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Kratom (Mitragyna speciosa) is a tree belonging to Southeast Asia. The leaves consist of a chemical called mitragynine, which works like opioids such as morphine.
Kratom has pain-relieving results like opioid drugs. It likewise has much of the very same severe security concerns as other opioids.
Individuals commonly utilize kratom for withdrawal from heroin, morphine, and other opioid drugs, as well as cough, depression, stress and anxiety, and lots of other conditions, however there is no good scientific evidence to support these uses. Using kratom can likewise be hazardous.
Kratom is banned in some states and nations due to serious security issues. The US FDA has actually cautioned customers to prevent utilizing items including kratom. 
Kratom is a tree that grows wild in the tropical regions of Southeast Asia. The trees are indigenous to nations such as Thailand, Malaysia, and Indonesia. The surrounding nations and provinces in the region are likewise house to the native types. All of those territories supply the much-needed climate and environmental conditions that are necessary for the plant to flourish in the wilderness.
The leaves of a kratom tree were utilized for generations by rural peasants in that area of the world as an organic remedy to battle pain, fatigue, diarrhea, and as a substitute for opium. We likewise find it was used by locals in spiritual ceremonies and to relax after operating in the uncompromising heat outside on the farms.
However despite the fact that the tree’s leaves were known as a folk treatment to occupants in the area for centuries, it never gained any traction in western civilization until Peter Willem Korthals– a botanist with the Dutch East India Service– found its presence in 1839. Korthals initially created the tree with the name Stephegyne speciosa. The taxonomic name and category went through several iterations throughout the years up until George Darby Haviland, a British cosmetic surgeon, offered it the name in 1859 that we still understand it as today: Mitragyna speciosa.
The plant would soon fade into obscurity afterward up until we see a resurgence of interest in the alkaloids found inside the plant at the start of the 21st century, played in part by the continuous opioid epidemic prevalent in American culture. 
Kratom has dark green oval-acuminate leaves and yellow globular flowers.
Kratom flowers and foliage
Mitragyna speciosa is an evergreen tree in the genus Mitragyna that can grow to a height of 25 m (82 feet). Its trunk may grow to a 0.9 m (3 feet) diameter. The trunk is generally straight, and the external bark is smooth and grey. The leaves are dark green and shiny and can grow to over 14– 20 cm (5.5– 7.9 in) long and 7– 12 cm (2.8– 4.7 in) broad when fully open, are ovate-acuminate in shape, and opposite in growth pattern, with 12– 17 sets of veins. The flowers, which are deep yellow, grow in clusters of three at the ends of the branches. The calyx-tube is 2 mm (0.08 in) long and has 5 lobes; the corolla-tube is 2.5– 3 millimetres (0.098– 0.12 in) long.
Mitragyna speciosa is indigenous to Thailand, Indonesia, Malaysia, Myanmar, and Papua New Guinea. It was first officially described by the Dutch colonial botanist Pieter Korthals in 1839, who named it Stephegyne speciosa; it was relabelled and reclassified several times prior to George Darby Haviland provided the final name and classification in 1859. 
The leaves of Mitragyna speciosa (frequently referred to as kratom), a tree endogenous to parts of Southeast Asia, have actually been utilized traditionally for their stimulant, mood-elevating, and analgesic results and have recently brought in substantial attention due to increased use in Western cultures as an alternative medicine. The plant’s active alkaloid constituents, mitragynine and 7-hydroxymitragynine, have been revealed to modulate opioid receptors, acting as partial agonists at mu-opioid receptors and competitive villains at kappa- and delta-opioid receptors. Furthermore, both alkaloids are G protein-biased agonists of the mu-opioid receptor and for that reason, might cause less breathing depression than classical opioid agonists. The Mitragyna alkaloids likewise appear to put in diverse activities at other brain receptors (consisting of adrenergic, serotonergic, and dopaminergic receptors), which may describe the complex medicinal profile of raw kratom extracts, although characterization of effects at these other targets remains very restricted. Through allometric scaling, doses of pure mitragynine and 7-hydroxymitragynine utilized in animal studies can be associated with single doses of raw kratom plant frequently taken in by humans, allowing preliminary analysis of expected behavioral and physiological results in male based upon this preclinical data and contrast to both anecdotal human experience and numerous epidemiological studies. Kratom exposure alone has actually not been causally related to human deaths to date. However, additional research study is needed to clarify the complex system of action of the Mitragyna alkaloids and open their complete therapeutic potential. 
