A Guide to 7-Hydroxymitragynine: Kratom’s Powerful Minor Alkaloid

A Guide to 7-Hydroxymitragynine: Kratom’s Powerful Minor Alkaloid

Kratom contains two primary active ingredients, mitragynine and 7-hydroxymitragynine, which act on the brain’s opioid receptors. These compounds are indole alkaloids native to the Southeast Asian plant, Mitragyna speciosa (kratom), traditionally used for its stimulant and analgesic (pain-relieving) properties. Mitragynine, the more abundant and well-known of the two, initially drew scientific interest for its role in kratom's effects. However, kratom testing and research have unveiled that 7-hydroxymitragynine, although present in smaller quantities, is crucial to kratom’s pain-relieving, mood-boosting potential.

7-hydroxymitragynine’s potent opioid receptor action is a focal point for understanding kratom’s safety and therapeutic value. Let’s dive in. 

What is 7-OH Mitragynine?

7-Hydroxymitragynine, also called 7-OH mitragynine or 7-OH, is an active metabolite of mitragynine, the kratom plant’s principal psychoactive alkaloid. This substance is critical in enhancing mitragynine’s pain-relieving effects by strongly activating mu-opioid receptors, similar to morphine. Interestingly, preliminary studies indicate that 7-OH binds to these receptors with even greater power than morphine. Along with opioid receptors, 7-hydroxymitragynine affects dopamine, serotonin, and adrenergic receptors

Mitragynine and 7-hydroxymitragynine

Source: Journal of medical toxicology

When the body metabolizes mitragynine, 7-OH mitragynine forms as an active metabolite. Specifically, mitragynine converts to 7-OH within the liver, facilitated by cytochrome P450 3A isoforms. This transformation significantly enhances 7-OH’s effectiveness as a pain reliever, making it substantially more potent than mitragynine despite being present in kratom leaves at lower concentrations. According to a Columbia University study, 7-hydroxymitragynine is responsible for most of kratom’s opioid-receptor-mediated narcotic effects. 

Columbia University’s animal study further elucidated that while mitragynine makes up two-thirds of kratom’s total active content, it does not directly activate opioid receptors in a significant manner.  In fact, 7-hydroxymitragynine was around fivefold more potent than oral mitragynine. Kratom’s pharmacological profile, therefore, is not solely dependent on the direct action of its alkaloids but also on their metabolism, which influences the overall effects.

7-Hydroxymitragynine Effects

Source: ACS central science

7-Hydroxymitragynine effects include various pharmacological actions due to its potent opioid-like properties. Preclinical research and consumer anecdotes have shown that kratom’s 7-OH content reduces pain, enhances mood, and provides sedative effects.

  • Pain Relief: 7-hydroxymitragynine is known for its potent analgesic effects, relieving pain by acting on the mu-opioid receptors. Research findings suggest that 7-OH is approximately 13 times more potent than morphine.
  • Addiction and Withdrawal Risk: 7-hydroxymitragynine, within the context of whole kratom leaves and extracts, appears to have milder withdrawal symptoms and a lower risk of developing an addiction than opioids. However, concentrated chronic use of 7-OH isolate could cause addiction, tolerance, and withdrawal symptoms.  
  • Euphoria and Sedation: At recreational levels, 7-hydroxymitragynine in whole kratom extracts can produce euphoria and sedation. 
  • Potential Medical Applications: 7-OH has shown promise in helping individuals wean off opioids, reducing opioid tolerance, and alleviating withdrawal symptoms. 

How to Convert Mitragynine to 7-hydroxymitragynine

Converting kratom’s mitragynine to 7-hydroxymitragynine involves a natural biochemical process that typically occurs after ingestion through the metabolism

Chemists can also synthesize this conversion in a laboratory, using enzymes such as cytochrome P450 (CYP) isoforms to catalyze mitragynine’s oxidation. This process introduces a hydroxy group at the 7-position of mitragynine, transforming it to 7-OH. 

A patent for converting mitragynine to 7-hydroxymitragynine offers an alternative method. This process uses a particular chemical, referred to as [bis(trifluoroacetoxy)iodo]benzene (PIFA), which sounds complex but can be thought of as a powerful reactant. PIFA catalyzes the transformation when mixed with two common solvents, tetrahydrofuran and water, under a blanket of argon gas to keep the environment stable and prevent unwanted reactions. After the chemical reaction is complete, the mixture is treated to neutralize and extract the desired compound, which is then purified to achieve high-quality 7-hydroxymitragynine. 

7-OH Mitragynine Products 

Various 7-OH mitragynine products exist, including beverages and tablets. Many of these formulas contain substantially higher concentrations of 7-OH than those found in raw kratom leaves. According to a commercial kratom product analysis, 7-hydroxymitragynine potency exceeded that found in naturally occurring material by up to 500%.

This significant increase strongly suggests “adulteration,” elevating debate regarding the safety, abuse potential, and addictive properties. Safety questions also extend to the process of creating 7-OH mitragynine.

