Harmala alkaloid: Difference between revisions

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Harmala alkaloids are a ~~class~~ of ~~chemicals that include compounds with~~ psychoactive effects.

Harmala alkaloids are a group of naturally occurring alkaloids, found primarily within the seeds of '''Peganum Harmala''' (''Syrian Rue''), which exhibit psychoactive effects.

==Chemistry==

Harmala alkaloids are based upon the molecule [[beta-Carbolines|''beta''-carboline]]s. ~~Beta~~-Carboline itself is ~~made up~~ of an indole ring attached to a pyridine ring.

Harmala alkaloids are based upon the molecule [[beta-Carbolines|''beta''-carboline]]s. The ''beta''-Carboline structure itself is comprised of an indole ring attached to a pyridine ring.

==Pharmacology==

Harmala alkaloids ~~all function as reversible inhibitors~~ of monoamine oxidase A ~~([[RIMAs]])~~. This is a ~~class~~ of drugs ~~which selectively~~ and ~~reversibly inhibits~~ the enzyme ~~known~~ as ~~monoamine oxidase~~ A (MAO-A) and is ~~therefore combined with ayahuasca brews~~, to ~~prevent~~ the ~~breakdown~~ of DMT ~~in the digestive system~~ by ~~inhibiting the enzyme~~ monoamine oxidase. ~~Due to their reversibility~~ and ~~selectivity~~, ~~RIMAs are~~ safer ~~than~~ the ~~older monoamine oxidase inhibitors (MAOIs) and do not require that people follow a tyramine-free diet~~.

Harmala alkaloids inhibit the activity of monoamine oxidase metabolic enzymes, of which two varieties exist; MOA-A and MOA-B. The alkaloids bind reversibly to the active site of the enzyme, inhibiting its endogenous function of destroying amine functions of neurotransmitters and externally administered centrally active drugs. This has the effect of potentiating and prolonging the central and peripheral activity of both neurotransmitters and a variety of drugs.

Harmala alkaloids are selective for MOA-A at reasonable doses and binds to the enzyme temporarily so is classed as a '''reversible inhibitor of Monoamine-A''' (''RIMA''). At higher doses, they also begin to affect the MOA-B enzyme. Because of the reversible selectivity for MAO-A, Harmala alkaloids are considered to be less dangerous in combination with food which contains tyramine and other substances with monoamine moieties, which are reliant on monoamine oxidase for decomposition, as is traditionally a respected consideration when using non-selective MAOIs in a clinical setting.

However, it is important to understand that this does not imply that Harmala alkaloids will not cause neurotoxicity. Harmala alkaloids temporarily disable the brain's primary mechanism for breaking down neurotransmitters and drugs, which can have negative consequences as material builds up in the synapses, leading to a huge range of downstream central and peripheral effects including; sedation, stimulation, anxiety, dysphoria, euphoria, headaches, eye strain, convulsions, etc.

Since DMT is broken down by monoamine oxidase-A, inhibition of this enzyme allows for the oral activation of DMT, and prolongs the experience for the duration of the harmala alkaloids' effects. In combination, harmala alkaloids and DMT is known as [[Ayahuasca]]. this of course is a dirty hack, and a much safer route would be to introduce protective moieties to the DMT molecule itself.

==Examples==

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Tetrahydroharmine does not inhibit monoamine oxidase A. Instead, it weakly inhibits [[serotonin]] reuptake. At dosages of 200mg, it has been reported to cause dream-like euphoria, pleasurable tingling sensations and a head space similar to that of [[LSD]].

Note: all three of these dosages seem wildly exaggerated to me. 100 molecules of harmaline will inhibit 100 molecules of MAO-A, since it must bind with the enzyme. Effective inhibition dose could be calculated by determining the concentration of MOA in the body. Harmine is certainly active at <100mg, and the synergistic property of combined harmala alkaloids as found within Peganum Harmala likely increases their efficacy; two MAO-A inhibitors will be more effective with less side effects than a higher quantity of one alkaloid alone.

==Toxicity and Harm Potential==

===Drug Interactions===

While safer than general [[MAOIs]], RIMAs still have highly dangerous and sometimes fatal interactions with many common drugs. In particular, they can cause serotonin syndrome or hypertensive crisis when combined with almost any antidepressant or stimulant, common migraine medications, certain herbs, or even most cold medicines (including decongestants, antihistamines, and cough syrup).

While safer than general [[MAOIs]], RIMAs still have highly dangerous and sometimes fatal interactions with many common drugs. In particular, they can cause serotonin syndrome or hypertensive crisis when combined with almost any antidepressant or stimulant, common migraine medications, certain herbs, or even most cold medicines (including decongestants, antihistamines, and cough syrup, nicotine, caffeine, etc). Sedatives are likely easier tolerated, but potentiation should be expected.

