Authors:
Manzanares J, Julian M, Carrascosa A.
Abstract:
Cannabis extracts and synthetic cannabinoids are still widely considered
illegal substances. Preclinical and clinical studies have suggested
that they may result useful to treat diverse diseases, including those
related with acute or chronic pain. The discovery of cannabinoid
receptors, their endogenous ligands, and the machinery for the
synthesis, transport, and degradation of these retrograde messengers,
has equipped us with neurochemical tools for novel drug design.
Agonist-activated cannabinoid
receptors, modulate nociceptive thresholds, inhibit release of
pro-inflammatory molecules, and display synergistic effects with other
systems that influence analgesia, especially the endogenous opioid system. Cannabinoid receptor agonists have shown therapeutic
value against inflammatory and neuropathic pains, conditions that are
often refractory to therapy. Although the psychoactive effects of these
substances have limited clinical progress to study cannabinoid actions in pain
mechanisms, preclinical research is progressing rapidly. For example,
CB(1)mediated suppression of mast cell activation responses,
CB(2)-mediated indirect stimulation of opioid receptors located in
primary afferent pathways, and the discovery of inhibitors for either
the transporters or the enzymes degrading endocannabinoids, are recent
findings that suggest new therapeutic approaches to avoid central nervous system side effects. In this review, we will examine promising indications of cannabinoid receptor agonists to alleviate acute and chronic pain episodes.
Recently, Cannabis sativa extracts, containing known doses of
tetrahydrocannabinol and cannabidiol, have granted approval in Canada
for the relief of neuropathic pain in multiple sclerosis. Further double-blind placebo-controlled clinical trials are needed to evaluate the potential therapeutic effectiveness of various cannabinoid agonists-based medications for controlling different types of pain.