What is 7OH: Understanding Its Benefits and Uses in Kratom Products

If you’ve been around the Cannabis block for a while, chances are you’ve encountered kratom. Among its notable compounds is 7-hydroxy mitragynine, otherwise known as 7-OH. 

Thsi element presents a breakthrough in medicinal chemistry, as it helps us understand the effects of kratom on the human body—especially in connection with its opioid-related benefits. 

When you take in Kratom (e.g., for analgesic purposes), your body converts it to one of Kratom’s main ingredients, mitragynine, into something far more potent—7-OH. The 7-OH compound not only nudges your brain’s opioid receptors but it activates them in a way that mirrors what happens when it comes in contact with morphine. 

In this post, we’ll break down how 7-OH works, its uses, its metabolic pathways, and how it compares to morphine. You’ll also learn what you need to know before you try out kratom products. Let’s explore!

What is 7-OH?

7-OH is a natural indole alkaloid that can be found in the leaves of the kratom plant (Mitragyna Speciosa). And while mitragynine makes up most of the kratom’s chemical profile (reaching up to an impressive 66% in some strains!), you may think of 7-OH as mitragynine’s distant cousin. 

You may then think of mitragynine as the “parent” molecule, which becomes 7-OH when processed by the liver. Studies suggest that 7-OH is 13 times stronger than morphine at binding to opioid receptors.

But what does this matter? Well, If you’ve ever used kratom for pain relief, relaxation, or even to curb opioid cravings, 7-OH is the key ingredient at work. This is due to its activation of mu-opioid receptors—the same receptors that help the body process prescription painkillers—which explains why kratom works so well as a painkiller and mood boosters. 

And yet, much unlike traditional opioids, 7-OH bounces off other receptors as well, such as serotonin and adrenergic systems. 

Mitragynine: The Primary Alkaloid in Kratom

Mitragyna Speciosa, also known as kratom, is a chemical compound created to interact with the human brain. Its most powerful weapon (or, in science-speak, psychoactive alkaloids) is mitragynine, an indole-based alkaloid that dominates the plant’s chemical profile. 

Racking up to 66% of Thai kratom’s alkaloid content, mitragynine interacts with a 7-hydroxy mitragynine (7-OH) for all of the effects we have come to associate with Kratom. 

Essentially, Mitragynine does all the hard work, with Kratom taking the credit. Its surplus alkaloids can be traced to the plant’s survival strategy, serving as a natural defense against pests and a mechanism for attracting pollinators. 

Some varieties, like Thai kratom, thrive in specific climates and have evolved to prioritize mitragynine production, filling its leaves with this compound to boost their chances of survival.

Molecular Structure 

In terms of its molecular structure, mitragynine belongs to a broader indole alkaloid family. This species is known for its complex ring structure that lets it bind effectively to human opioid receptors. 

Unlike classic opioids (e.g., morphine), however, mitragynine is known to be a partial agonist. This means it activates opioid reception with much less intensity, having only about 26% of the activity of morphine. This nuanced interaction means less risk of respiratory depression. 

How Opioids work

We’ve mentioned 7-OH and how it derives its effect from being able to bind strongly to mu-opioid receptors (the main receptors for the body’s opioids) in our central nervous system. 

But to truly grasp the full extent and nature of this interaction, it is important to know opioid receptors and how they function. 

Opioid receptors are a group of proteins usually found on nerve cells throughout the body. In particular, they can be seen in the spinal cord, brain, and gut. 

These receptors play a critical role in how they manage pleasure, pain, and addiction in the body, and they are classified into three types, namely: 

1. mu opioid receptor (μ); 
2. delta opioid receptor (δ); and 
3. kappa opioid receptor (κ) 

Each type affects certain changes in the body, like pain relief, mood changes, and physical dependence. 

When an opioid binds to these receptors, it becomes activated. This sends a signal to the brain that helps relieve chronic pain and induces feelings of pleasure. 

A special type of protein called G-proteins helps in this process, acting as a messenger inside the cells. So, when an opioid that binds to its receptor triggers a change in the G-protein, thereby affecting other cellular processes. 

An example of such change is a reduction in the production of a molecule known as Cyclic adenosine monophosphate (cAMP) — a molecule also responsible for signaling changes in cells. 

It is this reduction that helps to communicate changes that calm down nerve signals (which then reduces the body’s perception of the pain) 

Mu-opioid receptor activation

Of all the three opioid receptors, mu-opioids have the most relevance to 7-OH. When mu-opioid receptors (MOR) activate with the influence of compounds like 7-OH, certain opioid-like effects happen. 

