Neuropathic itch treated with oral cannabinoids: A case series

Neuropathic pruritus is defined as an itch arising from diseases of the central or peripheral nervous system, including nerve damage, compression, or irritation. It can be generalized or localized and is encompassed within a broad range of diagnoses, including notalgia paresthetica, brachioradialis pruritus, certain forms of vulvar itch, and small fiber neuropathy, amongst others. ¹ Brachioradial pruritus is a well-known type of neuropathic itch that is believed to result from an insult to cervical nerves C5-C8 from degenerative disc disease or trauma.² Symptoms include itch, burning, numbness, and tingling affecting the dorsolateral aspects of the upper extremities.

Although most cases of vulvar itch can be attributed to infectious causes or inflammatory dermatoses, such as psoriasis, lichen simplex chronicus, lichen sclerosus, or contact dermatitis, some cases of chronic vulvar itch can be categorized under the umbrella of genitofemoral neuralgia or vulvodynia.³ Classically regarded as a type of neuropathic pain, itch and burning can accompany vulvodynia in 20% and 70% of cases, respectively,⁴ and are similarly addressed in the same way with medications targeting neurogenic pathways.

In many cases of localized neuropathic itch, treatment can be challenging because topical therapies are limited and systemic treatments may provoke many side effects. Treatment options for neuropathic itch typically include topical local anesthesia, capsaicin formulations, calcineurin inhibitors, menthol or camphor, and systemic approaches with gabapentinoids, selective serotonin reuptake inhibitors, and tricyclic antidepressants.⁵  We report 3 cases of localized neuropathic itch successfully treated by dronabinol, an oral synthetic formulation of delta-9-tetrahydrocannabinol.

In recent years, the role of cannabinoid (CB) signaling and activation of CB receptors 1 (CB1) and 2 (CB2) in the skin has been an area of interest in dermatology and within the itch community. Increased CB1 and CB2 activity in the central and peripheral nervous systems has been shown to have analgesic and antipruritic effects.⁶ Pain and itch relief appear to be mediated in part by activation of CB1 in the central nervous system and by activation of CB1 and CB2 in the periphery.⁷ Given their wide distribution in the skin, CBs may exert antipruritic effects by influencing local immune or barrier function as well as by modulating neuronal circuits. CB receptors are found on mast cells, macrophages, and keratinocytes, in addition to cutaneous small nerve fibers.⁸ Treatment with a CB1 agonist reduced histamine-evoked neurogenic flares.⁹ Moreover, direct activity of CBs on neuronal receptors increased the nociceptive threshold.¹⁰ Derangement of endocannabinoid homeostasis has been implicated in several pruritic or painful dermatologic conditions.^9,11 Topical CB formulations have shown benefit in atopic dermatitis and uremic pruritus (Table I).^12,13 Similarly, a small case series of postherpetic neuralgia demonstrated reduction in mean pain scores by 87.8% in 5 of 8 patients treated with a cream containing N-palmitoylethanolamine, a CB receptor agonist.¹⁴

Dronabinol, delta-9-tetrahydrocannabinol, is a synthetic form of the cannabinoid found in the plant Cannabis sativa and is currently approved in the United States for AIDS-related anorexia and refractory chemotherapy-induced nausea. Its side effects include nausea, vomiting, tachycardia, somnolence, and dizziness. Ingestion will result in positive urine toxicology screening. Dronabinol 5 mg 3 times daily has been reported to reduce itch in cases of refractory cholestatic pruritus (Table I).¹⁵ In this report, patients described rapid-onset (up to 6 to 8 hours after ingestion) but transient relief. Our patients described a similar experience with quick-onset improvement in dysesthesia.