Kratom preparations consist of numerous phytochemicals in differing ratios rendering their correct medicinal assessment tough. Human medical studies are limited.
In general, the effects of kratom in human beings are dose-dependent: small doses produce ‘cocaine-like’ stimulation while larger does trigger ‘morphine-like’ sedative-narcotic impacts.
After taking a couple of grams of dried leaves, the invigorating effects and euphoria are felt within 10 minutes and last for one to one and half hours. Kratom users report increased work capability, alertness, sociability and often heightened libido. The pupils are usually typical or very slightly contracted; blushing may be kept in mind. In one of the few human scientific experiments, a 50 mg oral dosage of mitragynine produced motor excitement, followed by giddiness, loss of motor coordination (favorable Romberg’s test), and tremblings of the extremities and face. For routine kratom users, loss of weight, exhaustion, constipation, and hyperpigmentation of the cheek may be noteworthy adverse effects. The medicinal system responsible for stimulant activity is unclear.
Kratom taken in big, sedating doses corresponding to 10– 25 g of dried leaves may initially produce sweating, dizziness, queasiness and dysphoria but these effects are quickly superseded with calmness, euphoria and a dreamlike state that last for approximately 6 hours. Contracted pupils (miosis) are kept in mind.
Mitragynine and 7-hydroxymitragynine, the two alkaloids generally responsible for the results of kratom, are selective and complete agonists of the μ-subtype opioid receptor (MOR). The receptor agonist impact of kratom alkaloids is antagonised by the opioid receptor antagonist naloxone. In addition, 5-HT2a and postsynaptic α2-adrenergic receptors, along with neuronal Ca2+ channels are likewise involved in the special medicinal and behavioural activity of mitragynine.
In animal studies, the antinociceptive and cough-suppressant results of mitragynine were comparable to those of codeine. In mice, 7-hydroxymitragynine was numerous times more powerful analgesic than morphine even upon oral administration.
Kratom is a little hazardous to animals. Mice chronically treated with 7-hydroxymitragynine established tolerance, cross-tolerance to morphine and withdrawal indications that could be sped up by naloxone administration.
Regular kratom usage may produce dependence. The withdrawal signs in people are fairly mild and typically diminish within a week. Yearning, weakness and sleepiness, anxiety, restlessness, rhinorrhea, myalgia, queasiness, sweating, muscle discomfort, jerky motions of the limbs, tremor as well as sleep disruptions and hallucination may happen. Treatment, if needed, may consist of dihydrocodeine-lofexidine combination, non-steroidal antiinflammatory agents, antidepressants and/or anxiolytics.
The metabolic process of mitragynine in people happens via hydrolysis of the side-chain ester, O-demethylation of the methoxy groups, oxidative and/or reductive changes, and the development of glucuronide and sulfate conjugates. In a man who fatally overdosed propylhexedrine and kratom, the postmortem mitragynine concentrations varied from 0.01 mg/kg to 1.20 mg/l.
The intake of kratom concomitantly with other drugs can provoke major adverse effects. In fact, unfavorable drug interactions including kratom tea taken with carisoprodol, modafinil, propylhexedrine or Datura stramonium have actually been reported. A deadly case in the United States involved a blend of kratom, fentanyl, diphenhydramine, caffeine and morphine offered as herbal drug. 
Uses of kratom
At low dosages, kratom has been reported to work like a stimulant. Individuals who have utilized low dosages usually report having more energy, being more alert, and feeling more friendly. At greater dosages, kratom has actually been reported as being sedative, producing euphoric impacts, and dulling feelings and experiences.
The main active ingredients of kratom are the alkaloids mitragynine and 7-hydroxymitragynine. There is evidence that these alkaloids can have analgesic (pain alleviating), anti-inflammatory, or muscle relaxant impacts. For this reason, kratom is frequently used to relieve signs of fibromyalgia.
The plant’s dark green leaves are normally dried and either crushed or powdered. You can discover prepared kratom powders, usually green or light brown in color. These powders likewise contain extracts from other plants.
Kratom is also available in paste, capsule, and tablet type. In the United States, kratom is mainly brewed as a tea for the self-management of pain and opioid withdrawal.
