Propylhexedrine

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.

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 monoamine neurotransmitters dopamine, 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 PsychonautWiki contributors. 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 ☠.

Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

Additional experience reports can be found here:

• Erowid Experience Vaults: Pharms - Propylhexedrine

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.

It is strongly recommended that one use harm reduction practices when using this substance.

Tolerance and addiction potential

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 all dopaminergic stimulants, 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.

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, 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]
• 25x-NBOMe & 25x-NBOH - 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.
• Alcohol - 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.
• DXM - 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.
• MDMA - 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).
• MXE - Some reports suggest combinations with MXE may dangerously increase blood pressure and increase the risk of mania and psychosis.
• Dissociatives - Both classes carry a risk of delusions, mania and psychosis, and these risk may be multiplied when combined.
• Stimulants - 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.
• Tramadol - Tramadol is known to lower the seizure threshold^[12] and combinations with stimulants may further increase this risk.

• MAOIs - 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.

• 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]}

• Responsible use
• Stimulant
• Amphetamine
• Methamphetamine

• Propylhexedrine (Wikipedia)
• Propylhexedrine (Erowid Vault)
• Propylhexedrine (Isomer Design)