17 Jul Kratom (Mitragyna speciosa): What It Is & Effects
Kratom, the contentious plant consumed for centuries for its diuretic properties, has recently become the topic of an FDA public health advisory addressing the deadly dangers of its usage. Why do people use kratom, and what are the specific dangers? Keep reading to discover more.
Disclaimer: We strongly recommend against accepting kratom for any reason. Some of our readers who were taking the drug requested that we commission a post on it, and we are simply providing information that’s offered in the clinical and scientific literature.
Please consult with your medications with your doctor.
What’s Kratom?
You will know Kratom by its street names: Thang, Kakuam, Thom, Ketum, Biak-Biak, and Krypton (this one also contains O-Desmethyltramadol).
Kratom (Mitragyna speciosa) is an evergreen deciduous tree native to Southeast Asia. It’s a component of this coffee (Rubiaceae) family.
It grows naturally in Thailand, Malaysia, Indonesia, and Papua New Guinea.
Kratom leaves have been used for centuries by the indigenous people of Southeast Asia because of their stimulant properties. Kratom reportedly reduces fatigue during manual labor and extreme heat. It might also treat muscular pain, gut infection, coughing, and diarrhea.
In addition, it’s been utilized for self-treatment of opiate addiction.
Kratom inhibits the feeling of pain (anti-nociceptive, sensory nerves block pain stimulation ) and has euphoric, anti-inflammatory, anti-depressant, and muscle relaxant properties.
But, kratom has since transitioned into a recreational drug in both Southeast Asian and Western contexts.
Kratom is widely accessible via online stores in the form of a powder, extract, pill, or dried leaves. A cross-sectional survey in the USA recognized the most commonly consumed form to be kratom powder with a beverage or food.
Kratom is now legal in the United States, nevertheless, that the FDA released an advisory concerning the related deadly risks in November 2017 and an additional warning about unapproved kratom products in June 2019.
What Are the consequences of Kratom?
Users report that chills can be accomplished over 5 to 10 minutes of chewing the leaves and can last up to 1 hour.
Kratom functions as a depressant with reports of”morphine-like” nausea and sedation in high doses and a”cocaine-like” stimulant in low doses.
Mechanism of Action
Over 25 compounds have been identified in kratom extract. The active ingredients are mitragynine and 7-hydroxymitragynine.
Mitragynine is the most abundant alkaloid plus also a partial opioid receptor activator (agonist). It targets a portion of the brain that responds to opioids, which explains the reason why it has similar effects to morphine.
The small alkaloid, 7-hydroxymitragynine, is regarded as more powerful than morphine.
These lively alkaloids act on the mu (MOR), delta (DOR), and kappa (KOR) opioid receptors, and the alpha adrenergic and 5-HT2A receptors to make pain relief (analgesia) and euphoria
Kratom extract may also trigger dopamine D1 receptors (DRD1).
The activity of the receptors improves mood and reduces stress.
Changes in the body in reaction to these alkaloids contain secretion of stomach acid and inhibition of contraction of a portion of the small intestine (ileum) and male reproductive system (vas deferens).
Why do People Take Kratom?
Bear in mind that the FDA has issued multiple warnings about the hazards of kratom, for example, the risk of creating an addiction, like other drugs that trigger the opioid receptors. These effects have been found in clinical trials, but at the possible expense of addiction, liver damage, and cognitive impairment.
1) Pain Management
In an online survey of kratom users, pain relief was the most reported beneficial effect of the plant.
Although no well-controlled human studies are released, animal studies show that kratom extract improves various forms of pain. Mitragynine and 7-hydroxymitragynine relieved and blocked pain (they had been analgesic and anti-nociceptive) in creatures, together with opioid-like effects detected in organ samples.
Plants awarded kratom extracts shown decreased (nociceptive) responses to dangerous stimuli such as the hot plate, tail-flick, and acetic acid-induced writhing tests.
High levels of kratom in rats decrease nerve and muscle function by blocking the vulnerable sciatic nerve response to electrical stimulation in the nerve-muscle intersection.
2) Stress and Depression
In a 2016 online sectional survey in the US, 66 percent of the participants used kratom for mental conditions including depression and anxiety.
In particular, folks report that kratom helps to reduce social anxiety.
Both low and high doses of mitragynine in rats effectively decreased stress.
Antidepressant-like effects are observed in numerous animal models of depression. These are largely predicated on kratom’s action on opioid receptors.
