PMID- 33932409
OWN - NLM
STAT- MEDLINE
DCOM- 20211124
LR  - 20211124
IS  - 1873-5177 (Electronic)
IS  - 0091-3057 (Linking)
VI  - 206
DP  - 2021 Jul
TI  - Untapped endocannabinoid pharmacological targets: Pipe dream or pipeline?
PG  - 173192
LID - S0091-3057(21)00091-5 [pii]
LID - 10.1016/j.pbb.2021.173192 [doi]
AB  - It has been established that the endogenous cannabinoid (endocannabinoid) system 
      plays key modulatory roles in a wide variety of pathological conditions. The 
      endocannabinoid system comprises both cannabinoid receptors, their endogenous 
      ligands including 2-arachidonoylglycerol (2-AG), N-arachidonylethanolamine 
      (anandamide, AEA), and enzymes that regulate the synthesis and degradation of 
      endogenous ligands which include diacylglycerol lipase alpha (DAGL-alpha), 
      diacylglycerol lipase beta (DAGL-beta), fatty acid amide hydrolase (FAAH), 
      monoacylglycerol lipase (MAGL), alpha/beta hydrolase domain 6 (ABHD6). As the 
      endocannabinoid system exerts considerable involvement in the regulation of 
      homeostasis and disease, much effort has been made towards understanding 
      endocannabinoid-related mechanisms of action at cellular, physiological, and 
      pathological levels as well as harnessing the various components of the 
      endocannabinoid system to produce novel therapeutics. However, drug discovery 
      efforts within the cannabinoid field have been slower than anticipated to reach 
      satisfactory clinical endpoints and raises an important question into the 
      validity of developing novel ligands that therapeutically target the 
      endocannabinoid system. To answer this, we will first examine evidence that 
      supports the existence of an endocannabinoid system role within inflammatory 
      diseases, neurodegeneration, pain, substance use disorders, mood disorders, as 
      well as metabolic diseases. Next, this review will discuss recent clinical 
      studies, within the last 5 years, of cannabinoid compounds in context to these 
      diseases. We will also address some of the challenges and considerations within 
      the cannabinoid field that may be important in the advancement of therapeutics 
      into the clinic.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Wilkerson, Jenny L
AU  - Wilkerson JL
AD  - Department of Pharmacodynamics, College of Pharmacy, University of Florida, 
      Gainesville, FL, USA. Electronic address: jenny.wilkerson@cop.ufl.edu.
FAU - Bilbrey, Joshua A
AU  - Bilbrey JA
AD  - Department of Pharmacodynamics, College of Pharmacy, University of Florida, 
      Gainesville, FL, USA.
FAU - Felix, Jasmine S
AU  - Felix JS
AD  - Department of Pharmacodynamics, College of Pharmacy, University of Florida, 
      Gainesville, FL, USA.
FAU - Makriyannis, Alexandros
AU  - Makriyannis A
AD  - Center for Drug Discovery and Department of Pharmaceutical Sciences, Northeastern 
      University, Boston, MA 02115, USA; Departments of Chemistry and Chemical Biology, 
      Northeastern University, Boston, MA 02115, USA.
FAU - McMahon, Lance R
AU  - McMahon LR
AD  - Department of Pharmacodynamics, College of Pharmacy, University of Florida, 
      Gainesville, FL, USA. Electronic address: lance.mcmahon@cop.ufl.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210429
PL  - United States
TA  - Pharmacol Biochem Behav
JT  - Pharmacology, biochemistry, and behavior
JID - 0367050
RN  - 0 (Arachidonic Acids)
RN  - 0 (Cannabinoid Receptor Agonists)
RN  - 0 (Cannabinoids)
RN  - 0 (Endocannabinoids)
RN  - 0 (Glycerides)
RN  - 0 (Polyunsaturated Alkamides)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - 0 (Receptor, Cannabinoid, CB2)
RN  - 8D239QDW64 (glyceryl 2-arachidonate)
RN  - UR5G69TJKH (anandamide)
SB  - IM
MH  - Animals
MH  - Arachidonic Acids/metabolism
MH  - Cannabinoid Receptor Agonists/pharmacology
MH  - Cannabinoids/metabolism/pharmacology
MH  - Drug Discovery/*methods
MH  - Endocannabinoids/*metabolism/pharmacology
MH  - Glycerides/metabolism
MH  - Humans
MH  - Inflammation/drug therapy
MH  - Metabolic Diseases/drug therapy
MH  - Mood Disorders/drug therapy
MH  - Nervous System Diseases/drug therapy
MH  - Pain/drug therapy
MH  - Polyunsaturated Alkamides/metabolism
MH  - Receptor, Cannabinoid, CB1/metabolism
MH  - Receptor, Cannabinoid, CB2/metabolism
MH  - Substance-Related Disorders/drug therapy
OTO - NOTNLM
OT  - Addiction
OT  - Cannabinoid 2 receptor (CB(2)R)
OT  - Clinical trials
OT  - Drug dependence
OT  - Neuropathic pain
OT  - Preclinical
EDAT- 2021/05/02 06:00
MHDA- 2021/11/25 06:00
CRDT- 2021/05/01 20:08
PHST- 2020/09/29 00:00 [received]
PHST- 2021/04/18 00:00 [revised]
PHST- 2021/04/21 00:00 [accepted]
PHST- 2021/05/02 06:00 [pubmed]
PHST- 2021/11/25 06:00 [medline]
PHST- 2021/05/01 20:08 [entrez]
AID - S0091-3057(21)00091-5 [pii]
AID - 10.1016/j.pbb.2021.173192 [doi]
PST - ppublish
SO  - Pharmacol Biochem Behav. 2021 Jul;206:173192. doi: 10.1016/j.pbb.2021.173192. 
      Epub 2021 Apr 29.