Neural Pharm Podcast

References:

Psychedelics legislation in Colorado Springs: https://gazette.com/health/fountain-joins-colorado-springs-in-seeking-to-regulate-fledgling-psychedelic-mushroom-industry/article_22a66456-a1da-11ef-a515-57588c741084.html

Oregon Psilocybin Ballot Measure Results: https://www.opb.org/article/2024/11/07/psilocybin-ban-mushroom-hallucinogenic-ballot-politics-elections-oregon/

Vermont Psychedelic Working Group Final Report: chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://legislature.vermont.gov/assets/Legislative-Reports/The-Psychedelic-Therapy-Advisory-Working-Group_Final-Report.pdf

US Life Expectancy Expected to Decline to 66th Globally by 2050: https://www.healthdata.org/news-events/newsroom/news-releases/increases-us-life-expectancy-forecasted-stall-2050-poorer-health#:~:text=Life%20expectancy%20in%20the%20US,2022%20to%2066th%20in%202050

United Healthcare uses faulty AI to deny claims: https://www.cbsnews.com/news/unitedhealth-lawsuit-ai-deny-claims-medicare-advantage-health-insurance-denials/

DEA Funding chart: https://crsreports.congress.gov/product/pdf/R/R44576

See here also, Why is the FDA funded by the companies it regulates?: https://today.uconn.edu/2021/05/why-is-the-fda-funded-in-part-by-the-companies-it-regulates-2/

Other references to topics discussed on this edition of podcast:

See Colby’s previous article on Measure 110 in Oregon—which decriminalized nearly all categories of drugs, and has since been overturned:

Right to Try bill articles (since this was discussed on this edition of podcast):

Trump gave patients “Right to Try” but it hasn’t helped them: https://www.statnews.com/2024/08/02/trump-gave-patients-right-to-try-it-hasnt-helped-them/

DEA says Right to Try doesn’t include substances listed as Schedule I: https://www.marijuanamoment.net/in-case-on-psilocybin-access-for-cancer-patients-dea-says-federal-right-to-try-law-does-not-provide-any-exemptions-from-controlled-substance-act/

Understanding the Right to Try act: https://pmc.ncbi.nlm.nih.gov/articles/PMC7416898/

Show notes and references:

* Please note: This was recorded prior to the election on Nov 5. We will discuss the results and predictions for the future of healthcare policy in America in our next edition.”

Kanna references:

Bennett, A. C., et al. "Sceletium tortuosum may delay chronic disease progression via alkaloid-dependent antioxidant or anti-inflammatory action." Journal of physiology and biochemistry 74.4 (2018): 539-547.

Chiu, Simon, et al. "Proof-of-concept randomized controlled study of cognition effects of the proprietary extract Sceletium tortuosum (Zembrin) targeting phosphodiesterase-4 in cognitively healthy subjects: implications for Alzheimer’s dementia." Evidence-Based Complementary and Alternative Medicine 2014 (2014).

Chiu, S., et al. "Exploring Standardized Zembrin® Extracts from the South African plant Sceletium tortuosum in Dual Targeting Phosphodiesterase-4 (PDE-4) and Serotonin Reuptake Inhibition as potential treatment in Schizophrenia." Int J Complement Alt Med 6.5 (2017): 00203.

Coetzee, Dirk D., Víctor López, and Carine Smith. "High-mesembrine Sceletium extract (Trimesemine™) is a monoamine releasing agent, rather than only a selective serotonin reuptake inhibitor." Journal of Ethnopharmacology 177 (2016): 111-116.

Gericke, N., and Alvaro M. Viljoen. "Sceletium—a review update." Journal of Ethnopharmacology 119.3 (2008): 653-663.

Gericke, Johané. Evaluating the antidepressant-like properties of Sceletium tortuosum, alone and as adjunctive treatment. Diss. North-West University (South-Africa), 2020.

Louw, Letitia. Investigation into potential endocrine disruptive effects of Sceletium tortuosum. Diss. Stellenbosch: Stellenbosch University, 2018.

