Kratom, also known as Mitragyna speciosa, is a tree that grows in Southeast Asia, mainly in Malaysia and Thailand. People have used its leaves for a long time because they can boost energy, relieve pain, and create effects similar to opioids. The main reasons for these effects are special chemicals in the leaves called alkaloids, with two being the most important: mitragynine and 7-hydroxymitragynine. Knowing about these two alkaloids helps us better understand how kratom works and what it does in the human body.
Although mitragynine and 7-hydroxymitragynine are often mentioned together, they each work in slightly different ways. Mitragynine is found in the largest amount and is the main alkaloid in kratom. 7-hydroxymitragynine is found in much lower amounts but is much stronger. In this article, we’ll explain what these two alkaloids are, how much of them is in kratom, what effects they have, and how they interact in the body.
What Are Kratom Alkaloids?
Kratom alkaloids are chemicals that naturally occur in the leaves of the Mitragyna speciosa tree. They’re thought to be the main reason kratom affects the mind and body. People have used kratom by chewing the leaves or making tea, which lets these alkaloids enter the body and interact with different parts of the brain and nervous system.
Interest in kratom’s alkaloids has grown, especially as more people use kratom in places like the United States. Scientists are studying these compounds to see how they work, their possible medical uses, and to help make decisions about kratom’s regulation.
How Many Alkaloids Does Kratom Contain?
Kratom is a complex plant, with about 45 different alkaloids found so far. This mix is responsible for the wide range of effects people report. Besides mitragynine and 7-hydroxymitragynine, other main alkaloids include speciogynine, speciociliatine, and paynantheine. These usually make up about 0.2-0.5% of the dry leaf, but we know much less about what these other alkaloids do.
The number and amounts of these alkaloids can change based on things like the type of plant, how old it is, and when it’s harvested. This variety makes it hard to study kratom, but it also means the plant might have many different effects that we don’t fully understand yet.
Why Focus on Mitragynine and 7-Hydroxymitragynine?
Mitragynine and 7-hydroxymitragynine matter most because they have strong effects on the brain’s opioid receptors. Mitragynine is the most common in kratom and causes many of the plant’s effects. 7-hydroxymitragynine, though present in a much lower amount, is very powerful and especially important for kratom’s pain-relieving abilities.
Both of these alkaloids also act differently than standard opioids. While they do affect opioid receptors, their unique way of doing so might result in different side effects or risks compared to regular opioid medicines, possibly making them safer in some ways.
Mitragynine: What It Is, How It Works, and How Much Is in Kratom
Mitragynine is the most prominent alkaloid in kratom, making up most of the plant’s total alkaloid content. Because it’s found in such large amounts, it plays the biggest role in how kratom affects users.
Mitragynine is also the starting point for another alkaloid, 7-hydroxymitragynine, which the body can make from mitragynine. Studying both of these compounds gives a fuller picture of how kratom works.
The Structure of Mitragynine
Mitragynine is an indole alkaloid. Its molecular formula is C23H30N2O4 and its molecular weight is 398.50 g/mol. It has a structure that doesn’t dissolve in water but will dissolve in solvents like alcohol and acetone. Mitragynine forms white crystals that melt at about 102-106 °C. These properties help scientists work with and test the compound.
Mitragynine Amounts in Kratom Leaves
Mitragynine usually makes up about 1-2% of dry kratom leaf by weight. That’s roughly two-thirds of all the alkaloids in the plant. But this amount can change depending on the kratom variety, the plant’s age, where it was grown, and when it was picked. For example, Thai kratom can have up to 66% mitragynine in its alkaloids, while Malaysian types might have about 12%.
What Affects Mitragynine Levels?
Several things can influence how much mitragynine is found in kratom leaves:
- Type of kratom plant
- Where it’s grown (soil, climate, etc.)
- How mature the plant is
- When leaves are harvested
Because of these differences, kratom products can vary a lot in strength. This is why it’s important to know where kratom comes from.
What Does Mitragynine Do in the Body?