But being a mu-opioid receptor agonist, 7-OH will directly activate opioid receptors in the brain. When this happens, you begin to feel significant pain relief and euphoria.

This activation is central to 7-OH’s potential to relieve users of pain. 7-OH binding to MOR triggers the release of cellular signals to help to reduce the perception of pain in the body. (not the actual pain itself)

This involves modulating the neurotransmitters and ion channels which are responsible for calming nerve signals. 

As an example, activated MOR prevents the release of excitatory neurotransmitters and modulates ion channels, calming nerve signal

Downsides to mu-opioid receptor activation

Physical dependence can occur where opioids or opioid-like substances bind to MOR. The unfortunate result of this is that once the person stops using the substance, there is likely to be withdrawal symptoms.

When MORs are activated by 7-OH, it could worsen the symptoms, especially if used often, and can lead to adaptations in the brain that may result in dependence. 

7-OH Effects on Opioid Receptors

7-OH is unlike any other opioid. A partial agonist, its unique profile is made to avoid severe side effects (e.g., respiratory depression, which is usually associated with opioid use). it does not fully activate these pathways. 

Another pathway it fails to activate is the β-arrestin pathway (a signaling mechanism linked to opioid side effects. 

This difference means that 7-OH may offer a safer alternative to managing pain when compared to traditional opioids. 

Mu Opioid Receptor Activation

7-OH is known to have the effect of a competitive agonist in its interaction with both delta (δ) and kappa (κ) receptors. 

In terms of its effect on the human body, this interplay helps to reduce the risk of physical dependence and other common side effects usually associated with opioid use. 

To have its analgesic effects, mitragynine must convert to 7-OH through a metabolic process that starts out in the liver and goes through certain enzymes (which also impact it) that break down mitragynine into its more potent metabolite. 

Studies suggest that the brain has enough 7-OH to cause the opioid-based pain relief linked to mitragynine, which proves how critical it is that the body converts mitragynine into 7-OH. 

As better and safer alternatives to traditional opioids are being sought in research labs, it is expected that 7-OH can show us a lot about opioid receptor modulation and how they help with pain relief. 

Reducing Withdrawal Symptoms

7-OH strikes a unique balance that helps in the reduction of withdrawal symptoms. It achieves this by activating receptors rather mildly —just enough to curb symptoms like nausea, anxiety, and muscle aches. 

But it’s worth taking a look at how this works for users and how it benefits cannabis users and the cannabis industry:

How does 7-OH reduce withdrawal symptoms in users? 

A downside of THC use (especially chronic use) is how it indirectly dysregulates the endocannabinoid system (the endocannabinoid system is a network of receptors and chemical messengers in the human body that impacts bodily functions), in a way that indirectly interacts with opioid pathways in the body. 

When a chronic user abruptly stops using THC, the endocannabinoid system struggles to cope or regain its balance, which may trigger symptoms like insomnia, irritability, and loss of appetite. In modulating these receptors, 7-OH may stabilize these systems and ease the withdrawal process for the user during the withdrawal period. 

And how does 7-OH do this? It all starts with the 7-OH crossing the blood-brain barrier. Here, it tries to activate receptors in regions like the locus coeruleus (this area in the brain is often hyperactive during withdrawal). It also reduces norepinephrine release (which is responsible for anxiety and agitation in the user) to calm stress responses. 

At the same time, 7-OH interacts with dopamine and serotonin pathways, which restores the mood balance disrupted by THC dependence. For cannabis users, this could spell fewer cravings and less discomfort in withdrawal periods (which include tolerance breaks.) 

How does this benefit the cannabis industry? 

The cannabis industry is not left out from the world of good that 7-OH’s transformative potential means. For one, 7-OH’s medical potential will set the groundwork for the harm-reduction products (e.g., capsules or tinctures) that are created to help chronic users navigate their symptoms during withdrawal periods. 

As a bonus, this fits in well with widespread calls for ‘functional’ cannabis products that are built for wellness and not just recreation. 

Also, it brings focus to a more important issue: the need to tackle dependency. While there are basic THC offerings that often include compounds that support a safer and more sustainable use, there is more to be done to help chronic THC users in their journey to overcoming addiction or withdrawal symptoms.

