Cannabanoids and Pain control Flashcards
Name the three categories of pain
- Accute physiological pain
- Accute inflammatory pain
- Chronic Pain
What is accute physiological pain?
Pain that results from sudden physical trauma, such as touching a hot stove or pricking the finger on a needle. This activates the ‘withdraw’ reflex, helping the body avoid pain. In this way pain is a defensive mechanism aimed at preventing harm.
What is accute inflammatory pain?
Pain that result from the bodies inflammatory response. The body responds to injury with inflamation that is aimed at healing the tissue. Inflammatory pain can an be important way to alert us to problems withing the body, as in appendicitis.
What is chronic pain?
Pain that lost for more than 3 months. Nerve damage almost always result in chronic pain. Chronic pain loses it’s defensive value
What is Allodynia?
Super sensitization to otherwise non painful stimuli
What problems are caused by chronic pain?
Can interfere with activities of daily livining
Can lead to depression, dispair, hopeless
Can lead to a decrease in quality of life
Can deteriate relationships
Can lead to a loss of income
Can lead to addiction (Oppiodes)
Anually, Chronic pain costs the economy more than the combined cost of …?
Diabetes, heart disease, and cancer
How are pain signals generated.
nociceptors (pain receptors) around the body is activated through transduction, when a certain threshold is reached, generating a pains signal which is transported from the peripheral nervous sytem to the central nervous system.
Was Descartes correct in assuming that their is a single pain center in the brain responsible for the perception of pain?
No. There is no ‘single’ center in the brain that is responsible for pain perception. Pain pathways terminate in multiple areas of the brain. Some are responsible for perceiving different kinds of pain, others are responsible for our motor response to the pain and still others are responsible for our emotive response to pain.
How do nerve blocks stop the experience of accute pain?
By interfering with the conduction of the pain signal
How does tissue damage cause inflamation
The contents of damaged cells spills into the interstitial spaces where it irritates the nociceptors, which attracts inflammatory immune cells. These cells release hestimine which activates the bodies inflammatory response (increase in circulation and swelling)
How does tissue damage cause inflamation and pain?
The contents of damaged cells spills into the interstitial spaces where it irritates the nociceptors, which attracts immune cells. These cells release hestimine which activates the bodies inflammatory response (increase in circulation and swelling). The inflamatory chemicals and response in turn continues to agrivate the nociceptors, producing more pain through averactive transduction untill inflamation subsides
What is Hyperalgesia?
A condition that results in a drop of the threshold that activates nociceptors. This usualy occurs during inflamation and is why even a light touch to an inflamed area can be painful.
What is Neuropathic pain?
Pain not activated by transduction, but by ectopic pain signals produced by damage or disease process along the pain pathway. Patients with neuropathic pain report often report spontanious experience of pain and hyperalgesia.
What is stress induced analgesia?
A mechanism that modulates or reduces pain during extreme or life threatening situations, allowing us to preserve life by escaping the situation.
What is the role of the body’s pain modulating systems?
To regulate our sensitivity to pain
Why is the body’s pain modulating sytem called a “top down” system?
because they originate in the brain and terminate in the synaps between the central and peripheral junction.
How can the body’s pain modulation system be ‘activated’ in order to decrease sensitivity to pain.
Drugs Manual stimulation Hypnosis Acupuncture Relaxation
How do canabanoids relieve pain
- By interfering with transduction of nocireceptors
- By decreasing the sensitivity of nocireceptors
- By enhancing pain modulation
Name the 4 pain processes involved in the experience of pain
Transduction, Conduction, Synaptic Transmission, Perception
Name the 6 classes of pain killers
- simple analgesics:
- weak
- used for weak pain (paracetamol) - NSAID’s:
- reduce inflamation
- inhibit cox(cyclooxygenase and enzyme that mediates
inflamatory response) - Opioide analgesics:
- moderate to severe pain
- effective for accute and cancer related pain - Adjuvent drugs
- Drugs that do not primarily treat pain, but are useful in
the relieving of pain
- Antidepressants, Anticonvulsants
- useful for headache prophalaxis
- reduce neuropathic pain - Local Anesthetics
- used for the management of accute pain during and
after surgery, neuropathic pain and for intractable
migraines
- nerve and epidural blocks - Heterogenus drugs
- used for migraines
What are non-selective NSAID’s
NSAID’s that block both cox1 and cox2
Ibuprofen
Naproxen
Diclofenac
What is the difference between cox enzymes 1 and 2?
type 1 protects the stomach membrane, kidneys and blood clotting during inflamation
type 2 induces inflamation
What are selective NSAID’s
NSAID’s that block cox2 enzymes
Etoricoxib
Celecoxib
What are the advantages of selective NSAIDs over non-selective NSAIDs
Non selective NSAIDs inhibits cox1 enzymes responsible for protecting the stomach lining, which can lead to gastric problems such as ulcers, whereas selective NSAIDS only inhibits the cox2 enzyme responsible for inflamation
What are the risks associated with NSAIDS?
both selective and non-selective: increase risk of thrombobolic effects (heart attack, stroke)
non-selective: Gastric ulcers
Why should NSAIDS not be use for chronic pain?
