>> I never understood why Rick put obesity and ED together <<
It's just a reflection of where I believe that we're going in the next twenty years. I'm skinny. When I smoked pot as a youth, I got hungry and horny. So did my skinny girlfriends. My "more adequately padded" friends just went to sleep. Try the experiment yourself..... pick a variety of attractive Swedish women, and send them over here with a variety of herbs. We'll do controlled experiments, with your blind.
If THC were available by prescription? Pfizer's sales would drop precipitously.
:-)
But, you're correct..... the thread is based on where I believe we'll be, circa 2020. There should be separate subjects, but I didn't know that the "indication" threads would be this popular.
Three random abstracts, not intended as justification for my rambling.......
Neuroscience. 2003;118(3):755-62.
Ac-nle-c[asp-his-dphe-arg-trp-lys]-nh(2) induces penile erection via brain and spinal melanocortin receptors.
Wessells H, Hruby VJ, Hackett J, Han G, Balse-Srinivasan P, Vanderah TW.
Department of Urology, University of Washington School of Medicine, Harborview Medical Center, 325 Ninth Avenue, Washington 98195, Seattle, USA
Penile erection induced by alpha-melanocyte-stimulating hormone and melanocortin receptors (MC-R) in areas of the spinal cord and periphery has not been demonstrated. To elucidate sites of the proerectile action of melanocortin peptides, in awake male rats we administered the MC-R agonist Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH(2) (MT-II) i.c.v., intrathecal (i.th.) and i.v. and scored penile erection and yawning. Injection of the MC-R antagonist Ac-Nle-c[Asp-His-DNal(2')-Arg-Trp-Lys]-NH(2) (SHU-9119) i.c.v. or i.th. in combination with i.th. MT-II differentiated spinal from supraspinal effects. To exclude a site of action in the penis, we recorded intracavernous pressure responses to intracavernosal injection of MT-II in the anesthetized rat.I.c.v., i.th., and i.v. MT-II induced penile erections in a dose-dependent fashion. Yawning was observed with i.c.v. and i.v. MT-II, while spinal injection did not produce this behavior. Intrathecal delivery of MT-II to the lumbosacral spinal cord was more efficacious in inducing erections than i.c.v. or i.v. administration; SHU-9119 blocked the erectile responses to i.th. MT-II when injected i.th. but not i.c.v. Intracavernosal MT-II neither increased intracavernous pressure nor augmented neurostimulated erectile responses.We confirmed the central proerectile activity of MT-II and demonstrated that in addition to a site of action in the brain, the distal spinal cord contains melanocortin receptors that can initiate penile erection independent of higher centers. These results provide new insight into the central melanocortinergic pathways that mediate penile erection and may allow for more efficacious melanotropin-based therapy for erectile dysfunction.
Nat Neurosci. 2003 Jun 8 [Epub ahead of print].
Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor.
Xu B, Goulding EH, Zang K, Cepoi D, Cone RD, Jones KR, Tecott LH, Reichardt LF.
[1] Howard Hughes Medical Institute, University of California, San Francisco, California 94143, USA. [2] Present address: Department of Pharmacology, Georgetown University Medical Center, SE402 Medical/Dental Building, 3900 Reservoir Rd. NW, Washington, DC 20057, USA.
The melanocortin-4 receptor (MC4R) is critically involved in regulating energy balance, and obesity has been observed in mice with mutations in the gene for brain-derived neurotrophic factor (BDNF). Here we report that BDNF is expressed at high levels in the ventromedial hypothalamus (VMH) where its expression is regulated by nutritional state and by MC4R signaling. In addition, similar to MC4R mutants, mouse mutants that expresses the BDNF receptor TrkB at a quarter of the normal amount showed hyperphagia and excessive weight gain on higher-fat diets. Furthermore, BDNF infusion into the brain suppressed the hyperphagia and excessive weight gain observed on higher-fat diets in mice with deficient MC4R signaling. These results show that MC4R signaling controls BDNF expression in the VMH and support the hypothesis that BDNF is an important effector through which MC4R signaling controls energy balance.
Nature. 2001 Apr 12;410(6830):822-5.
Leptin-regulated endocannabinoids are involved in maintaining food intake.
Di Marzo V, Goparaju SK, Wang L, Liu J, Batkai S, Jarai Z, Fezza F, Miura GI, Palmiter RD, Sugiura T, Kunos G.
Endocannabinoid Research Group, Istituto per la Chimica di Molecole di Interesse Biologico, CNR, 80072, Arco Felice, Naples, Italy.
Leptin is the primary signal through which the hypothalamus senses nutritional state and modulates food intake and energy balance. Leptin reduces food intake by upregulating anorexigenic (appetite-reducing) neuropeptides, such as alpha-melanocyte-stimulating hormone, and downregulating orexigenic (appetite-stimulating) factors, primarily neuropeptide Y. Genetic defects in anorexigenic signalling, such as mutations in the melanocortin-4 (ref. 5) or leptin receptors, cause obesity. However, alternative orexigenic pathways maintain food intake in mice deficient in neuropeptide Y. CB1 cannabinoid receptors and the endocannabinoids anandamide and 2-arachidonoyl glycerol are present in the hypothalamus, and marijuana and anandamide stimulate food intake. Here we show that following temporary food restriction, CB1 receptor knockout mice eat less than their wild-type littermates, and the CB1 antagonist SR141716A reduces food intake in wild-type but not knockout mice. Furthermore, defective leptin signalling is associated with elevated hypothalamic, but not cerebellar, levels of endocannabinoids in obese db/db and ob/ob mice and Zucker rats. Acute leptin treatment of normal rats and ob/ob mice reduces anandamide and 2-arachidonoyl glycerol in the hypothalamus. These findings indicate that endocannabinoids in the hypothalamus may tonically activate CB1 receptors to maintain food intake and form part of the neural circuitry regulated by leptin.
(edit.... this one may be of interest as well)
Brain Res. 1998 Jan 5;780(1):168-71.
An invertebrate G-protein coupled receptor is a chimeric cannabinoid/melanocortin receptor
Elphick MR.
School of Biological Sciences, Queen Mary and Westfield College, University of London, Mile End Road, London E1 4NS, UK
Analysis of a G-protein coupled receptor fragment isolated from the leech CNS reveals that it is a chimeric cannabinoid/melanocortin receptor. Two regions of the leech sequence display high levels of amino acid identity with mammalian cannabinoid receptors while a third region is 98% identical to part of the bovine adrenocorticotropic hormone receptor. The leech receptor may therefore resemble the putative ancestor of mammalian cannabinoid and melanocortin receptors. |
