Journal Club with Dr. Jonathan Cachat

For a special 40th episode, Dr. Jon revisits research he led out of Tulane University in 2010 on psychoactive substance effects in zebrafish. Out of 40+ published papers from this research, we look at one focusing on zebrafish symptoms when in withdrawal from ethanol, diazepam, morphine and caffeine. We also talk about living in New Orleans, the process of obtaining a DEA license, why caffeine was surprisingly highly toxic on fish, a popular film on substance use in the animal kingdom, and the upcoming event at the Cannabis Museum in Athens, Ohio on Sat. April 22nd: Community Hemp Fair. https://www.instagram.com/p/Cp0kkZ4u0yo/

Reference: Cachat, J., Canavello, P., Elegante, M., Bartels, B., Hart, P., Bergner, C., Egan, R., Duncan, A., Tien, D., Chung, A., Wong, K., Goodspeed, J., Tan, J., Grimes, C., Elkhayat, S., Suciu, C., Rosenberg, M., Chung, K. M., Kadri, F., Roy, S., … Kalueff, A. V. (2010). Modeling withdrawal syndrome in zebrafish. Behavioural brain research, 208(2), 371–376. https://doi.org/10.1016/j.bbr.2009.12.004

Dr. Jonathan Cachat is on social media @jcachat and http://jcachat.com/

Dr. Jon Cachat and Brian look at a survey conducted from 2019-2020. The survey found the majority of the 2,296 respondents with psychiatric conditions reported improvement in their condition following the consumption of kratom. Recently published by the American Psychological Association, the survey was authored by five past Kratom Science Podcast guests: Drs. Oliver Grundmann, Kirsten Smith, Darshan Singh, Zach Walsh, and Marc Swogger.

References

Dr. Jonathan Cachat is on social media @jcachat and http://jcachat.com/

Thailand has recently decriminalized kratom after 79 years of prohibition. In today's episode of Kratom Science Journal Club, Dr. Cachat and Brian look at a study funded in part by the Thai government that analyzed kratom trees growing in various regions of Thailand. The team measured mitragynine levels, accounting for variables in climate such as light, temperature, humidity, and soil moisture. This information will be used to standardize a kratom product for future agriculture. In years to come, Thailand is set to be be a major exporter of kratom to the west, competing with Indonesia, where 95% of kratom imported into the United States comes from.

Reference

Dr. Jonathan Cachat is on social media @jcachat and http://jcachat.com/

Dr. Jon starts off talking about the art show that took place in October 2022 at the new Cannabis Museum in Athens Ohio. Then we cover a study out of Thailand on kratom's effects on alpha-glucosidase and lipase, enzymes that are inhibited by medications for the treatment of diabetes. We see how kratom and mitragynine compare to standard prescription medications, and talk about the traditional use and possible advantages and disadvantages of developing mitragynine into a diabetes treatment drug in the future.

• Sign up for the Cannabis Museum's email list at https://www.cannabismuseum.com and check out reddit.com/r/cannabismuseum

References:

• Limcharoen, T., Pouyfung, P., Ngamdokmai, N., Prasopthum, A., Ahmad, A. R., Wisdawati, W., Prugsakij, W., & Warinhomhoun, S. (2022). Inhibition of α-Glucosidase and Pancreatic Lipase Properties of Mitragyna speciosa (Korth.) Havil. (Kratom) Leaves. Nutrients, 14(19), 3909. https://doi.org/10.3390/nu14193909
• "Alpha-Glucosidase". https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/alpha-glucosidase
• Carlson, D. (2022). "Kratom & Metformin". https://kratom.org/interactions/metformin/

Dr. Jonathan Cachat is on social media @jcachat and http://jcachat.com/

Dr. Jon and Brian look at a study (Farkas et al., 2022 https://doi.org/10.1016/j.ibneur.2022.08.007) in mice out of Temple University exploring whether mitragynine can help attenuate chemotherapy-induced peripheral neuropathic (CIPN). The team used oxaliplatin, a chemotherapy drug, to induce this condition in an equal number of male and female mice. Mitragynine was also combined with four receptor agonists to reveal the compound's uniqueness - it's activity at not only opioid, but adrenergic receptors accounts for the analgesic effects of kratom's most abundant alkaloid.

We also talk about a company who filed a patent for a "deuterated" form of 7-hydroxymitragynine and whether that poses signficant risks.