Because long term use increase risk of heart attack and stroke.
What are the adverse effects of using opioides?
High potential for abuse, addiciton and overdose, fatality, nausea, sedation, unsteadiness.
What two catagories are opioides devided into?
Weak:
- Codeine
- Tramadol
Strong:
- Morpine
- Oxycodone
- Fentanyl
What are the side effects of adjuvent drugs used to treat pain?
constipation, drowsiness, sexual dysfunction, sedation
What is the main problem with using local anesthetics?
Short duration
Which heterogenus drugs are often used for migraines?
Triptans
In regards to pain, what should be considered before prescribing pain killers
- Type (neuropathic, inflamatory, headache, spasms)
- Context (cause of the pain)
- Intensity (mild, moderate, severe)
- Background
When prescribing pain killers, what should be considered?
- Type
- Dose
- Duration
- Adjustments for patient background.
What is ischemic pain?
pain caused by reduce blood flow
What is the principle objective in the treatment of chronic pain?
To improve quality of life, by reducing pain and increasing function
When pain reduction is no longer possible, what is the next step?
Pain management: Teaching the patient to manage their pain and improve quality of life and function despite residual pain.
How long is the growing season for canabis?
3 to 6 months
How tall do canabis plants get within their growing season?
up to 5 meters
What are the 3 main categories of cannabis?
sativa
indica
ruderalis
Differences between indica, sativa, ruderalis and hemp?
indica is shorter, darker leaves with fatter and fewer fingers (rarely more than 5). The buds tend to be wide, dense and bulky, flowering time is 6 - 8 weeks. Indica is more sedative, calming in its effects. It gets you stoned. (body high)
Sativa is taller, lighter in color and the leaves have longer thinner fingers often with many more fingers than indica. buds are longer and almost sausage shaped. flowering time is aobut 10 to 16 weeks. Sativa is more uplifting, energising and hallucinogenic in it’s effects. It gets you high (head high)
ruderalis is the short, and leaves often have only 3 fingers and the plant has a very short flowering cycle. They also tend to grow in low light. Is most often used by growers to create hybrids.
Hemp is a species of sativa that is grown for the industrial uses of it’s derived products, such as paper, oil, cbd oil, fiber, biofuel, etc. It has a low thc content
Of the more than 500 compounds found in cannabis, which 3 are considered to the therapuetic agents?
Cannabinoids
Terpenoids : flavour and fragrance
Flavanoids
What are the most common terpenoids found in cannabis?
Limonene, Myrcene, Alpha-pinene, Linalool, Beta-Caraphyllene, Caryophyllene
What are terpenes?
Hydrocarbons Isoprene C5H8 Monoterpene C10H16 Sesquiterpene C15H24 Diterpene C20H32 Triterpene C30H48
Which family of plants do canabis belong to
canabiceae
What are flavanoids?
polycyclic aromatic phenols
Of the 23 different kinds of flavanoids identified in cannabis, which ones are unique to cannabis?
cannflavin A, cannflavin B
What are some of the medicinal propperties of flavanoids in cannabis?
anti-inflammatory
anti-cancer
neuro-protective
Which receptors do cannabinoids act on?
cb1 and cb2
Which disorders are cannabinoids useful for?
anorexia pain inflammation MS Epilepsy Glaucoma Osteoperosis Cancer obesity Parkinsons
What are the 11 subclasses of cannabinoids?
CBG -cannabigerol ^9-THC -^9 Tetrahydrocannabinol ^8-THC - ^8 Tetrahydrocannabinol CBD - cannabidiol CBC - cannabichromene CBN - cannabinol CBL - cannabicyclol CBND - cannabinodial CBE - cannabielsoin CBT - cannabitriol Other
From which cannabidoid are the other subclasses derived from
CBG - cannabigerol
Which for classes of cannabinoids are biosynthesized in the cannabis plant?
CBC, CBD, CBG, ^9-THC,
The other classes of cannabinoids are the result of decomposition in the plant and/or storage conditions
Why does canabinoids need to be decarboxylated?
because the plant synthesizes cannabinoids as acids THCA, CBDA which has a low bio-availabillity. In order to make it useable for the human body the carboxyl group needs to be removed through heat.
What tempreture is required for decarboxylation?
approx 93 to 180 degrees celsius for about 60 - 90 minutes
What are some of the benefits of undecarboxylated cbd’s or cbda’s?
Prevents nausea and vomiting Anxiolytic (anti-anxiety) effects Antibacterial properties Inhibits breast cancer cell migration Potential to reduce seizures associated with epilepsy Pain and inflammation reduction
True or False: There is a specificity between the type or strain of cannabis and the type of cancer it can treat.
TRUE. The strain that treats prostate cancer might not be effect against other types of cancer such as breast cancer.
