Kratom、阿片类药物及其他天然药物的健康影响与风险 | Dr. Chris McCurdy

卡痛、阿片类药物及其他植物源性药物的健康影响与风险

摘要

佛罗里达大学药物化学教授 Chris McCurdy 博士与 Andrew Huberman 就卡痛（Mitragyna speciosa，又称帽柱木）的复杂药理学展开深入讨论。卡痛是一种东南亚植物，数百年来被用作兴奋剂、止痛药和情绪提升剂。对话涵盖了卡痛的剂量依赖性效应、其与阿片类系统的关系、传统叶制品与现代浓缩提取物/分离物之间的关键差异，以及其在应对阿片类药物成瘾方面的潜在作用——同时也探讨了严重风险，尤其是对年轻人以及使用高度加工形式产品的人群。

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核心要点

• 并非所有卡痛产品都相同：传统叶制品、浓缩提取物和半合成分离物的效力与风险差异悬殊——然而它们都以”卡痛”的名称销售。
• 份量至关重要：许多卡痛产品每瓶含有多个服用份量；饮用整瓶可能摄入远超预期的剂量，对浓缩产品尤为如此。
• 卡痛衍生分离物（如7-羟基帽柱木碱）的作用类似纯阿片类药物，动物研究表明其可引起与传统阿片类药物相当的呼吸抑制——可通过纳洛酮逆转。
• 调查显示，大多数使用者并非为了获得快感：最大规模的用户调查显示，人们使用卡痛主要是为了提振精力、改善情绪和管理疼痛。
• 长期使用卡痛会产生躯体依赖，戒断症状从类似咖啡因戒断（头痛、疲劳）到类似阿片类药物戒断症状（不宁腿综合征）不等，具体取决于产品类型和剂量。
• 卡痛对阿片类药物使用者已显示出实际益处：许多人报告成功借助卡痛叶制品戒除阿片类药物，并表示精力和生活质量得到恢复。
• 18至25岁以下人群应避免使用卡痛：发育中的大脑对精神活性物质较为脆弱，目前尚无卡痛对大脑发育影响的相关数据。
• 经验丰富的叶制品使用者信奉”少即是多”：使用叶基卡痛的常规用户报告在较低剂量下获益更大，而非剂量越高越好。
• 毒性取决于剂量，也取决于形式：传统全叶使用与分离生物碱有本质区别——正如古柯叶与可卡因的区别，或罂粟与吗啡的区别。

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详细笔记

什么是卡痛？

• 植物学名：Mitragyna speciosa；原产于马来西亚半岛与泰国交界地区的一种树木
• 主要在印度尼西亚种植和出口（约25万农户），大量进口至美国
• 估计在美国有超过2000万日常使用者（基于进口量数据；官方调查估计较低，约为200至250万人，但普遍认为存在严重低估）
• 在超市、加油站、便利店和网络平台有售——常以小字印刷出现在功能饮料风格的产品上

传统用途与现代产品

传统用法（东南亚）：

• 直接咀嚼新鲜叶片，或长时间煎煮成浸液（茶）
• 户外劳动者用于提振精力、增强体力、耐热、缓解疼痛和促进社交
• 傍晚较大量饮用可产生更强的镇静/欣快效果
• 历史上也用于缓解海洛因/鸦片戒断症状

现代西方产品：

• 干燥运输的叶料——研磨成粉末、装入胶囊或泡制成茶（最接近传统用法）
• 浓缩提取物：通过溶剂或液体预先提取生物碱；吸收速度更快，暴露量更高
• 分离物/半合成物：由卡痛生物碱化学改造而来；已无法追溯至植物本身；作用等同于纯阿片类药物

类比说明：传统叶制品 ≈ 淡啤酒；浓缩提取物 ≈ 烈酒；分离物 ≈ 190度Everclear高度酒

卡痛的活性成分（生物碱）

• 卡痛含有20至40种生物碱——多样化的化学”散弹枪”，同时作用于多个受体系统
• 帽柱木碱（Mitragynine）：叶片中含量最丰富的生物碱
• 7-羟基帽柱木碱（7-OH）：帽柱木碱在体内的代谢产物；可能并非由植物本身合成（未发现相应生物合成酶）
  • 作为纯阿片受体激动剂发挥作用
  • 目前已被化学合成并作为”卡痛衍生”产品商业销售
  • 动物数据显示其可引起与阿片类药物相当的呼吸抑制，可通过纳洛酮/Narcan完全逆转
• 生物碱的定义为含氮有机分子；氮的存在使其能够与体内蛋白质受体发生静电结合

剂量依赖性效应

剂量水平	主要效应
低剂量	兴奋、提振精力、增强专注、轻度情绪提升
中等剂量	情绪提升、轻度镇痛、促进社交
高剂量	欣快感、镇静、类阿片效应

谁在使用卡痛？为何使用？

基于与 Johns Hopkins 大学 Kirsten Smith 博士合作开展的生态瞬时评估（EMA）研究：

• 大多数使用者负责任且有目的地使用卡痛，主要目的并非为了获得快感
• 最常见用途：
  1. 提振精力（最常见）
  2. 改善情绪
  3. 疼痛管理（包括运动后恢复）
  4. 阿片类药物替代或戒断管理
  5. 运动前增强耐力
• 少数人使用是为了欣快/娱乐目的，通常使用较浓缩的产品
• 使用叶基产品的用户通常在醒来后30分钟内服用