Reay, Jonathon, et al. "Sceletium tortuosum (Zembrin®) ameliorates experimentally induced anxiety in healthy volunteers." Human Psychopharmacology: Clinical and Experimental 35.6 (2020): 1-7.

Reay J., Wetherell M.A., Morton E., Lillis J., Badmaev V. Sceletium tortuosum (Zembrin®) ameliorates experimentally induced anxiety in healthy volunteers. Hum. Psychopharmacol. Clin. Exp. 2020;35:1–7. doi: 10.1002/hup.2753. [PubMed] [CrossRef] [Google Scholar]    https://pubmed.ncbi.nlm.nih.gov/32761980/

Schell R. Bachelor’s Thesis. Scripps Colleges; Claremont, CA, USA: 2014. Sceletium tortuosum and Mesembrine: A Potential Alternative Treatment for Depression. [Google Scholar] [Ref list]    

Terburg, David, et al. "Acute effects of Sceletium tortuosum (Zembrin), a dual 5-HT reuptake and PDE4 inhibitor, in the human amygdala and its connection to the hypothalamus." Neuropsychopharmacology 38.13 (2013): 2708-2716.

Van der Walt, S. Development and evaluation of a medicated chewing gum containing Sceletium tortuosum. Diss. North-West University, 2018.

Villarreal M.L., Sharma A., Cardoso-Taketa A., Garcia G. A systematic updated review of scientifically tested selected plants used for anxiety disorders. Bot. Targets. 2012;2:21–39. doi: 10.2147/BTAT.S20593. [CrossRef] [Google Scholar]https://www.tandfonline.com/doi/abs/10.2147/BTAT.S20593

For more detailed information on kanna's safety and how to avoid withdrawals: All You Need to Know About Kanna's Safety, Risks, and Withdrawals

Psychedelics Today interview with Rick Doblin (Ph.D.), founder of MAPS, cited in the podcast: https://psychedelicstoday.com/2024/10/15/the-fda-mdma-and-public-perception-was-the-fda-fair-to-lykos/ October 15 2024.

**Note this was recorded the first week of July before President Biden announced he would not run for re-election. I know that feels like a lifetime ago but just jump in your time machine for a bit at the beginning of the podcast please. We will likely start our next episode on the pharmacology of Kanna with a “catch up” on Kamala Harris v Trump**

Footnotes, References and corrections:

See below to watch the live stream of the FDA advisory panel decision on MDMA Assisted Therapy; a review of the MAPP1 and MAPP2 trial data:

To review the MAPP1 and MAPP2 trials, listen to our first episode here

To read about how the FDA is funded, and what “user fees” are here

To read the open letter from the Heroic Hearts Project (referenced by Chris) on the FDA advisory panel’s decision on veterans mental health, click on this link:

To read a bipartisan letter to President Biden in support of MDMA assisted therapy, click here

To listen to an interview in Psychedelics Today referenced by Colby in the podcast with Dr. Amanda Holley, a regulatory consultant and pharmacologist in non-clinical drug development, click here.

To read about GLP1 compounding regulations, and how big pharma is lying about owning exclusivity to semaglutide and tirzepatide, click here for a statement from the Alliance for Pharmacy Compounding.

FACT CHECKS

—Colby erroneously said the FDA advisory panel reviewed only phase 2 trial data from Lykos; in reality it was phase 3 data from the MAPP1 and MAPP2 trials

—ICER, which is referenced several times in the episode stands for the Institute for Clinical and Economic Review, an organization that discusses the pharmacoeconomic utility of pharmaceutical therapies. Chris claimed they were mostly funded by user fees from manufacturers, similar to the FDA, but ICER claims they receive most funding from non-profit sources, with only 14% from manufacturers. To read more about ICER’s letter in regards to MDMA assisted therapy, review my previous article on the topic here. (Note the Heroic Hearts project uncovered ICER’s potential conflicts of interest not known to me at the time of this publication).