What are the different methdos of consumption
Inhalation
Sub-lingual
Oral
Topical
How long does it take for orally ingested cannabis to take effect?
approx 90 minutes
How is sub-lingual cannabis absorbed into circulation?
through the oral mucosa
What does bioavailabillity mean?
the percentage or amount of a substance found in the body of the total amount administered.
What is the bioavailabillity of cannabis when smoked and what factors influences the bioavailabillity?
2 - 56%
depth volume holding time frequency time between puffs
How long before THC can be detected in plasma after smoking?
Almost immediately. Plasma levels of thc peaks about 20 minutes after smoking and then slowly declines untill it is completely gone 2 hours after smoking.
What is the bioavailabillity of cannabis when ingested orally and what is it influenced by?
5 - 20%
Dose
Vehicle of ingested
physiological factors
When do peak plasma levels of thc appear during oral ingestion of cannabis?
1 - 5 hours after ingestion
When do peak plasma levels of thc appear during sub-lingual ingestion of cannabis?
1:30 to 4 hours after administration
and is completely eliminated from plama btween 12 to 24 hours after dosing
how many days after smoking can thc be detected in low concetration in the blood of chronic smokers?
4 days.
Some thc is absorbed by lipids or fat cells in the body and then slowly released back into circulation
How is thc metabolized in the body
thc is metabolized into two motabolites by enzyme cyp 450239:
active: 11 hydroxy thc (11-oh-thc)
inactive: 9 carboxy thc (9-cooh-thc)
Cannabinol (CBN) was also mainly metabolized to 11-hydroxy-CBN and 8-hydroxy-CBN by the microsomes
What is the bioavailabillity of sub-lingually administered thc
13 to 35%
What is the bioavailabillity of rectal administration of thc?
approx 13,5 %
What happens to thc when enzyme cyp450239 is reduced by toxins or other medictions?
Causes an accumulation of THC in the body
How is THC eliminated from the body?
Mainly through urine, with up to 90% eliminated within 5 days
How long can THC be detected within the urine after administration?
2 to 4 weeks
Where in the body are CB1 receptors found?
Typically in the central nervous system: Cortex Hippocampus (memory) Limbic system (emotion) Brainstem and spinal cord (pain processing)
What happend when cb1 receptors were blocked in animal studies?
Induced Hyperanalgesia or hyper sensitivity to pain
Where are cb2 receptors found?
Typically in the peripheral nervous system
What happens to the analgesic effect of cannabis over time?
It deminishes due to the down regulation of cb1 receptors in the CNS, which leads to an increase in tollerance
What happens to the analgesic effect of cannabis over time?
It deminishes due to the down regulation of cb1 receptors in the CNS, which leads to an increase in tollerance
studies in animals have also shown a down regulation of cb2 receptors
How does the activation of cb2 receptors reduce pain
cb2 receptors are found on immune cells, which when activated reduce inflamation
cb2 receptor are also found on nociceptors, when activated reduce the sensitivity of nociceptors
release of opiodes from skin cells, which further reduce pain.
How does the activation of cb2 receptors reduce pain?
cb2 receptors are found on immune cells, which when activated reduce inflamation
cb2 receptor are also found on nociceptors, when activated reduce the sensitivity of nociceptors
activation of peripheral cb2 receptors, initiate the release of opiodes from skin cells, which further reduce pain.
This means that cannabis exert a local effect on pain through topical application
cb2 receptors are also found in the central nervous system on astrocytes and microglia which are heavily involved in pain processing
How does the activation of cb1 receptor reduce pain?
cb1 receptors are found in the brian stem and spinal cour in areas associated with pain processing. activation of these receptors can interfere with pain processing.
cb1 receptors are also found near but outside the spinal cord, where there activation interferes with the pain processing in the peripheral nervous system.
What are FFAH inhibitors?
drugs that inhibit the degradation of endocanabinoids and therefore increase the level of canabinioids in the brain
Which kind of cannabis oil will be more effective in treating conditions with over inflamation?
Oils high in CBD, as CBD is anti-inflamatory
What kinds of pain benefits from cannabis?
accute pain inflamatory pain Headaches Joint pain Neuropathic pain Cancer pain Chronic pain
(important to note, that research is limited and seems to suggest that specificity exist, between strain used and type of pain treated)
Which psychiatric conditions can benefit from cannabis?
PTSD -reduced symptoms of anxiety and insomnia and increased abillity to cope.
Which psychiatric conditions can benefit from cannabis?
PTSD -improved mood, reduced symptoms of anxiety and insomnia and increased abillity to cope. (Stopping cannabis use can agravate PTSD symptoms due to withdrawel)
Depression -possitive effect on mood
Which neurological conditions can benefit from cannabis?
MS Parkinsons Epilepsy Spasticity Tourettes
What is the hallmark symptom of cannabis withdrawel?
difficulty sleeping
- night sweats
- nightmares
- strange dreams
- difficulty falling asleep
