Cannabinoids and Medicinal Benefits

Question 1

What is the ECS well established for?

Answer 1

A target for therapy of pain

Question 2

What system is the ECS apart of?

Answer 2

The endogenous antinociceptive system.

Question 3

What does CBR stand for?

Answer 3

Cannabinoid Receptor

Question 4

Where are these CBRs located?

Answer 4

Peripheral, spinal, and supraspinal neurons.

Question 5

What do the CBRs do in these specific neurons?

Answer 5

Supress nociceptive transmission

Question 6

Where are CBRs present?

Answer 6

Immune cells and regulate inflammatory responses.

Question 7

What are the CBR ligands an alternative for?

Answer 7

Opiods

Question 8

Is there risk with the administration of drugs targeting the ECS? What cannabinoid receptor in particular?

Answer 8

Yes, it comes with the risk of cognitive adverse effects/ disruption of the ECS regulation of reward system.

In particular, it is the issue with the CB1 receptor

Question 9

What prevents seizures?

Answer 9

Convential anti-epileptic drugs

Question 10

What does these anti-elipetic drugs do in particular?

Answer 10

Block sodium or calcium channels, OR enhance GABA function to reduce the release of excitatory glutamte.

Question 11

What does GABA stand for?

Answer 11

Gamma-aminobutyric acid

Question 12

What are the major side-effects of anti-eplieptic drugs?

Answer 12

-Impairment of motor function
-Cognitive dysfunction
-Emotional lability

Question 13

What specific cannabinoids have evidence of potentially reducing seizures?

Answer 13

THC and other CB1 agonists

Question 14

When and who was the main source of discovering the cannabinoids that could help with seizures?

Answer 14

Chesher, Jackson, and Starmer in 1974

Question 15

In 1973, (a) how did they administer the test to observe how THC effected seizures? (b) What animals did they test on? (c) Who wrote this paper?

Answer 15

(a) Orally (160-200 mg/kg doses)
(b) Mice
(c) Boggan, Steele, and Freedman

Question 16

What other CB1 agonist decreased the seizure severity in rodent models?

Answer 16

WIN55,212

Question 17

What does CB1 act synergistically with? And acts as a co-administor with what? What did this do as a result?

Answer 17

The 5-HT2B receptor and acts as a co-administor of WIN55,212 and 5-HT2B agonist RO60-0175. As a result it decreased seizures.

Question 18

What inhibition results in anti-seizure activity?

Answer 18

Monoacylglycerol, with 2-AG activating CB1

Question 19

What happens in FAAH inhibition?

Answer 19

Leads to increase in intracellular AEA levels and leads to pro-seizure activitiy

Question 20

What was the greatest succces in treating seizures?

Answer 20

CBD

Question 21

Does RO60-0175 have any effect on seizure patients on its own?

Answer 21

No.

Question 22

Increase of what two endocannabinoids would potentially be seen as an anti-seizure treatment?

Answer 22

AEA and A2-G

Question 23

Inhibition of what metabolic enzyme causes more seizure activity?

Answer 23

FAAH inhibition

Question 24

Inhibition of what endocannabinoid causes a decrease in seizure activity?

Answer 24

Anadamide

Question 25

What is an oral solution containing CBD?

Answer 25

Epidiolex

Question 26

What is the two forms of epliepsy?

Answer 26

-Lennox-Gastaut syndrome -Dravet syndrome

Question 27

What is negative allosteric modulation?

Answer 27

A substance that, by binding to a receptor at site other than the primary site, instead reduces the activity of the ligand that normally binds to the site.

Question 28

What is rimonabant known for?

Answer 28

Anti-obesity agent. A potent CB1 inverse agonist.

Question 29

What did rimonabant cause? Was it withdrawn from the market?

Answer 29

Depression and anxiety. Yes it was withdrawn from the market due to those reasons.

Question 30

What can targeting the ECS do?

Answer 30

Could be a potential strategy to design novel psychotic drugs, including anxiolytics.

Question 31

What would be a natural CB1 agonist?

Answer 31

THC

Question 32

What was supposed to be a promising direction to develop a new class of anxiolytic drugs?

Answer 32

CB1 Agonists

Question 33

What is one of the the methods in order to reduce anxiety in patients?

Answer 33

Inhibit eCB degrading enzymes in order to indirectly activate CB1 by 2-AG or AEA

Question 34

What did FAAH overexpression in hippocampal nuerons show?

Answer 34

Decreased levels in AEA in the hippocampus and resulted in anxiety-like behavior.

Question 35

How did they study the ability to reduce anxiety in rodents?

Answer 35

Scientists gave rodents NMDA in order to induce anxiety like behavior, then introduced the URB602 (an MAGL inhibitor) in order to to block MAGL and increase the 2-AG in the blood stream in order to reduce anxiety like behavior.

Question 36

What is NMDA?

Answer 36

N-methyl-D aspratate

Question 37

What is the strategy that includes the ECS in order to target depressive disorders?

Answer 37

Direct or indirect CB1 activation

Question 38

What is a CB1 and CB2 agonist that prevented anhedonia in a rodent model? What is the concentration?

