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'''Propylhexedrine''' (also known as '''Benzedrex''' and '''Obesin''') is a [[psychoactive class::stimulant]] substance of the [[chemical class:: cycloalkylamine]] class. It is a structural analog of [[methamphetamine]]. Propylhexedrine is widely used medicinally as a nasal decongestant (for relief of congestion due to colds, allergies and allergic rhinitis) and sometimes used recreationally as an over-the-counter "legal high".
'''Propylhexedrine''' (commonly known as '''Benzedrex''' and '''Obesin''') is a synthetic [[psychoactive class::stimulant]] and structural analog of [[methamphetamine]] that is widely used medicinally as a nasal decongestant (for relief of congestion due to colds, allergies and allergic rhinitis) and sometimes used recreationally as an over-the-counter "legal high".
Benzedrex was first manufactured by Smith, Kline and French after the Benzedrine inhaler, which contained racemic amphetamine, became unavailable following the placement of [[amphetamines]] on the US Schedule II status (i.e. highest abuse potential, yet with accepted medicinal uses). Propylhexedrine has also been used in Europe as an appetite suppressant under the trade name Obesin. In the United States, propylhexedrine is most commonly found in over-the-counter Benzedrex nasal inhalers.
In the United States, Propylhexedrine is most commonly found in over-the-counter Benzedrex inhalers. Benzedrex was first manufactured by Smith, Kline and French after the Benzedrine inhaler, which contained racemic amphetamine, became unavailable following the placement of amphetamines on the US Schedule II status (highest abuse potential, yet with accepted medicinal uses). Propylhexedrine has also seen use in Europe as an appetite suppressant under the trade name Obesin.
[[Subjective effects]] include [[stimulation]], [[focus enhancement]], [[motivation enhancement]], [[increased libido]], [[appetite suppression]], and [[euphoria]]. Anecdotal reports describe propylhexedrine's effects as similar to [[amphetamine]] or low-dose [[methamphetamine]]. However, it is reported to produce more peripheral effects like [[vasoconstriction]] as well as less euphoria, overall resulting in a less "clean" high. In the United States, propylhexedrine is sometimes extracted from over-the-counter Benzedrex nasal inhalers using lemon juice. The health risks of this practice have not been studied.
Due to its amphetamine-like euphoric effects, propylhexedrine is considered to have moderate abuse potential. Chronic use may result in tolerance, physical and psychological dependence. It is highly advised to use [[harm reduction practices]] if using this substance.
==Chemistry==
==Chemistry==
Propylhexedrine is structurally similar to phenylethylamine and its derivatives, with the only structural difference being the substitution of an alicyclic cyclohexyl group for the aromatic phenyl group of phenethylamine. It can be considered a structural analog of [[methamphetamine]], with the main difference being that propylhexedrine has a saturated cyclohexane ring where methamphetamine has a benzene ring.
Propylhexedrine is chemically classified as a [[cycloalkylamine]]. It is structurally similar to [[Phenethylamine_(compound)|phenethylamine]] and [[phenethylamines|its derivates]]. It is particularly similar in structure to [[methamphetamine]], with the only structural difference being the substitution of an cyclohexane ring for methamphetamine's phenyl ring. This makes propylhexedrine a structural analog of methamphetamine.
[[File:Comparison propylhexedrine.svg|alt=|center|369x369px|A comparison of similar amine group molecules.]]
Moreover, propylhexedrine is a chiral compound (the α-carbon is chiral), and the product contained in pharmaceutical products is racemic (RS)-propylhexedrine free base. (S)-Propylhexedrine, also known as levopropylhexedrine, is believed to be the more biologically active isomer of the two, although [[amphetamines]] with a "levo" prefix are less active than their counterparts. (S)-Propylhexedrine can be synthesized from methamphetamine.{{citation needed}}
[[File:propylhexedrineversusmethamphetaminewar.png|150px|center||A side by side comparison of these two molecules]]
[https://en.wikipedia.org/wiki/Free_base Freebase] propylhexedrine is nonpolar, volatile, oily liquid at room temperature, but it readily forms a polar salt when protonated with hydrochloric acid, citric acid, and acetic acid to form a crystalline white substance.{{citation needed}} As a volatile liquid, it evaporates over time, losing potency drastically quicker than crystalline substances; However, the salt forms are crystalline, and do not evaporate.
