Health Effects & Risks of Kratom, Opioids & Other Natural Occurring Medicines | Dr. Chris McCurdy

Episode 238 Jul 21, 2025 Episode Page ↗
Overview

Dr. Chris McCurdy, Professor of Medicinal Chemistry at the University of Florida, explores kratom's complex pharmacology, stimulant and opioid-like effects, and addiction potential. The discussion contrasts traditional uses with concentrated products, emphasizing safety and nuanced effects of plant compounds.

At a Glance
12 Insights
2h 44m Duration
20 Topics
6 Concepts

Deep Dive Analysis

Kratom's Origin, Traditional Use, and Dose-Dependent Effects

Traditional Kratom vs. Commercial Products & Absorption Differences

Kratom Product Types, Serving Sizes, and Label Understanding

Kratom Usage Patterns, Desired Effects, and Physical Dependence

Alkaloid Compounds: Definition, Examples, and Biological Interaction

Evolution of Medicine from Natural Products and Plant Alkaloids

Kratom Leaf vs. Extracts/Isolates: Potency and Risks

Kratom Use in Young People and Developing Brains

Kratom for Energy, Mood, and Pain Management: Tolerance Development

Respiratory Depression Risk with 7-Hydroxy Mitragynine Products

FDA Regulations and Advocacy for Kratom Product Guidelines

Kratom and Alcohol Consumption: Interaction and Harm Reduction

Kratom Alkaloids: Multiple Pathways for Mood, Stimulant, and Pain Relief

Plant Alkaloids as Chemical Defense and Antifungal Agents

White, Red, and Brown Vein Kratom: Marketing vs. Chemical Reality

Kratom as an Antidepressant and Discontinuing Use

Kratom, Drug Interactions, and Seizure Risk

Cacao Beans, Chocolate, and Theobromine Benefits

Coca-Cola, Coca Plant, and the History of Soft Drinks

Career Journey in Medicinal Chemistry and Natural Products Research

Alkaloid

An organic molecule characterized by having at least one nitrogen atom in its structure. This nitrogen allows it to act as a base, accept a proton, and develop a positive charge, which is crucial for interacting with negatively charged sites on proteins in the body, like a 'tractor beam' finding its target.

7-hydroxy mitragynine

A metabolite of mitragynine, the major alkaloid in kratom. While mitragynine has weak opioid receptor affinity and interacts with other systems, 7-hydroxy mitragynine is a pure opioid in its activity, interacting only with opioid receptors and causing respiratory depression equivalent to other opioids.

Kratom-derived/isolate products

These are commercial products where the active compounds, particularly 7-hydroxy mitragynine, have been extracted, concentrated, or even semi-synthetically produced from the kratom leaf. Unlike traditional leaf products, these are much more potent and can lead to faster absorption and significantly greater exposure to opioid-like effects.

Pharmacological Shotgun (Kratom)

A metaphor describing kratom's complex action due to its multiple alkaloids. These alkaloids target different systems in the body simultaneously, including opioid receptors, serotonergic systems (mood, satiety), and adrenergic receptors (stimulant, fight-or-flight). This multi-pronged approach may contribute to its reported pain relief and mood elevation with potentially less intense individual receptor activation.

Chemical Defense (Plants)

Plants produce various chemical compounds, such as alkaloids, not for human benefit but as a defense mechanism. In the case of kratom, its alkaloids are potent antifungal agents, helping the tree survive and thrive in hot, humid, swampy environments where fungal growth is prevalent.

Xanthine Alkaloid

A class of alkaloids that includes compounds like caffeine and theobromine (found in cacao). These molecules are structurally related, with caffeine being 'fully methylated' and theobromine missing one of those methyl groups, leading to similar but distinct stimulant and physiological effects.

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What is kratom and where does it come from?

Kratom (Mitragyna speciosa) is a tree native to Southeast Asia, particularly Malaysia and Thailand. Traditionally, laborers chew its fresh leaves or brew a tea for energy, stamina, mood elevation, and pain relief.

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How do traditional kratom use and commercial kratom products differ?

Traditional use involves fresh leaves, while commercial products in the Western world use dried, ground leaf material, concentrates, or extracts. Concentrates and extracts allow for much faster absorption of compounds, changing the physiological dynamics compared to traditional leaf consumption.

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What are the primary reasons people in the U.S. use kratom?

Most users in the U.S. report using kratom for energy, mood elevation, and pain treatment, often as an alternative to opioids. Some also use it as a pre-workout stimulant or post-workout pain treatment, with a smaller population seeking euphoric or sedative effects.

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Does kratom cause physical dependence?

Yes, regular utilization of kratom over time can cause physical dependence. Symptoms can range from mild headaches and lethargy, similar to caffeine withdrawal, to more severe signs like restless leg syndrome, especially with higher doses or concentrated products.

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Is it safe for children or young adults to consume kratom products?

No, it is not recommended for individuals under 24-25 years old due to ongoing brain development. There is no data on kratom's impact on developing brains, and the risk of accidental overconsumption or problematic use is higher in younger populations.

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Can kratom products cause respiratory depression similar to opioids?

While traditional kratom leaf is generally believed to cause less respiratory depression than clinical opioids, products containing isolated or semi-synthetic 7-hydroxy mitragynine have been shown in animal studies to cause respiratory depression equivalent to opioids, and this effect is reversible with naloxone.

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What are the risks of combining kratom with alcohol?

There are no definitive studies on combining kratom with alcohol. However, there are ongoing studies investigating kratom as a harm reduction agent for alcohol use disorder, with anecdotal reports suggesting it may reduce alcohol consumption or interest in drinking.

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How can someone get off kratom if they are dependent?