Plus, Dr. Jon announces the first event being held at the new Cannabis Museum in Athens, Ohio. "The Cannabis Museum Gallery is presenting a special collection of psychedelic and visionary art for sale. From art nouveau to counterculture, the poster has chronicled the evolution of society. Beginning in San Francisco before the 'Summer of Love' a new genre of advertising art and graphics evolved into a movement. This art documents our time and has transcended the zeitgeist for future generations. The show features art created for the Grateful Dead and other performers. Artists include Stanley Mouse, Rick Griffin, Alex Grey, and many others. It includes artist-signed posters and original paintings. Join us Friday, October 14. For a night of Psychedelic Art and Refreshments. Doors open from 4:20 to 8 pm at the Cannabis Museum. 16050 Canaanville Road, Athens, Ohio 45701. Proceeds of all sales benefit the Cannabis Museum. Please help support the Cannabis Museum with your donations at the door, become a supporter of the Cannabis Museum with a minimum donation of $30 or buy your tickets in advance at https://www.eventbrite.com/e/cannabis-museum-psychedelic-art-opening-reception-tickets-425023044367?fbclid=IwAR3dVzXrubSI5-SJVL4lnxz8PeZBoeSApijiNA2bWg-VGhmtypQsX9RgjhI

References

• Brown TJ, Sedhom R, Gupta A. (2019). Chemotherapy-Induced Peripheral Neuropathy. JAMA Oncol. 5(5):750. https://jamanetwork.com/journals/jamaoncology/fullarticle/2726030
• Farkas, D. J., Foss, J. D., Ward, S. J., & Rawls, S. M. (2022). Kratom alkaloid mitragynine: Inhibition of chemotherapy-induced peripheral neuropathy in mice is dependent on sex and active adrenergic and opioid receptors. IBRO neuroscience reports, 13, 198–206. https://doi.org/10.1016/j.ibneur.2022.08.007
• Gallagher, B. (2022). Is it a good idea to make a 7-hydroxymitragynine based drug? Kratom Science. https://www.kratomscience.com/2022/09/28/is-it-a-good-idea-to-make-a-7-hydroxymitragynine-based-drug/
• Finnerup, N. B., Attal, N., Haroutounian, S., McNicol, E., Baron, R., Dworkin, R. H., Gilron, I., Haanpää, M., Hansson, P., Jensen, T. S., Kamerman, P. R., Lund, K., Moore, A., Raja, S. N., Rice, A. S., Rowbotham, M., Sena, E., Siddall, P., Smith, B. H., & Wallace, M. (2015). Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. The Lancet. Neurology, 14(2), 162–173. https://doi.org/10.1016/S1474-4422(14)70251-0
• Kratom Science Podcast #45 https://www.kratomscience.com/podcast/45-dr-abisheak-sharma-pharmacokineticist-and-kratom-researcher/

Dr. Jonathan Cachat is on social media @jcachat and http://jcachat.com/

Dr. Jon and Brian explore a study out of Thailand where goats meat goats ate feed supplemented with dried kratom leaves. What effect did this have on the goats body weight, cholesterol, blood, and feed conversion ratio? Even if it does work, will farmers be able to afford kratom as a feed supplement, given the newly legal market in Thailand?

Also we look at a case of serotonin syndrome after a 63 year old man on multiple medications introduced kratom without consulting his doctor. Then we talk about Tom Segura and kratom.

References

• Chanjula, P., Wungsintaweekul, J., Chiarawipa, R., Phesatcha, K., Suntara, C., Prachumchai, R., Pakdeechanuan, P., & Cherdthong, A. (2022). Effects of Supplementing Finishing Goats with Mitragyna speciosa (Korth) Havil Leaves Powder on Growth Performance, Hematological Parameters, Carcass Composition, and Meat Quality. Animals : an open access journal from MDPI, 12(13), 1637. https://doi.org/10.3390/ani12131637
• Eudaley, S. T., Brooks, S. P., & Hamilton, L. A. (2022). Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents. Journal of pharmacy practice, 8971900221116009. Advance online publication. https://doi.org/10.1177/08971900221116009
• https://www.kratomscience.com/2022/08/23/comedian-tom-segura-loves-kratom/

Dr. Jonathan Cachat is on social media @jcachat and http://jcachat.com/

Dr. Jon and Brian take a break from kratom to look at the recently released Netflix documentary series hosted by Michael Pollan, How to Change Your Mind.

In related good news: the DEA backed off its decision to schedule five psychedelics. Hamilton Morris tweets. "Today the DEA withdrew their plan to prohibit DiPT, 4-HO-DiPT, 5-MeO-MiPT, 5-MeO-DET, and 5-MeO-αMT. As opposition mounted, they decided to cancel the hearing. Kratom was the first time public opposition prevented the prohibition of a substance, now we have five more successes!" https://twitter.com/HamiltonMorris/status/1550593819086929921

Dr. Jonathan Cachat is on social media @jcachat and http://jcachat.com/

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Dr. Cachat and Brian look at a letter (Smith et al, 2022) authored by former Kratom Science Podcast guests Dr. Kirsten Smith, Dr. Oliver Grundmann, Dr. Chris McCurdy, Dr. Darshan Singh, and other experts in the kratom field. The letter questions a systematic review (Broyan et al, 2022) of kratom case reports that offers buprenorphine as a solution to "kratom use disorder". Kratom-related case reports typically originate with patients showing up to emergency rooms and physicians' offices with symptoms. In these case reports, kratom product samples are rarely if ever tested for adulterants or contamination. The strength of the kratom product and dose levels seem to nearly always go unreported or wildly misreported (for example, the Broyan et al. review the Smith et al. letter addresses here claims the patients consumed an average of 92 grams of kratom per day). Furthermore, history or current use of other drugs is often overlooked.

