Talk:Yohimbine: Difference between revisions

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'''Yohimbine''' ~~hydrochloride~~ (also known as '''quebrachine''') is a [[naturally-occurring]] [[Psychoactive class::stimulant]] substance of the [[chemical class::~~indole alkaloid~~]] class derived from the bark of the African tree [[wikipedia:Pausinystalia johimbe|''Pausinystalia johimbe'']]~~. It is the major active constituent of the bark, with the active ingredient being yohimbine hydrochloride~~. It has various uses including as an aphrodisiac and a weight loss agent. Yohimbine is also used as a mydriatic and sympatholytic and has been suggested as an antidote to [[clonidine]] and [[wikipedia:xylazine|xylazine]] overdose.

'''Yohimbine''' (also known as '''quebrachine''') is a [[naturally-occurring]] [[Psychoactive class::stimulant]] substance of the [[chemical class::indoloquinolizidine]] class derived from the bark of the African tree [[wikipedia:Pausinystalia johimbe|''Pausinystalia johimbe'']]. It has various uses including as an aphrodisiac and a weight loss agent. Yohimbine is also used as a mydriatic and sympatholytic and has been suggested as an antidote to [[clonidine]] and [[wikipedia:xylazine|xylazine]] overdose.

According to many users, yohimbine, in comparison with other psychoactive [[stimulants]], is not a recreational substance and does not cause [[euphoria]].

==Chemistry==

Yohimbine is an indole alkaloid molecule of the ~~indole~~ chemical class. It is structurally related to [[wikipedia:mitragynine|mitragynine]] but shows a totally different pharmacology.

Yohimbine is an indole alkaloid molecule of the indoloquinolizidine chemical class. It is structurally related to [[wikipedia:mitragynine|mitragynine]] but shows a totally different pharmacology.

==Pharmacology==

~~{{pharmacology}}~~

The primary and most researched mechanism of yohimbine is antagonism of a class of receptors known as alpha-2 [[adrenergic]] [[receptors]], thus it increases [[noradrenaline]] levels by preventing their uptake into subsequent neurons. Blocking alpha-2 adrenoceptors increases blood pressure, releases insulin, and decreases blood sugar levels. Yohimbine also, however, blocking alpha-1 adrenergic receptors, albeit with lower affinity. It also has been shown to weak [[MAOI|inhibit monoamine oxidase]].<ref name="Toxic">Encyclopedia of Toxicology | https://www.sciencedirect.com/science/article/pii/B9780123864543007995</ref>

~~Yohimbine antagonize~~ alpha-2 [[adrenergic]] [[receptors]], ~~leading to increased blood flow to the genital area, where blocking the presynaptic alpha-2 receptors will lead to an increase in both nitric oxide and~~ [[noradrenaline]] ~~release~~. Blocking alpha-2 adrenoceptors increases blood pressure, releases insulin, and decreases blood sugar levels. Yohimbine also, however, ~~interacts with~~ alpha-1 adrenergic receptors, albeit with lower affinity, therefore, at higher doses an α1 blockade can occur and overwhelm the effects of the α2 blockade, making it difficult to predict the response (alpha-1 antagonism reduces blood pressure and overall CNS stimulation). It also has been shown to weak [[MAOI|inhibit monoamine oxidase]].<ref name="Toxic">Encyclopedia of Toxicology | https://www.sciencedirect.com/science/article/pii/B9780123864543007995</ref>

In high concentrations yohimbine behaves as an [[antagonist]] at [[dopamine]] D2 and D3 [[receptors]], [[serotonin]] 5-HT1B, 5-HT1D, and 5-HT2B receptors, and as a partial [[agonist]] at 5-HT1A.<ref>Agonist and antagonist actions of yohimbine as compared to fluparoxan at alpha(2)-adrenergic receptors (AR)s, serotonin (5-HT)(1A), 5-HT(1B), 5-HT(1D) and dopamine D(2) and D(3) receptors. Significance for the modulation of frontocortical monoaminergic transmission and depressive states. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/10611634</ref>

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==Subjective effects==

Compared to other [[stimulants]], yohimbine can be described as less recreational. For many users, it is unpleasant, and often even with a small dosage causes [[anxiety]] and [[irritability]].

