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

The plant’s effects are dose-dependent, with lower doses producing stimulant-like effects that enhance focus and energy, while higher doses induce sedative, euphoric, and opioid-like effects. Kratom has also been used traditionally for pain relief and even as a natural aphrodisiac, though the exact mechanisms behind these effects are complex and multifaceted. Dr. McCurdy emphasizes that the traditional use involves fresh or freshly dried leaves, which contrasts sharply with many of the processed kratom products now widely available in the United States and other Western countries.

Differences Between Traditional Kratom and Western Products

One of the critical distinctions Dr. McCurdy highlights is the difference between traditional kratom use and the forms commonly found in the U.S. market. Traditional use involves fresh or minimally processed leaves, often chewed or brewed into tea, which results in a slow and less efficient extraction of active compounds. In contrast, Western products typically consist of dried, powdered leaves that have been shipped long distances and often further processed into capsules, extracts, or concentrated tonics.

These processed products vary widely in concentration and bioavailability. Extracts and isolates, which are more potent and rapidly absorbed, can produce effects that differ significantly from those of the traditional leaf. This variability has led to confusion and, in some cases, harm among consumers who may not be aware of the differences in potency or the presence of isolated alkaloids. Dr. McCurdy draws an analogy to the alcohol industry, where beverages range from light beers to nearly pure ethanol, each with distinct effects and risks, yet all are broadly labeled as “alcohol.” He argues that kratom products require similar nuanced classification and regulation to ensure consumer safety.

Patterns of Kratom Use in the United States

Dr. McCurdy and his colleagues have conducted extensive surveys and ecological momentary assessments to understand how kratom is used in the U.S. Contrary to some public perceptions, the majority of users reportedly consume kratom responsibly and primarily for functional benefits rather than to achieve a “high.” The most common reasons for use include energy enhancement, mood elevation, and pain management. Many users liken kratom’s stimulant effects at low doses to caffeine, using it as a pre-workout supplement or a daily mood booster.

However, there is also a subset of users who seek the euphoric, sedative effects of higher doses or more concentrated products. This group often uses kratom recreationally, sometimes on weekends or social occasions. Additionally, a significant population uses kratom as a harm reduction tool to manage opioid withdrawal or to reduce opioid dependence. Dr. McCurdy notes that while anecdotal reports suggest kratom can help people transition off opioids, the scientific evidence remains preliminary, and the complexity of kratom’s pharmacology complicates treatment approaches.

Alkaloids in Kratom and Their Pharmacology

Kratom contains a complex mixture of 20 to 40 alkaloids, organic nitrogen-containing compounds that interact with various receptors in the nervous system. Dr. McCurdy explains that alkaloids are a broad class of molecules that include well-known substances such as caffeine, morphine, nicotine, and cocaine. The presence of nitrogen atoms in these molecules allows them to bind selectively to proteins, such as neurotransmitter receptors, through charge interactions, much like a “tractor beam” that facilitates specific biological effects.

The major alkaloid in kratom, mitragynine, has weak affinity for opioid receptors but also interacts with serotonin and adrenergic systems, contributing to its complex effects. Other alkaloids in the plant modulate serotonin pathways, which influence mood and pain perception, and adrenergic receptors, which are involved in stimulant and fight-or-flight responses. This multi-target pharmacology may explain why kratom can simultaneously produce stimulant, analgesic, and mood-elevating effects, making it unique compared to conventional single-target pharmaceuticals.

Risks of Kratom: Dependence, Addiction, and Withdrawal

Despite its potential benefits, kratom carries risks, particularly related to physical dependence and addiction. Dr. McCurdy emphasizes that while a single use is unlikely to cause dependence, chronic use can lead to withdrawal symptoms similar to those seen with caffeine or opioids, including headaches, anxiety, and restlessness. The severity of withdrawal appears to vary depending on the dose, duration of use, and the specific kratom product consumed.

Medical professionals have reported an increasing number of patients seeking treatment to discontinue kratom use, often requiring opioid replacement therapies such as buprenorphine or methadone. However, because kratom’s pharmacology involves multiple neurotransmitter systems beyond opioids, these treatments may not fully address all withdrawal symptoms. This complexity underscores the need for more research into effective treatment protocols for kratom dependence and highlights the importance of cautious use, especially with highly concentrated or isolated kratom products.

Kratom’s Relationship to the Opioid System and Respiratory Effects

Kratom’s interaction with the opioid system is nuanced. While mitragynine and its metabolite 7-hydroxymitragynine bind to opioid receptors, their effects differ from classical opioids like morphine. The metabolite 7-hydroxymitragynine, which is sometimes chemically synthesized and sold as an isolate, exhibits potent opioid activity and can cause respiratory depression comparable to traditional opioids in animal models. This raises significant safety concerns, especially since these isolates are often marketed without clear labeling or dosage guidelines.

