Pertwee · The AAPS journal 2005 · narrative review · n=?

The therapeutic potential of drugs that target cannabinoid receptors or modulate the tissue levels or actions of endocannabinoids.

Cited 204 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review of mechanisms and pharmacological strategies without systematic methodology

PubMed 16353941 · doi:10.1208/aapsj070364 · record verified 2026-08-26

What was done

This narrative review summarizes the biological mechanisms of the endocannabinoid system—including CB1 receptors on nerve terminals, CB2 receptors on immune cells, and endogenous ligands—and evaluates pharmacological strategies to modulate endocannabinoid levels or receptor activity across central and peripheral disorders.

What was found

The abstract reports no empirical data or quantitative effect sizes. It details several proposed therapeutic strategies: using brain-penetrant or peripherally restricted CB1/CB2 agonists or antagonists; local or intrathecal agonist administration; utilizing partial rather than full agonists; co-administering cannabinoid agonists with noncannabinoids like opioids; inhibiting or activating endocannabinoid synthesis, uptake, or enzymatic degradation; using CB1 allosteric modulators; and employing CB2 inverse agonists.

Why it matters

It outlines a structural classification of pharmacological approaches for drug discovery targeting the endocannabinoid system, noting that endogenous upregulation can be either protective or harmful depending on the underlying pathology.

Limits

As a broad narrative review, it presents no original data, sample sizes, clinical trial results, or systematic review methodology in the abstract. Clinical efficacy, safety, and specific patient population outcomes are not measured.

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