Pruritus - Medical Marijuana Research Papers Worldwide - 2000- 2017

Pruritus - Medical Marijuana Research Papers Worldwide - 2000- 2017


"Marriage is a difficult project. When seven years have passed and all your body's cells have been replaced, you're meant to experience that seven-year itch." - Yoko Ono


1 Preliminary observation with dronabinol in patients with intractable pruritus secondary to cholestatic liver disease. Neff et-al 2002. American Journal of Gastroenterology 97- 2117 to 2119.

All patients were started on 5 mg of d9THC (Marinol) at bedtime. All 3 patients reported a decrease in pruritus, marked improvement in sleep, and eventually were able to return to work. Resolution of depression occurred in two of three. Side effects related to the drug include one patient experiencing a disturbance in coordination. Marinol dosage was decreased to 2.5 mg in this patient with resolution of symptoms. The duration of antipruritic effect is approximately 4–6 hrs in all three patients, suggesting the desire for more frequent dosing. Δ-9-THC may be an effective alternative in patients with intractable cholestatic pruritus.


2 Histamine induced responses are attenuated by a cannabinoid receptor agonist in human skin Dvorak et-al 2003.  Inflammation Research 25- 238 to 245.


In humans, peripheral administration of a cannabinoid receptor agonist attenuates histamine-induced itch. The observation that protein extravasation was not decreased demonstrates that the alleviation of itch is not due to an anti-histaminergic property of HU210. The reduced neurogenic flare reaction indicates an attenuated antidromic nerve fibre activation and neuropeptide release.


"Sex is a momentary itch, love never lets you go."  - Kingsley Amis



3 Cannabinoid agonists attenuate capsaicin-induced responses in human skin. Journal of Pain. 102-283-288.  Rukwied, R., Watkinson, A., McGlone, F., Dvorak, M. 2003.

Histamine induced responses are attenuated by a cannabinoid receptor agonist in human skin. Inflamm. Res. 52-238-245. - Dvorak, M., Watkinson, A., McGlone, F., Ruckwied, R. 2003.


HU-210 is a synthetic cannabinoid that has similar effects as THC, It is 100 to 1000 times stronger than THC.  1 mg HU-210 is equivalent to 100 to 1000 mg of THC.  

 RESULTS - Experimentally induced itch was significantly reduced by peripheral administration of HU210 . Additionally, skin blood flow and neurogenic mediated flare responses were attenuated (dialed down), whereas protein extravasation due to histamine (inflammation) was enhanced by co-administration of HU210, as investigated by dermal microdialysis.

CONCLUSIONS - In humans peripheral administration of a cannabinoid receptor agonist attenuates histamine-induced itch. The observation that protein extravasation was not decreased demonstrates that the alleviation of itch is not due to an anti-histaminergic property of HU210. The reduced neurogenic flare reaction indicates an attenuated antidromic (opposite) nerve fibre activation and neuropeptide release.


In the present study, we topically administered the cannabinoid receptor ligand cannabinoid HU210 to human skin and investigated its effects on capsaicin-induced pain and hyperalgesia (hyper-pain). We demonstrated that pre-treatment with HU210 significantly reduced the perception of pain following the administration of capsaicin.

Heat pain thresholds were significantly reduced by capsaicin application measured 5 and 30min after administration. In contrast, at the HU210 pre-treated skin sites capsaicin failed to induce heat hyperalgesia during the fifth minute of administration. Secondary mechanical hyperalgesia to touch (allodynia) was measured during the fifth, 15th and 30th minute after capsaicin administration.


"Unanswered questions make my head itch." -  Kerry Greenwood



In comparison to the ethanol control site, the area of touch-evoked allodynia was significantly reduced at the HU210 skin site during the first two measures. However, 30min after the administration of capsaicin no significant differences of allodynia were observed between the HU210 and ethanol pre-treated skin. The present study provided evidence for analgesic and antihyperalgesic properties of a topically applied cannabinoid receptor ligand, which might have important therapeutic implications in humans.



4 Efficacy & tolerance of the cream containing structured physiological lipid endocannabinoids in the treatment of uremic pruritus- a preliminary study. Szepietowski et-al 2005. Acta Dermatovenerologica Croatica(Croatia) 13- 97 to 103.



After 3-weeks of therapy, pruritus was completely eliminated in 8 (38%) patients. Pruritus evaluation by both scales revealed a significant reduction of pruritus scores during the tested product application. At the beginning of the trial there was no significant correlation between the intensity of dry skin and severity of pruritus.

The 3-week treatment period resulted in complete reduction of xerosis in 17 (81%) patients, while xerosis scores were significantly reduced throughout the study period. The test product was very well tolerated by all patients. The test product appeared to be effective in reducing both pruritus and xerosis in hemodialysis patients.

It is very probable that the observed decrease of pruritus with the test product therapy was not only the result of dry skin improvement, but that the addition of endocannabinoids may have also played a role. These preliminary findings are encouraging, however, additional controlled studies are needed to clarify the exact usefulness of this product in the therapy of uremic pruritus.


"When once the itch of literature comes over a man, nothing can cure it but the scratching of a pen." - Samuel Lover



5 Frontiers in pruritus research- scratching the brain for more effective itch therapy. Journal of Clinical Investigation Paus et-al. 2006.  1174 to 1185.



 HOT - This Review highlights selected frontiers in pruritus research and focuses on recent insights into the neurophysiological, neuroimmunological, and neuroendocrine mechanisms underlying skin-derived itch (pruritogenic pruritus), which may affect future antipruritic strategies. - HOT

Special attention is paid to newly identified itch-specific neuronal pathways in the spinothalamic tract that are distinct from pain pathways and to CNS regions that process peripheral pruritogenic stimuli. In addition, the relation between itch and pain is discussed, with emphasis on how the intimate contacts between these closely related yet distinct sensory phenomena may be exploited therapeutically.