Dr. Jon also talks about his trouble getting public data on cannabis testing and use trends from the State of Ohio's Marijuana Enforcement Tracking Reporting & Compliance (METRC) program.

References

• Broyan, V. R., Brar, J. K., Allgaier Student, T., & Allgaier, J. T. (2022). Long-term buprenorphine treatment for kratom use disorder: A case series. Substance abuse, 43(1), 763–766. https://doi.org/10.1080/08897077.2021.2010250
• Smith, K. E., Dunn, K. E., Epstein, D. H., Feldman, J. D., Garcia-Romeu, A., Grundmann, O., Henningfield, J. E., McCurdy, C. R., Rogers, J. M., Schriefer, D., Singh, D., & Weiss, S. T. (2022). Need for clarity and context in case reports on kratom use, assessment, and intervention. Substance abuse, 43(1), 1221–1224. https://doi.org/10.1080/08897077.2022.2074608
• https://www.metrc.com/

Dr. Jonathan Cachat is on social media @jcachat and http://jcachat.com/

Today on Journal Club, Dr. Jon Cachat look at a study in 2021 out of University of Colorado, Boulder in cooperation with Leafly that examines nearly 90,000 cannabis samples. Does Indica, Sativa, and Hybrid really mean anything in terms of psychoactive effects? Are cannabis strains labelled consistently in terms of cannabinoid and terpene content? We also talk about an app Dr. Jon is working on where users report effects of different brands of cannabis matched with cannabinoids and terpenes, called The Cannabis Diary. Plus we talk briefly about a Spanish company, KREI, that is working on a patent for genetically tracking cannabis strains to their origin.

References

• Smith, C. J., Vergara, D., Keegan, B., & Jikomes, N. (2022). The phytochemical diversity of commercial Cannabis in the United States. PloS one, 17(5), e0267498. https://doi.org/10.1371/journal.pone.0267498 Full text: https://www.biorxiv.org/content/10.1101/2021.07.05.451212v1
• The Cannabis Diary, an app that helps consumers understand "what cannabinoids & terpenes profile (the entourage) works best for their desired effects" https://www.thecannabisdiary.co
• KREI Method - company from Spain working on tracking cannabis genetics. See overview below...

Dr. Jonathan Cachat is on social media @jcachat and http://jcachat.com/

Perhaps the most important paper Dr. Jon and Brian have covered so far, "Understanding Kratom: A Guide for Healthcare Providers" is a comprehensive introduction to kratom for those who provide direct care to kratom consumers, such as physicians or mental health specialists. In this paper spearheaded by past Kratom Science Podcast guest, Dr. Marc Swogger, reasons are listed for why people use kratom, what the possible risks and side effects are, and the damaging effects of drug hysteria and over-emphases in the medical literature on rare adverse events. Physicians then given recommendations for best practices, and urged to foster honesty by adopting a "non-stigmatizing and respectful" stance toward the patient. We consider this guide to be an important step toward eliminating one barrier to healthcare access, and to one day when every kratom consumer may say to their doctor, without fear of retribution, "I consume kratom".

References

• The main paper discussed is free to access in its entirety https://www.frontiersin.org/articles/10.3389/fphar.2022.801855/full
• Swogger, M. T., Smith, K. E., Garcia-Romeu, A., Grundmann, O., Veltri, C. A., Henningfield, J. E., & Busch, L. Y. (2022). Understanding Kratom Use: A Guide for Healthcare Providers. Frontiers in pharmacology, 13, 801855. https://doi.org/10.3389/fphar.2022.801855
• Relevant to this episode and Kratom Science Podcast #81: Dr. Kirsten Smith's "Afraid to Tell the Truth" about healthcare access as a former heroin user https://closler.org/lifelong-learning-in-clinical-excellence/afraid-to-tell-the-truth

Dr. Jon Cachat would like you to know about The Fentanyl Project, fentanylproject.org "Bringing test strips directly to the users most in need...Join us in our mission to reduce Fentanyl fatalities by distributing free fentanyl test kits, educating users about the dangers of mindless consumption patterns, and providing resources for those that are seeking help."

Dr. Jon would also like you to know about The Cannabis Museum, https://www.cannabismuseum.com/, opening soon in Athens, Ohio.

Dr. Jonathan Cachat is on social media @jcachat and http://jcachat.com/