Currently, medical practitioners often use opioid use disorder treatments like buprenorphine or methadone to help individuals get off kratom. However, due to kratom's complex pharmacology (involving opioid, serotonergic, and adrenergic systems), these treatments may only address part of the dependency, and medical professional help is strongly advised.

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Is there a significant difference between 'white vein,' 'red vein,' and 'brown vein' kratom products?

Most of the differentiation between 'vein' colors (white, red, brown, green, yellow) is marketing, related to how the leaves are cured or dried. While the appearance may change, analysis of alkaloid content shows they are very similar, suggesting effects may be more related to product type or placebo than inherent differences in leaf composition.

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Did Coca-Cola ever contain cocaine, and what is its connection to the coca plant today?

Yes, Coca-Cola's original formula contained cocaine. As cocaine became problematic, the company removed the cocaine alkaloids but retained a de-cocainized coca leaf extract for flavor. To this day, Coca-Cola is a major importer of coca leaves, with the cocaine being extracted and used pharmaceutically, and the remaining extract used as a flavoring agent in Coca-Cola Classic and Coke Zero.

1. Avoid 7-Hydroxy Kratom Isolates

Strictly avoid Kratom products labeled as ‘7-hydroxy mitragynine,’ ‘kratom derived,’ or ‘isolates.’ Research indicates these semi-synthetic compounds can cause respiratory depression equivalent to opioids, posing a significant risk to public safety.

2. No Kratom for Young Brains

Individuals under 24-25 years old should avoid Kratom products entirely, as their brains are still developing. The long-term impact of Kratom on brain development is unknown, and psychoactive substances can slow development and potentially lower IQ.

3. Check Kratom Serving Size

Always carefully check the serving size and total servings per container for any Kratom product. Highly concentrated products, especially liquids, can lead to much greater and faster exposure to compounds, increasing the risk of adverse effects if multiple servings are consumed at once.

4. Distinguish Kratom Product Forms

Understand the difference between traditional Kratom leaf material, concentrates/extracts, and isolates/derivatives. Leaf material is closer to traditional use, while concentrates and isolates (like 7-hydroxy mitragynine) are significantly more potent and carry higher risks due to faster absorption and increased compound exposure.

5. Seek Professional Help for Kratom Withdrawal

If experiencing Kratom dependence or withdrawal, seek professional medical help. While opioid use disorder treatments like buprenorphine or Suboxone may be used, the complex pharmacology of Kratom means these might not address all aspects of dependence, and supportive treatment like counseling is also crucial.

6. Kratom: Less Is More

For those using Kratom leaf products, a common user recommendation is ’less is more.’ Lower amounts are often reported to provide more benefit (e.g., mood elevation, energy) without pushing towards sedative or euphoric effects, and may help manage tolerance.

7. Kratom Tolerance Development

Be aware that tolerance can develop to Kratom’s pain-relieving properties, leading users to take more to achieve the same effect. Increasing dosage heightens the risk of problems, including potential off-target effects.

8. Kratom for Opioid Transition

Kratom has shown effectiveness in helping some individuals transition off traditional opioid drugs and manage withdrawal symptoms, providing energy and improving mood. This should ideally be done under medical supervision due to the complexities of dependence and potential risks.

9. Kratom for Energy & Pain

Many users responsibly utilize Kratom leaf for energy, mood elevation, and pain treatment, often as an alternative to opioids. It can also be used as a pre-workout stimulant for endurance or a post-workout treatment for muscle pain.

10. Kratom Vein Colors: Marketing

The marketing terms ‘white vein,’ ‘red vein,’ ‘green vein,’ etc., for Kratom products primarily relate to how the leaves were cured or dried, not significant differences in alkaloid content. The perceived differences in effects may largely be a placebo effect.

11. Responsible Cacao Consumption

Raw cacao beans and 100% chocolate offer health benefits due to polyphenols and alkaloids like theobromine, which can provide subtle stimulation and mood lift. Ensure products are from a clean, ethically sourced origin to avoid heavy metals and support fair labor practices, and consume in moderation.

12. Coke Syrup for Nausea

Coca-Cola syrup (without carbonation) has historically been used in pharmacies as a safe and effective remedy for nausea and vomiting, particularly for pregnant women, due to its ability to calm and settle the GI tract, a benefit also reported with traditional coca tea.

The poison is in the dose.

Chris McCurdy

Mitriganin does not equal kratom. Kratom is a complex natural product with all these other alkaloids in it.

Chris McCurdy

I look at this plant as almost a pharmaceutical shotgun. It's got different alkaloids that are targeting different systems in our body.

Chris McCurdy

If it walks like a duck, if it quacks like a duck, if it looks like a duck, it's a duck.

Chris McCurdy

We've lost totally in our culture where it is that medicines have come from.

Chris McCurdy

The best recommendations are, in my opinion, getting all the way up to that 24, 25, but I would be okay with people saying 18 or 21 because that seems to be more acceptable in society as to where we've set barriers in historical precedent.

Chris McCurdy
250,000
Estimated number of kratom farmers in Indonesia As of a year ago, producing and exporting raw materials globally, primarily to the United States.
Over 20 million
Estimated number of daily kratom users in the United States Based on product sales and import data, significantly higher than earlier literature reports of 2-2.5 million users.
1,950 metric tons
Metric tons of kratom imported to the U.S. per month Solid data from 2019.
75%
Percentage of FDA-approved medications derived from natural products Either discovered because of a natural product or modified natural products.
20 to 40
Number of alkaloids in kratom Mitragynine is the major alkaloid.
Almost 10%
Percentage of kratom research papers from Dr. McCurdy's lab Out of nearly 1,000 papers in PubMed on kratom.
18 or 21 (ideally 24-25)
Recommended minimum age for kratom use Due to ongoing brain development and higher risk in young people.