When you take kratom, mitragynine affects certain receptors in the brain, especially ones called mu-opioid receptors. By doing so, it can reduce pain and influence mood and energy. Mitragynine also acts on other receptors, like adrenergic and serotonin receptors. This helps explain why users can feel more awake, have better mood, or feel relaxed, depending on the dose.
| Receptor | Mitragynine’s Action | Effect |
|---|---|---|
| Mu-opioid | Partial agonist | Pain relief, mild euphoria |
| Adrenergic | Agonist | Arousal, alertness |
| Serotonergic (5-HT1A) | Agonist | Mood effects |
7-Hydroxymitragynine: Strength, Creation, and Role
7-hydroxymitragynine (often called 7-OH) is present in kratom in much lower amounts than mitragynine, but it is much stronger. Even a little bit of this alkaloid has a large effect, especially on pain. Knowing how 7-OH is made and works is important for a full understanding of kratom.
How Does 7-Hydroxymitragynine Relate to Mitragynine?
7-hydroxymitragynine is mostly produced in the body from mitragynine. This conversion happens in the liver after kratom is taken. While mitragynine has some opioid-like effects, 7-OH is stronger in this regard. So, the pain-relieving effect of kratom is mostly due to this transformation inside the body.
How Much 7-Hydroxymitragynine Is in Kratom?
Raw kratom leaves have only very little 7-hydroxymitragynine-less than 0.05% of the dry leaf. Some studies find even less than that. However, some commercial kratom products (especially extracts) may have more because makers process and concentrate the alkaloid, or create it from mitragynine in the lab. This increases their strength and can pose additional risks.
How Is 7-Hydroxymitragynine Formed?
The body turns mitragynine into 7-OH mainly in the liver. This is done by enzymes called CYP3A (especially CYP3A4 in humans). The creation of 7-OH is key to kratom’s pain-relief effect-without mitragynine being changed into 7-OH, kratom would not work the same way.
How Powerful Is 7-Hydroxymitragynine Compared to Mitragynine?
7-OH is much stronger than mitragynine. Studies show it is about 10 times more potent at the mu-opioid receptor. In animal tests, 7-OH works better than mitragynine for pain, even better than morphine in some cases-it may be up to 13 times stronger than morphine in reducing pain.
Kratom Alkaloids and Opioid Receptors
The way kratom alkaloids interact with opioid receptors is at the heart of why they provide pain relief or feel similar to opioid drugs. But they do not act like traditional opioids in all ways, and this can change their risk and benefit profile.
Do Mitragynine and 7-OH Act Like Opioids?
Both alkaloids act as opioid agonists-meaning they “turn on” opioid receptors. Mitragynine is a “partial” agonist, so it activates the receptor but not as strongly as some other opioids. 7-OH is a stronger partial agonist and works at a much lower dose. Here’s how they compare:
| Compound | Potency at Mu-Opioid Receptor (hMOR) | Max Activation (Emax) |
|---|---|---|
| Mitragynine | EC50: 339 nM | 34% |
| 7-OH | EC50: 34.5 nM | 47% |
How Are They Different from Regular Opioids?
The main difference is in how they activate the mu-opioid receptor. Traditional opioids trigger two pathways: a G protein pathway and a beta-arrestin pathway, with the latter causing many side effects. Kratom’s main alkaloids mostly activate the G protein pathway and less of the beta-arrestin pathway. This may lower the risk for side effects like slowed breathing or constipation, compared to regular opioids. Scientists are still studying this to see if kratom could be a safer option.
How Kratom Alkaloids Move Through the Body (Metabolism and Elimination)
Once you take kratom, the body changes its alkaloids-this is called metabolism. Mitragynine undergoes metabolic processes in the liver and converts partly to 7-OH. Both alkaloids are then further broken down so the body can remove them, mostly through urine.
Which Enzymes Break Down Mitragynine and 7-OH?
The liver enzyme CYP3A4 is mainly responsible for converting mitragynine to 7-OH. Other enzymes like CYP2D6, CYP2C9, and CYP2C19 help a little. Because these enzymes work differently in different people, kratom’s effects can vary.
Does Mitragynine Have Active Metabolites?
Yes, mitragynine’s main active metabolite is 7-hydroxymitragynine. The pain relief people feel from kratom is mostly due to the body changing mitragynine into 7-OH, not just mitragynine itself. Some medications or genetic traits can affect how fast someone can turn mitragynine into 7-OH, changing kratom’s effects for that person.
What Effects and Benefits Do Mitragynine and 7-OH Have?
Mitragynine and 7-OH are why kratom can work both as a stimulant (low doses) and as a painkiller or sedative (higher doses). They affect several systems in the body, leading to various reported effects, including mood improvement and help with opioid withdrawal. However, there are also risks, including the chance of addiction, which are not fully understood yet.