Moreover, propylhexedrine is a chiral compound (the α-carbon is chiral), and active ingredient contained in Benzedrex inhalers is racemic (RS)-propylhexedrine as the free base. (S)-Propylhexedrine, also known as levopropylhexedrine, is believed to be the more biologically active isomer of the two. (S)-Propylhexedrine can be synthesized from methamphetamine.
==Pharmacology==
==Pharmacology==
{{Pharmacology}}
{{Pharmacology}}
Propylhexedrine affects the central nervous system (CNS) by acting as a [[releasing agent]] for [[monoamine]] [[neurotransmitters]] such as [[dopamine]], [[norepinephrine]], and [[serotonin]] by binding to and reversing their transporters, leading to the release of them into the synaptic cleft. The increased level of monoamines within the synapse is thought to result in increased activity at these receptors. Additionally, propylhexedrine appears to antagonize the VMAT2 transporter, leading to a further increase in the aforementioned monoamines.
Propylhexedrine affects the central nervous system (CNS) by acting as a [[releasing agent]] for the [[monoamine]] [[neurotransmitters]] [[dopamine]], [[norepinephrine]], and [[serotonin]] ([https://en.wikipedia.org/wiki/Serotonin-norepinephrine-dopamine_releasing_agent SNDRA]), binding to and reversing their transporters, pumping these neurotransmitters from the cytosol to the synaptic cleft, where these neurotransmitters can bind to their respective receptors. Additionally, propylhexedrine inhibits [https://en.m.wikipedia.org/wiki/Vesicular_monoamine_transporter_2 VMAT2], leading to a further increase in the aforementioned monoamines, being that VMAT2 transports all 3 from the synaptic cleft to the cytosol.{{citation needed}}
Propylhexedrine, like [[phenethylamine]], [[amphetamine]], [[methamphetamine]], and [[MDMA]], agonizes [https://en.wikipedia.org/wiki/TAAR1 TAAR1]. TAAR1 agonism, through protein kinase A & C (PKA and PKC) signaling, causes dopamine transporter (DAT) phosphorylation. Both PKA and PKC result in non-competitive dopamine reuptake inhibition, although PKC alone results in dopamine release/DAT reversal.
The pharmacological actions of propylhexedrine are similar to those of [[phenethylamines]], such as [[Substituted amphetamine|amphetamines]], albeit in a generally less centrally active and recreationally desirable fashion.<ref name=":0" />
Since propylhexedrine has a cyclohexane ring in the place of methamphetamine's phenyl ring, it lacks the level of Brain-Blood Barrier permeability that the phenyl ring provides amphetamines, and therefore has a greater proportion of effects on the peripheral nervous system relative to the central nervous system.<ref>{{Citation | vauthors=PubChem | title=Propylhexedrine | url=https://pubchem.ncbi.nlm.nih.gov/compound/7558}}</ref>
Propylhexedrine has a half-life of 2.5 - 6.5 hours, which is variable based on urinary pH and the level of activity of certain Cytochrome P450 enzymes. Higher urinary pH elongates duration, while low urinary pH shortens duration. Higher activity of certain Cytochrome P450 enzymes also shortens duration.<ref name=":1" />
The pharmacological actions of propylhexedrine are similar to that of structurally similar stimulant phenethylamines, such as [[amphetamine]] or [[methamphetamine]], albeit in a generally less potent and recreationally desirable fashion.
Propylhexedrine is metabolized by certain Cytochrome P450 enzymes into norpropylhexedrine, cyclohexylacetoxime, ''cis''-4-hydroxypropylhexedrine and ''trans''-4-hydroxypropylhexedrine.<ref name=":1">{{cite journal | vauthors=((Midha, K. K.)), ((Beckett, A. H.)), ((Saunders, A.)) | journal=Xenobiotica | title=Identification of the Major Metabolites of Propylhexedrine in vivo (in man) and in vitro (in guinea pig and rabbit) | volume=4 | issue=10 | pages=627–635 | date= January 1974 | url=http://www.tandfonline.com/doi/full/10.1080/00498257409169765 | issn=0049-8254 | doi=10.1080/00498257409169765}}</ref>
==Subjective effects==
==Subjective effects==
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*'''[[Effect::Increased blood pressure]]'''{{citation needed}} - Propylhexedrine has been noted by users to raise blood pressure significantly more than other stimulants. It has been speculated that this is due to its higher affinity for [[noradrenaline]] relative to stimulants such as [[amphetamine]].
