients
If you take too much THC you can take some CBD and it'll soften the effects of the THC.
When giving small amounts of cannabinoids you need to have them in a form that's easy to measure and dose accurately if you're expecting consistent results.
- If you have 700 mg/gram how do you know the difference between 2mg and 3mg?Scales aren't going to be that sensitive.
- Infused oils let you get consistent dosing over time
- A whole plant extraction with carrier oils will allow you to get to minute doses.
How it works: Cancer
CBD: Lowers response of ID-1 gene, restricting the proliferation and metastasis of cancer cells. High levels of ID-1are found in brain, liver, skin, and thyroid gland cancer cells. It is also expressed in fetal cells and umbilical vein endothelial cells.
Cannabidiol as a major component of the cancer treatment protocol
* Non-small cell lung cancer
* Gastric Cancer
* Breast cancer
* Prostate cancer
* Melanoma
* Glioblastoma
* Hepatocarcinoma
* Anaplastic thyroid tumor
* Metastasis of certain cancers
If you’re treating any of these cancers you can start out with higher CBD:THC ratios to hopefully stop metastasis and proliferation.
After reviewing patient history and questionnaire determine
* dose goal
* terpene and cannabinoid profiles and ratios
Cannabis dosing defies conventional approaches.
* Age is more a determination than weight
* youngest patients took highest doses for Glioblastoma
* oldest patients took the highest doses
Dose chart: Glioblastoma
88-yr old male(63kg) - 75:30 (ablue Dream: ACDC)
58-yr old male (84kg) - 350:100 (Candyland:ACDC)
54-yr old male (59kg) - 300:100 (Blue Dream: Valentine X)
23-yr old male (84kg) - 300:100 (XJ13:ACDC)
61-yr old female (55kg) - 1000:200 (Blue Dream: Valentine X)
50-yr old female (77kg) - 150:50 (XJ13:ACDC)
28-yr old female (63kg) - 200:100 (Berry OG:ACDC)
3-yr old female (18kg) 409:350 (Sour Diesel: ACDC)
Breast Cancer
45-yr old female (63kg) - 250:250 (Sour Diesel:ACDC)
47-yr old female (59kg) - 100:100 (Sour Diesel: ACDC)
43-yr old female (61kg) - 159:150 (Sour Diesel:Valentine X)
44-yr old female (71kg) - 150:75 (Pepe le Pu:ACDC)
57-yr old female (57kg)* - 30:100 (Pepe me Pu:ACDC)
35-yr old female (57kg)* - 30:15 (Sour Diesel:ACDC
* only wanted to treat side effects, not cure
Questions For The Patient
* What’s the diagnosis?
* What’s the current cannabis use and experience?
* What pharmaceuticals and nutraceuticals are you on?
CBD will interfer with the CP450 pathway and will potentially cause certain medicines to build up to dangerous levels. Any medicine that cautions you against grapefruit juice is suspect and serum levels should be monitored more closely if using CBD.
*What’s your age?
* What’s your objective? What are you trying to accomplish?
How it works: Epilepsy
Epilepsy is a symptom of many, many diseases. To say you're treating epilepsy is a misnomer. You need to find the root cause of the seizures.
THC: Activation of CB1 receptor sites shorts out calcium ion pump on pre-synaptic neurons, potentially stopping grand mail seizures
Processes hydrocortisone-like anti-inflammatory mechanism
CBD: Proven to reduce seizures and has well-established neuroprotective effects that are at least partially mediated by seratonin receptors
THCa: Appears to work in a similar manner as CBD, but more mechanism of action studies are needed. Typical use is after patient acclimates to CBD and experiences increased seizure activityTHCa will often replace CBD when it stops working and vice versa
THCV: Similar to THC in mechanism of action. Euphoric benefit present without being uncomfortably overwhelming.
Ex: 7-yr old female (35kg) - 10.3:250 (ACDC)
To form an effective protocol to control epileptic seizure disorders lifestyle and dietary changes must become part of the program.
How it works: Intractable Nerve Pain
THC: There are 5 mechanism involved with pain reduction with eCB1 and eCB2 activation by THC:
- retards electrochemical reactions at peripheral pain receptors
- interrupts pain signal at Basal Root Ganglia
- interrupts pain signal at neuron
- activation of eCB2 at leukocytes provides major anti-inflammatory response
- psychoactive euphoric effects and short-term memory reduction mitigate stress response to pain
CBD: Anti-inflammatory mechanism provides 30-50 times hydrocortisone relief
without shutting down the adrenal gland.
All disease involves inflammation.
Ex: 78-yr old female taking 15 mg THCa, 5 mg THC, and 15 mg CBD (OG2xSour:Swiss Gold)
A closer look at the dosing adjustments:
- patient has intractable nerve pain
- hadn't slept well in 20 years
- was suicidal
1. Swiss Gold (infused in EVOO)
0.07% THC
0.69% CBD
CBD target dose: 15mg, in 3 daily doses
2.174g extract/tincture/day
0.725g/dose
Total THC/day:1.5 mg
2a. OG2xSour
3.7% THCa
0.01% CBD
THCa target dose: 15mg in a single daily dose of 0.405g
CBD dose is negligible
2b. OG2xSour
3.7% THCa
0.93%THC
THCa target dose: 15mg in a single daily dose of 0.405g of tincture.
Amt. THC: 3.8mg
2c. OG2xSour
0.93% THC
0.01% CBD
THC target dose: 3.8mg in a single daily dose of 0.405g of tincture
How it works: Insomnia
THC: Many indica-dominant chemovars of cannabis contain terpenes such as b-myrcene and other cannabinoids like CBN that will cause somnolence at the correct dose. This is assisted to a great degree by the entourage effect of cannabis.