躯体依赖与成瘾风险

• 单次使用：不会引起躯体依赖
• 长期使用：会引起躯体依赖；具体时间线尚未在受控的人体或动物试验中进行研究
• 叶基依赖：类似咖啡因戒断——头痛、精力低下、易激惹
• 高剂量/提取物依赖：可出现不宁腿综合征，戒断反应更为严重——类似阿片类药物戒断
• 对镇痛效果的耐受性随时间增加，导致使用者逐渐提高剂量
• 一款产品（小蓝瓶，含卡瓦和卡痛）被提及有用户从每天1瓶升至每天6瓶的逸事报告

卡痛与阿片类药物危机

• 东南亚传统使用者历史上在无法获得海洛因/鸦片时会增加卡痛茶的饮用量，以预防戒断反应
• McCurdy 博士的实验室研究卡痛帮助人们戒除阿片类药物的潜力
• 许多使用者报告卡痛让他们”从沙发上站了起来”——恢复了被阿片类药物摧毁的精力、家庭生活和社会功能
• 卡痛叶与多个受体系统相互作用（并非仅限于阿片受体），这使其有别于经典阿片类药物
• 然而纯7-OH分离物仅与阿片受体相互作用，携带与阿片类药物同等的风险，包括呼吸抑制

风险与安全注意事项

年轻人（18至25岁以下）：

• 大脑发育持续至约24至25岁
• 尚无卡痛对发育中大脑影响的研究
• McCurdy 博士建议至少等到18至21岁后再使用；个人倡议等到24至25岁
• 与大麻研究相呼应——早期使用大麻已被证实会导致智商降低和大脑发育迟缓

标签误导与产品混淆：

• 仅标注”卡痛”的产品可能含有叶制品、提取物、浓缩物或半合成分离物
• 消费者和急诊科医生往往无法区分不同产品类型
• 儿童可能将卡痛功能饮料误认为普通能量饮料而无意中摄入

任何卡痛产品使用者的关键安全准则：

1. 查看每份用量——切勿假设一瓶等于一份
2. 留意标签上的”卡痛衍生”或”卡痛分离物”字样——这些功能上不同且风险更高
3. 优先选择全叶或最低程度加工的粉末，而非提取物或分离物
4. 使用最低有效剂量；经验丰富的使用者反映”少即是多”

更广泛的背景：植物、生物碱与医学

• 约75%的FDA批准药物是从天然产物中发现或在天然产物基础上改造而来
• 讨论举例：
  • 阿司匹林 → 源自柳树皮中的水杨苷

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English Original 英文原文

Health Effects & Risks of Kratom, Opioids & Other Plant-Derived Medicines

Summary

Dr. Chris McCurdy, professor of medicinal chemistry at the University of Florida, joins Andrew Huberman to discuss the complex pharmacology of kratom (Mitragyna speciosa), a Southeast Asian plant used for centuries as a stimulant, pain reliever, and mood elevator. The conversation covers kratom’s dose-dependent effects, its relationship to the opioid system, the critical differences between traditional leaf products and modern concentrated extracts/isolates, and its potential role in addressing opioid addiction — alongside serious risks, particularly for young people and those using highly processed forms.

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Key Takeaways

• Not all kratom products are the same: Traditional leaf products, concentrated extracts, and semi-synthetic isolates have vastly different potency and risk profiles — yet all are sold under the same “kratom” label.
• Serving size is critical: Many kratom products contain multiple servings per bottle; consuming an entire bottle can deliver far more than intended, especially with concentrated products.
• Kratom-derived isolates (e.g., 7-hydroxymitragynine) behave like pure opioids and have been shown in animal studies to cause respiratory depression equivalent to traditional opioids — reversible with naloxone.
• Most surveyed users are NOT taking kratom to get high: The largest user surveys show people primarily use it for energy, mood elevation, and pain management.
• Kratom causes physical dependence with chronic use, ranging from caffeine-like withdrawal (headaches, fatigue) to opioid-like symptoms (restless leg syndrome) depending on the product and dose.
• Kratom has shown real-world benefit for opioid users: Many people report successfully transitioning off opioids using kratom leaf products, reporting restored energy and quality of life.
• Kratom should be avoided by those under 18–25: The developing brain is vulnerable to psychoactive substances; no data exists on kratom’s impact on brain development.
• “Less is more” among experienced leaf users: Regular users of leaf-based kratom report greater benefit at lower doses, not higher ones.
• The poison is in the dose AND the form: Traditional whole-leaf use is fundamentally different from isolated alkaloids — paralleling how coca leaf differs from cocaine, or opium poppy differs from morphine.

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Detailed Notes

What Is Kratom?