*'''[[Effect::Increased blood pressure]]'''{{citation needed}} - Propylhexedrine has been noted by users to raise blood pressure significantly more than other stimulants. It has been speculated that this is due to its higher affinity for [[noradrenaline]] relative to stimulants such as [[amphetamine]].
*'''[[Effect::Increased heart rate]]'''{{citation needed}} - Due to its pronounced peripheral nervous system activity, propylhexedrine tends to increase heart rate much more drastically than comparable dosages of other stimulants.
*'''[[Effect::Increased heart rate]]'''{{citation needed}} - Due to its pronounced peripheral nervous system activity, propylhexedrine tends to increase heart rate much more drastically than comparable dosages of other stimulants.
*'''[[Effect::Pupil dilation]]'''
*'''[[Effect::Appetite suppression]]'''
*'''[[Effect::Appetite suppression]]'''
*'''[[Effect::Bronchodilation]]'''
*'''[[Effect::Bronchodilation]]'''
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*'''[[Effect::Increased bodily temperature]]'''
*'''[[Effect::Increased bodily temperature]]'''
*'''[[Effect::Increased perspiration]]'''
*'''[[Effect::Increased perspiration]]'''
*'''[[Effect::Nausea]]''' - This effect is prominent on the onset and come up period when ingested via the cotton found inside "Benzedrex" inhalers, particularly when it is taken on an empty stomach.
*'''[[Effect::Nausea]]''' - This effect is prominent on the onset and come up period when ingested via the cotton found inside Benzedrex inhalers, particularly when it is taken on an empty stomach.
As with other [[stimulant]]s, the chronic use of propylhexedrine can be considered [[Addiction potential::extremely addictive with a high potential for abuse]] and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and [[withdrawal effects]] may occur if a person suddenly stops their usage.
As with other [[stimulants]], the chronic use of propylhexedrine can be considered highly addictive, and is capable of causing psychological and physiological dependence among certain users. When addiction has developed, cravings and [[withdrawal effects]] may occur if a person suddenly stops or drastically decreases their usage.
Tolerance to the effects of this compound likely occurs in the same general fashion as with [[amphetamine]] [[Time to full tolerance::rapidly develops with prolonged and repeated use]].<ref>Efficacy of psychostimulant drugs for amphetamine abuse or dependence (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/23996457</ref><ref>Amphetamines,
Tolerance to the effects of this compound likely occurs in the same general fashion as with [[amphetamine]] [[Time to full tolerance::rapidly develops with prolonged and repeated use]].<ref>{{cite journal | vauthors=((Pérez-Mañá, C.)), ((Castells, X.)), ((Torrens, M.)), ((Capellà, D.)), ((Farre, M.)) | journal=The Cochrane Database of Systematic Reviews | title=Efficacy of psychostimulant drugs for amphetamine abuse or dependence | issue=9 | pages=CD009695 | date=2 September 2013 | issn=1469-493X | doi=10.1002/14651858.CD009695.pub2}}</ref><ref>Amphetamines,
By Patrick G. O’Connor, MD, MPH, Yale University School of Medicine | http://www.merckmanuals.com/home/special_subjects/drug_use_and_abuse/amphetamines.html</ref> This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about [[Time to half tolerance::3 - 7 days]] for the tolerance to be reduced to half and [[Time to zero tolerance::1 - 2 weeks]] to be back at baseline (in the absence of further consumption). Propylhexedrine presents cross-tolerance with [[Cross-tolerance::all [[dopamine]]rgic [[stimulant]]s]], meaning that after the consumption of propylhexedrine all [[stimulant]]s will have a reduced effect.
By Patrick G. O’Connor, MD, MPH, Yale University School of Medicine | http://www.merckmanuals.com/home/special_subjects/drug_use_and_abuse/amphetamines.html</ref> This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about [[Time to half tolerance::3 - 7 days]] for the tolerance to be reduced to half and [[Time to zero tolerance::1 - 2 weeks]] to be back at baseline (in the absence of further consumption). Propylhexedrine presents cross-tolerance with [[Cross-tolerance::all [[dopamine]]rgic [[stimulant]]s]], meaning that after the consumption of propylhexedrine all [[stimulant]]s will have a reduced effect.