* Activation of CB1 receptor sites by THC at presynaptic neurons slows neural activity at the synaptic crest (Homeostasis).
* Activation of CB1 and CB2 receptor sites by THC causes relaxation by stimulating vasodilation of blood vessels (Homeostasis).
* Anti-anxiety action of THC at correct dose AIDS sleep
CBD: Mechanics of action not completely understood as sleep agent. Studies have been done for sleep and for wak-inducing properties.
- CBD is known to be an "alerting" cannabinoid and shouldn't be taken too close to bedtime.
Ex: 60-yr old man (82.5kg) - 25.0 (Granddaddy Purple)
You want a chemovar high in myrcene to help pass the BBB and one with higher CBN
- You can push CBN with time and sunlight.
- Take a bit of last year's harvest and store it poorly to generate more CBN for later when you want to make more oils for sleep.
How it works: Hypertension
THC:
* Activation of CB1 and CB2 receptor sites by THC
- causes vasodilation of blood vessels, lowering BP
- causes relief of stress by blocking production of acetylcholine within the brain
- slows down neurotransmission at the synaptic cleft
Ex: 57-yr old male - 30mg THC/day plus 13mg CBD/day (EVOO infusion)
- was looking at forced disability due to health issues
- on numerous meds that were ineffective
*** One of the reasons THC works so well for PTSD is the blockage of acetylcholine, which helps tremendously with short-term memory.
You can take acetylcholine supplements, but this
is not advised for cancer patients due to the vasodilation.
Some patients with hypertension are similar to PTSD adrenaline push, stuck in fight or flight mode. You need THC to break the momentum.
This patient demonstrates how you work to replace one chemovar with another that closely matches the one you now can't get a supply of. In this case that happened twice.
1. Cotton Candy Deisel
0.6% THC
0.26% CBD
THC target daily dose: 30mg in a single daily dose of inhaled oil
Amt CBD: 13mg
After running out of Cotton Candy Diesel they replaced it with a compound formulation of Cookies and ACDC.
Cookies
0.64% THC
0.01% CBD
ACDC
0.02% THC
0.53% CBD
THC target dose: 30mg in a single dose of inhaled infused oil
* 4.482g Cookies + 2.109g ACDC
Amt CBD: 13mg
When they ran out of Cookies they switched to a combo of Swiss Gold and Pepe Le Pu.
Pepe Le Pu
0.91% THC
0.01% CBD
Swiss Gold
0.07% THC
0.69%CBD
THC target dose: 30mg in a single inhaled dose of infused EVOO
3.133 mg of Pepe Le Pu
2.129mg Swiss Gold
Amt CBD: 13mg
How it works: Irritable Bowel Syndrome (IBS) - Chron's Disease
THC: Activation of CB1 and CB2 receptors in gut by THC relieves motility and inhibits secretions that cause inflammation.
CBD: Reduction of inflammation leads to relief of many IBS symptoms
- Anti-bacterial properties relieve opportunistic abscesses often seen in Chron's
Ex: 54-yr old female - 30:15 (Pepe Le Pu:ACDC)
These patients respond to systemic administration(think capsules, edibles, suppositories), but can do well with inhallation as well.
Mara had another patient having problems with abscesses (fistula wouldn't heal) and she had him taking CBD by suppository while taking THC and CBD sublingually and vaping the same extract for breakthrough.
How it works: PTSD, ADHA, Tourette's Syndrome
THC:
*Blocks production of acetylcholine, which acts as a short-term memory transmitter, providing effective relief of reaccuring traumatic memories
* Activates CB1 receptors in brain providing psychotropic relief with proper dose and strain
* Cannabis chemovars that contain cannabinoid and terpene profiles which make them very energetic (pure sativas) will have a calming effect for patients with ADHD, much like prescription stimulants
without side effects
Ex: 50-yr old female - 15:5 (Pepe Le Pu:ACDC)
Someone with PTSD who uses a sativa high in A-pinene will get a calming effect where someone else may be totally stressed out by the same chemovar.
These patients are most likely to have opposite effects than others have p, due to acetylcholine blockage
Conclusions:
* Cannabis is greater than the sum of its parts (entourage effect)
- Without the entourage effect you're missing out on the best effects available from the plant.
*Endo and exo (phyto) cannabinoids play a significant role in treating
all disease
* It's important to choose the right chemovar (cannabinoid ratios and terpene profiles)
* It's possible to dose correctly and consistently
* Individual treatment plans are necessary
* Seperating the THC and CBD doses by at least two hours influences your results
- you'll be able to reduce the doses and still have the effect you seek
- CBD is an antagonist to the eCBRs, which means it can interfer with THC signalling
* cannabis medicines need to be lab tested to guarantee patient outcomes
- If you don't know what's really in the medicine you can't reasonably predict outcomes.
* Without THC most disease states wouldn't be responsive to cannabis therapies.
Q & A responses:
CBD will create one of three responses from a patient
1. make you energetic
2. make you sleepy
3. feel nothing different
Mara speculates that those who prefer sativas high in limonene and A-pinene get sleepier with CBD chemovars than those who prefer indicas.
People who can't adjust to cannabis therapies lack the ability to let go of control. They are eithe incapable or unwilling to relax into it. They have fear and a need to control.
Allergic reactions are to the terpenes in the chemovar.
- wear a mask while trimming to lessen potential allergic reactions
- One of Mara's patients would check for allergic reaction by rubbing the plant material on her skin.