According to the European Tracking Centre for Drugs and Drug Dependency (EMCDDA), a little dose that produces stimulant impacts is just a couple of grams. The effects typically take place within 10 minutes after ingesting it and can last approximately 1 1/2 hours. These effects can include:.
- lowered motor coordination
A bigger dose of between 10 and 25 grams of dried leaves can have a sedative effect, with sensations of calmness and bliss. This might last for up to six hours. 
Benefits of kratom
When consumed at low dosages, kratom tends to exhibit symptoms comparable to a moderate stimulant. Lots of users report an unexpected burst of energy, focus, psychological clearness and a sense of increased sociability after consuming this herbal supplement. The energy can be compared to caffeine high. If you up the dose, the impacts may lean towards a more sedative scale. It might make an occasional user feel mildly dull (emotionally) and physically.
The main active alkaloids responsible for the majority of physiological modifications happening upon usage are mitragynine and 7-hydroxymitragynine. These alkaloids add to several health advantages a few of which are–.
Kratom could pain and swelling
A study from 2017 shed some light on kratom’s immunity-enhancing and anti-inflammatory impacts. Many kratom users would swear that this herbal supplement helps them rid of years old pains and pains. It’s not uncommon for individuals to change to opioids and over the counter pills/drugs to relieve the discomfort.
With that said, kratom might use a more natural method to deal with or handle the discomfort and inflammation. While we do require more considerable evidence that might help bring kratom in the mainstream market, anecdotal evidence is accumulating every day.
Many individuals suffering from fibromyalgia and persistent pains find relief from HCG injections. Kratom could, to a particular degree, have comparable pain-relieving effects.
Kratom could supply some relief from anxiety
History has it that the locals of nations like Thailand and Malaysia, where kratom originates from would chew a couple of kratom leaves before participating in social gatherings or occasions. The concept was to stay calmer and more unwinded that made them more friendly and less distressed.
To this day, kratom is largely utilized for its possible ability to control traffic of thoughts. Lots of people feel that kratom helps them feel more friendly and talkative. Anxiety is an international health concern, and while discussing the tools to manage stress and anxiety, including kratom into that discussion might be worth it.
It might provide a helping hand in handling depression
The method kratom works its way into the system is pretty much like an opioid, although it’s not opioid-like codeine and morphine. However, the impacts are quite similar. The active alkaloid, mitragynine binds itself with opioid receptors thus rendering the sensation of pain relief and relief. This action might be responsible for the anti-anxiety and antidepressant-like impacts as many users would declare. Presently, there’s really little research product out there on kratom’s impacts on state of mind and stress and anxiety.
It is essential to discuss that not all pressures and not all kinds of kratom items might render anti-anxiety results. A user would need to do research and learn an appealing product in the market. It’s also crucial to establish an ideal individual dose to expect any of those impacts. Therefore, it’s important to buy kratom and kratom items from a reputable source/vendor only. It’s likewise essential to consume it in moderate doses. Kratom could keep anxiety and anxiety at bay momentarily.
It may help get rid of specific addictions
In May 2019, International Journal of Drug Policy published a paper. The goal was to answer a few of the common concerns surrounding kratom and kratom use. The scientists observed blended results. While there is no dearth of anecdotal proof and reports drifting all throughout the internet, we do need more controlled medical trials that are essential for regulative authorizes like the FDA. Based only on those clinical trials can kratom qualify as a safe and reliable drug for conquering opioids and other dependencies.
It’s interesting that even in the middle of an obvious lack of big scale studies, users continue to switch to kratom for conquering addictions. A small-scale research study from 2009 by Malaysia men demonstrated how kratom assisted with withdrawal symptoms.
Kratom can be an excellent energy booster
It’s important to keep in mind that kratom has various stress. Each stress carries various properties. While some may make you feel dull, others can have coffee-like effects. They may make you feel more energetic and inspired to do daily jobs more quickly. Many individuals are beginning to change their early morning coffee with a cup of kratom tea.
Kratom works by improving particular metabolic processes. This leads to much better flow and an increase in oxygenated blood supply. All of that combined can lead to a burst of energy. Thai kratom, Maeng Da, and white vein kratom could be possibly good for patients of fatigue syndrome. 