Like with [[amphetamine]] and methamphetamine the evidence on effective treatments for dependence and abuse is limited.<ref>Treatment for amphetamine dependence and abuse (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/11687171</ref> In light of this, [[fluoxetine]] and [[imipramine]] appear to have some limited benefits in treating abuse and addiction<ref>Treatment for amphetamine dependence and abuse (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/11687171</ref>
Like with [[amphetamine]] and methamphetamine the evidence on effective treatments for dependence and abuse is limited.<ref name="Srisurapanont2001">{{cite journal | vauthors=((Srisurapanont, M.)), ((Jarusuraisin, N.)), ((Kittirattanapaiboon, P.)) | journal=The Cochrane Database of Systematic Reviews | title=Treatment for amphetamine dependence and abuse | issue=4 | pages=CD003022 | date= 2001 | issn=1469-493X | doi=10.1002/14651858.CD003022}}</ref> In light of this, [[fluoxetine]] and [[imipramine]] appear to have some limited benefits in treating abuse and addiction<ref name="Srisurapanont2001"></ref>
In highly dependent [[amphetamine]] and [[methamphetamine]] abusers, "when chronic heavy users abruptly discontinue methamphetamine use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose".<ref>Treatment for amphetamine withdrawal (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19370579</ref> Withdrawal symptoms in chronic, high-dose users are frequent, occurring in up to 87.6% of cases, and persist for three to four weeks with a marked "crash" phase occurring during the first week.<ref>Treatment for amphetamine withdrawal (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19370579</ref> Methamphetamine withdrawal symptoms can include anxiety, drug craving, dysphoric mood, fatigue, increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness, and vivid or lucid dreams.<ref>Treatment for amphetamine withdrawal (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19370579</ref> Withdrawal symptoms are associated with the degree of dependence (i.e., the extent of abuse).<ref>Treatment for amphetamine withdrawal (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19370579</ref> The mental depression associated with methamphetamine withdrawal lasts longer and is more severe than that of [[cocaine]] withdrawal.<ref>Methamphetamine abuse (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/17990840</ref>. It is likely that propylhexedrine abuse is subject to these same outcomes.
In highly dependent [[amphetamine]] and [[methamphetamine]] abusers, "when chronic heavy users abruptly discontinue methamphetamine use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose".<ref name="ShoptawKaoHeinzerlingLing2009">{{cite journal | vauthors=((Shoptaw, S. J.)), ((Kao, U.)), ((Heinzerling, K.)), ((Ling, W.)) | journal=The Cochrane Database of Systematic Reviews | title=Treatment for amphetamine withdrawal | issue=2 | pages=CD003021 | date=15 April 2009 | issn=1469-493X | doi=10.1002/14651858.CD003021.pub2}}</ref> Withdrawal symptoms in chronic, high-dose users are frequent, occurring in up to 87.6% of cases, and persist for three to four weeks with a marked "crash" phase occurring during the first week.<ref name="ShoptawKaoHeinzerlingLing2009"></ref> Methamphetamine withdrawal symptoms can include anxiety, drug craving, dysphoric mood, fatigue, increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness, and vivid or lucid dreams.<ref name="ShoptawKaoHeinzerlingLing2009"></ref> Withdrawal symptoms are associated with the degree of dependence (i.e., the extent of abuse).<ref name="ShoptawKaoHeinzerlingLing2009"></ref> The mental depression associated with methamphetamine withdrawal lasts longer and is more severe than that of [[cocaine]] withdrawal.<ref name=":0">{{cite journal | vauthors=((Winslow, B. T.)), ((Voorhees, K. I.)), ((Pehl, K. A.)) | journal=American Family Physician | title=Methamphetamine abuse | volume=76 | issue=8 | pages=1169–1174 | date=15 October 2007 | issn=0002-838X}}</ref>. It is likely that propylhexedrine abuse is subject to these same outcomes.
