Plants and Pain

Question 1

Plants used for halucinogenic modulating effects

Answer 1

1. psilocibin - serotonin agonist
2. ayahuasca - monoamine oxidase inhibitory (increase synaptic serotonin levels)

Question 2

Plants used for Stimulant modulating effects

Answer 2

1. coca leaves - dopamine reuptake inhibitor (increase synaptic dopamine levels)
   - tobacco - cholinergic agonist nicotinic receptors
   - coffee bean - adenosine receptor antagonist

Question 3

Analgesic drugs derived from plants include

Answer 3

• salicylic acid (asprin)
• opiates (morphine, opium, thebaine)
• cannabis
• capsaicin
• menthol
• salvinorin

Question 4

Primary Afferents

Answer 4

• sensory neurons in the periphery (skin, organs)
• two classes: A fibers and C fibers

Question 5

Nociceptors

Answer 5

primary afferents that detect pain

Question 6

A fibers are:

Answer 6

• myelinated (fast conducting, insulates the axon)
• end in specialized structures (Ruffini, Pacianian, Meissner)
• each structure detects specific non-painful stimuli (touch, temp, vibration)

Question 7

C fibers are:

Answer 7

• unmyelinated (slow conducting)
• end as free nerve endings in the superficial layers of the skin
• detect many types of painful stimuli (thermal, mechanical, chemical, electrical)
• polymodal nociceptor

Question 8

How are Painful Stimuli Detected?

Answer 8

• on the free nerve nerve endings of C fibres by specialized receptors
• TRPV1 : ion channel, activated by heat (> 43 degrees) and capsaicin, causes burning pain
• TRPA1 : allyl isothionate, burning, inflammation

Question 9

Urishol

Answer 9

• found in poison ivy, crosses the skin and initates and inflammatory reaction that activates NK, BK and cytokine receptors
• causes itch and pain

Question 10

How does info get sent up to the brain?

Answer 10

• C fibre primary afferents synapse onto secondary afferents in the dorsal horn of the spinal cord
• secondary afferents carry nociceptive information up the spinal cord to the brain

Question 11

Nociception vs. Pain

Answer 11

• nociception does not equal pain
• nociception: relay of pain signal from periphery to the brain
• pain: integration of that pain signal with cognitive and emotional context (requires the brain, always a subjective experience)

Question 12

Define opium, opiates, opioid

Answer 12

• opium : dried latex obtained from the poppy
• opiates : any drug derived from opium
• opioid: any drug that binds to an opioid receptor. Includes opiates, as well as synthetic opioid agonists (fentanyl, heroin, oxycontin)

Question 13

Opioid Receptors in the body and their affect

Answer 13

• brain : many regions are involved in pain perception, emotion, reward and addiction
• brainstem : can affect breathing by quieting neurons that control respiration
• spinal cord
• peripheral neurons
• intestine

Question 14

Agonists

Answer 14

• ex. morphine
• activate opioid receptors, but that activation leads to decreased likelihood that the neuron will fire

Question 15

What are the 3 classes of opioid receptors?

Answer 15

mu, delta, kappa

Question 16

receptor activation and typical agonists of mu opioid receptors

Answer 16

• receptor activation leads to analgesia euphoria
• typical agonists: heroin, morphine, oxycodone, fentanyl

Question 17

receptor activation and typical agonists of delta opioid receptors

Answer 17

• receptor activation leads to decrease in anxiety
• typical agonists: some drugs being developed to treat chronic pain conditions, like migraine (SNC80)

Question 18

receptor activation and typical agonists of kappa opioid receptors

Answer 18

• receptor activation leads to analgesia, dysphoria, hallucinations
• typical agonists: salvinorin

Question 19

Dopamine

Answer 19

• dopamine is involved in motivated behavior
• dopamine neurons are located primarily in the VTA
• opioid recpetors in teh VTA are located on inhibitory GABAergic interneurons
• opioids inhibit inhibition (disinhibition) leading to dopamine release

Question 20

How do opioid receptors inhibit pain?

Answer 20

1. decreasing nociception at the level of the C fibre, in the spinal cord, and in the thalamus
2. decreasing the emotional and cognitive aspects of pain (make the pain bother you less)

Question 21

Define Cannabis and Cannabinoids

Answer 21

• cannabis: genus of flowering plant.Contains many bioactive compounds, but most studied are THC and CBD. THC is the primary psychoactive compound in cannabis
• cannabinoids: class of chemical compounds that act at the cannabinoid receptors

Question 22

CB1 versus CB2 receptors

Answer 22

• CB1 receptors are among the most abundant GPCRs, found in brain, peripheral organs (heart, liver, fat, stomach, testes) and peripheral nerves
  -CB2 receptor distribution mostly on immune cells

Question 23

How Do Cannabinoids Work?

Answer 23

-cannabinoid receptors are inhibitory
G-protein coupled receptors (Gi
coupled)
- Cannabinoid receptors are located
on the presynaptic membrane
- cannabinoid receptors leads to decrease in cyclic adenosine
monophosphate (cAMP)
accumulation which inhibits the influx of calcium in the firing neuron and
inhibits neurotransmitter release.
- decrease synaptic transmission,
inhibit neurotransmitter release

Question 24

THC Effects (general, potential therapeutic, and unwanted)

Answer 24

• is a partial agonist at CB1
• general : euphoria, relaxation, disinhibition, changes in perception, vasodilation, increase pulse rate
• potential therapeutic: attenuation of nausea, increased appetite, decreased intraocular pressure, chronic pain relief
• unwanted: memory impairment, dysphoric state, visual hallucinations, depersonalization, psychotic episodes, anxiety

Question 25

CBD Effects

Answer 25

- some preclinical research suggests CBD has therapeutic potential for management of inflammation, anxiety, emesis, nausea, inflammatory pain, and epilepsy - strong clinical data lacking for these claims - pediatric epilepsy is the only condition in which high quality clinical data (oral CBD significantly reduced frequency of seizures more than placebo)

Question 26

Adverse Effects of THC

Answer 26

- acute effects: panic attacks, severe anxiety, psychosis, paranoia, convulsions, hyperemesis - prenatal effects: neuroanatomical and behavioral changes in offspring (dose-response relationship not identified) - lung cancer: smoked cannabis - driving: increase risk of accident - no documented evidence of death - sparsity of CB1 receptors in the brain stem region that controls respiratory and cardiovascular systems

Question 27

Define Psychological Dependence

Answer 27

compulsive drug-seeking behavior in which the individual uses the drug receptively for personal satisfaction, often in the face of known risks to health

Question 28

Define Physiological Dependence

Answer 28

revealed when withdrawal of the drug produces symptoms and signs that are frequently opposite of those sought by the user

Question 29

Cannabis Withdrawal

Answer 29

- is relatively mild and short-lived - symptoms of restlessness, irritability, mild agitation, insomnia, nausea and cramping - may be worse in chronic, long-term users and may contribute to continues drug use

Question 30

Define Addiction (Substance use disorder)

Answer 30

inability to control the use of legal or illegal substances despite negative consequences

Question 31

The Challenge of Cannabinoid Pharmacology

Answer 31

- smoked cannabis may be effective at treating conditions like chronic pain, chemotherapy induced nausea and others - smoked plant not ideal because hard to control dose - efforts to design synthetic cannabinoids (CB1 or CB2 agonists) - some success, but not nearly as effective as smoked cannabis