History and Pharmacology

Kratom (Mitragyna speciosa) has been used for centuries in Southeast Asia as a remedy for fatigue and sore muscles. The leaves can be chewed fresh or steeped in tea. Kratom contains over 40 alkaloids, and 2 of these are primarily responsible for its effects: mitragynine, and 7-hydroxymitragynine (7-OH).

In raw leaf material, mitragynine is the dominant alkaloid, comprising up to 2% of the leaf’s weight. Mitragynine itself has a very weak opioid effect, about 1/10th the potency of morphine.

After kratom ingestion, the liver (via the CYP3A4 enzyme) converts about 5–10% of absorbed mitragynine to 7-hydroxymitragynine (7-OH). 7-OH is a much more potent opioid than mitragynine with over 10x the effect of morphine, similar to oxycodone – mg for mg. 7-OH is likely responsible for most of the opioid-like effects of kratom, but fortunately this metabolic conversion occurs relatively slowly over 1–2 hours, so we don’t see a massive spike of 7-OH from consuming kratom leaf, whole-leaf powder, or tea. There is also a tiny amount of 7-OH in the leaf itself, about 0.05%, but most of the 7-OH effect comes from metabolized mitragynine.

In traditional uses of kratom, the volume of leaf material you’d need to consume to achieve a high-dose opioid effect acts as a natural “ceiling.” Nausea and vomiting occur before a user can reach opioid overdose levels.

After centuries of traditional use, the modern consumer market needed only a few years to chemically bypass that ceiling, optimizing for addiction before regulators could react.

The first approach to make kratom more potent was to extract and concentrate mitragynine itself from the leaf. While leaf kratom contains up to 2% mitragynine, concentrated products often contain 45–80%, with 20–40x the potency of leaf powder. 7-OH was originally considered an undesirable contaminant when these concentrated products first emerged, often kept under 2% of the product weight. A user still metabolically converts 5–10% of the consumed mitragynine to 7-OH, but because this conversion takes 1–2 hours, we do not see rapid 7-OH spikes, significant respiratory depression, or opioid overdose death from uncontaminated mitragynine extracts. We do see opioid tolerance, withdrawal, and addiction.

Around 2020, some manufacturers began synthesizing 7-OH and adding it to these concentrated products, often labelled as a kratom extract blend. By 2023, it was clear these products were highly profitable, and brands began marketing them openly as 7-OH. These are semi-synthetic: manufacturers extract concentrated mitragynine from the leaf, then add a hydroxyl group through chemical oxidation. 7-OH is as potent as pharmaceutical opioid pain medications, and consumption results in a rapid spike in 7-OH blood levels with no metabolic delay. These products can cause opioid tolerance, withdrawal, and addiction on a short timeframe, and they can cause death from opioid overdose.

Legal Standing

The DEA first proposed classifying kratom as a Schedule I controlled substance in 2016, but met with intense opposition from advocacy groups and withdrew their proposal. As of early 2026, the DEA is engaged in the rulemaking process to consider scheduling 7-OH itself. Congress could also take the rare step of scheduling 7-OH through legislation before the DEA completes their process. While this regulatory action continues to unfold, 7-OH remains available on store shelves in most US states.

In California, 7-OH was largely removed from stores by early 2026 through enforcement of existing state law, treating it as an unapproved new drug.

Development of Opioid Use Disorder

Opioid Use Disorder (OUD) is the medical term for addiction to opioids. Simplified, there are 2 primary components:

(1) physical dependence on an opioid, and

(2) inability to stop or control use despite a desire to do so and harm from continued use.

We see OUD develop from both mitragynine (MIT) extracts and 7-OH, but it happens faster and becomes more severe with 7-OH.

Development of OUD tends to progress through 3 phases:

Phase 1: (Perceived) Beneficial Use

Initially, mitragynine and 7-OH products, just like other opioids, relieve pain and can produce an energized feeling, or a sedated feeling depending on dose. When used for acute severe pain, pharmaceutical opioids are important beneficial medications, but they begin to lose that benefit after only a few days of repeated use.

Each use results in dopamine release in the brain.  This sets up a positive feedback loop, essentially telling your brain: whatever you just did, do it again. The feedback loop is reinforced with each repetition. As use is repeated, opioid receptors throughout the body begin to develop tolerance, and you find that you need higher and higher doses to produce the same effect.  

