Cannabinoid Analgesia as a Potential New Therapeutic Option in the Treatment of Chronic Pain

Department of Pharmacy Practice, Creighton University, Omaha, Nebraska, United States
Annals of Pharmacotherapy (Impact Factor: 2.06). 03/2006; 40(2):251-60. DOI: 10.1345/aph.1G217
Source: PubMed


To review the literature concerning the physiology of the endocannabinoid system, current drug development of cannabinoid agonists, and current clinical research on the use of cannabinoid agonists for analgesia.
Articles were identified through a search of MEDLINE (1966-August 2005) using the key words cannabis, cannabinoid, cannabi*, cannabidiol, nabilone, THC, pain, and analgesia. No search limits were included. Additional references were located through review of the bibliographies of the articles identified.
Studies of cannabinoid agonists for treatment of pain were selected and were not limited by pain type or etiology. Studies or reviews using animal models of pain were also included. Articles that related to the physiology and pharmacology of the endocannabinoid system were evaluated.
The discovery of cannabinoid receptors and endogenous ligands for these receptors has led to increased drug development of cannabinoid agonists. New cannabimimetic agents have been associated with fewer systemic adverse effects than delta-9-tetrahydrocannabinol, including recent development of cannabis medicinal extracts for sublingual use (approved in Canada), and have had promising results for analgesia in initial human trials. Several synthetic cannabinoids have also been studied in humans, including 2 cannabinoid agonists available on the international market.
Cannabinoids provide a potential approach to pain management with a novel therapeutic target and mechanism. Chronic pain often requires a polypharmaceutical approach to management, and cannabinoids are a potential addition to the arsenal of treatment options.

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Available from: Tammy L Burns, Nov 18, 2015
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    • "Analgesics typically used to treat neuropathic pain appear to be relatively ineffective in alleviating pain from CIPN (opioids: Cherny et al. 1994; gabapentin: Rao et al. 2007; amitriptyline: Kautio et al. 2008; for review, see Wolf et al. 2008). It is well known that cannabinoids reduce pain and hyperalgesia in models of inflammatory, neuropathic, and cancer pain (see reviews: Walker et al. 2001; Walker and Huang 2002; Burns and Ineck 2006; Rice et al. 2002). There is interest in whether the endogenous cannabinoids could be modulated in the periphery to attenuate or prevent CIPN. "
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    ABSTRACT: Painful neuropathy frequently develops as a consequence of commonly used chemotherapy agents for cancer treatment, and is often a dose-limiting side effect. Currently available analgesic treatments are often ineffective on pain induced by neurotoxicity. Although peripheral administration of cannabinoids, endocannabinoids, and inhibitors of endocannabinoid hydrolysis has been effective in reducing hyperalgesia in models of peripheral neuropathy, including chemotherapy-induced peripheral neuropathy (CIPN), few studies have examined cannabinoid effects on responses of nociceptors in vivo. In this study we determined whether inhibition of fatty acid amide hydrolase (FAAH), which slows the breakdown of the endocannabinoid anandamide (AEA) reduced sensitization of nociceptors produced by chemotherapy. Over the course of a week of daily treatments, mice developed robust mechanical hyperalgesia that coincided with sensitization of cutaneous C-fiber nociceptors as indicated by the development of spontaneous activity and increased responses to mechanical stimulation. Administration of the FAAH inhibitor URB597 into the receptive field of sensitized C-fiber nociceptors decreased spontaneous activity, increased mechanical response thresholds, and decreased evoked responses to mechanical stimuli. Co-treatment with CB1 (AM281) or CB2 (AM630) receptor antagonists showed that the effect of URB597 was mediated primarily by CB1 receptors. These changes following URB597 were associated with an increase in the endocannabinoid, anandamide, in the skin. Our results suggest that enhanced signaling in the peripheral endocannabinoid system could be utilized to reduce nociceptor sensitization and pain associated with CIPN. Copyright © 2014, Journal of Neurophysiology.
    Full-text · Article · Dec 2014 · Journal of Neurophysiology
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    • "The use of C. sativa for medical purposes is supported by experimental evidence showing that it controls and improves symptoms of several disorders, including multiple sclerosis (associated with muscle spasticity, pain, and sleep disorders), psychosis, bipolar disorder, anxiety, chronic pain, anorexia, and cancer (Arias Horcajadas 2007; Borgelt et al. 2013; Burns and Ineck 2006; Crippa et al. 2012; de Jong et al. 2005; Grant et al. 2012; Hollister, 1986; Kalant 2001; O'Sullivan et al. 2005; Robson 2001; Sarne and Mechoulam 2005; Swartz 2010). If C. sativa can ameliorate sleep disorders then the question arises as to what molecule(s) from this plant would be most effective at treating these disorders? "
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    ABSTRACT: Sleep is a universal phenomenon that occurs in every species studied so far. A normal sleep period fluctuates in a regular cycle of two basic forms: slow wave sleep (SWS) and rapid eye movement (REM) sleep. The sleep–wake cycle is modulated by diverse brain circuits and neuromodulators as well as by several endogenous and exogenous molecules, including cannabinoids. Here, we describe the effects of certain cannabis-derived and synthetic cannabinoids on sleep. Additionally, we provide an overview of current knowledge about potential uses of natural or synthetic cannabinoids for the treatment of sleep disorders.
    Full-text · Chapter · Dec 2014
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    • "That the therapeutic benefits for sleep hours, nightmares, and pain were typically dramatic and noted within 1 to 2 weeks of starting on the drug and maintained throughout the trial suggests, however, that the nabilone was in large measure responsible for these therapeutic benefits. The crudeness of the pain measure is likely mitigated, given the already strong evidence for nabilone’s effectiveness in chronic pain.5,6 Given the lack of illicit cannabis within the STU, the effectiveness for nabilone as a harm reduction approach was not possible to test. "
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    ABSTRACT: Nabilone is a synthetic cannabinoid that has shown promise for the treatment of posttraumatic stress disorder (PTSD)-related insomnia and nightmares as well as efficacy in the management of chronic pain. It has also been proposed for harm reduction in cannabis dependence. Its effectiveness for management of concurrent disorders in seriously mentally ill correctional populations has not been evaluated. This retrospective study of 104 male inmates with serious mental illness prescribed nabilone analyzes the indications, efficacy, and safety of its use. Medications discontinued with the initiation of nabilone were also reviewed. The results showed nabilone targeting a mean of 3.5 indications per patient, thus likely reducing polypharmacy risk. The mean final dosage was 4.0 mg. Results indicated significant improvement in PTSD-associated insomnia, nightmares, PTSD symptoms, and Global Assessment of Functioning and subjective improvement in chronic pain. Medications associated with greater risk for adverse effects or abuse than nabilone were often able to be discontinued with the initiation of nabilone, most often antipsychotics and sedative/hypnotics. There was no evidence of abuse within this high-risk population or reduction of efficacy when nabilone was given in powder form with water rather than as a capsule. This study supports the promise of nabilone as a safe, effective treatment for concurrent disorders in seriously mentally ill correctional populations. Prospective, randomized controlled trials are required to confirm our preliminary results. Follow-up in the community will be required to confirm effectiveness in harm reduction.
    Full-text · Article · Jul 2014 · Journal of Clinical Psychopharmacology
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