Dynorphin B and spinal analgesia: induction of antinociception by the cannabinoids CP55,940, Δ9-THC and anandamide1Published on the World Wide Web on 18 January 2000.1

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

“…Cannabinoid agonists may also release endogenous opioids, and a functional interplay between the endocan-ENDOCANNABINOID SYSTEM AND DISEASE nabinoid and opioid systems in modulating analgesic responses has been suggested by numerous studies (Pugh et al, 1997;Manzanares et al, 1999a,b;Houser et al, 2000;Ibrahim et al, 2005;Tham et al, 2005;Vigano et al, 2005a,b;Williams et al, 2006).…”

“…Cannabinoids also modulate GABAergic transmission and the release of the peptide cholecystokinin, which may contribute to both anxiolytic and anxiogenic effects (Onaivi et al, 1990;Katona et al, 1999Katona et al, , 2001Marsicano and Lutz, 1999;Tsou et al, 1999;Beinfeld and Connolly, 2001;Rotzinger and Vaccarino, 2003). Furthermore, cannabinoids enhance the release of endogenous opioids and a functional interplay between the endocannabinoid and opioid systems modulates analgesic responses and is involved in antidepressant-like effects and in various addiction-related processes (Pugh et al, 1997;Manzanares et al, 1999b;Houser et al, 2000;Zimmer et al, 2001;Ghozland et al, 2002). From studies with THC and CP55,940, it appears that -and ␦-opioid receptors mediate certain anxiolytic effects, whereas activation of -opioid receptors leads to increased anxiety (Pugh et al, 1997;Houser et al, 2000;Zimmer et al, 2001;Berrendero and Maldonado, 2002;Ghozland et al, 2002;Marin et al, 2003).…”

“…Furthermore, cannabinoids enhance the release of endogenous opioids and a functional interplay between the endocannabinoid and opioid systems modulates analgesic responses and is involved in antidepressant-like effects and in various addiction-related processes (Pugh et al, 1997;Manzanares et al, 1999b;Houser et al, 2000;Zimmer et al, 2001;Ghozland et al, 2002). From studies with THC and CP55,940, it appears that -and ␦-opioid receptors mediate certain anxiolytic effects, whereas activation of -opioid receptors leads to increased anxiety (Pugh et al, 1997;Houser et al, 2000;Zimmer et al, 2001;Berrendero and Maldonado, 2002;Ghozland et al, 2002;Marin et al, 2003). There are also interactions between the endocannabinoid and serotonergic systems (Arevalo et al, 2001;Malone and Taylor, 2001;Fride and Shohami, 2002;Marin et al, 2003;Marco et al, 2004;Steffens and Feuerstein, 2004;reviewed in Viveros et al, 2005), although their role in anxiety-like behaviors has not been explored In contrast to earlier dogma, recent findings indicate that neurogenesis occurs in the adult brain.…”

Synergistic and additive interactions of the cannabinoid agonist CP55,940 with μ opioid receptor and α2‐adrenoceptor agonists in acute pain models in mice

“…leading to potentiation of opioid antinociception (Cichewicz & McCarthy, 2003); the spinal dynorphin system and other opioid peptides have been implicated (Manzanares et al, 1999;Houser et al, 2000). In the rat, CP55,940 (i.t.)…”

“…Further, in the rodent spinal cord, i.t. D 9 -THC elicits release of dynorphin A, whereas CP55,940 causes release of dynorphin B (Pugh et al, 1997;Houser et al, 2000). Opioid agonists may also act supraspinally on spinal function through the activation of descending noradrenergic inhibitory pathways.…”