===Psychosis===
===Psychosis===
{{Main|Stimulant psychosis}}
{{Main|Stimulant psychosis}}
Like with the abuse of methamphetamine, propylhexedrine abuse can result in a stimulant-induced psychotic state that may present with a variety of symptoms (e.g., [[Paranoia|paranoia]], [[External hallucinations|hallucinations]], [[Delusions|delusions]]), though likely to a lesser degree.<ref>http://www.drugabuse.gov/drugs-abuse/emerging-trends</ref><ref name="amppsychosis">Shoptaw, S. J., Kao, U., & Ling, W. (2009). Treatment for amphetamine psychosis. The Cochrane Library.</ref> A review on treatment for amphetamine, [[amphetamine|dextroamphetamine]], and [[methamphetamine]] abuse-induced psychosis states that about 5–15% of users fail to recover completely.<ref name="amppsychosis" /><ref>Hofmann FG (1983). A Handbook on Drug and Alcohol Abuse: The Biomedical Aspects (2nd ed.). New York: Oxford University Press. p. 329. ISBN 9780195030570.</ref> The same review asserts that, based upon at least one trial, [[antipsychotic]] medications effectively resolve the symptoms of acute amphetamine psychosis.<ref name="amppsychosis" />
Like with the abuse of methamphetamine, propylhexedrine abuse can result in a stimulant-induced psychotic state that may present with a variety of symptoms (e.g., [[Paranoia|paranoia]], [[External hallucinations|hallucinations]], [[Delusions|delusions]]), though likely to a lesser degree.<ref>{{Citation | vauthors=((National Institute on Drug Abuse)) | title=Emerging Trends | url=https://nida.nih.gov/research-topics/emerging-trends-alerts}}</ref><ref name="amppsychosis">{{cite book | vauthors=((Shoptaw, S. J.)), ((Kao, U.)), ((Ling, W. W.)) | veditors=((The Cochrane Collaboration)) | date=8 October 2008 | chapter=The Cochrane Database of Systematic Reviews (Complete Reviews) | title=Treatment for amphetamine psychosis | publisher=John Wiley & Sons, Ltd | pages=CD003026.pub2 | url=https://doi.wiley.com/10.1002/14651858.CD003026.pub2 | doi=10.1002/14651858.CD003026.pub2}}<nowiki>}}</nowiki></ref> A review on treatment for amphetamine, [[amphetamine|dextroamphetamine]], and [[methamphetamine]] abuse-induced psychosis states that about 5–15% of users fail to recover completely.<ref name="amppsychosis" /><ref>{{cite book | vauthors=((Hofmann, F. G.)) | date= 1983 | title=A handbook on drug and alcohol abuse: the biomedical aspects | publisher=Oxford University Press | edition=2nd ed | isbn=9780195030563}}</ref> The same review asserts that, based upon at least one trial, [[antipsychotic]] medications effectively resolve the symptoms of acute amphetamine psychosis.<ref name="amppsychosis" />
===Dangerous interactions===
===Dangerous interactions===
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*'''[https://en.wikipedia.org/wiki/Tricyclic_antidepressant Tricyclic antidepressants]''' - Propylhexedrine may increase the effects of tricyclic antidepressants to dangerous levels.<ref>Adderall Prescription info | http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf</ref>
*'''[https://en.wikipedia.org/wiki/Tricyclic_antidepressant Tricyclic antidepressants]''' - Propylhexedrine may increase the effects of tricyclic antidepressants to dangerous levels.<ref>Adderall Prescription info | http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf</ref>
{{DangerousInteractions/Stimulants}}
{{DangerousInteractions/Stimulants}}
*'''[[MDMA]]''' - Like with [[amphetamine]]s, the neurotoxic effects of [[MDMA]] may be increased when combined with propylhexedrine.
{{DangerousInteractions/MAOI|nt=dopamine}}
{{DangerousInteractions/MAOI|nt=dopamine}}
*'''[[Cocaine]]''' - This combination may increase strain on the heart to dangerous levels.
*'''[[Cocaine]]''' - This combination may increase strain on the heart to dangerous levels.
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==Legal status==
==Legal status==
{{LegalStub}}
{{LegalStub}}
* '''United States''' - Propylhexedrine is a legal OTC drug. It is designed not to be recreationally used unless the user decides to bypass the manufacturer's intended design with which it was granted approval to market as a nasal decongestant. The simple consumption of this substance is not technically considered illegal.
*'''Canada''': Propylhexedrine is not controlled under the schedules to the Controlled Drugs And Substances Act.{{citation needed}}
*'''Germany''': Propylhexedrine is a prescription only medicine, according to Anlage 1 AMVV (''Medicine Prescribing Regulation, Schedule 1'').<ref>{{cite web|url=https://www.gesetze-im-internet.de/amvv/anlage_1.html|title=Anlage 1 AMVV|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 28, 2019|language=de}}</ref>
*'''Switzerland''': Propylhexedrine is not controlled under Buchstabe A, B, C and D. It is sporadically used medicinally.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>
*'''United States''': Propylhexedrine is a legal OTC drug. It is designed not to be recreationally used unless the user decides to bypass the manufacturer's intended design with which it was granted approval to market as a nasal decongestant. The simple consumption of this substance is not technically considered illegal.{{citation needed}}
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Propylhexedrine (also known as Benzedrex and Obesin) is a stimulant substance of the cycloalkylamine class. It is a structural analog of methamphetamine. Propylhexedrine is widely used medicinally as a nasal decongestant (for relief of congestion due to colds, allergies and allergic rhinitis) and sometimes used recreationally as an over-the-counter "legal high".