• Botanical name: Mitragyna speciosa; a tree native to the border region of Peninsula Malaysia and Thailand
• Primarily grown and exported from Indonesia (~250,000 farmers); imported heavily to the United States
• Estimated 20+ million daily users in the US (based on import volume data; official survey estimates are lower at ~2–2.5 million, but considered a significant undercount)
• Sold in supermarkets, gas stations, convenience stores, and online — often in fine print on energy shot-style products

Traditional Use vs. Modern Products

Traditional use (Southeast Asia):

• Fresh leaves chewed directly or boiled into a decoction (tea) for hours
• Used by outdoor laborers for energy, stamina, heat tolerance, pain relief, and social lubrication
• Higher evening consumption produced more sedative/euphoric effects
• Also used historically to stave off heroin/opium withdrawal symptoms

Modern Western products:

• Dried, shipped leaf material — ground into powder, packed into capsules, or brewed as tea (closest to traditional use)
• Concentrated extracts: Alkaloids pre-extracted by a solvent or liquid; absorbed much faster, delivering higher exposure
• Isolates / semi-synthetics: Chemically modified compounds derived from kratom alkaloids; no longer traceable to the plant; behave as pure opioids

Analogy used: Traditional leaf ≈ light beer; concentrated extract ≈ spirits; isolate ≈ 190-proof Everclear

Kratom’s Active Compounds (Alkaloids)

• Kratom contains 20–40 alkaloids — a diverse chemical “shotgun” targeting multiple receptor systems simultaneously
• Mitragynine: The most abundant alkaloid in the leaf
• 7-Hydroxymitragynine (7-OH): A metabolite of mitragynine produced in the body; likely not synthesized by the plant itself (no biosynthetic enzymes found)
  • Acts as a pure opioid agonist
  • Now being chemically synthesized and sold commercially as “kratom-derived” products
  • Animal data shows respiratory depression equivalent to opioids, fully reversible with naloxone/Narcan
• An alkaloid is defined as an organic molecule containing nitrogen; the nitrogen enables electrostatic binding to protein receptors in the body

Dose-Dependent Effects

Dose Level	Primary Effects
Low dose	Stimulant, energy boost, focus, mild mood elevation
Moderate dose	Mood elevation, mild analgesia, social lubrication
High dose	Euphoria, sedation, opioid-like effects

Who Is Using Kratom and Why?

Based on Ecological Momentary Assessment (EMA) studies conducted with Dr. Kirsten Smith at Johns Hopkins:

• Most users take kratom responsibly and purposefully, not primarily to get high
• Top reported uses:
  1. Energy (most common)
  2. Mood elevation
  3. Pain management (including post-workout recovery)
  4. Opioid substitution or withdrawal management
  5. Pre-workout endurance enhancement
• A subset uses it for euphoric/recreational effects, typically with more concentrated products
• Users taking leaf-based products typically dose within the first 30 minutes of waking

Physical Dependence and Addiction Risk

• Single use: Does not cause physical dependence
• Chronic use: Causes physical dependence; timeline varies and has not been studied in controlled human or animal trials
• Leaf-based dependence: Resembles caffeine withdrawal — headaches, low energy, irritability
• Higher-dose/extract dependence: Can include restless leg syndrome, more severe withdrawal — resembling opioid withdrawal
• Tolerance to pain-relieving effects develops over time, leading users to escalate dose
• The product in question (small blue bottle, kava + kratom) was noted anecdotally to escalate from 1 bottle/day to 6 bottles/day in one user

Kratom and the Opioid Crisis

• Traditional users in Southeast Asia historically increased kratom tea consumption when heroin/opium was unavailable to prevent withdrawal
• Dr. McCurdy’s lab studies kratom’s potential to help people transition off opioids
• Many users report that kratom “got them off the couch” — restored energy, family life, and functioning that opioids had destroyed
• Kratom leaf interacts with multiple receptor systems (not exclusively opioid), which distinguishes it from classical opioids
• Pure 7-OH isolates, however, interact only with opioid receptors and carry opioid-equivalent risks including respiratory depression

Risks and Safety Concerns

Young people (under 18–25):

• Brain development continues until approximately age 24–25
• No studies on kratom’s effect on the developing brain
• Dr. McCurdy recommends avoiding use until at least 18–21; personally advocates for 24–25
• Parallels drawn to cannabis research showing reduced IQ and slowed brain development with early use

Mislabeling and product confusion:

• Products labeled simply as “kratom” may contain leaf, extract, concentrate, or semi-synthetic isolates
• Consumers and emergency room physicians often cannot distinguish between product types
• Kids may inadvertently pick up kratom energy shots mistaking them for conventional energy products

Key safety rules for anyone using kratom products:

1. Check serving size — never assume one bottle = one serving
2. Look for “kratom-derived” or “kratom isolate” language on labels — these are functionally different and higher-risk products
3. Prefer whole-leaf or minimally processed powder over extracts or isolates
4. Use the lowest effective dose; experienced users report “less is more”

Broader Context: Plants, Alkaloids, and Medicine

• ~75% of FDA-approved drugs were discovered from or modified from natural products
• Examples discussed:
  • Aspirin → from salicin in willow bark