Category Archives: Pain

Antinociceptive activity of Delta9-tetrahydrocannabinol non-ionic microemulsions.

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“Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), the major psychoactive constituent of Cannabis sativa L., has been widely studied for its potential pharmaceutical application in the treatment of various diseases and disturbs.

The aim of this work was to develop a stable aqueous Delta(9)-THC formulation acceptable for different ways of administration, and to evaluate the therapeutic properties of the new Delta(9)-THC based preparation for pain treatment.

Significant antinociceptive activity has been detected by both intraperitoneal and intragastric administration of the new Delta(9)-THC pharmaceutical preparation.”

http://www.ncbi.nlm.nih.gov/pubmed/20399844

Therapeutic utility of cannabinoid receptor type 2 (CB(2)) selective agonists.

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“The cannabinoid receptor type 2 (CB2) is a class A GPCR that was cloned in 1993 while looking for an alternative receptor that could explain the pharmacological properties of Δ(9)-tetrahydrocannabinol.

CB2 was identified among cDNAs based on its similarity in amino acid sequence to the CB1receptor and helped provide an explanation for the established effects of cannabinoids on the immune system.

In addition to the immune system, CB2 has widespread tissue expression and has been found in brain, peripheral nervous system, and gastrointestinal tract.

Several “mixed” cannabinoid agonists are currently in clinical use primarily for controlling pain, and it is believed that selective CB2 agonism may afford a superior analgesic agent devoid of the centrally mediated CB1 effects.

Thus, selective CB2 receptor agonists represent high value putative therapeutics for treating pain and other disease states. In this Perspective, we seek to provide a concise update of progress in the field.”

http://www.ncbi.nlm.nih.gov/pubmed/23865723

Activation of CB2 receptors as a potential therapeutic target for migraine: evaluation in an animal model.

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“Experimental animal models of migraine have suggested the existence of interactions between the endocannabinoid system and pain mediation in migraine.

Extensive evidence has demonstrated a role for the cannabinoid-1 (CB1) receptor in antinociception.

…recent research suggests that also CB2 receptors, especially located outside the central nervous system, play a role in the perception of pain…

In this study we evaluated the role of CB2 receptors in two animal models of pain that may be relevant for migraine…

CONCLUSION:

These findings suggest that the pharmacological manipulation of the CB2 receptor may represent a potential therapeutic tool for the treatment of migraine.”

http://www.ncbi.nlm.nih.gov/pubmed/24636539

CB2 cannabinoid receptor mediation of antinociception.

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“Management of acute pain remains a significant clinical problem. In preclinical studies, CB2 cannabinoid receptor-selective agonists inhibit nociception without producing central nervous system side effects.

The experiments reported here further test the hypothesis that CB2 receptor activation inhibits nociception…

The CB2 receptor-selective agonist produces antinociceptive… activation of CB2 receptors results in antinociception…

…confirm the potential therapeutic relevance of CB2 cannabinoid receptors for the treatment of acute pain.”

http://www.ncbi.nlm.nih.gov/pubmed/16563625

Nonclassical cannabinoid analgetics inhibit adenylate cyclase: development of a cannabinoid receptor model.

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“Extensive structure-activity relationship studies have demonstrated that specific requirements within the cannabinoid structure are necessary to produce potent analgesia.

A three-point association between the agonist and the receptor mediating analgesia consists of: 1) the C ring hydroxyl, 2) the phenolic A ring hydroxyl, and 3) the A ring alkyl hydrophobic side chain. Potent tricyclic and bicyclic structures were synthesized as “nonclassical” cannabinoid analgetics that conform to this agonist-receptor three-point interaction model.

At the cellular level, centrally active cannabinoid drugs inhibit adenylate cyclase activity in a neuroblastoma cell line. The structure-activity relationship profile for inhibition of adenylate cyclase in vitro was consistent with this same three-point association of agonists with the receptor.

A correlation exists between the potency of drugs to produce analgesia in vivo and to inhibit adenylate cyclase in vitro.

Based on the parallels in structure-activity relationships and the enantioselective effects, it is postulated that the receptor that is associated with the regulation of adenylate cyclase in vitro may be the same receptor as that mediating analgesia in vivo.

A conceptualization of the cannabinoid analgetic receptor is presented.”

http://www.ncbi.nlm.nih.gov/pubmed/3352594

Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8.

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“… we have reported here for the first time the potent and efficacious modulatory effects by some phytocannabinoids on TRPA1- and TRPM8-mediated [Ca2+]ielevation…

Our findings suggest that phytocannabinoids and cannabis extracts exert some of their pharmacological actions also by interacting with TRPA1 and TRPM8 channels, with potential implications for the treatment of pain and cancer.”

http://jpet.aspetjournals.org/content/325/3/1007.long

Cannabichromene and tetrahydrocannabinol determination in mouse blood and brain by gas chromatography-mass spectrometry.

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“Cannabichromene (CBC) is a phytocannabinoid, the second most abundant cannabinoid quantitatively in marijuana. CBC has been shown to produce antinociception and anti-inflammatory effects…”

 http://www.ncbi.nlm.nih.gov/pubmed/21871159

Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action.

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“Two non-psychoactive cannabinoids, cannabidiol (CBD) and cannabichromene (CBC), are known to modulate in vitro the activity of proteins involved in nociceptive mechanisms, including transient receptor potential (TRP) channels of vanilloid type-1 (TRPV1) and of ankyrin type-1 (TRPA1), the equilibrative nucleoside transporter and proteins facilitating endocannabinoid inactivation. Here we have tested these two cannabinoids on the activity of the descending pathway of antinociception…

CONCLUSIONS AND IMPLICATIONS:

CBD and CBC stimulated descending pathways of antinociception and caused analgesia by interacting with several target proteins involved in nociceptive control.

These compounds might represent useful therapeutic agents with multiple mechanisms of action.”

http://www.ncbi.nlm.nih.gov/pubmed/20942863

(+)-Cannabidiol analogues which bind cannabinoid receptors but exert peripheral activity only.

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“We have tested a series of (+)-cannabidiol derivatives… for central and peripheral (intestinal, antiinflammatory and peripheral pain) effects in mice…

We conclude that centrally inactive (+)-cannabidiol analogues should be further developed as antidiarrheal, antiinflammatory and analgesic drugs for gastrointestinal and other peripheral conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/15588739