Both the animal and cell-based experiments show mitragynine also interacting with adrenergic and serotonergic receptors. All these non-opioid receptors are common targets of antidepressant medications and might contribute to the antidepressant effects of kratom.
No well-controlled human clinical trials have supported these findings.
3) Energy
In a cross-sectional survey of 293 northern Malaysian consumers, kratom was utilized to enhance physical energy by 27 to 28% of moderate – and long-term customers.
Many of these people used kratom to enhance work performance and swallowed it as an”energy-boosting drink”.
In addition, an online survey identified increased energy as one of the most reported advantages of the substance.
According to a review of human and animal studies, kratom causes stimulant effects and holds off exhaustion.
In rats, a low dose of mitragynine caused nonstop motion (hyperactivity), a nature of increased physical energy.
4) Euphoria
In an analysis of 120 journal articles ranging from animal to human research, the euphoria was one of kratom’s reported consequences.
Nevertheless, only 6% to 12% of 136 active users in northern Malaysia reported euphoria for a reason they use kratom.
Euphoria can also be connected to kratom’s dependence potential because it’s presumably caused by the activation of adrenal gland.
In a case report, a 44-year-old patient took a dose increase in 4 grams to 8 grams twice per day to experience the desirable euphoria.
5) Opiate Withdrawal
Kratom has been utilized as an opium substitute because the 19th century.
At elevated doses, kratom induces a”morphine-like” effect of calmness (sedation).
Opioid abusers occasionally resort to kratom for self-treatment of addiction and also to alleviate symptoms of withdrawal. For the time being, kratom isn’t hard to buy, requires no medical prescription, and is less expensive than other opioid replacement treatments (e.g., buprenorphine, methadone).
Mechanistically, kratom (mitragynine and 7-hydroxymitragynine) can reduce symptoms of opiate withdrawal from interacting with opioid receptors (MOR and DOR); descending serotonin, norepinephrine, dopamine (monoaminergic) projections, chiefly from the brain stem; and by blocking neuron calcium stations.
However, kratom itself poses a possibility of addiction.
6) Comfort
Users report feelings of relaxation and tiredness after consumption of a higher dose of kratom.
Multiple animal studies reveal that kratom extract and mitragynine both decrease muscle twitch, highlighting their direct effect on muscle relaxation.
7) Inflammation
Mitragynine, the key active ingredient of kratom, decreased inflammation (by inhibiting the bacterial endotoxin/LPS-stimulated production of COX-2 and PGE2) in response to an immune stimulant.
Dangers of Kratom
FDA Warnings
The FDA has introduced multiple specific safety warnings regarding kratom. In 2017, the FDA cautioned of acute toxic effects and calls to poison control associated with kratom use. In 2019, it cautioned companies producing kratom goods for opioid withdrawal these products were marketed, unapproved, and likely dangerous. The FDA’s overall policy on kratom is the fact that it presents dangers of dependence, dependence, and abuse.
In case reports, consumer testimonials, and animal research, kratom has additionally generated severe and chronic adverse consequences.
1) Learning and Performance
Although no well-controlled human studies have been published, animal studies show that chronic mitragynine therapy impairs memory and learning.
In rat and mice models, mitragynine caused cognitive impairments. It hindered the capacity to avoid a reaction that routinely leads to punishment (passive avoidance learning), and memory care and recovery.
2) Liver Damage
In a case report, a young man kratom user-produced jaundice and pruritus and had alkaloids in his urine sample after two weeks of usage. These clinical signs indicate the inability of the liver to cleanse the body of the alkaloids and correlate with liver damage (intrahepatic cholestasis).
Kratom use may be linked to cholestatic liver injury. In another case report, a middle-aged guy who used a very low dose of kratom for 3 months developed jaundice and liver abnormalities. Interestingly, his jaundice reversed upon withdrawal and reappeared upon resuming the consumption of kratom.
Mitragynine inhibits three liver cytochrome P450 enzymes (CYP2C9, CYP2D6, and CYP3A4) necessary for the breakdown of drugs and toxins. Without all these, the liver alternative detoxification pathways can become overtaxed.
