Are you a Kratom user who is tired of its effects wearing off too soon? Well lucky for you, recent research suggests that a drug called Tagamet has a positive interaction with mitragynine, giving a very potent and long-lasting combination. However, every claim needs facts, and we have listed down everything necessary to ensure that this certainly is a safe mixture.
Overview Of Kratom
Kratom (often known as Mitragyna speciose) is a Southeast Asian tropical evergreen tree belonging to the coffee family. It’s native to Thailand, Indonesia, Malaysia, Myanmar, and Papua New Guinea, where it has had utilization in herbal medicine since the 1800s. Kratom contains narcotic characteristics as well as stimulating qualities.
Kratom had various benefits in traditional medicine in places where the plant thrives. Chewing the leaves relieves musculoskeletal discomfort while simultaneously increasing energy, hunger, and sexual drive in the same manner as khat and coca do. The leaves or extracts from them can act as a local anesthetic and treat wounds. Coughs, diarrhea, and intestinal illnesses have all shown signs of improvement using these extracts and leaves. In some indigenous regions, some native people also used them in deworming processes.
Kratom is a frequent supplement for physically demanding or tiresome jobs to combat weariness. Additionally, it also has mood-enhancing and pain-suppressing effects. In the past, people served Kratom to guests as an exotic delicacy. It also had involvement in the religious ceremonies of ancestors and deities in Thailand. Because the plant is bitter, it is usually mixed with a sweetener to make the taste more bearable.
The short-term effects of Kratom are complicated and vary due to the drug’s unique chemical combination. The balance between stimulant-like and opiate-like effects is dependent on the amount, and even when taking the same amount, various users have had dramatically diverse experiences with the substance.
The stimulant-like effects of Kratom at low doses (1-5 g) predominate. These can be felt in as little as 10 minutes and can last anywhere from 60 to 90 minutes. While most users believe that these effects are pleasant, some individuals report feeling anxious and agitated. Kratom’s principal stimulant-like influences are comparable to amphetamine but less powerful and include the following:
- Increased alertness and stamina
- Suppressed appetite
- Improvement in sociability
- Increased libido
Kratom has mostly opioid-like effects that continue for many hours at moderate to high dosages (5-15 g).
The drug’s euphoric “high” is said to be less potent relative to other opioids, and some consumers perceive it as unpleasant or dysphoric. The following are some of its opiate-like effects:
- Pain relief (Analgesia)
- Hallucinatory state of mind
- Repression of coughing
- Lessening of opioid withdrawal symptoms
Any Kratom dose that is higher than 15 g causes effects comparable to high opioid dosages, including profound drowsiness and, in rare cases, loss of consciousness.
Biochemistry Of Kratom
Mitragynine is a tetracyclic relative of the pentacyclic indole alkaloids yohimbine and voacangine. Many of the primary psychoactive substances in Kratom are indole alkaloids linked to mitragynine. Mitragynine and 7-hydroxy mitragynine (7-HMG), in particular, make up a substantial fraction of the natural compounds extracted from the supplement.
Furthermore, at least forty other chemical compounds, including twenty-five extra alkaloid components, are present in Mitragyna speciosa leaves. These include raubasine/ajmalicine, corynanthidine, mitraphylline, mitragynine pseudoindoxyl, and rhynchophylline.
Pharmacology Of Kratom
Much of Kratom’s pharmacological aspect was unknown as of 2017, including stimulating effects at low dosages, an opioid-like impact at larger doses, and anesthetic/sensory-suppressive effects.
At nanomolar doses, both mitragynine and 7-HMG exhibited partial agonist action at the human-opioid receptors. However, 7-HMG appears to have a greater affinity. At micromolar quantities, other alkaloids exhibit antagonistic activity. Therefore, Kratom’s effects might be due to the interaction of these other alkaloids.
Mitragynine also activates 2-adrenergic receptors, blocking the production of norepinephrine (noradrenaline). Other chemical substances in this family include sedative dexmedetomidine and clonidine. These particular compounds treat anxiety and several opioid withdrawing symptoms. This action might explain why Kratom, when used with other sedatives, can be problematic.
Overview of Tagamet
Tagamet is a brand name for cimetidine, a histamine H2 receptor antagonist. Ever since the introduction of newer histamine H2 receptors, cimetidine’s use has suffered a significant reduction. These antagonists, such as ranitidine and famotidine, have fewer medication interactions and side effects. Tagamet is still considerably usable, but it is no longer among the most extensively preferred H2 receptor antagonists.