{{effects/base

|{{effects/physical|

*'''[[Effect::Stimulation]]''' - ~~Stimulation~~ is ~~especially noticeable once you begin an activity~~ that ~~increase adrenaline output,~~ such as ~~training~~.

*'''[[Effect::Stimulation]]''' - In terms of its effects on the physical energy levels of the user, yohimbine is usually considered to be mildly to moderately energetic and stimulating in a fashion that is considerably weaker in comparison to that of traditional recreational stimulants such as [[amphetamine]] or [[cocaine]], but stronger than [[caffeine]].

*'''[[Effect::Appetite suppression]]'''<ref>Yohimbine and rauwolscine reduce food intake of genetically obese (obob) and lean mice. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/6145164</ref>

*'''[[Effect::Dizziness]]'''<ref name="Toxic"/>

*'''[[Effect::Headaches]]'''<ref name="Toxic"/>

*'''[[Effect::Increased blood pressure]]'''<ref name="Biomedical"/>

*'''[[Effect::Increased blood pressure]]'''<ref name="Biomedical">Reference Module in Biomedical Sciences | https://www.sciencedirect.com/science/article/pii/B9780128012383988627</ref>

*'''[[Effect::Decreased blood pressure]]'''

*'''[[Effect::Increased heart rate]]'''<ref name="Toxic"/>

*'''[[Effect::Increased perspiration]]'''

*'''[[Effect::Stamina enhancement]]'''

*'''[[Effect::Vasoconstriction]]'''

*'''[[Effect::Vasodilation]]'''

*'''[[Effect::Increased salivation]]'''<ref>Evidence for activation of both adrenergic and cholinergic nervous pathways by yohimbine, an alpha 2-adrenoceptor antagonist. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/7557820</ref>

*'''[[Effect::Tactile enhancement]]'''

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*'''[[Effect::Motor control loss|Incoordination]]'''<ref name="Toxic"/>

*'''[[Effect::Frequent urination]]'''<ref name="Biomedical"/>

*'''[[Effect::Hyperthermia]]'''

}}

|{{effects/cognitive|

*'''[[Effect::Anxiety suppression]]''' - Yohimbine decrease social anxiety and increased mood. <ref>Yohimbine enhancement of exposure therapy for social anxiety disorder: a randomized controlled trial. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/24237691</ref><ref>Cognitive Enhancers for Anxiety Disorders (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114287/</ref>

*'''[[Effect::Analysis enhancement]]'''<ref>Differential effects of noradrenergic drugs on anxiety and arousal in healthy volunteers with high and low anxiety. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/9004342</ref>

*'''[[Effect::Anxiety]]'''<ref name="Toxic"/>

*'''[[Effect::Anxiety]]'''<ref name="Toxic"/> - Due to effectively increasing noradrenaline, the neural side-effects of excess noradrenaline may result if too high a dose is taken.

*'''[[Effect::Increased libido]]'''

*'''[[Effect::Irritability]]'''

*'''[[Effect::Memory enhancement]]''' - Yohimbine improve long-term memory by increasing norepinephrine levels.<ref>Stimulation of the noradrenergic system enhances and blockade reduces memory for emotional material in man. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/10576300</ref>

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

*'''[[Effect::Thought acceleration]]'''

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*'''[[Effect::Cognitive dysphoria]]'''

*'''[[Effect::Emotion enhancement]]'''

*'''[[Effect::Dream potentiation]]'''

}}

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==Toxicity and harm potential==

Yohimbine has a [[Toxicity::low toxicity]] relative to dose. ~~Side effects associated with the use of yohimbine include anxiety, an increased urinary frequency, and increases~~ in ~~blood pressure at higher~~ doses~~.<ref name="Biomedical">Reference Module~~ in ~~Biomedical Sciences | https://www~~.~~sciencedirect.com/science/article/pii/B9780128012383988627</ref>~~ Higher doses (200 – 5,000 mg) result in stronger side effects and can be toxic to the brain. Extremely high doses (above 5,000 mg) can be lethal.<ref>Case study: two fatal case reports of acute yohimbine intoxication. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/23846025</ref>

