Cannabinoids and the Brain by Parker Linda A.;

Author:Parker, Linda A.;
Language: eng
Format: epub
Publisher: MIT Press
Published: 2016-03-01T05:00:00+00:00

CBD

Initial investigations of the analgesic effects of CBD in several animal models of acute pain (e.g., hot plate) revealed no evidence for an effect of CBD on pain (Sofia, Vassar, and Knobloch 1975). On the other hand, CBD was subsequently found to be effective in a model of chronic pain when given orally (Formukong, Evans, and Evans 1988). These conflicting results suggested that CBD was not effective against acute pain but was effective against chronic pain. Subsequently, the analgesic properties of CBD were tested specifically in models of persistent and inflammatory pain. Costa et al. (2004) have since found that giving very low oral doses of CBD (15 mg/kg) one hour before carrageenan reduced paw edema within three hours. Even lower doses of CBD (5–7.5 mg/kg, oral) administered two hours after carrageenan-induced inflammation reduced the pain behavior, and higher doses (10–40 mg/kg) eliminated pain behavior and edema. These effects were found to be mediated by the action of TRPV1 receptors as the TRPV1-receptor antagonist (capsazepine) reversed CBD’s attenuation of pain (Costa, Giagnoni, Franke, Trovato, and Colleoni 2004). In addition, CBD has been shown to be effective in relieving neuropathic chemotherapy-induced pain in rats, and in diabetic mice (Ward et al. 2014), without the development of tolerance. An additional benefit of CBD is that it has been shown to block the progression of arthritis in a mouse model of collagen-type-II-induced arthritis (Malfait et al. 2000); the synovial (joint) cells from mice treated with an optimal dose of CBD (5 mg/kg, ip, for ten days) released significantly less TNFα, which suggested that the therapeutic effect of CBD on arthritis may be suppression of TNFα, a pro-inflammatory cytokine known to be a major mediator of arthritis.

The molecular targets of CBD that could be responsible for the analgesic effects are numerous, including not only TRPV1 agonism but also agonism of 5-HT1A, antagonism of GPR55 receptors, weak antagonism at CB1 and CB2 receptors, and positive allosteric modulation of glycine receptors. (See Pertwee 2009.) There is evidence for a role of each of these mechanisms in the analgesic effects of CBD. For instance, a recent report suggests that CBD suppresses neuropathic pain in rats with ligation of the spinal nerve by targeting the α3 glycine receptor (Xiong et al. 2012)—mice lacking the α3 glycine receptor, but not CB1 or CB2 receptors, were resistant to the analgesic effect of CBD. More recently, the CBD-induced antagonism of the GPR55 receptor has been shown to play a role in nociceptive signaling. That receptor is highly expressed by mouse primary sensory neurons, and GPR55 knockout mice do not develop hyperalgesia in response to inflammatory or neuropathic stimuli. CBD may also desensitize TRPA1, TRPV1, and TRPV2 channels, resulting in a reduction in hypersensitivity to thermal, chemical, and mechanical stimuli associated with neuropathies (Costa and Comelli 2014). Clearly, there is pre-clinical evidence that CBD attenuates chronic pain through several mechanisms. Because CBD is not psychotropic, it is a strong candidate for treatment of chronic inflammatory and neuropathic pain.

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