7-OH occurs only in trace amounts in kratom plants. So, 7-OH extracts are likely a semi-synthetic product of mitragynine created through complex chemical reactions using various solvents, chemicals, and reactants. The process is often perfectly safe if the manufacturer purifies the final mixture.

Only third-party kratom testing can confirm that 7-hydroxymitragynine extracts are free from residual chemicals and contain appropriate potency levels. Brands producing kratom beverages, capsules, vapes, and edibles must test products for purity and potency. And consumers must look for brands that publish the test results through a Certificate of Analysis on their website.

Kratom and 7-Hydroxymitragynine Regulations 

On a federal level, the Drug Enforcement Administration (DEA) has not scheduled kratom or its active compounds, including 7-OH, under the Controlled Substances Act (CSA). The DEA proposed placing mitragynine and 7-hydroxymitragynine in Schedule in 2016 but withdrew the notice due to public feedback. 

The FDA has not approved any kratom products and considers them unapproved new dietary ingredients.

States have taken varied approaches, with some banning kratom outright and others regulating its sale and possession. Alabama, Arkansas, Indiana, Rhode Island, Vermont, and Wisconsin ban mitragynine and 7-hydroxymitragynine. Other states regulate sales, with variations in:

  • Age restrictions
  • Marketing to children
  • Adulteration and contamination standards
  • Labeling requirements
  • Testing and sampling protocols
  • Registration and permitting
  • Handling of synthetic alkaloids
  • Local authority
  • Private right of action
  • Taxation

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Potential Addiction Risks 

Kratom and its components, including 7-hydroxymitragynine, have been controversial due to concerns over the potential for abuse and addiction. However, proponents argue that kratom offers a viable alternative to opioids, with fewer risks and significant potential for managing pain and addiction. The truth lies somewhere in the middle.

Research findings are mixed when it comes to 7-OH’s addictive potential. 

One preclinical animal study showed that neither mitragynine nor 7-hydroxymitragynine exhibits rewarding effects. In this study, "rewarding effects" refer to feelings of reinforcement in the brain that contribute to misuse. In contrast, morphine showed typical rewarding effects. Interestingly, a high dose of 7-hydroxymitragynine actually had an aversive effect. So instead of inducing pleasurable or rewarding sensations, the high dose of 7-hydroxymitragynine led to unpleasant or aversive feelings in the brain.

Another rodent study published in the Addiction Biology Journal came to a different conclusion. This study trained rats to self-administer morphine as a reference point. Then, the rats were allowed to self-administer either mitragynine or 7-hydroxymitragynine, allowing researchers to see if these kratom compounds could substitute for morphine. After the tests, the researchers evaluated how the rats responded to morphine again. 

The key findings of the study revealed 7-HO’s potential to illicit abusive behaviors:

  • Substitution Behavior: 7-hydroxymitragynine, but not mitragynine, sometimes substitutes for morphine in the self-administration tests, indicating its potential for producing morphine-like effects.
  • Increased Morphine Intake: Rats exposed to 7-OH showed an increase in subsequent morphine intake, suggesting that prior exposure may enhance the morphine’s reinforcing effects.
  • Decreased Morphine Intake: Conversely, exposure to mitragynine decreased morphine intake, indicating that kratom’s primary alkaloid may not possess significant abuse potential and could even reduce morphine intake.

Bottom Line

7-hydroxymitragynine exhibits effective pain-relieving properties, approximately 13 times more potent than morphine. Additionally, 7-OH in whole kratom extracts may come with milder withdrawal symptoms and reduced dependency risk. These incredible findings warrant further 7-OH research. However,  isolated extracts might have higher dependency potential due to their potency and the lack of other alkaloids, like mitragynine, that might mitigate the risks. This breadth of findings underscores the importance of further clinical research paired with kratom lab testing to fully understand 7-OH’s pharmacological profile and therapeutic potential​​. 


What percentage of kratom is 7-OH mitragynine?

The percentage of 7-hydroxymitragynine (7-OH mitragynine) in kratom can vary widely depending on the specific strain and preparation method. Generally, 7-OH mitragynine constitutes a small percentage of kratom’s total alkaloid content, typically around 0.01% to 0.04%. However, 7-OH mitragynine extracts can contain a significantly higher ratio. 

One study found that alkaloid-rich fractions, ethanolic extracts, lyophilized teas, and commercial kratom products contained up to 2.8% 7-OH. Another study found concentrations as high as 500% more 7-OH than the average kratom plant. 

How is 7 hydroxymitragynine like morphine?

7-hydroxymitragynine is like morphine in that it acts as an opioid receptor agonist, explicitly targeting the mu-opioid receptors in the brain. Both substances can produce analgesic (pain-relieving) effects and may induce euphoria or sedation. However, 7-hydroxymitragynine is structurally different and is derived from the kratom plant, whereas morphine is a naturally occurring opiate derived from the opium poppy plant. Additionally, 7-hydroxymitragynine is generally considered to be more potent than morphine in terms of its effects on opioid receptors, although potentially less addictive. 

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