Targeting the endocannabinoid system with cannabinoid receptor agonists

pharmacological strategies and therapeutic possibilities

Roger G. Pertwee*

*Corresponding author for this work

Research output: Contribution to journalLiterature review

176 Citations (Scopus)

Abstract

Human tissues express cannabinoid CB1 and CB2 receptors that can be activated by endogenously released 'endocannabinoids' or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB1/CB2 receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; Delta(9)-tetrahydrocannabinol (Delta(9)-THC)) and Sativex (Delta(9)-THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). This review mentions several possible additional therapeutic targets for cannabinoid receptor agonists. These include other kinds of pain, epilepsy, anxiety, depression, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB2 receptors, and/or (v) adjunctive 'multi-targeting'.

Original languageEnglish
Pages (from-to)3353-3363
Number of pages11
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume367
Issue number1607
DOIs
Publication statusPublished - 5 Dec 2012

Keywords

  • Delta(9)-tetrahydrocannabinol
  • cannabinoid CB1 and CB2 receptors
  • cannabinoid receptor agonists
  • therapeutic applications and strategies
  • blood-brain barrier
  • PENTYLENETETRAZOLE-INDUCED SEIZURE
  • AMYOTROPHIC-LATERAL-SCLEROSIS
  • CENTRAL-NERVOUS-SYSTEM
  • ANXIETY-LIKE BEHAVIOR
  • MU-OPIOID RECEPTOR
  • RAT FORMALIN TEST
  • CB2 RECEPTOR
  • NEUROPATHIC PAIN
  • LIVER-DISEASES
  • MOUSE MODEL

Cite this

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title = "Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities",
abstract = "Human tissues express cannabinoid CB1 and CB2 receptors that can be activated by endogenously released 'endocannabinoids' or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB1/CB2 receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; Delta(9)-tetrahydrocannabinol (Delta(9)-THC)) and Sativex (Delta(9)-THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). This review mentions several possible additional therapeutic targets for cannabinoid receptor agonists. These include other kinds of pain, epilepsy, anxiety, depression, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB2 receptors, and/or (v) adjunctive 'multi-targeting'.",
keywords = "Delta(9)-tetrahydrocannabinol, cannabinoid CB1 and CB2 receptors, cannabinoid receptor agonists, therapeutic applications and strategies, blood-brain barrier, PENTYLENETETRAZOLE-INDUCED SEIZURE, AMYOTROPHIC-LATERAL-SCLEROSIS, CENTRAL-NERVOUS-SYSTEM, ANXIETY-LIKE BEHAVIOR, MU-OPIOID RECEPTOR, RAT FORMALIN TEST, CB2 RECEPTOR, NEUROPATHIC PAIN, LIVER-DISEASES, MOUSE MODEL",
author = "Pertwee, {Roger G.}",
year = "2012",
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TY - JOUR

T1 - Targeting the endocannabinoid system with cannabinoid receptor agonists

T2 - pharmacological strategies and therapeutic possibilities

AU - Pertwee, Roger G.

PY - 2012/12/5

Y1 - 2012/12/5

N2 - Human tissues express cannabinoid CB1 and CB2 receptors that can be activated by endogenously released 'endocannabinoids' or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB1/CB2 receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; Delta(9)-tetrahydrocannabinol (Delta(9)-THC)) and Sativex (Delta(9)-THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). This review mentions several possible additional therapeutic targets for cannabinoid receptor agonists. These include other kinds of pain, epilepsy, anxiety, depression, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB2 receptors, and/or (v) adjunctive 'multi-targeting'.

AB - Human tissues express cannabinoid CB1 and CB2 receptors that can be activated by endogenously released 'endocannabinoids' or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB1/CB2 receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; Delta(9)-tetrahydrocannabinol (Delta(9)-THC)) and Sativex (Delta(9)-THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). This review mentions several possible additional therapeutic targets for cannabinoid receptor agonists. These include other kinds of pain, epilepsy, anxiety, depression, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB2 receptors, and/or (v) adjunctive 'multi-targeting'.

KW - Delta(9)-tetrahydrocannabinol

KW - cannabinoid CB1 and CB2 receptors

KW - cannabinoid receptor agonists

KW - therapeutic applications and strategies

KW - blood-brain barrier

KW - PENTYLENETETRAZOLE-INDUCED SEIZURE

KW - AMYOTROPHIC-LATERAL-SCLEROSIS

KW - CENTRAL-NERVOUS-SYSTEM

KW - ANXIETY-LIKE BEHAVIOR

KW - MU-OPIOID RECEPTOR

KW - RAT FORMALIN TEST

KW - CB2 RECEPTOR

KW - NEUROPATHIC PAIN

KW - LIVER-DISEASES

KW - MOUSE MODEL

U2 - 10.1098/rstb.2011.0381

DO - 10.1098/rstb.2011.0381

M3 - Literature review

VL - 367

SP - 3353

EP - 3363

JO - Philosophical Transactions of the Royal Society B: Biological Sciences

JF - Philosophical Transactions of the Royal Society B: Biological Sciences

SN - 0962-8436

IS - 1607

ER -