Ep. 46 - FAAH-Out: The Curious Case of Joanne Cameron
Manage episode 453983946 series 3546136
Several years ago, a medical case appeared that took the scientific and medical community by storm. A patient appeared for surgery who reported never feeling anxiety, depression, or pain, despite numerous injuries and surgeries for which she required treatment. As scientists analyzed her genetic profile, they discovered something amazing - Joanne Cameron lacked the genetic code that was responsible for transmitting pain and creating anxiety and depression.
In this episode of Cannabis Nurse Truths, we examine the curious case of Joanne Cameron that has led to some very surprising research that targets this important physiological phenomenon, and drug companies are furiously developing drugs to capitalize on this incredible potential to decrease pain, anxiety, depression, and treat a number of psychological and physical disorders. One of the most incredible findings linked to this case: cannabinoids, like CBD, also enhances the natural physiological activities of the body where inflammation is halted (reducing pain), while also reducing or eliminating anxiety and depression.
EPISODE RESOURCES
Ahn, K., Johnson, D. S., & Cravatt, B. F. (2009). Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders. Expert Opinion on Drug Discovery, 4(7), 763–784. https://pmc.ncbi.nlm.nih.gov/articles/PMC2882713/pdf/nihms-116402.pdf
Bartel, S. J., Sherry, S. B., & Stewart, S. H. (2020). Self-isolation: A significant contributor to cannabis use during the COVID-19 pandemic. Substance Abuse, 41(4), 409–412. https://pubmed.ncbi.nlm.nih.gov/33044893/
Bisogno, T., & Maccarrone, M. (2013). Latest advances in the discovery of fatty acid amide hydrolase inhibitors. Expert Opinion on Drug Discovery. https://www.researchgate.net/publication/236044861_Latest_advances_in_the_discovery_of_fatty_acid_amide_hydrolase_inhibitors
Boileau, I., Mansouri, E., Williams, B., Le Foll, B., Rusjan, P., Mizrahi, R., Tyndale, R. F., Huestis, M. A., Payer, D. E., Wilson, A. A., Houle, S., Kish, S. J., & Tong, J. (2016). Fatty acid amide hydrolase binding in brain of cannabis users: Imaging with the novel radiotracer [11C]CURB. Biological Psychiatry, 80(9), 691–701. https://pubmed.ncbi.nlm.nih.gov/27345297/
Bornscheuer, L., Lundin, A., Forsell, Y., Lavebratt, C., & Melas, P. A. (2023). Functional variation in the FAAH gene is directly associated with subjective well-being and indirectly associated with problematic alcohol use. Genes, 14(9), 1826. https://pubmed.ncbi.nlm.nih.gov/37761966/
Cravatt, B.F., & Lichtman, A.H. (2003). Fatty acid amide hydrolase: An emerging therapeutic target in the endocannabinoid system. Current Opinion in Chemical Biology, 7(4), 469–475. https://pubmed.ncbi.nlm.nih.gov/12941421/
Di Marzo, V., & Petrosino, S. (2007). Endocannabinoids and the regulation of their levels in health and disease. Current Opinion in Lipidology, 18(2), 129–140. https://pubmed.ncbi.nlm.nih.gov/17353660/
D’Souza, D. C., Cortes-Briones, J., Creatura, G., Bluez, G., Thurnauer, H., Deaso, E., Bielen, K., Surti, T., Radhakrishnan, R., Gupta, A., Gupta, S., Cahill, J., Sherif, M. A., Makriyannis, A., Morgan, P. T., Ranganathan, M., & Skosnik, P. D. (2019). Efficacy and safety of a fatty acid amide hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in men: A double-blind, placebo-controlled, parallel group, phase 2a single-site randomised controlled trial. Lancet Psychiatry, 6(1), 35–45. https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(18)30427-9/abstract
Girella, A., Di Bartolomeo, M., Dainese, E., Buzzelli, V., Trezza, V., & D’Addario, C. (2024). Fatty acid amide hydrolase and cannabinoid receptor type 1 genes regulation is modulated by social isolation in rats. Neurochemical Research, 49(5),1278-1290. http://www.ncbi.nlm.nih.gov/pubmed/38368587
Giuffrida, A., Leweke, F. M., Gerth, C. W., Schreiber, D., Koethe, D., Faulhaber, J., Klosterkötter, J., & Piomelli, D. (2004). Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology, 29(11), 2108–2114. https://www.nature.com/articles/1300558
Habib, A. M., Okorokov, A. L., Hill, M. N., Bras, J. T., Lee, M.-C., Li, S., Gossage, S. J., van Drimmelen, M., Morena, M.,Houlden, H., Ramirez, J. D., Bennett, D. L. H., Srivastava, D., & Cox, J. J. (2019). Microdeletion in a FAAH pseudogene identified in a patient with high anandamide concentrations and pain insensitivity. British Journal of Anaesthesia, 123(2), e249–e253. https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6676009&blobtype=pdf
Haseltine, W.A., (2023). No pain, FAAH-OUT. Forbes.