Benzedrex was first manufactured by Smith, Kline and French after the Benzedrine inhaler, which contained racemic amphetamine, became unavailable following the placement of amphetamines on the US Schedule II status (i.e. highest abuse potential, yet with accepted medicinal uses). Propylhexedrine has also been used in Europe as an appetite suppressant under the trade name Obesin. In the United States, propylhexedrine is most commonly found in over-the-counter Benzedrex nasal inhalers.
Due to its amphetamine-like euphoric effects, propylhexedrine is considered to have moderate abuse potential. Chronic use may result in tolerance, physical and psychological dependence. It is highly advised to use harm reduction practices if using this substance.
Propylhexedrine is chemically classified as a cycloalkylamine. It is structurally similar to phenethylamine and its derivates. It is particularly similar in structure to methamphetamine, with the only structural difference being the substitution of an cyclohexane ring for methamphetamine's phenyl ring. This makes propylhexedrine a structural analog of methamphetamine.
A comparison of similar amine group molecules.
Moreover, propylhexedrine is a chiral compound (the α-carbon is chiral), and the product contained in pharmaceutical products is racemic (RS)-propylhexedrine free base. (S)-Propylhexedrine, also known as levopropylhexedrine, is believed to be the more biologically active isomer of the two, although amphetamines with a "levo" prefix are less active than their counterparts. (S)-Propylhexedrine can be synthesized from methamphetamine.[citation needed]
Freebase propylhexedrine is nonpolar, volatile, oily liquid at room temperature, but it readily forms a polar salt when protonated with hydrochloric acid, citric acid, and acetic acid to form a crystalline white substance.[citation needed] As a volatile liquid, it evaporates over time, losing potency drastically quicker than crystalline substances; However, the salt forms are crystalline, and do not evaporate.
Propylhexedrine affects the central nervous system (CNS) by acting as a releasing agent for the monoamineneurotransmittersdopamine, norepinephrine, and serotonin (SNDRA), binding to and reversing their transporters, pumping these neurotransmitters from the cytosol to the synaptic cleft, where these neurotransmitters can bind to their respective receptors. Additionally, propylhexedrine inhibits VMAT2, leading to a further increase in the aforementioned monoamines, being that VMAT2 transports all 3 from the synaptic cleft to the cytosol.[citation needed]
Propylhexedrine, like phenethylamine, amphetamine, methamphetamine, and MDMA, agonizes TAAR1. TAAR1 agonism, through protein kinase A & C (PKA and PKC) signaling, causes dopamine transporter (DAT) phosphorylation. Both PKA and PKC result in non-competitive dopamine reuptake inhibition, although PKC alone results in dopamine release/DAT reversal.
The pharmacological actions of propylhexedrine are similar to those of phenethylamines, such as amphetamines, albeit in a generally less centrally active and recreationally desirable fashion.[1]
Since propylhexedrine has a cyclohexane ring in the place of methamphetamine's phenyl ring, it lacks the level of Brain-Blood Barrier permeability that the phenyl ring provides amphetamines, and therefore has a greater proportion of effects on the peripheral nervous system relative to the central nervous system.[2]
Propylhexedrine has a half-life of 2.5 - 6.5 hours, which is variable based on urinary pH and the level of activity of certain Cytochrome P450 enzymes. Higher urinary pH elongates duration, while low urinary pH shortens duration. Higher activity of certain Cytochrome P450 enzymes also shortens duration.[3]
Propylhexedrine is metabolized by certain Cytochrome P450 enzymes into norpropylhexedrine, cyclohexylacetoxime, cis-4-hydroxypropylhexedrine and trans-4-hydroxypropylhexedrine.[3]
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWikicontributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
Physical effects
Stimulation - In terms of its effects on the physical energy levels of the user, propylhexedrine is usually considered to be extremely energetic and stimulating in a fashion that is extremely similar to that of amphetamine or methamphetamine, and stronger than that of modafinil, caffeine, and methylphenidate. It is similar to the stimulation experienced on racemic or the levorotorary form of amphetamine or the racemic methamphetamine, encouraging physical activities such as dancing, socializing, running, or cleaning. The particular style of stimulation which propylhexedrine presents can be described as forced or pressing and is noticeably more adrenergic and tense on the body. This means that at higher dosages, it becomes difficult or impossible to keep still as jaw clenching, involuntarily bodily shakes and vibrations become present, resulting in extreme shaking of the entire body, unsteadiness of the hands, and a general lack of motor control.
