Talk:Saffron: Difference between revisions

(12 intermediate revisions by the same user not shown)

Line 9:

For tips on how to properly format a substance article, please refer to this document: [[Content Style Guide - Substance]]

Saffron is a herb that is often sold as a dietary supplement and is researched as an antidepressant, anxiolytic, ADHD treatment, wakefulness-promoting agent, aphrodisiac, and other purposes. It has also been historically used to improve mood, energy, and as an aphrodisiac. Saffron is largely used as a nootropic, and recreational use is uncommon, however saffron is capable of producing stimulant and enactogen effects comparable to but milder than substances like [[methylone]] at doses considerably higher than the doses used for medicinal purposes, according to many experience reports.

==History and culture==

Line 16:

Line 18:

Saffron contains ~~several~~ psychoactive ~~components, including crocin~~, crocetin, safranal, ~~trans~~-crocetin, trans-~~crocin~~, ~~picrocrocin~~, ~~and kaempferol~~.

Saffron contains three major psychoactive compounds - cis-crocetin, trans-crocetin, and safranal. Saffron contains crocins which do not pass the blood-brain barrier and are not absorbed into the bloodstream, however a portion of crocins are converted to cis-crocetin, trans-crocetin, and safranal, which are responsible for the majority of its psychoactive effects.<ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013346/</ref><ref>https://pubmed.ncbi.nlm.nih.gov/25636868/</ref><ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000812/</ref>

==Pharmacology==

Saffron ~~has a complex mechanism of action~~, and is shown to be ~~a serotonin-dopamine-norepinephrine reuptake inhibitor,~~ a monoamine oxidase A & B inhibitor~~, an acetylcholinesterase~~ inhibitor, ~~an NMDA antagonist,~~ and a GABAa agonist. <ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000812/~~#B60-molecules-27-02076~~</ref> ~~Saffron contains multiple active compounds that are responsible for its effects, the most well characterised being crocin~~ and safranal. ~~Crocin is shown to be stimulating and have dopaminergic effects, and safranal tends to be more sedating and possibly serotonergic~~. <ref>https://pubmed.ncbi.nlm.nih.gov/~~17962007~~/</ref>

Saffron contains multiple active compounds that are responsible for its effects, cis-crocetin, trans-crocetin, and safranal being responsible for the majority of its effects <ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013346/</ref><ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000812/</ref><ref>https://pubmed.ncbi.nlm.nih.gov/25636868/</ref>. Cis-crocetin is shown to be stimulating and act as a monoamine oxidase A & B inhibitor and potentially a dopamine-norepinephrine reuptake inhibitor, and safranal tends to be sedating and possibly acts as a GABAa agonist and serotonin reuptake inhibitor, and does not inhibit monoamine oxidase.<ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000812/</ref><ref>https://pubmed.ncbi.nlm.nih.gov/17962007/</ref> Both cis-crocetin and safranal act as acetylcholinesterase inhibitors.<ref>https://pubmed.ncbi.nlm.nih.gov/22655699/</ref> Trans-crocetin acts as an NMDA antagonist.<ref>https://pubmed.ncbi.nlm.nih.gov/25636868/</ref>

==Subjective effects==

Line 27:

Line 29:

The effects of saffron tend to be described as similar to [[stimulant|stimulants]] and [[psychedelic]] [[microdose|microdoses]]. It is often used as a nootropic and to reduce symptoms associated with mental disorders like depression and ADHD.

The effects of saffron tend to be described as similar to [[stimulant|stimulants]] and [[psychedelic]] [[microdose|microdoses]]. It is often used as a nootropic and to reduce symptoms associated with mental disorders like depression and ADHD. Very high doses have been compared to empathogens such as [[mdma]] and [[methylone]], but with weaker effects.

The effects of saffron tend to be more stimulating during the onset and come up and fade into a more sedating effect, likely due to the short half life of crocetin which is responsible for its stimulant effexts.

{{effects/base

Line 36:

Line 40:

You may select physical effects to add below [[Subjective effect index#Physical effects|here]].

*'''[[Effect::Stimulation]]''' - Saffron typically is stimulating in a similar but weaker manner to substances such as [[methylphenidate]], and encourages physical activity

*'''[[Effect::Stimulation]]''' - Saffron typically is stimulating in a similar but weaker manner to substances such as [[methylphenidate]], and encourages physical activity. Saffron produces stimulation through increasing dopamine and norepinephrine via reuptake inhibition and monoamine oxidase inhibition.

*'''[[Effect::Sedation]]'''

*'''[[Effect::Nausea]]'''

Line 50:

Line 54:

*'''[[Effect::Anemia]]''' - Long term use of saffron can lead to reduced blood cell count and anemia can develop as a result in some individuals <ref>https://pubmed.ncbi.nlm.nih.gov/18693099/</ref>

*'''[[Effect::Increased bodily temperature]]'''

*'''[[Effect::Frequent urination]]'''

*'''[[Effect::Diarrhea]]''' - This typically only occurs at high doses

*'''[[Effect::Increased heart rate]]'''

*'''[[Effect::Abnormal heartbeat]] - This effect usually only occurs in very high doses

*'''[[Effect::Dehydration]]''' - This effect is milder in comparison to other stimulants like [[amphetamine]]

}}

{{effects/visual|

Line 67:

Line 75:

You may select from a list of cognitive effects to add below [[Subjective effect index#Cognitive effects|here]].

