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Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb.

By August 7, 2013No Comments

pm2Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb.

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Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy. aaizzo@unina.it

Erratum in

  • Trends Pharmacol Sci. 2009 Dec;30(12):609.

Abstract

Delta(9)-tetrahydrocannabinol binds cannabinoid (CB(1) and CB(2)) receptors, which are activated by endogenous compounds (endocannabinoids) and are involved in a wide range of physiopathological processes (e.g. modulation of neurotransmitter release, regulation of pain perception, and of cardiovascular, gastrointestinal and liver functions). The well-known psychotropic effects of Delta(9)-tetrahydrocannabinol, which are mediated by activation of brain CB(1) receptors, have greatly limited its clinical use. However, the plant Cannabis contains many cannabinoids with weak or no psychoactivity that, therapeutically, might be more promising than Delta(9)-tetrahydrocannabinol. Here, we provide an overview of the recent pharmacological advances, novel mechanisms of action, and potential therapeutic applications of such non-psychotropic plant-derived cannabinoids. Special emphasis is given to cannabidiol, the possible applications of which have recently emerged in inflammation, diabetes, cancer, affective and neurodegenerative diseases, and to Delta(9)-tetrahydrocannabivarin, a novel CB(1) antagonist which exerts potentially useful actions in the treatment of epilepsy and obesity.
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 19729208
[PubMed – indexed for MEDLINE]

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Figure 1.

Pharmacological actions of non-psychotropic cannabinoids (with the indication of the proposed mechanisms of action).

Abbreviations: Δ9-THC, Δ9-tetrahydrocannabinol; Δ8-THC, Δ8-tetrahydrocannabinol; CBN, cannabinol; CBD, cannabidiol; Δ9-THCV, Δ9-tetrahydrocannabivarin; CBC, cannabichromene; CBG, cannabigerol; Δ9-THCA, Δ9-tetrahydrocannabinolic acid; CBDA, cannabidiolic acid; TRPV1, transient receptor potential vanilloid type 1; PPARγ, peroxisome proliferator-activated receptor γ; ROS, reactive oxygen species; 5-HT1A, 5-hydroxytryptamine receptor subtype 1A; FAAH, fatty acid amide hydrolase.

(+), direct or indirect activation; ↑, increase; ↓, decrease.

Table 1.Proposed molecular mechanisms of the actions of non-psychotropic phytocannabinoids
NR = not reported.
Abbreviations: CBD, cannabidiol; Δ9-THCV, Δ9-tetrahydrocannabivarin; CBC, cannabichromene; CBG, cannabigerol; Δ9-THCA, Δ9-tetrahydrocannabinolic acid;, CBDA, cannabidiolic acid; Δ9-THC, Δ9-tetrahydrocannabinol; CBN, cannabinol; TRPV1, transient receptor potential vanilloid type 1; TRPV2, transient receptor potential vanilloid type 2; TRPA1, transient receptor potential ankyrin type 1; TRPM8, transient receptor potential melastatin type 8; COX-2, cycloxygenase-2; 5-HT1A, 5-hydroxytryptamine receptor subtype 1A; FAAH, fatty acid amide hydrolase.
 
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Abbreviations: CBD, cannabidiol; Δ9-THCV, Δ9-tetrahydrocannabivarin; CBC, cannabichromene; CBG, cannabigerol; Δ9-THCA, Δ9-tetrahydrocannabinolic acid;, CBDA, cannabidiolic acid; Δ9-THC, Δ9-tetrahydrocannabinol; CBN, cannabinol; peroxisome proliferator-activated receptor γ (PPARγ), TRPV1, transient receptor potential vanilloid type 1; TRPV2, transient receptor potential vanilloid type 2; TRPA1, transient receptor potential ankyrin type 1; TRPM8, transient receptor potential melastatin type 8; COX-2, cycloxygenase-2.
 
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Abbreviations: fMLP, formyl-methionyl-leucyl-phenylalanine; IFN-γ, interferon-γ, IL, interleukin; LPS, lipopolysaccharide; MIP-1, Macrophage Inflammatory Protein-1; ROS, reactive oxygen species; TNF-α, tumor necrosis factor α.
 
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