Other Side Effects
Reported side effects of kratom use include:
- Headache
- Nausea
- Chills/sweats
- Dizziness
- Vomiting
- Anorexia
- Dry-mouth
- Increased production of urine (diuresis)
- Increased heart speed and blood pressure
- Respiratory depression
- Posterior reversible leukoencephalopathy syndrome (an aggravation, confusion, seizures, and visual loss)
- Liver toxicity
- Constipation
With the exception of diarrhea, an online poll of American users shows that all unwanted effects are dose-dependent, with higher doses producing more side effects compared to lower doses.
Risk of Kratom Addiction and Withdrawal
The euphoric feeling of being “high” can advocate users to continuously consume kratom, resulting in potential addiction.
In animal research where kratom was administered for 5 days or more, the animals acquired a physical dependence — addiction. Withdrawal symptoms similar to opioid withdrawal were also detected.
Animals withdrawing from chronic mitragynine therapy had symptoms of opioid-like withdrawal, such as movement hypersensitivity to other drugs or stimulation, and enhanced stress.
Acute human side effects related to withdrawal may occur with chronic use. These unwanted effects include aggression, aggression, anxiety, loss of libido, muscle aches, severe weight loss, and sleeplessness.
Confusion and delusion were also reported.
Hyperpigmentation of the lips and face can occur after chronic kratom use because mitragynine can raise the melanocyte-stimulating material, melanin.
Long-term users appear thin with swollen stomachs, unhealthy complexions, dark lips, and dry skin.
Using Kratom
Dosage
There is no safe dose for kratom because kratom is an unapproved new drug that poses a significant safety threat. Below is a summary of the dosages used in scientific research, outlined for informational purposes. We strongly recommend against using kratom for any reason.
According to customers, kratom outcomes are dose-dependent:
- Low to moderate (1 to 5 g) doses result in moderate stimulant effects
- Moderate to high (5 to 15 g) doses trigger opioid-like effects (analgesia, euphoria)
- Very high (> 15 g) doses result in sedating effects
There is not sufficient safety data to determine the relative risks of these doses. Low doses may present as much of a risk of dependence as substantial doses.
Can You Overdose on Kratom?
Kratom is on the DEA’s listing of drugs of concern owing to its potential toxicity and risk of miscarriage. A rise from 26 to 263 calls to poison centers linked with kratom use occurred between 2010 and 2015, with over 40% of the calls rated as serious or life threatening cases.
Signs and symptoms of kratom overdose include:
- Nausea
- Rapid heart rate (tachycardia)
- Hypertension
- Agitation or irritability
- Seizures
- Drowsiness
- Coma
The risk of overdose is raised with co-consumption of alcohol and other drugs (ex.: benzodiazepines, narcotics).
Additional substances were present in the urine and blood samples and led to the deaths of 9 kratom overdose victims in a study between 2009 and 2010.
An animal toxicity study demonstrated that mitragynine had a relatively low toxicity.
But, two rat studies that orally administered a higher dose of 200 mg/kg of kratom extract led to death.
Medication Interactions
There is potential for drug interaction when mitragynine and 7-hydroxymitragynine are co-administered with medications that get broken down from P-glycoprotein (e.g. colchicine, tacrolimus, and quinidine) or UG72B7.
Laboratory experiments show that kratom extracts block select CYP enzymes (CYP3A4, CYP2D6, CYP1A2) necessary for drug metabolism, which may lead to interactions with prescription and over-the-counter drugs.
These drug interactions can lead to a build-up of the active constituents of kratom and other drugs, contributing to liver damage.
This is not necessarily a comprehensive list of possible interactions between kratom along with other medications. To avoid abrupt interactions, we strongly recommend against using kratom.
Resources
Kratom leaves and smaller stalks can be consumed fresh by chewing dried or dried and smoked, steeped in water, prepared as an extract or a crushed powder in the kind of a herbal supplement.
Two distinct leaf types are common, the red-veined and white-veined varieties.
Founded in Bali, the red variety is most often used to alleviate pain, while white-veined varieties originating from Malaysia are reported to generate a powerful stimulant effect.
The chemically-based potency of distinct versions is unknown, provided that they aren’t regulated by the FDA; hence, they are not well-documented.
User Experiences
A qualitative evaluation of kratom consumer’s first-hand experiences highlighted themes of pain relief, improved mood, reduced anxiety, and possible for management of opioid withdrawal.
User experiences from online blogs note that kratom provided pain relief with no”feeling spacey,” and helped keep a clear head for a few hours. If too large a dose is accepted, nausea, vomiting, and sleepiness were commonly reported side effects.
Negative reaction topics were also noted, for example, nausea and kratom dependency.
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