Furthermore, newly identified or unduly neglected intracutaneous itch mediators (e.g., endo vanilloids, proteases, cannabinoids, opioids, neurotrophins, and cytokines) and relevant receptors (e.g., vanilloid receptor channels and proteinase-activated, cannabinoid, opioid, cytokine, and new histamine receptors) are discussed. In summarizing promising new avenues for managing itch more effectively, we advocate therapeutic approaches that strive for the combination of peripherally active antiinflammatory agents with drugs that counteract chronic central itch sensitization.

The cannabinoid system provides another putative itch frontier. Cannabinoid receptor 1 (CB1) and TRPV1 show marked colocalization in sensory neurons. Moreover, CB1 agonists effectively suppress histamine-induced pruritus, suggesting the involvement of CB1 receptor signaling in the initiation of itch. Furthermore, under inflammatory conditions cannabinoids also activate the TRPV1 pathway and thereby switch their neuronal effect from inhibition to excitation and sensitization.

Since Cannabinoids, just like TRPV1, are also expressed by non-neuronal human skin cells, Cannabinoids may be involved in the neuronal/nonneuronal cellular network of pruritogenic stimuli arising in the skin. Thus, coadministration of a TRPV1 agonist with a Cannabinoid1 receptor agonist would be expected to serve as a potent antipruritic regimen. In addition, this would prevent the acute burning sensation initiated by capsaicin, since Cannabinoid agonists anandamide and HU210 prevent the excitation induced by capsaicin.



6 Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat. Rev. Immunol.

5-400-411 - Klein, T.W. 2005.


In the nineteenth century, marijuana was prescribed by physicians for maladies ranging from eating disorders to rabies. However, as newer, more effective drugs were discovered and as the potential for abuse of marijuana was recognized, its use as a therapeutic became restricted, and only recently has its therapeutic potential been re-evaluated.

Modern studies in animal models and in humans have produced promising results for the treatment of various disorders such as obesity, cancer, and spasticity and tremor due to neuropathology with drugs based on marijuana-derived cannabinoids. Moreover, a wealth of information also indicates that these drugs have immunosuppressive and anti-inflammatory properties; therefore, on the basis of this mode of action, the therapeutic usefulness of these drugs in chronic inflammatory diseases is now being reassessed


7 Distribution of cannabinoid receptor 1 and 2  on sensory nerve fibers and adnexal structures in human skin. J. Dermatol. Sci. 38-177-188. Stander, S., Schmelz, M., Metze, D., Luger, T., Rukwied, R. 2005.



RESULTS- Cannabinoid1 receptor and Cannabinoid2 receptor immunoreactivity was observed in cutaneous nerve fiber bundles, mast cells, macrophages, epidermal keratinocytes, and the epithelial cells of hair follicles, sebocytes and eccrine sweat glands. In epidermal keratinocytes, hair follicle and sebaceous glands, Cannabinoid1 receptor and Cannabinoid2 receptor were distributed in a complementary fashion. Double-immunostaining with an anti-CGRP antibody suggested the presence of cannabinoid receptors on small afferent peptidergic nerves.

CONCLUSION- The abundant distribution of cannabinoid receptors on skin nerve fibers and mast cells provides implications for an anti-inflammatory, anti-nociceptive action of cannabinoid receptor agonists and suggests their putatively broad therapeutic potential.


8 Cannabinoids reduce hyperalgesia and inflammation via interaction with peripheral Cannabinoid1 receptors. Journal of Pain. 75-111-119. Richardson, J.D., Kilo, S., Hargreaves, K.M. 1998.


Central antinociceptive effects of cannabinoids have been well documented. We determined the effect of cannabinoids on nerve cells - neurotransmitter....capsaicin-evoked neuropeptide release from isolated rat hindpaw skin. Our results indicate that cannabinoids produce anti hyperalgesia (sensitivity to pain) via interaction with a peripheral Cannabinoid1 receptor. Peripheral, but not systemic, administration of 0.01 ng anandamide inhibited the induction of hyperalgesia (sensitivity to pain).


 Peripheral administration of anandamide also attenuated hyperalgesia after its development via interaction with the Cannabinoid1 cannabinoid receptor subtype as indicated by its reversal with the Cannabinoid1 receptor antagonist SR141716A. Additionally, peripheral, but not systemic, administration of 0.01 ng anandamide inhibited edema. Peripherally administered cannabinoids also interacted with Cannabinoid1 receptors to inhibit capsaicin-evoked plasma extravasation.


One potential mechanism for the anti-inflammatory actions of the cannabinoids is the inhibition of neurosecretion from the peripheral terminals of nociceptive primary afferent fibers. This hypothesis is supported by the finding that anandamide inhibited capsaicin-evoked release of calcitonin gene-related peptide from isolated hindpaw skin. Collectively, these results indicate that cannabinoids reduce inflammation via interaction with a peripheral Cannabinoid1 receptor. A potential mechanism for this effect is the inhibition of neurosecretion from capsaicin-sensitive primary afferent fibers.


MMJDoctorOnline Notes - To treat your itch with medical marijuana or even recreational marijuana, until 2018, everyone must have a licensed medical doctor's 420 evaluation before they can purchase MMJ from a dispensary, delivery service, cannabis club or other point of access.  Our online process makes it very quick and easy to get your cannabis ID.  Just fill out the online form and a doctor will evaluate your file the same day or even within the hour, depending on patient volumes.  Patients don't pay, unless their Cannabis ID, 420 recommendation or cultivation permit is approved.


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