Posted by You’ve likely read that kratom products, including 7-OH, Oxonol, and Pseudo, are not legally classified as opioids nor as controlled substances, although they have “opioid-like effects.” That doesn’t sound quite right, especially for everything other than kratom, which is energizing at low doses and so can also have stimulating properties.
Personally, I call kratom and all its derivatives atypical opioids. There are a few different reasons for this. Let’s get into it.
Plant-Based Origin
The traditional, classical, or typical opioids we know about come from the opium poppy plant somehow. Those are all based on natural, synthetic, or semi-synthetic derivatives of the opiates morphine, codeine, or (occasionally) thebaine. Opiates are the bioactive compounds in opium poppy that bind to opioid receptors in the brain and nervous system, and their main effects are pain relief and euphoria.
Both traditional and atypical opioids have an origin in plants in some way. Atypical opioids don’t come from opium poppies at all, yet their effects seem to be very much like those of traditional opioids.
How They Act on Opioid Receptors
Rather than tell you “I’ve had traditional opioids as well as kratom and 7-OH and they have certain similarities, trust me, bro,” and leave it at that, I’d rather go into detail as to what kratom, 7-OH, and derivatives like Oxonol and Pseudo do to the brain. What they all have in common is that they bind to mu-opioid receptors, the main one that’s responsible for pain relief and euphoria. MORs release GABA, which inhibits the release of dopamine, resulting in disinhibition and stimulation of the brain’s dopamine reward system.
Traditional opioids do the same, so what then? The difference is this: Traditional opioids (like morphine) tend to bind fully to mu-opioid receptors, and so are known as full mu-opioid receptor agonists. But kratom, 7-OH, and the like are partial mu-opioid receptor agonists, because they only bind partially. Already, you might guess that means they won’t overwhelm you and put you sleep like traditional opioids can and do.
Pain Relief Potency
Here’s another thing, one that makes the kratom alkaloids and derivatives different from even each other: The degree to which they partially bind to those mu-opioid receptors can be quantitatively measured. So in a comparison of all four – kratom, 7-OH, and the 7-OH alternatives of Oxonol, and Pseudo – Pseudo does the most, followed by 7-OH and then Oxonol. Kratom does the least, which is why people need to take moderate to high doses of it to get the pain-relieving effects.
More Opioid Receptor Action
Mu, delta, and kappa are the brain’s opioid receptors. Other than mu, we need to look at whether kratom, 7-OH, Oxonol, and Pseudo act on delta and kappa, because their behavior on them will contribute to the effects of each botanical.
- Kratom: Partial MOR agonist and distinct blocking or antagonism at DOR and KOR.
- 7-OH: Same as kratom, but even more so.
- Oxonol: Partial agonist at MOR and DOR, with minimal binding at KOR.
- Pseudo: Partial MOR agonist and DOR antagonist.
As you can see, these botanicals have either a dual-agonist, multiple agonist, or mixed agonist/antagonist profiles. The full MOR agonist activity of traditional opioids doesn’t really leave room for anything else. Kratom and 7-OH have fewer adverse effects than full MOR agonists (like morphine), while Oxonol and Pseudo have fewer adverse effects than 7-OH. Also, unlike full agonist opioids, these botanicals have a “ceiling effect” where analgesia doesn’t increase after a certain amount.
Neurotransmitters and Signaling Bias
Serotonin, also known as serotonin 5-HT, often gets talked about as a type of receptor, the happy chemical. It’s really a whole receptor family.
While opioids do not directly trigger or activate any type of serotonin, they do act through the serotonergic system, which regulates mood, appetite, and sleep. They do so by stopping serotonin from being transported away, leaving higher serotonin levels than normal. “System” here refers to a network of neurons that use a neurotransmitter (such as serotonin) to regulate physiological processes. Much of the serotonergic system is within the brainstem.
Opioids also act through the adrenergic system to a lesser degree. There, they block the release of the neurotransmitters norepinephrine (noradrenaline) and epinephrine, which can cause higher blood pressure and heart rate. This system is part of the sympathetic nervous system, a division of the autonomic nervous system that regulates involuntarily bodily functions like heart rate, blood pressure, respiration, and digestion. It produces the “fight or flight” response in survival situations or where there’s a perceived threat.
While all of these common factors make it sound like kratom alkaloids work much the same way traditional opioids do, there’s a crucial difference. Traditional opioids tend to favor Beta-arrestin pathways, whereas kratom alkaloids favor G-protein pathways. This difference also accounts for their fewer adverse effects that go beyond the brain alone, but consider the entire body.
Pharmacokinetics
We’ve talked about the effects of atypical opioids on the body, known as pharmacodynamics. Now it’s time to learn about the effects of the body on atypical opioids.
Since the liver is the organ that handles botanicals, let’s look at how it breaks them down. The liver converts mitragynine (the main alkaloid in kratom) to 7-OH. Pseudoindoxyl mitragynine (Pseudo) is a metabolite of 7-OH.
At the same time though, full-spectrum kratom has up to 40 alkaloids that include both mitragynine and 7-hydroxymitragynine (7-OH). It has even more analgesic effect than the standard kratom or MIT isolate alone.
Some traditional opioids must be converted in the liver for people to get the pain-relieving effects, and others do not. Regardless, the breakdown by the liver produces certain metabolites from opioids – whether traditional or not – depending on the chemical structure of the opioid in question. 7-OH, Oxonol, and Pseudo take the next step to alter the structure of mitragynine or 7-hydroxymitragynine to give alkaloids that would naturally occur in the breakdown process, only more concentrated.
Legal Issues
Last but not least in consideration are the differences in legal status between traditional opioids and kratom alkaloids. Traditional opioids include both controlled substances available in medical settings or prescription along with illicit drugs. These two opposite ends of the legal spectrum have their own drawbacks: Illicit drugs are dangerous and illegal, and controlled substances are hard to get.
Alternatives to traditional opioids came about to fulfill the desire for personal control with easier access and fewer adverse effects. But while kratom, 7-OH, Oxonol, and Pseudo are all legal at the federal level, that status doesn’t translate to the state level for all of them:
- Kratom: Banned in some states and municipalities
- 7-OH: Banned in some states and municipalities
- Oxonol: Formulated for compliance, but may be banned in certain areas
- Pseudo: Formulated for compliance and legal everywhere in the United States
Not Your Typical Botanicals
Understanding what makes kratom, 7-OH, Oxonol, and Pseudo atypical gives you a good idea of how they’re different from traditional opioids and why people choose them as alternatives. Each product from the kratom plant is already distinct from traditional opioids for many reasons, but they’re also distinct from each other. Neither one is necessarily better than another; they serve unique purposes.
For the best botanicals you can trust, consider Real Botanicals. They’ve got their own premium quality standards that give you meticulously-crafted products with total control over your experience to suit your wellness lifestyle.
See “7-OH vs. Opioids: How Do They Compare As Analgesics?”
You might be interested in “A Comparison of Kratom to Other Opioids.”