With this simple Kratom Tea dish, you can enjoy the benefits of Kratom Powder in a soft, delicious drink. Whether the tea is hot or refreshingly cool like iced tea, it does not matter – the impact will not lose its power if you put your Kratom in a tea.
The Kratom leaves of Southeast Asia are famous for their many benefits. For countless years, indigenous cultures have actually chewed on the leaves, dried them and made them into a powder, and boiled in a ritualistic tea. Why? The heating of Kratom permits the effective alkaloids to be released quicker than simply chewing on fresh leaves. As soon as it enters the water, the alkaloids are taken in into your bloodstream much faster.
Thankfully, boiled water does not damage the psychoactive alkaloids in Kratom. Unlike plants like poppy, Kratom alkaloids are incredibly stable in temperature levels far beyond what your water can reach when boiling. 
Health advantages of kratom tea
Although some health blog writers have suggested that Kratom tea brings health advantages, there is extremely little reliable clinical proof to support such claims.
One 2017 survey suggests that Kratom usage may alleviate discomfort, and may relieve the symptoms of mood conditions, such as anxiety and depression.
However, studies are based on self-reporting. This makes them unreliable and more quickly vulnerable to bias.
Others have declared that Kratom tea may aid with signs of opioid withdrawal. This is since Kratom leaves contains mitragynine and 7-hydroxymitragynine, chemicals that communicate with the opioid receptors in a person’s brain.
Animal research studies have revealed that Kratom might enhance opioid tolerance in mice. Nevertheless, this does not necessarily mean that comparable effects would happen in people. 
How do you make strong kratom tea?
When you make Katom tea, you require to prevent boiling the water. Kratom contains alkaloids and when they are boiled, they can break down. You then lose the results that the alkaloids provide. What you require to do is use hot water.
This can be boiled water that has been enabled to cool down or water that is simply below the boiling point. You will get strong Kratom tea when you do it that way. The amount of water you put in your Kratom tea depends on the dosage you are taking.
A lot of Kratom veins have a bitter taste. When they are focused meaning with less water per dose, they can be rather unpalatable. A great way to navigate this is to add more water. One to 4 cups per dose is perfect. Just ensure that you finish all of it.
When you take Kratom, it is likewise essential to stay hydrated throughout the day. Drink lots of water throughout the day and you’ll be fine.
Here are some Kratom tea dishes that you can give a try. They are excellent way to experience Kratom tea while reducing the bitter taste that it has.
Apple cider kratom tea
The very first Kratom tea dish is the apple cider vinegar recipe. It’s an excellent method of getting one of the most out of Kratom tea. As we’ve already discussed, acids assist to stabilize the mitragynine in Kratom. It suggests that you get the best out of it.
It is believed that the potency of Kratom will be significantly affected by very hot water. Including an acid assists keep them undamaged. It also helps highlight the alkaloids from the Kratom.
For this recipe you will require:.
- 5grams Kratom powder or leaves
- 2 to 4 cups Water
- 1 teaspoon baking soda
- Apple cider vinegar
Put the water into a pot or kettle. Bring it to a simmer just under boiling. Include some apple cider vinegar to the water. Turn off the heat on the range and add 5 grams of Kratom to this mix. Enable it to sit for 10 to 20 minutes.
By this time, the Kratom would have settled at the bottom of the pot or kettle. Pour the liquid into a container. You then need to include some sodium bicarbonate to the option. This will remove the acidic taste from your Kratom tea.
Make certain to stir or shake the tea after every sip. This is carried out in order to ensure that the mitragynine mixes with the water. It is denser than water and tends to settle at the bottom of the mixture. Shaking or stirring guarantees that it keeps well blended.
If you wish to make this mixture a bit more palatable, you can include some honey or sugar to it. Honey is best as it is a natural product and won’t have the unfavorable results connected with sugar.
Lemon/lime kratom tea
Another excellent method to ensure that your Kratom tea keeps its alkaloids composition and they do not break down instead of including apple cider vinegar is by including lemon to it. This will prevent the alkaloids from breaking down under intense heat.
There are numerous ways to make Kratom tea. Here is an excellent method to make some Kratom tea. This is by no suggests a fast procedure where you just discard your Kratom and other active ingredients into a tea pot and brew for a couple of minutes.
You require at least an hour to prepare this Kratom tea. Here is a list of the things you’ll need:.