Tagamet is used to treat duodenal and benign gastric ulcers, including those caused by NSAIDs, recurring and stomal ulcers, oesophageal reflux syndrome. There are also other situations in which Tagamet shows usefulness in reducing stomach acid.
In overdose, Tagamet seems to be pretty safe, causing no problems even with enormous dosages.
Cytochrome P450 Inhibition
This chemical substance is an efficacious inhibitor of cytochrome P450 (CYP) enzymes. These are the enzymes that operate as monooxygenases and include heme as a cofactor.
The medication chiefly inhibits CYP1A2, CYP2D6, and CYP3A4 and is classified as a moderate inhibitor for each of these enzymes. This blockage is significant because CYP-mediated drug biotransformations require these three CYP isoenzymes.
However, some of these cytochrome P450 enzymes oxidatively metabolize some drugs, making pharmacokinetic interactions possible.
Tagamet is a competitive and reversible inhibitor of numerous CYP enzymes. But mechanism-based (suicide) irreversible inhibition of CYP2D6 can also happen in some cases. It blocks the oxidation of other medications by reversibly inhibiting CYP enzymes through direct interactions with the complexed heme-iron of the binding site. It happens via one of the imidazole ring nitrogen atoms.
Antiandrogenic And Estrogenic Impacts
Even though it has weak antiandrogenic activity in high concentrations, some effects are visible to a certain extent.
It acts as a directly competitive antagonist for the androgen receptor (AR), the biological target of androgens like testosterone and dihydrotestosterone. Tagamet has shown mild but considerable antiandrogenic effects at sufficiently high dosages, including weight decreases in male accessory glands such as the prostate gland.
Additionally, this drug also prevents the 2-hydroxylation of estradiol (through suppressing CYP450 enzymes responsible for the metabolic deactivation of estradiol), resulting in higher estrogen concentration.
Individual case studies have also indicated that the drug reduces testosterone production and increases prolactin levels, symptoms indirectly related to elevated estrogen levels.
Overview of Kratom and Tagamet together
Pharmacokinetics Of Kratom
Thanks to its potent alkaloids, Kratom has a strong influence on the body. The effects of the supplement ordinarily start about 10 to 15 minutes after ingestion. A small dosage can stay active in the system for up to two hours, while greater dosages can last up to eight hours. Kratom’s influence peaks around 1.5 to 2.5 hours after a person consumes it.
The cytochrome P450 enzymes are responsible for the breakdown of various chemical compounds, including mitragynine. Due to this reason, Kratom has a half-life of around a day in the body.
Pharmacokinetics Of Tagamet
Regardless of the administration route, the body rapidly absorbs this drug. As far as oral bioavailability is concerned, it ranges between sixty and seventy percent. The onset of action occurs after approximately half an hour, with the most comprehensive influence between one and three hours. However, Tagamet also undergoes rapid elimination, giving it a half-life of about 123 minutes. To sum it up, this medication’s duration action is around 4-8 hours.
Interaction Of Kratom And Tagamet
Even though Tagamet does not directly affect Kratom’s longevity, an alternate link does exist.
Since the enzymes responsible for breaking down Kratom are the cytochrome P450 family, hindering them would leave Kratom free in the body.
Coincidentally, Tagamet’s chemical properties make it a cytochrome P450 enzyme inhibitor, which means it is not just a histamine receptor antagonist. If you take Kratom while having Tagamet in your body system, the mitragynine will not undergo breakdown. As the mitragynine compound stays in circulation for a lengthier time, the user will experience longer-lasting effects. The best part is that you don’t have to worry about the two interacting with each other and leading to an undesirable consequence.
Are There Any Side Effects Of The Combination?
There are suggestions that if chronic Kratom users couple it up with Tagamet, it could lead to nasty side effects such as:
- Body aches
- Feelings of nausea
- Disturbed sleep cycle
Other than that, if this supplement stays in the bloodstream for too long, the user could suffer from Kratom dependence and future withdrawal symptoms.
As far as Tagamet is concerned, there usually aren’t any adverse effects with overdose. In some cases, however, the user may experience:
Tagamet and Kratom seem like an odd pairing. One is a heartburn drug phased out in favor of more effective alternatives, while the other is a Southeast Asian tropical plant. Nonetheless, Tagamet’s ability to extend the presence of mitragynine and other alkaloids in your system is intriguing. For anyone wanting to try these two together, make sure to purchase from a reliable supplier for utmost precaution.