Yohimbine is not known to cause harm in reasonable doses, and has an [[Toxicity::low toxicity]] relative to dose. Various studies have shown that in reasonable doses in a careful context, it presents few negative cognitive, psychiatric or toxic physical consequences, though some exist. Higher doses (200 – 5,000 mg) result in stronger side effects and can be toxic to the brain. Extremely high doses (above 5,000 mg) can be lethal.<ref>Case study: two fatal case reports of acute yohimbine intoxication. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/23846025</ref>

It is strongly recommended that one be familiar with [[responsible drug use|harm reduction practices]] when using this drug.

===Dependence and abuse potential===

Yohimbine ~~may potentially~~ be [[Addiction potential::~~mildly~~ habit forming]] and the desire to use it ~~may~~ actually ~~''increase''~~ with use. ~~However, in comparison~~ to ~~other more traditional~~ [[~~stimulants~~]] ~~such as~~ [[~~amphetamine~~]] or [[~~methylphenidate~~]]~~, it is~~ not ~~nearly as addictive or compulsive~~.

Yohimbine is not known to be [[Addiction potential::not habit-forming]] and the desire to use it can actually decrease with use. It is most often self-regulating.

Tolerance to the effects of yohimbine are quickly built [[Time to full tolerance::after repeated and frequent usage]]. After that, it takes about [[Time to half tolerance::7 days]] for the tolerance to be reduced to half and [[Time to zero tolerance::14 days]] to be back at baseline (in the absence of further consumption). Yohimbine does not produce cross-tolerance with most other [[stimulants]].

===Dangerous interactions===

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==Legal status==

Yohimbine is legal in nearly all parts of the world.