*'''[[Effect::Cognitive euphoria]]''' - Saffron is known to have powerful mood-enhancing effects and is often used as an antidepressant for this effect <ref>https://jpnim.com/index.php/jpnim/article/view/e110222</ref>

*'''[[Effect::Cognitive euphoria]]''' - Saffron is known to have powerful mood-enhancing effects and is often used as an antidepressant for this effect.<ref>https://jpnim.com/index.php/jpnim/article/view/e110222</ref> At very high doses, this effect has been compared to empathogens like [[methylone]], but milder, likely due to the shared mechanism of increasing dopamine and serotonin.

*'''[[Effect::Focus enhancement]]''' - Saffron is shown to have similar efficacy to [[methylphenidate]] in treating ADHD <ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9573091/</ref>

*'''[[Effect::Motivation enhancement]]'''

Line 104:

Line 112:

It is strongly recommended that one use [[responsible use|harm reduction practices]] when using this substance.

There is evidence that saffron may produce kidney and lung toxicity, however the toxicity of saffron is not well studied or understood. Negative side effects are rare and there has not been any reports of long term medical complications caused by saffron.

===Lethal dosage===

A lethal dose of saffron has not been established, and the toxicity of saffron is still debated, with some studies suggesting potential lethal toxicity and doses only a few times higher than a regular medicinal dose, others suggesting toxicity only occurs at very high doses. No lethal dose has been reported in humans.

===Tolerance and addiction potential===

===Dangerous interactions===

*'''[[5-HTP]]''' - Saffron may cause serotonin syndrome when combined with 5-HTP

*'''[[Caffeine]]''' - Saffron may inhibit the metabolism of caffeine, leading to stronger and prolonged effects, and potentially leading to effects like [[anxiety]]

*'''[[Stimulants]]''' - Saffron has strong synergy with stimulants due to its MAOI activity, which could cause negative effects like [[anxiety]], [[abnormal heartbeat]], and [[serotonin syndrome]]

*'''[[Opioids]]''' - Saffron potentiates opioids and could lead to excessive respiratory depression, and combining opioids with serotonergic substances can cause [[serotonin syndrome]]

