PARIS — Cannabinoid agonists and opioid receptor antagonists are among the novel treatments being explored for chronic pruritus, Dr. med. Sonja Ständer reported at the Fourth International Academy of Cosmetic Dermatology World Congress.
Cannabinoid receptors are promising therapeutic targets because they play an important role in a variety of processes, including metabolic regulation, pain, craving, and anxiety. They can be influenced directly by agonists or antagonists, or indirectly through manipulation of the endocannabinoid metabolism.
Two cannabinoid receptors, CB1 and CB2, are the primary targets of endogenous cannabinoids, and are expressed in central and peripheral neurons.
Recent research by Dr. Ständer and colleagues at the University Hospital in Münster, Germany, has shown that CB1 and CB2 are also present in abundance in human cutaneous nerve fibers and mast cells (J. Dermatol. Sci. 2005;38:177–88).
“Since cannabinoid receptors are expressed on cutaneous nerve fibers, topical cannabinoid agonists directly inhibit the transmission of pruritus and therefore represent a promising new therapeutic modality,” she said.
In a pilot study, 22 patients with chronic pruritus, aged 25–82 years, were treated with one application of a topical cream containing a cannabinoid receptor agonist. Itching was significantly reduced in 14 of 22 patients, 8 patients were completely healed, and 8 were nonresponders.
Overall the response was very rapid, with patients experiencing relief within 2 days to 2 weeks, she said. The treatment was effective even in patients with a long history of itching.
Opioid receptor antagonists, developed to treat patients with opioid and alcohol dependence, represent another potential treatment. They block opioid receptors in the brain and spinal cord and activate pain-transmitting nerves, which themselves inhibit itch-transmitting neurons.
In a study of 133 patients with pruritic dermatoses and systemic diseases, naltrexone was evaluated at 25 mg in 6 patients (4.5%), at 50 mg in 61 (45.9%), at 75 mg in 4 (3%), at 100 mg in 57 (42.9%), and at 150 mg in 5 patients (3.8%). Therapy was maintained individually between 3 weeks and 6 years.
A significant reduction in itching, defined as a 40%–60% decrease, or complete relief was reported within 11 days in 86 of 133 (64.7%) patients, although 46 (34.6%) did not respond. Among patients with chronic pruritus of unknown origin, 15 of 19 (79%) responded to the therapy.
With the exception of 28 patients, itching usually recurred when the therapy was interrupted, she said.
Dr. Ständer stressed that patients should be informed before treatment with naltrexone of potential side effects, such as nausea and vomiting. Such side effects are common, but are limited to the first few days of treatment.
Finally, single case reports suggest that selective serotonin reuptake inhibitors (SSRIs) also may relieve chronic itching.
An ongoing study of 80 patients with chronic pruritus has shown that itching can be relieved after 4 days of treatment with either paroxetine (Paxil) or fluvoxamine (Luvox) applied in low therapeutic dosages.
This approach isn't recommended for elderly patients because of cardiovascular side effects, such as arrhythmias and increased bleeding, associated with SSRIs, she said.