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: 2.92). 03/2006; 40(2):251-60. DOI: 10.1345/aph.1G217
Source: PubMed

ABSTRACT 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.

  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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.
    Journal of Neurophysiology 12/2014; 113(5):jn.00692.2014. DOI:10.1152/jn.00692.2014 · 3.04 Impact Factor
  • Source
    • "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? "
    [Show abstract] [Hide abstract]
    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.
    Handbook of Cannabis, Edited by Roger Pertwee, 12/2014: chapter 29: pages 538-46; Oxford University Press., ISBN: 9780199662685
  • Source
    • "Marijuana (Cannabis sativa) is a psychoactive plant that is widely used throughout the world. The marijuana plant contains approximately 70 cannabinoid compounds (Burns and Ineck, 2006). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Marijuana impairs learning and memory through actions of its psychoactive constituent, delta-9-tetrahydrocannabinol (Delta(9)-THC), in the hippocampus, through activation of cannabinoid CB1 receptors (CB1R). CB1Rs are found on glutamate and GABA neuron axon terminals in the hippocampus where they control neurotransmitter release. Previous studies suggest that Delta(9)-THC is a partial agonist of CB1Rs on glutamate axon terminals in the hippocampus, whereas its effects on GABA terminals have not been described. Using whole-cell electrophysiology in brain slices from C57BL6/J mice, we examined Delta(9)-THC effects on synaptic GABA IPSCs and postsynaptic GABA currents elicited by laser-induced photo-uncaging (photolysis) of alpha-carboxy-2-nitrobenzyl (CNB) caged GABA. Despite robust inhibition of synaptic IPSCs in wildtype mice by the full synthetic agonist WIN55,212-2, using a Tween-80 and DMSO vehicle, Delta(9)-THC had no effects on IPSCs in this, or in a low concentration of another vehicle, randomly-methylated beta-cyclodextrin (RAMEB, 0.023%). However, IPSCs were inhibited by Delta(9)-THC in 0.1% RAMEB, but not in neurons from CB1R knockout mice. Whereas Delta(9)-THC did not affect photolysis-evoked GABA currents, these responses were prolonged by a GABA uptake inhibitor. Concentration-response curves revealed that the maximal effects of Delta(9)-THC and WIN55,212-2 were similar, indicating that Delta(9)-THC is a full agonist at CB1Rs on GABA axon terminals. These results suggest that Delta(9)-THC inhibits GABA release, but does not directly alter GABA(A) receptors or GABA uptake in the hippocampus. Furthermore, full agonist effects of Delta(9)-THC on IPSCs likely result from a much higher expression of CB1Rs on GABA versus glutamate axon terminals in the hippocampus.
    Neuropharmacology 07/2010; 59(1-2):121-7. DOI:10.1016/j.neuropharm.2010.04.013 · 4.82 Impact Factor
Show more


Available from