==See also==

@@ Line 3: / Line 3: @@
 {{Talk:SubstanceBox/Yohimbine}}
-'''Yohimbine''' hydrochloride (also known as '''quebrachine''') is a [[naturally-occurring]] [[Psychoactive class::stimulant]] substance of the [[chemical class::indole alkaloid]] class derived from the bark of the African tree [[wikipedia:Pausinystalia johimbe|''Pausinystalia johimbe'']]. It is the major active constituent of the bark, with the active ingredient being yohimbine hydrochloride. It has various uses including as an aphrodisiac and a weight loss agent. Yohimbine is also used as a mydriatic and sympatholytic and has been suggested as an antidote to [[clonidine]] and [[wikipedia:xylazine|xylazine]] overdose.
+'''Yohimbine''' (also known as '''quebrachine''') is a [[naturally-occurring]] [[Psychoactive class::stimulant]] substance of the [[chemical class::indoloquinolizidine]] class derived from the bark of the African tree [[wikipedia:Pausinystalia johimbe|''Pausinystalia johimbe'']]. It has various uses including as an aphrodisiac and a weight loss agent. Yohimbine is also used as a mydriatic and sympatholytic and has been suggested as an antidote to [[clonidine]] and [[wikipedia:xylazine|xylazine]] overdose.
+According to many users, yohimbine, in comparison with other psychoactive [[stimulants]], is not a recreational substance and does not cause [[euphoria]].
 ==Chemistry==
 {{chemistry}}
-Yohimbine is an indole alkaloid molecule of the indole chemical class. It is structurally related to [[wikipedia:mitragynine|mitragynine]] but shows a totally different pharmacology.
+Yohimbine is an indole alkaloid molecule of the indoloquinolizidine chemical class. It is structurally related to [[wikipedia:mitragynine|mitragynine]] but shows a totally different pharmacology.
 ==Pharmacology==
-{{pharmacology}}
+The primary and most researched mechanism of yohimbine is antagonism of a class of receptors known as alpha-2 [[adrenergic]] [[receptors]], thus it increases [[noradrenaline]] levels by preventing their uptake into subsequent neurons. Blocking alpha-2 adrenoceptors increases blood pressure, releases insulin, and decreases blood sugar levels. Yohimbine also, however, blocking alpha-1 adrenergic receptors, albeit with lower affinity. It also has been shown to weak [[MAOI|inhibit monoamine oxidase]].<ref name="Toxic">Encyclopedia of Toxicology | https://www.sciencedirect.com/science/article/pii/B9780123864543007995</ref>
-Yohimbine antagonize alpha-2 [[adrenergic]] [[receptors]], leading to increased blood flow to the genital area, where blocking the presynaptic alpha-2 receptors will lead to an increase in both nitric oxide and [[noradrenaline]] release.  Blocking alpha-2 adrenoceptors increases blood pressure, releases insulin, and decreases blood sugar levels. Yohimbine also, however, interacts with alpha-1 adrenergic receptors, albeit with lower affinity, therefore, at higher doses an α<sub>1</sub> blockade can occur and overwhelm the effects of the α<sub>2</sub> blockade, making it difficult to predict the response (alpha-1 antagonism reduces blood pressure and overall CNS stimulation). It also has been shown to weak [[MAOI|inhibit monoamine oxidase]].<ref name="Toxic">Encyclopedia of Toxicology | https://www.sciencedirect.com/science/article/pii/B9780123864543007995</ref>
 In high concentrations yohimbine behaves as an [[antagonist]] at [[dopamine]] D<sub>2</sub> and D<sub>3</sub> [[receptors]], [[serotonin]] 5-HT<sub>1B</sub>, 5-HT<sub>1D</sub>, and 5-HT<sub>2B</sub> receptors, and as a partial [[agonist]] at 5-HT<sub>1A</sub>.<ref>Agonist and antagonist actions of yohimbine as compared to fluparoxan at alpha(2)-adrenergic receptors (AR)s, serotonin (5-HT)(1A), 5-HT(1B), 5-HT(1D) and dopamine D(2) and D(3) receptors. Significance for the modulation of frontocortical monoaminergic transmission and depressive states. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/10611634</ref>
@@ Line 17: / Line 18: @@
 ==Subjective effects==
 {{EffectStub}}
+Compared to other [[stimulants]], yohimbine can be described as less recreational. For many users, it is unpleasant, and often even with a small dosage causes [[anxiety]] and [[irritability]].
 {{Preamble/SubjectiveEffects}}
 {{effects/base
 |{{effects/physical|
-*'''[[Effect::Stimulation]]''' - Stimulation is especially noticeable once you begin an activity that increase adrenaline output, such as training.
+*'''[[Effect::Stimulation]]''' - In terms of its effects on the physical energy levels of the user, yohimbine is usually considered to be mildly to moderately energetic and stimulating in a fashion that is considerably weaker in comparison to that of traditional recreational stimulants such as [[amphetamine]] or [[cocaine]], but stronger than [[caffeine]].
 *'''[[Effect::Appetite suppression]]'''<ref>Yohimbine and rauwolscine reduce food intake of genetically obese (obob) and lean mice. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/6145164</ref>
