Very low doses of Δ8-THC increase food consumption and alter neurotransmitter levels following weight loss

Avraham, Yosefa; Ben‐Shushan, Dikla; Breuer, Aviva; Zolotarev, Olga; Okon, Avital; Fink, Nir; Katz, Vered; Berry, Elliot M.

doi:10.1016/j.pbb.2004.01.015

Cited by 42 publications

(19 citation statements)

References 51 publications

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“…Cannabimimetic compounds influence anterior pituitary hormone secretion, through effects exerted mainly at the hypothalamic level (see Murphy et al, 1998, for review), and are also orexigenic agents, through effects exerted on several mediators mainly located in the anterior hypothalamus (see Osei-Hyiaman et al, 2006, for review). In both cases, both serotonin and norepinephrine seem to be involved (Arévalo et al, 2001;Tzavara et al, 2001;Avraham et al, 2004), so we can hypothesize that these two transmitters may be the key targets for hypothalamic effects of UCM707.…”

Section: Discussionmentioning

confidence: 96%

Neurochemical effects of the endocannabinoid uptake inhibitor UCM707 in various rat brain regions

et al. 2007

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Section: Discussionmentioning

confidence: 96%

Neurochemical effects of the endocannabinoid uptake inhibitor UCM707 in various rat brain regions

et al. 2007

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“…The stereochemistry and in vivo and in vitro metabolism profiles of both compounds (Δ 8 -THC and Δ 9 -THC) are similar. However, Δ 8 -THC is easier and less expensive to prepare and is considered to be less psychotropic than Δ 9 -THC (15)(16)(17)(18). Additionally, Δ 8 -THC is chemically more stable, does not undergo oxidation to cannabinol and has a much longer shelf life than Δ 9 -THC (15).…”

Section: Introductionmentioning

confidence: 99%

Enhanced Solubility, Stability, and Transcorneal Permeability of Delta-8-Tetrahydrocannabinol in the Presence of Cyclodextrins

et al. 2011

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Abstract. The purpose of this study was to investigate the effect of cyclodextrins (CDs) on aqueous solubility, stability, and in vitro corneal permeability of delta-8-tetrahydrocannabinol (Δ 8 -THC). Phase solubility of Δ 8 -THC was studied in the presence of 2-hydroxypropyl-β-cyclodextrin (HPβCD), randomly methylated-β-cyclodextrin (RMβCD) and sulfobutyl ether-β-cyclodextrin sodium salt (SβCD). Stability of Δ 8 -THC in 5% w/v aqueous CD solutions, as a function of pH, was studied following standard protocols. In vitro corneal permeation of Δ 8 -THC (with and without CDs) across excised rabbit cornea was also determined. Phase-solubility profile of Δ 8 -THC in the presence of both HPβCD and RMβCD was of the A P type, whereas, with SβCD an A L type was apparent. Aqueous solubility of Δ 8 -THC increased to 1.65, 2.4, and 0.64 mg/mL in the presence of 25% w/v HPβCD, RMβCD, and SβCD, respectively. Significant degradation of Δ 8 -THC was not observed within the study period at the pH values studied, except for at pH 1.2. Transcorneal permeation of Δ 8 -THC was dramatically improved in the presence of CDs. The results demonstrate that CDs significantly increase aqueous solubility, stability, and transcorneal permeation of Δ 8 -THC. Thus, topical ophthalmic formulations containing Δ 8 -THC and modified beta CDs may show markedly improved ocular bioavailability.