Second, it spurs the industry to confront the dependency issue head-on, moving past THC-based products to include compounds that support safer, more sustainable use. We can already see this with medical labs researching how 7-OH can be used as a medication-assisted therapy.

Metabolic Pathway of 7OH

The metabolism of 7-OH is typically a series of enzymatic reactions in the liver. When mitragynine first enters the body—usually through oral ingestion (for instance, when you take Kratom)—it travels down the bloodstream and to the liver. Then, specialized enzymes begin breaking it down. 

The cytochrome P450 (CYP) enzymes (in particular, CYP3A4), are crucial in this process. They oxidize mitragynine by simply adding a hydroxyl group (-OH) to the 7th position of its chemical structure. 

Shortly after, 7-OH forms as an active metabolite. In other words, Mitragynine transforms into 7-OH mitragynine—a stronger compound than mitragynine—in your liver, binding to your body’s pain relief and mood-altering receptors (the mu-opioid receptors) more tightly, which is why its effects are instant. 

After 7-OH forms, it does not remain in the liver. It goes from the bloodstream, traveling to places like your brain, where it activates your receptors. After this, 7-OH breaks down into further smaller, less active pieces with the help of more enzymes. 

This may add other molecules (like glucuronic acid) to help it stay water-soluble. The end product, which is the new version of 7-OH, then flushes out of your body through the kidneys (through urine) or intestine (through feces). 

Factors Influencing 7-OH Metabolic Process

The metabolic process depends on certain factors like your age, genetics, liver health, and the food you eat. Some people’s enzymes break down mitragynine into 7-OH faster, while others process it slower. 

Medications may also slow down or speed up these enzymes, changing how much 7-OH is made and how long it stays active. This explains why two people may feel different effects, although they took the same dose.

7OH Products and Regulations

Certain 7-OH products (for instance, chewable tablets and beverages) are popping up on shelves and in online stores. But there’s also been a lot of uncertainty regarding their legal status. 

Most of these products are made out of Kratom, a plant containing 7-OH, a compound that interacts with the body in a way that’s similar to how opioids work. 

It’s quite common to find 7-OH items marketed as “natural wellness” aids; Chewables may look like vitamins, and beverages come in the form of herbal teas or energy drinks. 

But these items are subject to different laws. For instance, in some states in the US, like Alabama, Arkansas, Indiana, Rhode Island, and Wisconsin, there is an outright ban on Kratom, making all 7-OH products illegal in these regions. 

Other cities, like Denver and San Diego, also restrict sales.

But outside of the U.S., the rules even differ more. Countries like Australia, Thailand, and parts of Europe strictly control or ban kratom and 7-OH products. 

Ultimately, before you buy anything, you should check your local laws. Sources like your government websites can give you useful pointers on what’s legal and what isn’t. 

The FDA regulation

In terms of FDA regulation, there has been little oversight regarding the use of 7-OH. Given the lack of regulation, there is no general guarantee on its safety and quality. 

There are also no specified guidelines on the dosing. With this lack of clarity comes several risks. A major risk in 7-OH products is that some brands may not list accurate amounts of ingredients in their products. Another is the contamination risk (of bacterial or heavy metals)that is commonly associated with products of this nature.  

On a functional level, scientists and medical professionals are concerned about the risks of 7-OH. While some people use it for analgesic or relaxation purposes, they risk side effects like dizziness, nausea, and addiction. When taken in high doses, they may also lead to severe medical issues like breathing problems or seizures.

These issues have led groups like the American Kratom Association to lead the charge in pushing for stricter quality controls and honest labeling. However, not all companies follow these guidelines. At this moment, the safest thing to do is to confirm from the drug enforcement administration where you live that 7-OH is legal and have a healthcare provider advise you on whether or not to consume this product.

Remember, it is your responsibility to research brands, read customer reviews, and look out for third-party lab testing results to reduce your risk exposure.

Potential addiction risks

To answer the question “Is 7-OH addictive?”, scientists have dug their heels in the lab, trying to solve what is an ongoing debate among researchers. The result is neither here no there.

According to some studies, 7-OH, despite being one of the best mitragynine related indole alkaloids. does not have the rewarding effects that are known to traditional opioids. 

Elsewhere, another preclinical animal study hinted that neither mitragynine nor 7-OH produced the rewarding effects usually known with addictive substances. What this finding means is that these compounds may not lead to the same level of abuse usually known with more popular opioids like morphine. 