Answer 38

WIN55,212-2 (0.5 mg/kg)

Question 39

What is anhendonia?

Answer 39

Inability to feel pleasure

Question 40

What is targeted in depressive disorders?

Answer 40

eCB degrading enzymes

Question 41

In a rodent model what prevented anhedonia? What was the concentration?

Answer 41

FAAH inhibitor, URB597. 0.3 mg/kg

Question 42

What is indirect activation?

Answer 42

By inhibiting degrading enzymes

Question 43

Which strain of cannabis is known for a mild potential for addiction?

Answer 43

C. Sativa

Question 44

What is a way to potentially omit the problem of addiction?

Answer 44

CB1neutral antagonists

Question 45

What was tested in rodent models of opiod addiction? What did it also decrease in mice?

Answer 45

AM4113. It also decreased alcohol consumption.

Question 46

What can be helpful for withdrawal symptoms?

Answer 46

CB1 agonists

Question 47

What also increase eCB levels?

Answer 47

Physical exercise, this can also be part of the treatment of withdrawl syndromes

Question 48

What is the second most prominent target in ECS for fighting the addiction?

Answer 48

CB2

Question 49

What increased ethanol intake?

Answer 49

CB2 antagonist (AM630)

Question 50

What decrease ethanol intake?

Answer 50

CB2 agonist (JWH133)

Question 51

Where can CB2 also be found?

Answer 51

The brain

Question 52

What happens when combining CB1 antagonism with CB2 agonism?

Answer 52

May be a reasonable strategy for fighting addiction because of recent finding that opposing action on these two receptors has a synergistic effect on reward processing?

Question 53

What activation impairs memory?

Answer 53

CB1 activation

Question 54

What enhances memory?

Answer 54

CB1 antagonists

Question 55

What are symptons of tramatic brain injury (TBI)?

Answer 55

Impaired spacial learning and memory

Question 56

What is the impaired spacial learning and memory connected to?

Answer 56

Increased 2-AG levels

Question 57

What did the administartion of CB1 antagonist AM281 in mice do?

Answer 57

Ameliorates symptons of impaired spacial learning and memory

Question 58

What did low dosages of Delta-9-THC show?

Answer 58

Improved cognitive performance of old mice in which CB1 was crucial

Question 59

What is hormesis?

Answer 59

A substance that is typically a problem at higher doses, can be useful at lower doses?

Question 60

What is neurodegeneration?

Answer 60

Neuron deteration in brain/CNS

Question 61

What is neurogenesis?

Answer 61

The generation of new neurons

Question 62

What takes in part in the regulation of neurogenesis?

Answer 62

CB1, CB2, GPR55

Question 63

What is crucial for proligeration and differentiation of neural stem cells?

Answer 63

CB1 and GPR55

Question 64

Why may endocannabinoid signaling be beneficial?

Answer 64

Impact on attenuating neurotoxicity and neuroinflammation

Question 65

What worsens symptoms in Alzheimer's disease?

Answer 65

CB1 deletion

Question 66

What did the CB1 agonist ACEA exhibit?

Answer 66

Anti-apoptotic action on neurons and reduced and cognitive impairment in the Alzheimer's disease rodent model?

Question 67

What is anti-apoptotic?

Answer 67

Anti cell death

Question 68

What does the activation of CB2 do?

Answer 68

Leads to anti-inflammatory action

Question 69

Do cannabinoids increase or decrease appetite?

Answer 69

Increase appetite

Question 70

How is the increase of appetite mediated?

Answer 70

By CB1 activation in the forebrain neurons, hypothalmus and in a mesolimbic dopamine system

Question 71

What does ECS deregulation contribute to?

Answer 71

Type 2 Diabetes Mellitus

Question 72

What was shown to reverse diabetic neuropath? Via what?

Answer 72

CB1 antagonists (JD5037) via the modulation of glucose transport 2 expression and activity in renal proximal tubule cells.

Question 73

What occurs in diabetes?

Answer 73

CB1 receptors are upregulated in the kidney contributing to: renal inflammation, oxidative stress, tubular dysfunction, and glucose reabsorption abnormalitites

Question 74

What does JD5037 not cross? Why is this important? What does this mean about its location?

Answer 74

It does not cross the blood-brain barrier. Avoids sides effects such as depression or anxiety that had been seen in examples like rimonabant. This means its localized peripherally.

Question 75

What can happen to the cardiovascular system?

Answer 75

Has adverse effect which includes ischemic stroke.

Question 76

What does the modulation of the ECS result in?

Answer 76

Alleviation of hypertension, atheroscierosis, mycardial ischemia, and related diseases

Question 77

What did CB1 and CB2 agonists show related to cancer?

Answer 77

Shown to elicit antitumor properties both in vitro and in vivo.

Question 78

What is something to look at for a cause of cancers?

Answer 78

ECS ovexpression in tumor cells

Question 79

What has shown a positive result in triple negative breast cancer studies? What was the result?

Answer 79

A combination with photodynamic therapy with CB2 agonist (JWH-133). This resulted in synergistic inhibition of tumor growth and extended survival time in mice.