 *'''[[Effect::Dizziness]]'''<ref name="Toxic"/>
 *'''[[Effect::Headaches]]'''<ref name="Toxic"/>
-*'''[[Effect::Increased blood pressure]]'''<ref name="Biomedical"/>
+*'''[[Effect::Increased blood pressure]]'''<ref name="Biomedical">Reference Module in Biomedical Sciences | https://www.sciencedirect.com/science/article/pii/B9780128012383988627</ref>
-*'''[[Effect::Decreased blood pressure]]'''
 *'''[[Effect::Increased heart rate]]'''<ref name="Toxic"/>
 *'''[[Effect::Increased perspiration]]'''
 *'''[[Effect::Stamina enhancement]]'''
 *'''[[Effect::Vasoconstriction]]'''
-*'''[[Effect::Vasodilation]]'''
 *'''[[Effect::Increased salivation]]'''<ref>Evidence for activation of both adrenergic and cholinergic nervous pathways by yohimbine, an alpha 2-adrenoceptor antagonist. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/7557820</ref>
 *'''[[Effect::Tactile enhancement]]'''
@@ Line 39: / Line 40: @@
 *'''[[Effect::Motor control loss|Incoordination]]'''<ref name="Toxic"/>
 *'''[[Effect::Frequent urination]]'''<ref name="Biomedical"/>
+*'''[[Effect::Hyperthermia]]'''
 }}
 |{{effects/cognitive|
-*'''[[Effect::Anxiety suppression]]''' - Yohimbine decrease social anxiety and increased mood. <ref>Yohimbine enhancement of exposure therapy for social anxiety disorder: a randomized controlled trial. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/24237691</ref><ref>Cognitive Enhancers for Anxiety Disorders (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114287/</ref>
 *'''[[Effect::Analysis enhancement]]'''<ref>Differential effects of noradrenergic drugs on anxiety and arousal in healthy volunteers with high and low anxiety. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/9004342</ref>
-*'''[[Effect::Anxiety]]'''<ref name="Toxic"/>
+*'''[[Effect::Anxiety]]'''<ref name="Toxic"/> - Due to effectively increasing noradrenaline, the neural side-effects of excess noradrenaline may result if too high a dose is taken.
 *'''[[Effect::Increased libido]]'''
 *'''[[Effect::Irritability]]'''
-*'''[[Effect::Memory enhancement]]''' - Yohimbine improve long-term memory by increasing norepinephrine levels.<ref>Stimulation of the noradrenergic system enhances and blockade reduces memory for emotional material in man. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/10576300</ref>
 *'''[[Effect::Motivation enhancement]]'''
 *'''[[Effect::Thought acceleration]]'''
@@ Line 53: / Line 53: @@
 *'''[[Effect::Cognitive dysphoria]]'''
 *'''[[Effect::Emotion enhancement]]'''
+*'''[[Effect::Dream potentiation]]'''
 }}
 }}
@@ Line 60: / Line 61: @@
 ==Toxicity and harm potential==
-Yohimbine has a [[Toxicity::low toxicity]] relative to dose. Side effects associated with the use of yohimbine include anxiety, an increased urinary frequency, and increases in blood pressure at higher doses.<ref name="Biomedical">Reference Module in Biomedical Sciences | https://www.sciencedirect.com/science/article/pii/B9780128012383988627</ref> Higher doses (200 – 5,000 mg) result in stronger side effects and can be toxic to the brain. Extremely high doses (above 5,000 mg) can be lethal.<ref>Case study: two fatal case reports of acute yohimbine intoxication. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/23846025</ref>
+Yohimbine is not known to cause harm in reasonable doses, and has an [[Toxicity::low toxicity]] relative to dose. Various studies have shown that in reasonable doses in a careful context, it presents few negative cognitive, psychiatric or toxic physical consequences, though some exist. Higher doses (200 – 5,000 mg) result in stronger side effects and can be toxic to the brain. Extremely high doses (above 5,000 mg) can be lethal.<ref>Case study: two fatal case reports of acute yohimbine intoxication. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/23846025</ref>
+It is strongly recommended that one be familiar with [[responsible drug use|harm reduction practices]] when using this drug.
 ===Dependence and abuse potential===
-Yohimbine may potentially be [[Addiction potential::mildly habit forming]] and the desire to use it may actually ''increase'' with use. However, in comparison to other more traditional [[stimulants]] such as [[amphetamine]] or [[methylphenidate]], it is not nearly as addictive or compulsive.
+Yohimbine is not known to be [[Addiction potential::not habit-forming]] and the desire to use it can actually decrease with use. It is most often self-regulating.
+Tolerance to the effects of yohimbine are quickly built [[Time to full tolerance::after repeated and frequent usage]]. After that, it takes about [[Time to half tolerance::7 days]] for the tolerance to be reduced to half and [[Time to zero tolerance::14 days]] to be back at baseline (in the absence of further consumption). Yohimbine does not produce cross-tolerance with most other [[stimulants]].
 ===Dangerous interactions===
@@ Line 71: / Line 76: @@
 ==Legal status==
+{{LegalStub}}
+Yohimbine is legal in nearly all parts of the world.
 ==See also==