- 5 grams crushed Kratom leaves or powder
- 2 tablespoons of lemon/lime juice or apple cider vinegar
- 2 cups of water
- A filter or strainer
- Ginger powder
Put your Kratom and lemon/lime juice or apple cider vinegar into a kettle or pot. Let them soak for 20 minutes. As soon as you have actually done that, add your water. Let this mix simmer for about 20 minutes. As soon as that it is done simmering, let it high for even more 20 minutes.
This process assists get all the alkaloids out of the Kratom leaves into the liquid. Your next action is to put a generous quantity of honey and ginger into the jar or container you wish to keep the Kratom in.
Pour your tea from the pot through a filter into the container that you want to save it in. Seal the container and leave it in the fridge overnight. This further permits all the ingredients to mix in well. This Kratom Tea recipe is terrific for a variety of factors.
It’s rapidly absorbed into your blood stream. This is because all the alkaloids have actually been extracted and your body doesn’t have to do the extra work of pulling them from the leaves.
Secondly, it tastes a lot much better than having to take Kratom as a paste. The bitter taste doesn’t completely go away but it is substantially minimized.
Kratom tea can be refrigerated and taken later on. When compared to other Kratom extract products on the marketplace like the liquids, Kratom tea has shown to be of the exact same or comparable strength. You are also ensured that there are no additives or preservatives when you make your own Kratom tea in your home.
Another factor that Kratom tea is proving to be popular with the Kratom crowd instead of paste is due to the fact that the sludge from Kratom leaves or powder can be hard to swallow. When you take Kratom as a paste, it’s finest to blend it with warm water instead of cold.
When people take it by doing this, they produce a paste which they chug down followed by water or fruit juice. This is due to the fact that the paste is both hard to swallow along with bitter. Taking Kratom tea means that you do not need to deal with these issues. 
Negative effects of kratom
The most typical negative effects of kratom are:
- Modified psychological status.
- Stress and anxiety and irritability.
- Deception and hallucination.
- Drowsiness and sedation.
- Dry mouth.
- Frequent urination.
- Nausea and vomiting.
- Tongue pins and needles.
Other severe kratom side effects consist of:
- Cardiac problems, such as heart attack, unusual heart rhythms and high blood pressure.
- Encephalopathy (brain disease).
- Hypothyroidism (underactive thyroid).
- Liver damage and liver failure.
- Rhabdomyolysis (A condition that causes kidney damage when muscles disintegrate and launch a protein into the blood).
- Respiratory anxiety (problem breathing).
Long-term kratom users might likewise experience:
- Increased cheek coloring.
- Anorexia nervosa.
- Weight-loss. 
It is essential to know kratom dose
Kratom dosage is necessary, as it will figure out the impact you get. Different stress have various effects from bulk kratom pills, so beginning little will assist you identify the very best way to get the best results. Lower dosages tend to offer energy-boosting and revitalizing effects, while higher doses produce more peaceful results. While these are just general guidelines, they are still helpful for brand-new users. Simply remember to talk to a health care company before starting any brand-new supplement or drug regimen.
The first time you attempt kratom, you must take one to 2 grams. This amount will help you get utilized to the herb and figure out just how much you require. Once you’ve established a tolerance, you can increase your dosage appropriately. In general, you need to take two to four grams of kratom a day. The optimum dose for kratom is 4 grams. Nevertheless, some users find that consuming kratom three to six grams daily produces a more powerful result.
The most affordable kratom dosage is best for novices
Novices ought to start with the most affordable kratom dose. Most experts advise taking no more than a couple of grams of any specific stress. Afterwards, you can increase your dosage by a half or one full gram every hour. Most routine users take anywhere in between 2 and 5 grams of premium kratom powder a day. There are numerous aspects to think about when picking the correct kratom dosage. The main thing to keep in mind is that the right amount depends upon your body type and level of sensitivity. 
Medications altered by the liver (Cytochrome P450 1A2 (CYP1A2) substrates) interaction ranking: Moderate Beware with this combination. Talk with your health service provider.
Some medications are altered and broken down by the liver. Kratom may decrease how rapidly the liver breaks down some medications. Taking kratom in addition to some medications that are altered by the liver may increase the impacts and adverse effects of these medications. Prior to taking kratom, talk with your doctor if you take any medications that are altered by the liver.