—Not necessarily a fact check, as at the time we recorded our information was correct, but as news moves quickly it has been revealed through toxicology testing that some Diamond Shruumz products do contain psilocybin despite the manufacturers claims they don’t. The FDA possibly didn’t know this either at the time of their original publication. To our listeners, please do not consume any products from this brand, as they have already been associated with 113 illnesses and 2 deaths nationwide.

For more information on Shuna’s work visit:

https://www.shunamorelli.com/

**To learn more about Danielle and the services she provides, go to the Microdosing Humboldt website: https://www.microdosinghumboldt.com/home or follow her on Instagram at: https://www.instagram.com/microdosinghumboldt/ **

Thanks for reading Neural Pharm! Subscribe for free to receive new posts and support my work.

References:

Cassels B, et al. Dark classics in chemical neuroscience: mescaline. ACS Publications. 9 Sept 2018. https://pubs.acs.org/doi/10.1021/acschemneuro.8b00215

Dinis-Oliveira RJ, et al. Pharmacokinetic and pharmacodynamic aspects of peyote and mescaline: clinical and forensic repercussions. 1 Aug 2019. Current Molecular Pharmacology.https://www.ingentaconnect.com/contentone/ben/cmp/2019/00000012/00000003/art00003

Engel L, et al. Mescaline, peyote, and San Pedro: is sustainability important for cacti consumers? 18 Aug 2023. Journal of Psychedelic Studies. https://akjournals.com/view/journals/2054/7/2/article-p135.xml

Jay M. A Century of mescaline. Chacruna. 30 April 2021. https://chacruna.net/century_of_mescaline/

Kolaczynska K, et al. Receptor interaction profiles of 4-alkoxy-3,5-dimethoxy-phenylethylamines (mescaline derivatives) and related amphetamines. Frontiers in Pharmacology. 8 Feb 2022. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.794254/full

Pollan, Michael. This is Your Mind on Plants. 2021. Penguin Press. New York.

Uthang MV, et al. The epidemiology of mescaline use: pattern for use, motivations for consumption, and perceived consequences, benefits, and acute and enduring subjective effects. 5 May 2021. British Association for Psychopharmacology. https://journals.sagepub.com/doi/full/10.1177/02698811211013583

Thanks for reading Neural Pharm! Subscribe for free to receive new posts and support my work.

Footnotes:

—Yes I will acknowledge that I mispronounced “anecdotal” a few times during this interview. For some reason this is always one of those tricky words for me to say, and even past Presidents and Presidential candidates have mispronounced words from time to time. If you want to roast me for it (politely) feel free to leave a comment.

—For reference to the article that Ben Malcolm mentioned in the interview about Ketamine being non-inferior to Electro-Convulsive Therapy (ECT), please see the following article:

Anand A, et al. Ketamine vs ECT for Non-Psychotic Treatment Resistant Major Depression. NEJM. 2023; 388: 2315-2325. https://www.nejm.org/doi/10.1056/NEJMoa2302399

In summary: This study analyzed 405 patients aged 21 to 75 years old with treatment resistant major depression, and randomized patients to either ketamine or ECT. Patients received 0.5 mg/kg twice a week or ECT three times a week over a three week treatment period, and found a response rate of 55% for ketamine vs 41% for ECT. As ECT has often been considered the “gold standard” for resistant depression, this was a major finding. We did not cover this on our previous Ketamine episode but you can listen here for review of this episode.

Thanks for reading Neural Pharm! Subscribe for free to receive new posts and support my work.

References:

Arrone L, et al. Continued Treatment with Tirzepatide for Maintenance of Weight Reduction in Adults with Obesity: the SURMOUNT-4 Randomized Clinical Trial. JAMA. 11 Dec 2023. https://jamanetwork.com/journals/jama/fullarticle/2812936

Attia P and Gifford B. Outlive: The Science & Art of Longevity First edition., Harmony, 2023.