===Lethal Dosage===

@@ Line 1: / Line 1: @@
-Harmala alkaloids are a class of chemicals that include compounds with psychoactive effects.
+Harmala alkaloids are a group of naturally occurring alkaloids, found primarily within the seeds of '''Peganum Harmala''' (''Syrian Rue''), which exhibit psychoactive effects.
 ==Chemistry==
-Harmala alkaloids are based upon the molecule [[beta-Carbolines|''beta''-carboline]]s. Beta-Carboline itself is made up of an indole ring attached to a pyridine ring.
+Harmala alkaloids are based upon the molecule [[beta-Carbolines|''beta''-carboline]]s. The ''beta''-Carboline structure itself is comprised of an indole ring attached to a pyridine ring.
 ==Pharmacology==
-Harmala alkaloids all function as reversible inhibitors of monoamine oxidase A ([[RIMAs]]). This is a class of drugs which selectively and reversibly inhibits the enzyme known as monoamine oxidase A (MAO-A) and is therefore combined with ayahuasca brews, to prevent the breakdown of DMT in the digestive system by inhibiting the enzyme monoamine oxidase. Due to their reversibility and selectivity, RIMAs are safer than the older monoamine oxidase inhibitors (MAOIs) and do not require that people follow a tyramine-free diet.
+Harmala alkaloids inhibit the activity of monoamine oxidase metabolic enzymes, of which two varieties exist; MOA-A and MOA-B. The alkaloids bind reversibly to the active site of the enzyme, inhibiting its endogenous function of destroying amine functions of neurotransmitters and externally administered centrally active drugs. This has the effect of potentiating and prolonging the central and peripheral activity of both neurotransmitters and a variety of drugs.
+Harmala alkaloids are selective for MOA-A at reasonable doses and binds to the enzyme temporarily so is classed as a '''reversible inhibitor of Monoamine-A''' (''RIMA''). At higher doses, they also begin to affect the MOA-B enzyme. Because of the reversible selectivity for MAO-A, Harmala alkaloids are considered to be less dangerous in combination with food which contains tyramine and other substances with monoamine moieties, which are reliant on monoamine oxidase for decomposition, as is traditionally a respected consideration when using non-selective MAOIs in a clinical setting.
+However, it is important to understand that this does not imply that Harmala alkaloids will not cause neurotoxicity. Harmala alkaloids temporarily disable the brain's primary mechanism for breaking down neurotransmitters and drugs, which can have negative consequences as material builds up in the synapses, leading to a huge range of downstream central and peripheral effects including; sedation, stimulation, anxiety, dysphoria, euphoria, headaches, eye strain, convulsions, etc.
+Since DMT is broken down by monoamine oxidase-A, inhibition of this enzyme allows for the oral activation of DMT, and prolongs the experience for the duration of the harmala alkaloids' effects. In combination, harmala alkaloids and DMT is known as [[Ayahuasca]]. this of course is a dirty hack, and a much safer route would be to introduce protective moieties to the DMT molecule itself.
 ==Examples==
@@ Line 24: / Line 30: @@
 Tetrahydroharmine does not inhibit monoamine oxidase A. Instead, it weakly inhibits [[serotonin]] reuptake. At dosages of 200mg, it has been reported to cause dream-like euphoria, pleasurable tingling sensations and a head space similar to that of [[LSD]].
+Note: all three of these dosages seem wildly exaggerated to me. 100 molecules of harmaline will inhibit 100 molecules of MAO-A, since it must bind with the enzyme. Effective inhibition dose could be calculated by determining the concentration of MOA in the body. Harmine is certainly active at <100mg, and the synergistic property of combined harmala alkaloids as found within Peganum Harmala likely increases their efficacy; two MAO-A inhibitors will be more effective with less side effects than a higher quantity of one alkaloid alone.
 ==Toxicity and Harm Potential==
 ===Drug Interactions===
-While safer than general [[MAOIs]], RIMAs still have highly dangerous and sometimes fatal interactions with many common drugs. In particular, they can cause serotonin syndrome or hypertensive crisis when combined with almost any antidepressant or stimulant, common migraine medications, certain herbs, or even most cold medicines (including decongestants, antihistamines, and cough syrup).
+While safer than general [[MAOIs]], RIMAs still have highly dangerous and sometimes fatal interactions with many common drugs. In particular, they can cause serotonin syndrome or hypertensive crisis when combined with almost any antidepressant or stimulant, common migraine medications, certain herbs, or even most cold medicines (including decongestants, antihistamines, and cough syrup, nicotine, caffeine, etc). Sedatives are likely easier tolerated, but potentiation should be expected.
 ===Lethal Dosage===