Diuretic Effects of Cannabinoids

Paronis, Carol A.; Thakur, Ganesh A.; Bajaj, Shama; Nikas, Spyros P.; Vemuri, V. Kiran; Makriyannis, Alexandros; Bergman, Jack

doi:10.1124/jpet.112.199331

Cited by 25 publications

(27 citation statements)

References 39 publications

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“…Abel's early review of the effects of cannabis on hunger and thirst reported a decrease in water intake and increase in food intake, both of which affect fluid homeostasis (Abel, 1975). Early human studies (Ames, 1958) as well as studies in the rat (Sofia, Dixit, & Barry, 1977) implicated THC as a diuretic agent, while a more recent study showed that THC decreased urine volume and urinary frequency in patients suffering from multiple sclerosis (Paronis et al, 2013). Cannabinoids were also found to directly affect vasoconstriction, as systemic administration of anandamide caused hypotension in rats (Varga, Lake, Martin, & Kunos, 1995).…”

Section: Endocannabinoids and Fluid Homeostasismentioning

confidence: 99%

Endocannabinoid Regulation of Neuroendocrine Systems

Tasker

Chen

Fisher

et al. 2015

International Review of Neurobiology

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Section: Endocannabinoids and Fluid Homeostasismentioning

confidence: 99%

Endocannabinoid Regulation of Neuroendocrine Systems

Tasker

Chen

Fisher

et al. 2015

International Review of Neurobiology

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“…Hypothermia, diuresis, and rate-decreasing effects (food-maintained responding) served as indices of adverse effects. Hypothermia and diuresis have been reported for both cannabinoids and k opioids (Dykstra et al, 1987;Adler and Geller, 1993;McGregor et al, 1996;Wadenberg, 2003;Rawls and Benamar, 2011;Paronis et al, 2012Paronis et al, , 2013Chopda et al, 2013). Foodmaintained responding was used to assess behavioral suppression.…”

Section: Introductionmentioning

confidence: 99%

Behavioral Characterization of κ Opioid Receptor Agonist Spiradoline and Cannabinoid Receptor Agonist CP55940 Mixtures in Rats

Minervini¹,

Dahal²,

France³

2016

J Pharmacol Exp Ther

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Pain is a significant clinical problem, and there is a need for more effective treatments with reduced adverse effects that currently limit the use of m opioid receptor agonists. Synthetic k opioid receptor agonists have no abuse liability and well-documented antinociceptive effects; however, adverse effects (diuresis, dysphoria) preclude their use in the clinic. Combining k opioids with nonopioid drugs (cannabinoid receptor agonists) allows for smaller doses of each drug to produce antinociception. This study tested whether a potentially useful effect of the k opioid receptor agonist 2-Cumulative dose-response functions were determined in eight male Sprague-Dawley rats for spiradoline (0.032-32.0 mg/kg, i.p.) and CP55940 (0.0032-1.0 mg/kg, i.p.) for antinociception, hypothermia, food-maintained responding, and diuresis. Alone, each drug dose dependently increased tail withdrawal latencies from 50°C water, decreased body temperature by ∼4°C, and eliminated food-maintained responding. Spiradoline, but not CP55940, significantly increased urine output at doses that eliminated responding. Smaller doses of spiradoline and CP55940 in mixtures (3:1, 1:1, and 1:3 spiradoline:CP55940) had effects comparable to those observed with larger doses of either drug administered alone: the interaction was additive for antinociception and additive or greater than additive for hypothermia and food-maintained responding. Collectively, these data fail to provide support for the use of these mixtures for treating acute pain; however, k opioid/cannabinoid mixtures might be useful for treating pain under other conditions (e.g., chronic pain), but only if the adverse effects of both drugs are not enhanced in mixtures.

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“…We recently reported that cannabinoid-induced diuresis is a CB1-receptor mediated effect in rodents and, additionally, that these diuretic actions in mice are biphasic (Chopda et al, 2013;Paronis et al, 2013). Diuretic effects of cannabinoids were first reported anecdotally, and subsequently confirmed, in early studies of cannabis in humans (Parker and Wrigley, 1947;Ames, 1958).…”

Section: Introductionmentioning

confidence: 95%

Tolerance to the Diuretic Effects of Cannabinoids and Cross-Tolerance to a -Opioid Agonist in THC-Treated Mice

Chopda

Parge

Thakur

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Daily treatment with cannabinoids results in tolerance to many, but not all, of their behavioral and physiologic effects. The present studies investigated the effects of 7-day exposure to 10 mg/kg daily of D 9-tetrahydrocannabinol (THC) on the diuretic and antinociceptive effects of THC and the synthetic cannabinoid AM4054. Comparison studies determined diuretic responses to the k-opioid agonist U50,488 and furosemide. After determination of control dose-response functions, mice received 10 mg/kg daily of THC for 7 days, and dose-response functions were re-determined 24 hours, 7 days, or 14 days later. THC and AM4054 had biphasic diuretic effects under control conditions with maximum effects of 30 and 35 ml/kg of urine, respectively. In contrast, antinociceptive effects of both drugs increased monotonically with dose to .90% of maximal possible effect. Treatment with THC produced 9-and 7-fold rightward shifts of the diuresis and antinociception doseresponse curves for THC and, respectively, 7-and 3-fold rightward shifts in the AM4054 dose-response functions. U50,488 and furosemide increased urine output to .35 ml/kg under control conditions. The effects of U50,488 were attenuated after 7-day treatment with THC, whereas the effects of furosemide were unaltered. Diuretic effects of THC and AM4054 recovered to near-baseline levels within 14 days after stopping daily THC injections, whereas tolerance to the antinociceptive effects persisted longer than 14 days. The tolerance induced by 7-day treatment with THC was accompanied by a 55% decrease in the B max value for cannabinoid receptors (CB1). These data indicate that repeated exposure to THC produces similar rightward shifts in the ascending and descending limbs of cannabinoid diuresis doseeffect curves and to antinociceptive effects while resulting in a flattening of the U50,488 diuresis dose-effect function.

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Diuretic Effects of Cannabinoids

Cited by 25 publications

References 39 publications

Endocannabinoid Regulation of Neuroendocrine Systems

Endocannabinoid Regulation of Neuroendocrine Systems

Behavioral Characterization of κ Opioid Receptor Agonist Spiradoline and Cannabinoid Receptor Agonist CP55940 Mixtures in Rats

Tolerance to the Diuretic Effects of Cannabinoids and Cross-Tolerance to a -Opioid Agonist in THC-Treated Mice

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