A few of these medications that are changed by the liver consist of clozapine (Clozaril), cyclobenzaprine (Flexeril), fluvoxamine (Luvox), haloperidol (Haldol), imipramine (Tofranil), mexiletine (Mexitil), olanzapine (Zyprexa), pentazocine (Talwin), propranolol (Inderal), tacrine (Cognex), theophylline, zileuton (Zyflo), zolmitriptan (Zomig), and others.
Medications changed by the liver (Cytochrome P450 2C19 (CYP2C19) substrates) interaction rating: Moderate Be cautious with this combination. Talk with your health service provider.
Some medications are changed and broken down by the liver. Kratom might decrease how quickly the liver breaks down some medications. Taking kratom with these medications that are changed by the liver might increase the effects and negative effects of these medications. Before taking kratom, speak to your doctor if you take any medications that are altered by the liver.
A few of these medications that are altered by the liver include amitriptyline (Elavil), carisoprodol (Soma), citalopram (Celexa), diazepam (Valium), lansoprazole (Prevacid), omeprazole (Prilosec), phenytoin (Dilantin), warfarin (Coumadin), and many others.
Medications altered by the liver (Cytochrome P450 2D6 [CYP2D6] substrates) interaction ranking: Moderate Beware with this mix. Talk with your health service provider.
Some medications are altered and broken down by the liver. Kratom might reduce how quickly the liver breaks down some medications. Taking kratom together with some medications that are broken down by the liver may increase the effects and side effects of these medications. Prior to taking kratom, talk with your doctor if you are taking any medications that are altered by the liver.
Some medications altered by the liver consist of amitriptyline (Elavil), codeine, desipramine (Norpramin), flecainide (Tambocor), haloperidol (Haldol), imipramine (Tofranil), metoprolol (Lopressor, Toprol XL), ondansetron (Zofran), paroxetine (Paxil), risperidone (Risperdal), tramadol (Ultram), venlafaxine (Effexor), and others.
Medications changed by the liver (Cytochrome P450 3A4 [CYP3A4] substrates) interaction ranking: Moderate Be cautious with this combination. Talk with your health supplier.
Some medications are changed and broken down by the liver. Kratom may reduce how quickly the liver breaks down some medications. Taking kratom in addition to some medications that are broken down by the liver may increase the impacts and side effects of these medications. Prior to taking kratom, speak with your doctor if you are taking any medications that are altered by the liver.
Some medications changed by the liver consist of cyclosporin (Neoral, Sandimmune), lovastatin (Mevacor), clarithromycin (Biaxin), indinavir (Crixivan), sildenafil (Viagra), triazolam (Halcion), and lots of others.
Modafinil (Provigil) interaction score: Moderate Be cautious with this mix. Talk with your health provider.
Seizures have been reported in a person who took kratom in addition to the drug modafinil (Provigil). It is not yet understood how taking this combination might cause seizures. Until more is understood, people taking modafinil (Provigil) must prevent using kratom. 
Although not an epidemic in its own right, the present patterns in kratom usage are cause for progressively growing issue, and it is likely to become a significant public problem in the future if it continues on its existing trajectory. In looking for to address it, the problem should be understood within the higher context of the existing epidemic of opioid abuse, as the desire to ease opioid withdrawal symptoms is an important factor accounting for patients who look for and abuse kratom. Since it is primarily a consequence of the opioid crisis, it will be hard to adequately address this problem up until the larger opioid issue is solved. Even then, use of kratom will continue amongst non-addicts who want to abuse it for recreational purposes. In this regard, doing something about it to restrict gain access to may be called for. However even in case kratom is arranged as a controlled substance, it will likely stay available through private dealings, just as lots of currently managed illicit substances are. Offered the possibility of drawn-out need for kratom use, health companies and medical educators ought to take efforts to improve awareness of this still fairly unknown drug.
In addition to promoting awareness among healthcare experts, there is a great need for more substantial, high-quality studies to better comprehend the system of its toxicity and to formulate particular and reputable guidelines for the management of kratom ingestion. Clients must be warned of the possible harm kratom poses, including predictable risks such as reliance and toxicity, and unforeseeable dangers associated with item quality and contamination. Nevertheless, the rising significance and interest in this problem provides brand-new opportunities for research on kratom in the context of opioid pharmacology, and ultimately will support the development of brand-new and better analgesic agents.