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“…We chose to examine the effects of WIN 55,212-2 and AM 251 on food intake in presatiated rats to further delineate the role of endogenous cannabinoids in energy balance. Our data represent the first attempt to directly examine the effect of cannabinoids on serotonin (5-HT) release; there are few reports in the literature examining the interactions of catecholamine and cannabinoids and the resulting effect on food intake (16) . Abbreviations: CB 1 , cannabinoid type 1; 5HIAA, acetic acid 5-hydroxy-indol; 5-HT, serotonin; icv, intracerebroventricular; ipt, intraperitoneal; TBS, Tris-buffered saline; Tris, 2-amino-2-hydroxymethyl-1,3-propanediol.…”

mentioning

confidence: 99%

Influence of intracerebroventricular or intraperitoneal administration of cannabinoid receptor agonist (WIN 55,212-2) and inverse agonist (AM 251) on the regulation of food intake and hypothalamic serotonin levels

Merroun

Errami

Hoddah

et al. 2009

BJN

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The effect of intracerebroventricular or intraperitoneal administration of cannabinoid receptor agonist WIN 55,212-2 or inverse agonist AM 251 on food intake and extracellular levels of serotonin and acetic acid 5-hydroxy-indol from presatiated rats was studied. Compared to the vehicleinjected control, the intracerebroventricular administration of WIN 55,212-2 was associated with a significant increase in food intake, whereas the administration of AM 251 caused a significant reduction in this respect. These results were accompanied by considerable reductions or increases in serotonin and acetic acid 5-hydroxy-indol levels compared to the vehicle-injected control and the baseline values for the different experimental groups studied. Intraperitoneal administration of WIN 55,212-2 at doses of 1 and 2 mg/kg promoted hyperphagia up to 6 h after injection, whereas administration of a higher dose (5 mg/kg) significantly inhibited food intake and motor behaviour in partially satiated rats. Administration of any of the AM 251 doses studied (0·5, 1, 2, 5 mg/kg) led to a significant decrease in the amount of food ingested from 2 h after the injection, compared to the vehicle-injected control group, with the most striking effect being observed when the 5 mg/kg dose was injected.Cannabinoid system: CB 1 receptors: Food intake: Nutritional value: WIN 55,212-2: AM 251: Serotonin: Acetic acid 5-hydroxy-indol: c-fos Expression Advances in understanding the physiology and pharmacology of the endogenous cannabinoid system have potentiated the interest of cannabinoid receptors as potential therapeutic targets. The endogenous cannabinoid system is involved in mechanisms that regulate energy metabolism, and interacts with many other signalling systems that play an important role in metabolic regulation (1) . The cannabinoid type 1 (CB 1 ) receptor has been strongly implicated in the regulation of food intake (2) . CB 1 receptors are present in the brain and in the periphery. In the brain, CB 1 receptors have been identified in pathways responsible for reward and energy balance (3 -5) , whereas in the periphery, CB 1 receptors have been identified in the gut (6 -8) , as well as in hepatocytes (9) and adipocytes (3,10) . CB 1 receptor agonists such as D 9 -tetrahydrocannabinol, together with the endocannabinoids, anandamide and 2-arachidonoylglycerol, increase food intake in both man and animals (11) . The enhancement of food intake can also be induced by other cannabinoid CB 1 receptor agonists such as WIN 55, . This action is blocked or reversed by the selective CB 1 receptor antagonist SR 141716A (13) and by the structurally and pharmacologically similar compound AM 251 (14,15) .Since the nutritive utilization of any foodstuff can be significantly affected by the amount of food consumed, we undertook the study of food intake regulation at the central and peripheral level using the CB 1 receptor agonist WIN 55,212-2 and the CB 1 inverse agonist AM 251 administered at different doses by means of intracerebroventricular (icv) or ...

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Very low doses of Δ8-THC increase food consumption and alter neurotransmitter levels following weight loss

Cited by 42 publications

References 51 publications

Neurochemical effects of the endocannabinoid uptake inhibitor UCM707 in various rat brain regions

Neurochemical effects of the endocannabinoid uptake inhibitor UCM707 in various rat brain regions

Enhanced Solubility, Stability, and Transcorneal Permeability of Delta-8-Tetrahydrocannabinol in the Presence of Cyclodextrins

Influence of intracerebroventricular or intraperitoneal administration of cannabinoid receptor agonist (WIN 55,212-2) and inverse agonist (AM 251) on the regulation of food intake and hypothalamic serotonin levels

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