The whirlpool
A diet drug, a framework, and the biology under it
▶ Play this chapter The script
Every line as it is spoken in the film, in order.
That blocker, rimonabant, had already been sold as a diet drug. It shut CB1 down to curb appetite. Europe approved it in 2006. By 2008 it was suspended. People taking it had about twice the risk of psychiatric problems, above all depression.
The biologist Bob Melamede had a picture for this. Life is a whirlpool. It only exists while energy flows through it.
A cell that clings to its old pattern fights the flow. A cell that can let go moves with it. That's his framework, not textbook science.
The neurologist Ethan Russo has a framework too. He proposes that some cases of migraine, fibromyalgia and irritable bowel syndrome come from too little endocannabinoid tone. It's still a hypothesis.
But the biology underneath it is real. The same system helps switch off the stress response once the danger has passed. And a second lock, CB2, sits on your immune cells.
In Bob's picture, a cell that can't let go is stuck in its past. Your own system is how it lets go. The plant is how we found it.
Sources
Every claim in this chapter with its grade: E established · M emerging (one or two studies, or animals only) · F framework.
- EEuropean Medicines Agency. European Medicines Agency recommends suspension of the marketing authorisation of Acomplia, 23 October 2008. link
- ERinaldi-Carmona M et al. SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett 1994;350:240–4. (rimonabant) link
- FRobert (Bob) Melamede, PhD. Backward-looking and forward-looking: a far-from-equilibrium reading of the endocannabinoid system. His framework, not scientific consensus.
- FRusso EB. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett 2004;25:31–9. (the hypothesis, proposed from overlapping symptoms and the response to cannabis) link
- FRusso EB. Clinical endocannabinoid deficiency reconsidered: current research supports the theory in migraine, fibromyalgia, irritable bowel, and other treatment-resistant syndromes. Cannabis Cannabinoid Res 2016;1:154–65. (the author’s own review; formal trials are still lacking) link
- EHill MN, Tasker JG. Endocannabinoid signaling, glucocorticoid-mediated negative feedback, and regulation of the hypothalamic-pituitary-adrenal axis. Neuroscience 2012;204:5–16. (review) link
- EMunro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993;365:61–5. (CB2) link