Bliss M. The History of a Wonderful Thing We Call Insulin. American Diabetes Association. 1 July 2019. https://diabetes.org/blog/history-wonderful-thing-we-call-insulin

Hendershot C. Use of GLP-1 Receptor Agonists to Treat Substance and Alcohol Use. University of North Carolina. 5 Dec 2023. https://news.unchealthcare.org/2023/12/use-of-glp-1-receptor-agonists-to-treat-substance-and-alcohol-use-disorders-is-promising-but-premature/.

Jay M. Walmart says users of weight loss drug are buying less food. NBC News. 5 Nov 2023. https://www.nbcnews.com/business/consumer/ozempic-drug-users-are-buying-less-food-walmart-says-rcna119000

Klausen M, et al. The Role of Glucagon Like 1 Peptide (GLP-1) in Addictive Disorders. British Journal of Pharmacology. Feb. 2022. https://pubmed.ncbi.nlm.nih.gov/34532853/

Leslie M. Hot Weight Loss Drugs Tested Against Addiction. Science. Sept 2023. https://www.science.org/content/article/hot-weight-loss-drugs-tested-addiction-treatments

Lingvay I, et al. Efficacy and Safety of Once Weekly Semaglutide versus daily Canagliflozin as add-on to Metformin in Patients with Type 2 Diabetes (SUSTAIN 8)…The Lancet. Nov 2019. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30311-0/fulltext

Mansour N, et al. Effects of Early Adjunctive Pharmacotherapy on Serum Levels of Brain Injury Biomarkers in Patients with Traumatic Brain Injury: A Systematic Review of Randomized Controlled Studies. Frontiers in Pharmacology. 4 May 2023. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1185277/full

Mckenzie H. GLP-1 Drugs Show Promise in Alcohol, Opioid Use Disorders. Biospace. 3 Aug 2023. https://www.biospace.com/article/glp-1-drugs-show-promise-in-alcohol-opioid-use-disorders-/.

Quianzon C, et al. History of Current Non-Insulin Medications for Diabetes Mellitus. Journal of Community Hospital: Internal Medicine Perspectives. 15 Oct 2012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714066/

Reger M, et al. Tramautic Brain Injury and Veteran Mortality After the War in Afghanistan. JAMA. 11 Feb 2022. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788981#:~:text=Estimates%20suggest%20that%20between%209,service%20members%20experienced%20a%20TBI.&text=Complicating%20matters%20further%2C%20many%20veterans,the%20worst%20lifetime%20injury%20sustained

Shevchouck O, at al. An Overview of Appetite-Regulatory Peptides in Addiction Processes: From Bench to Bed Side. Frontiers in Neuroscience. 8 Dec 2021. https://www.frontiersin.org/articles/10.3389/fnins.2021.774050/ful

Ibogaine References:

Alper K, et al. Ibogaine: Scientific Literature Overview. International Center for Ethnobotanical Education. 2012. Available at: chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.iceers.org/Documents_ICEERS_site/Scientific_Papers/ibogaine/ICEERS2012_Ibogaine_literature_compilation.pdf

Corkery JM. Ibogaine as a Treatment for Substance Misuse: Potential Benefits and Practical Dangers. Progress in Brain Research. 2018(242); 217-257. https://www.sciencedirect.com/science/article/abs/pii/S0079612318300979?via%3Dihub

Dalton C. A Detox Drug Promises Miracles if it Doesn’t Kill You First. Wired. 15 Sept 2019. https://www.wired.com/story/a-detox-drug-promises-miraclesif-it-doesnt-kill-you-first/

Davis AK, et al. Subjective Effectiveness of Ibogaine Treatment for Problematic Opioid Consumption: Short and Long Term Outcomes and Current Psychological Functioning. Journal of Psychedelic Studies. 2017. https://akjournals.com/view/journals/2054/1/2/article-p65.xml

Kock P, et al. A Systematic Literature Review of Clinical Trials and Therapeutic Applications of Ibogaine. Journal of Substance Abuse Treatment. 2022. https://www.sciencedirect.com/science/article/pii/S0740547221004438

Mash D. Breaking the Cycle of Opioid Use Disorder. Multi-Disciplinary Association of Psychedelic Studies convention. Presented 22 June 2023. Accessed 17 Dec 2023.