==Legal status==

@@ Line 9: / Line 9: @@
 For tips on how to properly format a substance article, please refer to this document: [[Content Style Guide - Substance]]
+Saffron is a herb that is often sold as a dietary supplement and is researched as an antidepressant, anxiolytic, ADHD treatment, wakefulness-promoting agent, aphrodisiac, and other purposes. It has also been historically used to improve mood, energy, and as an aphrodisiac. Saffron is largely used as a nootropic, and recreational use is uncommon, however saffron is capable of producing stimulant and enactogen effects comparable to but milder than substances like [[methylone]] at doses considerably higher than the doses used for medicinal purposes, according to many experience reports.
 ==History and culture==
@@ Line 16: / Line 18: @@
 {{chemistry}}
-Saffron contains several psychoactive components, including crocin, crocetin, safranal, trans-crocetin, trans-crocin, picrocrocin, and kaempferol.
+Saffron contains three major psychoactive compounds - cis-crocetin, trans-crocetin, and safranal. Saffron contains crocins which do not pass the blood-brain barrier and are not absorbed into the bloodstream, however a portion of crocins are converted to cis-crocetin, trans-crocetin, and safranal, which are responsible for the majority of its psychoactive effects.<ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013346/</ref><ref>https://pubmed.ncbi.nlm.nih.gov/25636868/</ref><ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000812/</ref>
 ==Pharmacology==
 {{pharmacology}}
-Saffron has a complex mechanism of action, and is shown to be a serotonin-dopamine-norepinephrine reuptake inhibitor, a monoamine oxidase A & B inhibitor, an acetylcholinesterase inhibitor, an NMDA antagonist, and a GABAa agonist. <ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000812/#B60-molecules-27-02076</ref> Saffron contains multiple active compounds that are responsible for its effects, the most well characterised being crocin and safranal. Crocin is shown to be stimulating and have dopaminergic effects, and safranal tends to be more sedating and possibly serotonergic.  <ref>https://pubmed.ncbi.nlm.nih.gov/17962007/</ref>
+Saffron contains multiple active compounds that are responsible for its effects, cis-crocetin, trans-crocetin, and safranal being responsible for the majority of its effects <ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013346/</ref><ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000812/</ref><ref>https://pubmed.ncbi.nlm.nih.gov/25636868/</ref>. Cis-crocetin is shown to be stimulating and act as a monoamine oxidase A & B inhibitor and potentially a dopamine-norepinephrine reuptake inhibitor, and safranal tends to be sedating and possibly acts as a GABAa agonist and serotonin reuptake inhibitor, and does not inhibit monoamine oxidase.<ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000812/</ref><ref>https://pubmed.ncbi.nlm.nih.gov/17962007/</ref> Both cis-crocetin and safranal act as acetylcholinesterase inhibitors.<ref>https://pubmed.ncbi.nlm.nih.gov/22655699/</ref> Trans-crocetin acts as an NMDA antagonist.<ref>https://pubmed.ncbi.nlm.nih.gov/25636868/</ref>
 ==Subjective effects==
@@ Line 27: / Line 29: @@
 {{Preamble/SubjectiveEffects}}
-The effects of saffron tend to be described as similar to [[stimulant|stimulants]] and [[psychedelic]] [[microdose|microdoses]]. It is often used as a nootropic and to reduce symptoms associated with mental disorders like depression and ADHD.
+The effects of saffron tend to be described as similar to [[stimulant|stimulants]] and [[psychedelic]] [[microdose|microdoses]]. It is often used as a nootropic and to reduce symptoms associated with mental disorders like depression and ADHD. Very high doses have been compared to empathogens such as [[mdma]] and [[methylone]], but with weaker effects.
+The effects of saffron tend to be more stimulating during the onset and come up and fade into a more sedating effect, likely due to the short half life of crocetin which is responsible for its stimulant effexts.
 {{effects/base
@@ Line 36: / Line 40: @@
 You may select physical effects to add below [[Subjective effect index#Physical effects|here]].
-*'''[[Effect::Stimulation]]''' - Saffron typically is stimulating in a similar but weaker manner to substances such as [[methylphenidate]], and encourages physical activity
+*'''[[Effect::Stimulation]]''' - Saffron typically is stimulating in a similar but weaker manner to substances such as [[methylphenidate]], and encourages physical activity. Saffron produces stimulation through increasing dopamine and norepinephrine via reuptake inhibition and monoamine oxidase inhibition.
 *'''[[Effect::Sedation]]'''
 *'''[[Effect::Nausea]]'''
@@ Line 50: / Line 54: @@
 *'''[[Effect::Anemia]]''' - Long term use of saffron can lead to reduced blood cell count and anemia can develop as a result in some individuals <ref>https://pubmed.ncbi.nlm.nih.gov/18693099/</ref>
 *'''[[Effect::Increased bodily temperature]]'''
+*'''[[Effect::Frequent urination]]'''
+*'''[[Effect::Diarrhea]]''' - This typically only occurs at high doses
+*'''[[Effect::Increased heart rate]]'''
+*'''[[Effect::Abnormal heartbeat]] - This effect usually only occurs in very high doses
+*'''[[Effect::Dehydration]]''' - This effect is milder in comparison to other stimulants like [[amphetamine]]
 }}
 {{effects/visual|
@@ Line 67: / Line 75: @@
 You may select from a list of cognitive effects to add below [[Subjective effect index#Cognitive effects|here]].
-*'''[[Effect::Cognitive euphoria]]''' - Saffron is known to have powerful mood-enhancing effects and is often used as an antidepressant for this effect <ref>https://jpnim.com/index.php/jpnim/article/view/e110222</ref>
+*'''[[Effect::Cognitive euphoria]]''' - Saffron is known to have powerful mood-enhancing effects and is often used as an antidepressant for this effect.<ref>https://jpnim.com/index.php/jpnim/article/view/e110222</ref> At very high doses, this effect has been compared to empathogens like [[methylone]], but milder, likely due to the shared mechanism of increasing dopamine and serotonin.
 *'''[[Effect::Focus enhancement]]''' - Saffron is shown to have similar efficacy to [[methylphenidate]] in treating ADHD <ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9573091/</ref>
 *'''[[Effect::Motivation enhancement]]'''
@@ Line 104: / Line 112: @@
 {{toxicity}}
 It is strongly recommended that one use [[responsible use|harm reduction practices]] when using this substance.
+There is evidence that saffron may produce kidney and lung toxicity, however the toxicity of saffron is not well studied or understood. Negative side effects are rare and there has not been any reports of long term medical complications caused by saffron.
 ===Lethal dosage===
+A lethal dose of saffron has not been established, and the toxicity of saffron is still debated, with some studies suggesting potential lethal toxicity and doses only a few times higher than a regular medicinal dose, others suggesting toxicity only occurs at very high doses. No lethal dose has been reported in humans.
 ===Tolerance and addiction potential===
 ===Dangerous interactions===
 {{DangerousInteractions}}
 {{DangerousInteractions/Intro}}
+*'''[[5-HTP]]''' - Saffron may cause serotonin syndrome when combined with 5-HTP
+*'''[[Caffeine]]''' - Saffron may inhibit the metabolism of caffeine, leading to stronger and prolonged effects, and potentially leading to effects like [[anxiety]]
+*'''[[Stimulants]]''' - Saffron has strong synergy with stimulants due to its MAOI activity, which could cause negative effects like [[anxiety]], [[abnormal heartbeat]], and [[serotonin syndrome]]
+*'''[[Opioids]]''' - Saffron potentiates opioids and could lead to excessive respiratory depression, and combining opioids with serotonergic substances can cause [[serotonin syndrome]]
 ==Legal status==