Do These Alkaloids Relieve Pain?
Yes, both provide pain relief because they act on mu-opioid receptors. 7-OH, even in small amounts, plays a main role in kratom’s pain-relieving action. Studies on animals and reports from people support this use. Traditional use in Asia also supports kratom as a pain reliever.
Do They Have Other Uses?
Besides relieving pain, kratom alkaloids may help as a stimulant for energy, as a mood-lifter, and for calming nerves. Some people use kratom to help stop or reduce opioid use and manage withdrawal, though no large studies in humans have confirmed these uses. The unique way kratom alkaloids act in the body means they might have a different side effect risk compared to classic opioids.
Are Kratom Alkaloids Addictive?
There’s still uncertainty about how addictive kratom alkaloids are. Regular use can lead to dependence, and withdrawal symptoms can appear if someone stops after steady use. These symptoms are usually milder than those after stopping other opioids and can include anxiety, trouble sleeping, and aches. In lab studies, 7-OH seems more likely to lead to addiction than mitragynine, which might even protect against addiction in some tests. More research is needed to understand how kratom affects humans in this way.
Risks, Side Effects, and Safety
Kratom alkaloids can cause side effects, especially at higher doses. There are also safety issues because kratom products are not always regulated, so strength and purity can vary.
Possible Side Effects
- Sweating
- Dizziness
- Nausea
- Low mood or feeling “down”
- Constipation
- Weight loss
- Fatigue
- Dark patches on the skin (on cheeks)
- Pupil constriction in high doses
In rare cases, especially with other drugs, there can be more serious effects such as liver damage, seizures, or heart problems.
Can Kratom Interact with Other Drugs?
Yes, kratom’s alkaloids are broken down by liver enzymes that also handle many other medications. Kratom can slow down or speed up how these drugs are processed. Mixing kratom with other substances-either prescription drugs or illicit drugs-can be dangerous. There are reports of serious side effects, or even death, especially when kratom is taken with other drugs.
Is Overdose a Concern?
When taken by itself, kratom is less likely than traditional opioids to cause breathing problems or a deadly overdose. This might be because key side effect pathways are less activated and the body can only use so much at a time. Most deaths linked to kratom involved other drugs as well. Differences in kratom product strength remain a concern, so anyone using it should be cautious.
Kratom Laws and Regulation
Kratom’s legal status depends on where you are. There is no single worldwide rule. Some countries and some US states have banned kratom or its main alkaloids, but others haven’t. This makes it confusing for people who want to buy, sell, or research kratom.
Are Mitragynine and 7-OH Illegal?
Globally, kratom and its alkaloids are not scheduled under United Nations drug conventions. In the US, kratom and its main compounds are not federally controlled but are considered “drugs of concern” by the DEA and FDA. The FDA does not approve kratom products, which means they are sold as unapproved supplements.
How Do Laws Differ by Region?
Some countries-including Denmark, France, Malaysia, and Thailand-ban kratom. Other places regulate or restrict it. In the US, states like Alabama, Arkansas, Indiana, Rhode Island, Vermont, and Wisconsin have banned mitragynine and 7-OH. Other states have rules like age restrictions or required labeling. This patchwork of rules means you need to check your local or state laws.
| Region | Status |
|---|---|
| United States (federal) | Not scheduled, but not FDA approved |
| Several U.S. states | Banned or regulated |
| Many European and Asian countries | Often banned |
Common Questions About Kratom Alkaloids
How Much 7-Hydroxymitragynine Is There in Kratom?
In plain kratom leaves, 7-OH is found in tiny amounts-between 0.01% and 0.04% of total alkaloids, often less than can be measured. Extracts can contain much more, which changes their strength and effects.
Is 7-Hydroxymitragynine Stronger Than Morphine?
Yes, lab studies show that 7-OH can work better than morphine at the opioid receptor for blocking pain. Some studies find it about 13 times more potent for pain relief. But the very small amount naturally present in kratom means its effects are usually balanced by other compounds and the way the body processes kratom overall.
Will Kratom Alkaloids Show Up on Drug Tests?
Regular workplace drug tests do not usually test for kratom alkaloids. Special laboratory tests (such as GC-MS or HPLC-MS) can find mitragynine or 7-OH in urine, blood, or hair, but these are not common and are mainly used in research or special legal cases. How long these alkaloids stay in the body depends on dosage, frequency, and metabolism.