Mash D, et al. Ibogaine Detoxification Transitions Opioid and Cocaine Users between Dependence and Abstinence: Clinical Observations and Treatment Outcomes. Frontiers in Pharmacology. 2018. https://www.frontiersin.org/articles/10.3389/fphar.2018.00529/full

Mash D and Luz M. Evaluating the toxicity and therapeutic potential of ibogaine in the treatment of chronic opioid abuse. Drug Metabolism and Toxicology. 2021. https://www.tandfonline.com/doi/full/10.1080/17425255.2021.1944099

Oaklander M. Inside Ibogaine: One of the most Promising and Perilous Psychedelics for Addiction. Time Magazine. 5 April 2021. https://time.com/5951772/ibogaine-drug-treatment-addiction/

Popik P, et al. Pharmacology of Ibogaine and Ibogaine Related Alkaloids. Progress in Brain Research. 2018.

Siebert A. Kentucky Summit to Explore Ibogaine Treatment for Opioid Use Disorder. Forbes. 17 Nov 2023. https://www.forbes.com/sites/amandasiebert/2023/11/17/kentucky-summit-to-explore-ibogaine-treatment-for-opioid-use-disorder/

GLP-1 references (discussed in intro):

Could Obesity Drugs Take a Bite out of the Food Industry? Morgan Stanley. 5 Sept 2023. https://www.morganstanley.com/ideas/obesity-drugs-food-industry

Lilly’s Zepbound Achieved Additional 6.7% Weight Loss….[press release]. Associated Press. 11 Dec 2023.

Thompson D. The Weight Loss Drug Revolution Part 1. Plain English [podcast], The Ringer podcast network. Aired 12 Dec 2023.

Footnotes:

For more on how to help our nation’s veterans:

https://www.va.gov/REACH/ Veteran crisis line: Dial 988 and press 1. Or text 838255.

Seasonal Affectiveness Disorder. National Institute of Mental Health. https://www.nimh.nih.gov/health/publications/seasonal-affective-disorder

Kentucky Ibogaine Initiative: https://www.kentuckyibogaineinitiative.com/

Huberman, Andrew. Mental Health Toolkit: Tools to bolster your mood and mental health. Huberman Lab [podcast]. 30 Oct 2023

References on Kratom:

FDA and Kratom. https://www.fda.gov/news-events/public-health-focus/fda-and-kratom. 21 July 2023.

Gandhi D, et al. Kratom induced severe cholestatic liver injury histologically mimicking primary biliary cholangitis: a case report. World Journal of Hepatology. 27 Oct 2020; 12(10): 863-869. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643221/

Gianutsos G. The DEA Changes its mind on Kratom. https://www.uspharmacist.com/article/the-dea-changes-its-mind-on-kratom#:~:text=In%20making%20this%20determination%20on,safety%20for%20use%20under%20medical. US Pharmacist. 17 March 2017

Happy Hippo. https://happyhippo.com/blogs/kratom-blog/the-benefits-of-agmatine-sulfate-as-a-kratom-potentiator

Jentsch MJ, Pippin MM. Kratom. Stat Pearls. 28 August 2023. https://www.ncbi.nlm.nih.gov/books/NBK585120/

Kratom. Natural Medicines Comprehensive Database. Updated 6 June 2023.

Kratom. California Poison Control System. 22 June 2016.

Rexer B. Is Kratom legal? Kratom legality by state. Sprout Health Group. https://www.sprouthealthgroup.com/substances/is-kratom-legal-by-state/

Settle A and Yang C. A Case of Severe Kratom Addiction Contributing to a Suicide Attempt. Cureus. 2022 Sept; 14(9): e29698. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616552/

Ya K, et al. Pharmacokinetics of mitragynine, a major analgesic alkaloid in kratom: a systematic review. 2019(43): 73-82. https://www.sciencedirect.com/science/article/abs/pii/S1876201819302114