Phase 2: The Plateau

The user has developed a strong tolerance to the substance, and it no longer produces any beneficial effect. Instead, you feel withdrawal when not using MIT or 7-OH. Withdrawal means that your nervous system has adapted to needing continuous MIT/7-OH stimulation to feel “normal,” and without it, you feel the opposite of those earlier beneficial effects: pain, agitation, fatigue, and depressed mood.

This plateau period can continue for many years. You may try to cut back or stop, only to find that withdrawal is intolerable. You may successfully make it through the withdrawal period, but the large majority of people who do will begin using again because the dopamine feedback loop persists for much longer than physical withdrawal. It produces a reflexive urge to use, especially in specific situations, and cravings that can persist for years after withdrawal has fully resolved.

If you find yourself in phase 2 and unable to stop or control your kratom, MIT, or 7-OH use, that is the time to seek effective treatment. Don’t wait for phase 3.

Phase 3: Decompensation

This is when the financial, emotional, or physical cost of maintaining the plateau phase eventually gets the better of you. It may begin with loss of employment, loss of meaningful relationships, or physical illness, and tends to worsen. In some older frameworks, this phase might be called “rock bottom,” but it’s not a universal feature of addiction, and it shouldn’t be a prerequisite for seeking help.

Stopping 7-OH, and the Role of Treatment

If you or a loved one are struggling with 7-OH, the most important thing to know is that you’re not alone, and you’re experiencing a well-understood medical condition with known, effective treatment available. 7-OH is a potent opioid that has done 2 things: conditioned your nervous system to experience withdrawal without it, and rewired your brain’s reward pathways to produce strong urges to use more, even when you have good reason not to. The same tools we use to treat traditional opioid addiction are remarkably effective for 7-OH addiction.

Buprenorphine (Suboxone, Subutex, Brixadi, Sublocade)

Buprenorphine is a long-acting partial opioid agonist, and perhaps the most effective tool we have for 7-OH. It has 3 important features that are responsible for its safety and effectiveness. 

The Ceiling Effect: Buprenorphine binds very tightly to the same receptors 7-OH uses, but only “turns them on” partially. This is enough to stop withdrawal and feel consistently normal, not enough to produce any sort of high.  

The Blockade Effect: Because it binds so tightly, it prevents other opioids (like 7-OH) from attaching. If a person on an appropriate buprenorphine dose takes 7-OH, they usually feel nothing.  

Stability: It’s very long-acting, typically dosed once daily. This breaks the cycle of withdrawal and reward, and begins to give your brain the time it needs to slowly “forget” the problematic reward pathways reinforced by 7-OH. Giving yourself enough time to heal is critical for minimizing the long-term likelihood of relapse.

Methadone

Methadone is similar to buprenorphine but more potent, and harder to access. It is not recommended as a first-line treatment for kratom, MIT, or 7-OH use disorder. For those with extremely high-tolerance 7-OH habits who don’t succeed with buprenorphine, methadone may be appropriate.

Naltrexone (Vivitrol)

Naltrexone is an opioid receptor blocker. It sits on the receptor and does nothing but block the effects of opioids, including 7-OH. It is the only effective treatment option that does not maintain some degree of opioid tolerance, but it requires the patient to be fully detoxed from all opioids (including 7-OH) for at least 7 days before starting. It is considerably less effective than buprenorphine, and patients tend to discontinue it and return to problematic opioid use at higher rates.

I generally don’t recommend it first-line, but it has two important niches:

1. Naltrexone is very useful for patients who have already stabilized and would like to stop buprenorphine after enough time in treatment to permit brain healing (often 1–2 years). It provides ongoing relapse protection without sustaining tolerance.

2. Naltrexone is also effective for alcohol use disorder, and may be the right choice for patients who are struggling with both problem drinking and opioid addiction.

Behavioral Health and Support

This does not mean mandatory therapy or group support. We know that doesn’t work for everyone. What does work is any regular, healthy relational activity that has meaning for you. By relational, I mean involving at least one other person. The activity can be a hobby, an exercise routine, a learning project, a job you enjoy, or a more traditional support group or therapy relationship. What matters is that it gives you a sense of accomplishment and at least one other person to share it with. That combination, meaning plus accountability, is a remarkably strong predictor of successful outcomes.