Abnormal heartbeat[citation needed] - Heart palpitations are commonly reported on common to heavy doses of this substance due to its significant peripheral nervous system activity.
Increased blood pressure[citation needed] - Propylhexedrine has been noted by users to raise blood pressure significantly more than other stimulants. It has been speculated that this is due to its higher affinity for noradrenaline relative to stimulants such as amphetamine.
Increased heart rate[citation needed] - Due to its pronounced peripheral nervous system activity, propylhexedrine tends to increase heart rate much more drastically than comparable dosages of other stimulants.
Nausea - This effect is prominent on the onset and come up period when ingested via the cotton found inside Benzedrex inhalers, particularly when it is taken on an empty stomach.
Vasoconstriction - Propylhexedrine has been noted by users as being particularly vasoconstrictive in comparison to other stimulants. It has been speculated that this is due to its higher affinity for noradrenaline relative to stimulants such as amphetamine.
Visual effects
As with amphetamine or methamphetamine, the visual effects of propylhexedrine are usually less consistent and are only mildly noticeable at higher dosages. They are somewhat comparable to the visual effects produced by deliriants and are generally more frequent in darker areas.
Suppressions
Double vision - An uncommon effect that only occurs at very high, potentially dangerous or toxic dosages.
Distortions
Drifting - This effect is usually subtle and barely noticeable and only occurs at higher dosages or when combined with cannabis. Commonly this consists of level 1-2 drifting.
The cognitive effects of propylhexedrine can be broken down into several components which progressively intensify proportional to dosage. The general head space of propylhexedrine is described by many as one of moderate to extreme mental stimulation, increased focus, and powerful euphoria. It contains a large number of typical stimulant cognitive effects. Although negative side effects are usually mild at low to moderate dosages, they become increasingly likely to manifest themselves with higher amounts or extended usage. This particularly holds true during the offset of the experience.
The most prominent of these cognitive effects generally include:
The effects which occur during the offset of a stimulant experience generally feel negative and uncomfortable in comparison to the effects which occurred during its peak. This is often referred to as a "comedown" and occurs because of neurotransmitter depletion. Its effects commonly include:
Depression - Due to depletion of the essential neurotransmitters serotonin,dopamine, and norepinephine, propylhexedrine can cause moderate to strong feelings of depression after large doses.
The toxicity of recreational propylhexedrine use has not been studied as extensively as that of amphetamine or methamphetamine but it is reasonable to assume that most if not all of the same risks apply.
As with other stimulants, the chronic use of propylhexedrine can be considered highly addictive, and is capable of causing psychological and physiological dependence among certain users. When addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops or drastically decreases their usage.
Tolerance to the effects of this compound likely occurs in the same general fashion as with amphetamine rapidly develops with prolonged and repeated use.[4][5] This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). Propylhexedrine presents cross-tolerance with [[Cross-tolerance::all dopaminergicstimulants]], meaning that after the consumption of propylhexedrine all stimulants will have a reduced effect.
Like with amphetamine and methamphetamine the evidence on effective treatments for dependence and abuse is limited.[6] In light of this, fluoxetine and imipramine appear to have some limited benefits in treating abuse and addiction[6]
In highly dependent amphetamine and methamphetamine abusers, "when chronic heavy users abruptly discontinue methamphetamine use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose".[7] Withdrawal symptoms in chronic, high-dose users are frequent, occurring in up to 87.6% of cases, and persist for three to four weeks with a marked "crash" phase occurring during the first week.[7] Methamphetamine withdrawal symptoms can include anxiety, drug craving, dysphoric mood, fatigue, increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness, and vivid or lucid dreams.[7] Withdrawal symptoms are associated with the degree of dependence (i.e., the extent of abuse).[7] The mental depression associated with methamphetamine withdrawal lasts longer and is more severe than that of cocaine withdrawal.[1]. It is likely that propylhexedrine abuse is subject to these same outcomes.
