synergistic

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Treatment of acute cannabinoid overdose with naloxone infusion opioid, synergistic

The overlapping endocannabinoid and endogenous opioid systems may explain this patient's response to therapy, and this synergistic relationship is discussed.
The endocannabinoid and endogenous opioid systems are syngergistic, which may explain the effect of naloxone in cannabis toxicity. Cannabinoid and opioid receptors belong to the rhodopsin subfamily of G-protein-coupled receptors which, when activated, reduce cellular levels of cyclic adenosine monophosphate (cAMP) by inhibiting adenylyl cyclase [8
Robledo P, Berrendero F, Ozaita A, et al. Advances in the field of cannabinoid–opioid cross-talk. Addict Biol. 2008;13:213–224. [Google Scholar]]. Both cannabinoid and opioid receptors are located primarily at presynaptic terminals, and their activation inhibits the release of several neurotransmitters. Opioid and cannabinoid receptor activation also modifies the permeability of sodium, potassium, and calcium channels [8Robledo P, Berrendero F, Ozaita A, et al. Advances in the field of cannabinoid–opioid cross-talk. Addict Biol. 2008;13:213–224. [Google Scholar]]. Receptors of both systems coexist in the central nervous system (CNS) with overlapping distribution in the brain, brainstem, and spinal cord [9Scavone JL, Sterling RC, Van Bockstaele EJ. Cannabinoid and opioid interactions: implications for opiate dependence and withdrawal. Neurosci. 2013;248:637–654. [Google Scholar]]. Cannabinoid and opioid receptors also co-localize in γ-Aminobutyric acid (GABA)ergic neurons with potential coupling to a second messenger systems and formation of heterodimers between the two receptors [11Pickel VM, Chan J, Kash TL, et al. Compartment-specific localization of cannabinoid 1 (CB1) and mu opioid receptors in rat nucleus accumbens. Neurosci. 2004;127:101–112. [Google Scholar]
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