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Mitragyna speciosa

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Mitragyna speciosa

Mitragyna speciosa is a tropical evergreen tree of the Rubiaceae family native to Southeast Asia. It is indigenous to Cambodia, Thailand, Indonesia, Malaysia, Myanmar, and Papua New Guinea, where its dark green, glossy leaves, known as kratom, have been used in herbal medicine since at least the 19th century. They have also historically been consumed via chewing, smoking, and as a tea. Kratom has opioid-like properties and some stimulant-like effects. The efficacy and safety of kratom are unclear. In 2019, the United States Food and Drug Administration (FDA) stated that there is no evidence that kratom is safe or effective for treating any condition. Some people take it for managing chronic pain, for treating opioid withdrawal symptoms, or for recreational purposes. It is under preliminary research for possible antipsychotic and antidepressant properties. Kratom contains over fifty alkaloids—primarily mitragynine and 7-hydroxymitragynine—which act as partial agonists at μ-opioid receptors with complex, receptor-specific effects and additional interactions across various neural pathways. Anecdotal reports describe increased alertness, physical energy, talkativeness, sociability, sedation, changes in mood, and pain relief following kratom use at various doses. The onset of effects typically begins within five to ten minutes and lasts for two to five hours. Common side effects include appetite loss, erectile dysfunction, nausea and constipation. More severe side-effects may include respiratory depression (decreased breathing), seizure, psychosis, elevated heart rate and blood pressure, trouble sleeping, and liver injury. Addiction is a possible risk with regular use: when use is stopped, withdrawal symptoms may occur. Serious toxicity is relatively rare and generally appears at high doses or when kratom is used with other substances. A small number of deaths have been connected to the use of kratom, most commonly when mixed with other substances. As of 2018, kratom is a controlled substance in sixteen countries. Some countries, like Indonesia and Thailand, have recently moved toward regulated legal production for medical use. There is growing international concern about a possible threat to public health from kratom use. In some jurisdictions its sale and importation have been restricted, and several public health authorities have raised alerts.

Tables

Mitragyna speciosa alkaloids at opioid receptors · Pharmacology
MORTooltip μ-Opioid receptor
MORTooltip μ-Opioid receptor
Compound
MORTooltip μ-Opioid receptor
Affinities (Ki (nM)Tooltip Inhibitor constant)
DORTooltip δ-Opioid receptor
Affinities (Ki (nM)Tooltip Inhibitor constant)
KORTooltip κ-Opioid receptor
Affinities (Ki (nM)Tooltip Inhibitor constant)
MOR:DOR:KOR
7-Hydroxymitragynine
7-Hydroxymitragynine
Compound
7-Hydroxymitragynine
Affinities (Ki (nM)Tooltip Inhibitor constant)
13.5
Affinities (Ki (nM)Tooltip Inhibitor constant)
155
Affinities (Ki (nM)Tooltip Inhibitor constant)
123
Ratio
1:11:9
Mitragynine
Mitragynine
Compound
Mitragynine
Affinities (Ki (nM)Tooltip Inhibitor constant)
7.24
Affinities (Ki (nM)Tooltip Inhibitor constant)
60.3
Affinities (Ki (nM)Tooltip Inhibitor constant)
1,100
Ratio
1:8:152
Mitragynine pseudoindoxyl
Mitragynine pseudoindoxyl
Compound
Mitragynine pseudoindoxyl
Affinities (Ki (nM)Tooltip Inhibitor constant)
0.087
Affinities (Ki (nM)Tooltip Inhibitor constant)
3.02
Affinities (Ki (nM)Tooltip Inhibitor constant)
79.4
Ratio
1:35:913
Compound
Affinities (Ki (nM)Tooltip Inhibitor constant)
Ratio
Ref
MORTooltip μ-Opioid receptor
DORTooltip δ-Opioid receptor
KORTooltip κ-Opioid receptor
MOR:DOR:KOR
7-Hydroxymitragynine
13.5
155
123
1:11:9
Mitragynine
7.24
60.3
1,100
1:8:152
Mitragynine pseudoindoxyl
0.087
3.02
79.4
1:35:913
Table 1: Pharmaceutical profile of Kratom · Pharmacology
Bioavailability:
Bioavailability:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
Bioavailability:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
PO estimated at 30%
Onset:
Onset:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
Onset:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
PO: 30 minutes
Peak plasma time:
Peak plasma time:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
Peak plasma time:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
1-4.5 hrs
Duration:
Duration:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
Duration:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
3 or more hours
Half-life:
Half-life:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
Half-life:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
12–45 hours
Receptors:
Receptors:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
Receptors:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
Kappa: competitive antagonistDelta: competitive antagonistMu: partial agonistα2 adrenergicAdenosine A2aDopamine D2Serotonin receptors 5-HT2C and 5-HT7
Mechanism of action:
Mechanism of action:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
Mechanism of action:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
Competitive antagonist at Kappa opioid receptors with stronger affinity compared to other receptors, competitive antagonist at Delta opioid receptors. Partial agonist at Mu opioid receptors. Causes G-protein linked second messenger activation, and calcium channel blocker.
Metabolism:
Metabolism:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
Metabolism:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
Cytochrome P-450, inhibitor of CYP2D6 and CYP3A
Excretion:
Excretion:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
Excretion:
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
Renally
Kratom (Mitragynine, 7-Hydroxy-Mitragynine, Speciogynine, Paynantheine, Speciociliatine, Corynantheidine, Corynoxeine, Corynoxine B, Speciofoline)
Bioavailability:
PO estimated at 30%
Onset:
PO: 30 minutes
Peak plasma time:
hrs
Duration:
3 or more hours
Half-life:
12–45 hours
Receptors:
Kappa: competitive antagonistDelta: competitive antagonistMu: partial agonistα2 adrenergicAdenosine A2aDopamine D2Serotonin receptors 5-HT2C and 5-HT7
Mechanism of action:
Competitive antagonist at Kappa opioid receptors with stronger affinity compared to other receptors, competitive antagonist at Delta opioid receptors. Partial agonist at Mu opioid receptors. Causes G-protein linked second messenger activation, and calcium channel blocker.
Metabolism:
Cytochrome P-450, inhibitor of CYP2D6 and CYP3A
Excretion:
Renally

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