In contrast, traditional kratom leaf products appear to have a much lower risk of respiratory depression, a major cause of death in opioid overdoses. However, the lack of comprehensive human studies means that the full respiratory risk profile of kratom remains uncertain. Dr. McCurdy stresses the importance of distinguishing between whole leaf products and concentrated or synthetic derivatives when assessing safety and regulatory policies.

Age Restrictions and Recommendations for Kratom Use

Given the developing brain’s vulnerability to psychoactive substances, Dr. McCurdy advises that kratom use should be restricted to adults, ideally those over 21 or even 24 to 25 years old, aligning with the age at which the prefrontal cortex fully matures. There is little evidence of traditional kratom use among youth in Southeast Asia, and the potential risks to brain development in younger individuals are unknown but likely significant.

For adults using kratom primarily for stimulant-like effects, responsible use at low doses may resemble caffeine consumption, with mild withdrawal symptoms upon cessation. However, the risk of dependence and adverse effects increases with higher doses and more potent products. Dr. McCurdy advocates for clear labeling, education, and regulation to protect vulnerable populations, especially young people who may be unaware of the risks associated with kratom.

Kratom’s Potential Role in Pain Management and Mood Elevation

Kratom’s unique pharmacological profile, targeting opioid, serotonin, and adrenergic systems simultaneously, offers a novel approach to pain management and mood enhancement. Unlike conventional painkillers that focus on a single receptor, kratom’s multi-target effects may provide effective analgesia with potentially fewer side effects or lower doses of each active compound. Many users report significant pain relief and mood elevation without intense psychoactive effects, suggesting a therapeutic window that could be harnessed clinically.

The mood-enhancing properties of kratom, possibly mediated through serotonin pathways, also warrant further investigation as potential antidepressant effects. While anecdotal evidence is promising, rigorous clinical trials are needed to establish efficacy, safety, and appropriate dosing. Dr. McCurdy highlights the importance of understanding the full spectrum of kratom’s alkaloids and their interactions to develop safer and more effective treatments derived from this plant.

Broader Context of Natural Products in Medicine

Dr. McCurdy situates kratom within the broader historical and scientific context of natural products as sources of medicine. He notes that approximately 75% of FDA-approved drugs are derived from or inspired by natural compounds, including aspirin from willow bark, metformin from plant alkaloids, and GLP-1 analogs from the saliva of the Gila monster. This rich tradition underscores the value of studying plants like kratom for novel therapeutic agents.

He also discusses parallels with other plant-derived substances such as cocoa and coca leaves. While cocaine, an alkaloid from coca, is highly addictive and harmful, the whole coca leaf has nutritional and mild stimulant properties and is still used traditionally in South America. Similarly, cocoa contains theobromine, a mild stimulant related to caffeine, and other compounds that may support mood and cardiovascular health. These examples illustrate the complexity of natural products and the importance of considering whole-plant effects versus isolated compounds.

The History and Chemistry of Soft Drinks and Plant Alkaloids

An intriguing part of the discussion focuses on the origins of popular soft drinks like Coca-Cola, Pepsi, and 7Up, which were initially developed as medicinal tonics containing plant alkaloids. Coca-Cola famously included coca leaf extract, which contained cocaine until it was removed due to safety concerns. However, the decocainized coca leaf extract remains a key flavoring ingredient, highlighting the enduring presence of natural products in everyday consumables.

Similarly, 7Up once contained lithium, a mood-stabilizing agent, and Pepsi included digestive enzymes. These historical facts reveal how plant-derived compounds have long been integrated into consumer products for their pharmacological effects, often before their risks and benefits were fully understood. Dr. McCurdy’s recounting of this history emphasizes the ongoing interplay between natural products, medicine, and culture.

Challenges and Future Directions in Kratom Research and Regulation

Dr. McCurdy concludes by addressing the challenges facing kratom research and regulation. The wide variability in product types, concentrations, and user intentions complicates scientific study and public health responses. Advocacy groups are pushing for clearer labeling, quality control, and age restrictions, but regulatory agencies like the FDA face legal and practical hurdles, especially given kratom’s status as a dietary supplement and the presence of synthetic derivatives.

He stresses the urgent need for more rigorous clinical trials, toxicology studies, and pharmacological investigations to delineate kratom’s benefits and risks accurately. Understanding how to treat kratom dependence effectively and how to harness its therapeutic potential without exacerbating addiction issues remains a priority.