https://www.forbes.com/sites/williamhaseltine/2023/06/19/no-pain-faah-out/
Huggins, J. P., Smart, T. S., Langman, S., Taylor, L., & Young, T. (2012). An efficient randomised, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocannabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of the knee. Pain, 153(9), 1837–1846. https://pubmed.ncbi.nlm.nih.gov/22727500/
Jacobson, M. R., Watts, J. J., Silva, T. D., Tyndale, R. F., Rusjan, P. M., Houle, S., Wilson, A. A., Ross, R. A., Boileau, I., & Mizrahi, R. (2020). Fatty acid amide hydrolase is lower in young cannabis users. Addiction Biology, 26(1), e12872.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7944390/
Lever, I. J., Robinson, M., Cibelli, M., Paule, C., Santha, P., Yee, L., Hunt, S. P., Cravatt, B. F., Elphick, M. R., Nagy, I., & Rice, A. S. C. (2009). Localization of the endocannabinoid-degrading enzyme fatty acid amide hydrolase in rat dorsal root ganglion cells and its regulation after peripheral nerve injury. Journal of Neuroscience, 29(12), 3766–3780. https://doi.org/10.1523/JNEUROSCI.4071-08.2009
Leweke, F. M., Giuffrida, A., Wurster, U., Emrich, H. M., & Piomelli, D. (1999). Elevated endogenous cannabinoids in schizophrenia. Neuroreport, 10(8), 1665–1669. https://pubmed.ncbi.nlm.nih.gov/10501554/
Leweke, F. M., Piomelli, D., Pahlisch, F., Muhl, D., Gerth, C. W., Hoyer, C., Klosterkötter, J., Hellmich, M., & Koethe, D. (2012). Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Translational Psychiatry, 2(3), e94–e94. https://www.nature.com/articles/tp201215
Machado-Vieira, R, & Haseeb, A. (2024). A trial of the fatty acid amide hydrolase inhibitor palmitoylethanolamide in bipolar depression. Identifier NCT06229977. https://clinicaltrials.gov/study/NCT06229977?cond=DEPRESSION%20&term=FAAH&rank=1&a=1
Mikaeili, H., Habib, A. M., Yeung, C. W.-L., Santana-Varela, S., Luiz, A. P., Panteleeva, K., Zuberi, S., Athanasiou-Fragkouli, A., Houlden, H., Wood, J. N., Okorokov, A. L., & Cox, J. J. (2023). Molecular basis of FAAH-OUT-associated human pain insensitivity. Brain: A Journal of Neurology, 146(9), 3851–3865. https://pubmed.ncbi.nlm.nih.gov/37222214/
Minkkila, A. M., Saario, S., & Nevalainen, T. (2010). Discovery and development of endocannabinoid-hydrolyzing enzyme inhibitors. Current Topics in Medicinal Chemistry, 10(8), 828–858. https://doi.org/10.2174/156802610791164238
Patel, S., Hill, M. N., Cheer, J. F., Wotjak, C. T., & Holmes, A. (2017). The endocannabinoid system as a target for novel anxiolytic drugs. Neuroscience and Biobehavioral Reviews, 76(Pt A), 56–66. https://pmc.ncbi.nlm.nih.gov/articles/PMC5407316/pdf/nihms843439.pdf
Pfizer. (2009). A multiple dose trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of PF-04457845 in healthy volunteers. Identifier NCT00836082. https://clinicaltrials.gov/study/NCT00836082?term=pf%2004457845&checkSpell=&rank=1&tab=table
Pfizer. (2010). A study to establish the effects of PF-04457845 on sleep in healthy volunteers. Identifier NCT01092845. https://clinicaltrials.gov/study/NCT01092845?term=pf%2004457845&checkSpell=&rank=7&a=7
Pfizer. (2019). A study to investigate whether PF-04457845 is effective in treating pain, is safe and tolerable in patients with osteoarthritis of the knee. Identifier NCT00981357.
https://clinicaltrials.gov/study/NCT00981357?cond=osteoarthritis%20&term=FAAH&rank=1
Sanofi-Aventis. (2013). An eight-week study of SSR411298 as treatment for major depressive disorder in elderly patients (FIDELIO). Identifier NCT00822744. https://clinicaltrials.gov/study/NCT00822744?term=SSR-411298&rank=1&a=9
Schlosburg, J. E., Kinsey, S. G., & Lichtman, A. H. (2009). Targeting fatty acid amide hydrolase (FAAH) to treat pain and inflammation. AAPS Journal, 11(1), 39. https://pmc.ncbi.nlm.nih.gov/articles/PMC2664876/pdf/12248_2008_Article_9075.pdf
Tripathi, R. K. P. (2020). A perspective review on fatty acid amide hydrolase (FAAH) inhibitors as potential therapeutic agents. European Journal of Medicinal Chemistry, 188, 111953. https://pubmed.ncbi.nlm.nih.gov/31945644/
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