Download Name ______________________________ CH 204, Fall 2014 Assignment 9 – Cannabinoids

Name ______________________________
CH 204, Fall 2014
Assignment 9 – Cannabinoids
For the following questions, refer to: Pacher, P.; Kunos, G. Modulating the Endocannabinoid System in
Human Health and Disease – Successes and Failures. FEBS Journal, 2013, 280, 1918-1943.
1) The authors indicate modulation of the endocannabinoid system (ECS) may have therapeutic
potential for:
a.
b.
c.
d.
e.
f.
Cancer
Neurodegenerative disorders
Inflammatory conditions
Cardiovascular disease
All of the above
None of the above
2) This article discusses potential
therapeutics either globally acting or
peripherally restricted. Specifically,
how do these compounds differ in
their membrane permeability?
3) Two well-characterized
endocannabinoids include
arachidonoyl ethanolamide
(AEA, or anandamide) and
2-arachidonoyl glycerol
(2-AG). Circle and label the
three types of functional
groups in each of these
molecules.
Globally acting:
Peripherally restricted:
O
N
H
AEA
OH
O
OH
O
2-AG
Two cannabinoid receptors have been characterized to-date – the CB1 and CB2 receptors. Signaling
through these receptors is complex, as it may involve both G-protein dependent and independent
pathways.
4) To which receptor does AEA bind more strongly?
5) To which receptor does 2-AG bind more strongly?
OH
6) CB1 receptors are localized:
a.
b.
c.
d.
Only within the brain
Predominately within the brain
Predominately within peripheral tissues
Only within the peripheral tissues
7) CB2 receptors are predominately located in
what type(s) of cells?
8) The endocannabinoids AEA and 2-AG
are degraded via hydrolysis of the
AEA (arachidonoyl ethanolamide):
amide or ester bonds. Indicate the
major enzymes responsible for their
metabolism (full names or appropriate 2-AG (2-arachidonoyl glycerol):
acronyms are sufficient). Note these
enzymes are also involved in the degradation of other bioactive lipids.
9) Based on the results of knockout (genetic ablation) studies as well as pharmacological blockade
studies (e.g. use of drugs to inhibit protein function), researchers have determined the
endocannabinoid system (ECS) plays an important role:
a. Predominately under normal physiological conditions
b. Predominately under physiological stress
c. Both in normal conditions and in pathological states
10) A study was performed at the National Institute on Drug Abuse (NIDA) on 13 healthy male daily
cannabis smokers, residing on a secure research unit over the course of six days. In this specific trial,
researchers noted the subjects:
a. Developed tolerance to the subjective intoxicating effect of THC and the hypotensive and
tachycardic effects of THC
b. Developed tolerance to the subjective intoxicating effect of THC but not to the hypotensive and
tachycardic effects of THC
c. Developed tolerance to the cardiovascular effects of THC but not to the subjective intoxicating
effects of THC
d. Developed no tolerance to the cardiovascular effects of THC or to its subjective intoxicating
effects
11) Surinabant is a selective CB1 antagonist that can inhibit the THC-induced adverse CNS and
cardiovascular effects, providing supporting evidence these effects are largely mediated by which
receptor(s):
a.
b.
c.
d.
CB1
CB2
Both CB1 and CB2
Neither CB1 nor CB2
12) Overall, the authors summarize ECS cardiovascular data supporting:
a. CB1 and CB2 signaling may promote cardiovascular disease progression
b. CB1 and CB2 signaling may activate cardioprotective mechanisms
c. CB1 signaling may promote cardiovascular disease progression while CB2 signaling may active
cardioprotective mechanisms.
d. CB2 signaling may promote cardiovascular disease progression while CB1 signaling may active
cardioprotective mechanisms.
13) A summary of studies using THC, THC+CBD, or CBD in multiple sclerosis (MS) patients with
neuropathic pain overall demonstrated consistent improvements in:
a.
b.
c.
d.
Objective outcome measures
Subjective outcome measures
Both objective and subjective outcome measures
Neither objective nor subjective outcome measures
14) To date, the synthetic cannabinoids Marinol® (dronabinol) and Cesamet® (nabilone) have been
approved by the FDA, and Sativex® (THC and CBD from cannabis) is currently in Phase III clinical
trials. Due to its administration route, which of these best allows for individual dose titration?
a. Marinol®
b. Cesamet®
c. Sativex®
15) Which agent demonstrated more positive effects in preclinical models of primary diabetes and
diabetic complications?
a. THC
b. CBD
c. Both compounds show similar efficacy
16) The CB1 inverse agonist rimonabant (Acomplia®) is an
anorectic/anti-obesity drug withdrawn from the
market due to CNS side effects in a statistically
significant number of patients, including anxiety,
depression, and/or suicidal ideations. How might a
CB1 inverse agonist or antagonist be redesigned to
promote weight loss while avoiding CNS side effects?
17) A number of studies have supported the role of CB2 activation
in reducing inflammation. Indeed, CB2 agonists may limit
injury under sterile inflammatory responses, though enhance
or increase tissue damage in pathogen-induced inflammation,
due to what physiological effect of CB2 activation?
18) Scientists are not only examining agonists, antagonists, and inverse agonists of the cannabinoid
receptors, but also the enzymes involved in the degradation of endocannabiniods. For instance,
FAAH knockout mice or mice treated with a FAAH inhibitor would have increased levels of:
a.
b.
c.
d.
e.
THC
CBD
AEA
2-AG
MAGL
19) In the Acknowledgement section, the authors “apologize to
colleagues whose important work could not be cited because
of space limitations.” How many references are listed in this
review article?