And, of course, there have been contrasting results that tell a different story, Another research found that 7-OH could trigger abusive behavior since it acts on the body’s opioid receptors in a way that is similar to morphine. This raises concerns about its addictive properties. 

Whichever side of the debate you lean towards, one thing is for certain: 7-OH is here to stay. Experts have warned that since it is sold in highly concentrated forms without labeling or proper regulation, it is likely for users to expose themselves to risks. 

The fact that 7-OH products are often marketed alongside kratom makes the situation even more delicate. Over the years, kratom itself has been used traditionally for various purposes. However, the isolated and synthetic forms of 7-OH do not share the same safety profile as whole kratom leaves. 

This has led researchers to note that consumers may likely mistakenly associate kratoms’ safety with that of these potent derivatives. Given this, there are now concerns that chronic users of 7-OH could suffer physical dependence and behaviour that is similar to that of a classic opioid addiction.

The need for more comprehensive studies is clear. Since current evidence does not provide a complete picture of how 7-OH affects humans (or how likely it is for users to develop an addiction), there is a need for further investigation to help users understand the full extent of the risks associated with this compound.

Comparison to Morphine

How does 7-OH stack up to Morphines? Granted. Both are powerful painkillers, but they work differently and have some key differences. 

In terms of chemical make up, 7-OH is an opioid agonist structurally different from the typical mu-opioid receptor agonists (such as morphine).

Impact-wise, 7-OH is also stronger than morphine, which means you’d need a smaller dose of 7-OH to get the same analgesic ‘hit’ (in this context, pain relief) as morphine. 

The way they work is also similar in that both drugs bind to receptors in the body (called opioid receptors) and brain to block plain signals and reduce pain, creating a feeling of relaxation, or even a “high”. 

Furthermore, Morphine targets only one type of receptor (the mu-opioid receptors). On the other hand, 7-OH may interact with multiple receptors, including those that may not trigger addiction as easily. 

Athough morphine comes with a lot of painkilling power, it also comes with the risk of addiction and other dangerous side effects like slowed breathing. This is because it strongly activates the brain’s reward system, which makes the user crave more of morphine. 

On the other hand, 7-OH seems to avoid these pitfalls, with the scientific evidence suggesting that it may not stimulate those addiuction pathways as strongly. This makes 7-OH more suitable and safer for longer-term use. 

On the legal front, morphine is a tightly controlled substance, while 7-OH, as of today, exists in somewhat of a legal gray area. (its legal status is up in the air)

The side effects that both drugs trigger (e.g., nausea, constipation, respiratory depression, and drowsiness) may spell difficulties for users. Notably, it is far less pronounced in 7-OH because its unique receptor activity will reduce how frequently or severely these side effects may happen.

Research and Studies

The analgesic effects of 7-OH has led to an upsurge in research. A major reason why researcher are taking particular interest is that it appears to be better at relieving pain than morphine — a product who’s claim to fame is as a well-known painkiller. 

This is important because it may help us create new medicines that are more effective and safer. The icing on the cake is that it seems to work in a way that may avoid some of the well-knowing negative side effects that are associated with opiods (e.g., respiratory problems), thereby presenting a better alternative to morphines. 

In experiments, scientists have seen that 7-OH forms after mitragynine is broken down by enzymes in the liver. One of such enzymes is the CYP3A4, which is useful in converting mitragynine into 7-OH. This process happens both in test tubes and inside living animals, helping us to see how kratom in the body. 

There have also been studies carried out in animals (mice) where it has been shown to have equally pain-relieving effects. All in all, there is a lot of research on 7-OH, which is exciting due to potential innovations in this space that could mean safer and more effective treatments.

Conclusion

In other news, some companies are already making semi-synthetic versions of 7-OK that are hyper-concentrated and taken in different ways. 

Understandably, regulators are up in arms about this approach, as these products raise serious concerns, as since they are more potent, they could lead to dependence or other health issues. 

On the bright side, this also shows how much interest there is in using a safer, more sustainable orally active opioid analgesic to create new medicines. 

Of all opioid agonists structurally different from other opioid ligands, 7-OH is the most exciting. And it’s easy to see why: there’s a lower risk of tolerance and dependence (these structural differences may even alter how 7-OH interacts with receptors, possibly activating alternative pathways, e.g., biased agonism).

Ultimately, it’s effect on opioid receptors, mu-opioid receptor activation, and its unique metabolic pathways make for human’s most promising attempt at helping people taper off opioids.