Like with the abuse of methamphetamine, propylhexedrine abuse can result in a stimulant-induced psychotic state that may present with a variety of symptoms (e.g., paranoia, hallucinations, delusions), though likely to a lesser degree.[8][9] A review on treatment for amphetamine, dextroamphetamine, and methamphetamine abuse-induced psychosis states that about 5–15% of users fail to recover completely.[9][10] The same review asserts that, based upon at least one trial, antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis.[9]
Dangerous interactions
Warning:Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
Tricyclic antidepressants - Propylhexedrine may increase the effects of tricyclic antidepressants to dangerous levels.[11]
"[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] & "[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - 25x compounds are highly stimulating and physically straining. Combinations with Propylhexedrine should be strictly avoided due to the risk of excessive stimulation and heart strain. This can result in increased blood pressure, vasoconstriction, panic attacks, thought loops, seizures, and heart failure in extreme cases.
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Combining alcohol with stimulants can be dangerous due to the risk of accidental over-intoxication. Stimulants mask alcohol's depressant effects, which is what most people use to assess their degree of intoxication. Once the stimulant wears off, the depressant effects will be left unopposed, which can result in blackouts and severe respiratory depression. If mixing, the user should strictly limit themselves to only drinking a certain amount of alcohol per hour.
"[[UnsafeInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Combinations with DXM should be avoided due to its inhibiting effects on serotonin and norepinephrine reuptake. There is an increased risk of panic attacks and hypertensive crisis, or serotonin syndrome with serotonin releasers (MDMA, methylone, mephedrone, etc.). Monitor blood pressure carefully and avoid strenuous physical activity.
"[[UnsafeInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Any neurotoxic effects of MDMA are likely to be increased when other stimulants are present. There is also a risk of excessive blood pressure and heart strain (cardiotoxicity).
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Some reports suggest combinations with MXE may dangerously increase blood pressure and increase the risk of mania and psychosis.
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Both classes carry a risk of delusions, mania and psychosis, and these risk may be multiplied when combined.
"[[UnsafeInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Propylhexedrine may be dangerous to combine with other stimulants like cocaine as they can increase one's heart rate and blood pressure to dangerous levels.
"[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Tramadol is known to lower the seizure threshold[12] and combinations with stimulants may further increase this risk.
"[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - This combination may increase the amount of neurotransmitters such as dopamine to dangerous or even fatal levels. Examples include syrian rue, banisteriopsis caapi, and some antidepressants.[13]
Cocaine - This combination may increase strain on the heart to dangerous levels.
As such, it may contain incomplete or wrong information. You can help by expanding it.
Canada: Propylhexedrine is not controlled under the schedules to the Controlled Drugs And Substances Act.[citation needed]
Germany: Propylhexedrine is a prescription only medicine, according to Anlage 1 AMVV (Medicine Prescribing Regulation, Schedule 1).[14]
Switzerland: Propylhexedrine is not controlled under Buchstabe A, B, C and D. It is sporadically used medicinally.[15]
United States: Propylhexedrine is a legal OTC drug. It is designed not to be recreationally used unless the user decides to bypass the manufacturer's intended design with which it was granted approval to market as a nasal decongestant. The simple consumption of this substance is not technically considered illegal.[citation needed]
↑ 1.01.1Winslow, B. T., Voorhees, K. I., Pehl, K. A. (15 October 2007). "Methamphetamine abuse". American Family Physician. 76 (8): 1169–1174. ISSN0002-838X.
↑Pérez-Mañá, C., Castells, X., Torrens, M., Capellà, D., Farre, M. (2 September 2013). "Efficacy of psychostimulant drugs for amphetamine abuse or dependence". The Cochrane Database of Systematic Reviews (9): CD009695. doi:10.1002/14651858.CD009695.pub2. ISSN1469-493X.
↑ 6.06.1Srisurapanont, M., Jarusuraisin, N., Kittirattanapaiboon, P. (2001). "Treatment for amphetamine dependence and abuse". The Cochrane Database of Systematic Reviews (4): CD003022. doi:10.1002/14651858.CD003022. ISSN1469-493X.
↑Hofmann, F. G. (1983). A handbook on drug and alcohol abuse: the biomedical aspects (2nd ed ed.). Oxford University Press. ISBN9780195030563.CS1 maint: Extra text (link)
↑Talaie, H.; Panahandeh, R.; Fayaznouri, M. R.; Asadi, Z.; Abdollahi, M. (2009). "Dose-independent occurrence of seizure with tramadol". Journal of Medical Toxicology. 5 (2): 63–67. doi:10.1007/BF03161089. eISSN1937-6995. ISSN1556-9039. OCLC163567183.
. eISSN 1471-6771. ISSN 0007-0912. OCLC 01537271. PMID 16051647.