|Summary sheet: Lisdexamfetamine|
|Molecular structure of Lisdexamfetamine|
|Common names||Lisdexamfetamine, Vyvanse|
|Chemical class||Substituted amphetamine|
|Routes of Administration|
Lisdexamfetamine (also known as Lisdextroamphetamine, L-lysine-dextroamphetamine and sold under the brand names Vyvanse and Elvanse) is a widely-prescribed synthetic stimulant pharmaceutical drug of the amphetamine chemical class that produces long-lived, classical amphetamine-type stimulating, focus enhancing, and euphoric effects when administered.
Lisdexamfetamine is a prodrug for the enantiopure d-isomer form of amphetamine (dextroamphetamine), which is known to be a strong central nervous system (CNS) stimulant. It is indicated and widely prescribed for the medical treatment of ADHD and moderate to severe binge-eating disorder. This means that outside of the oral route, its effects are independent of route of administration. Other routes of administration like insufflation, smoking or injection do not provide faster absorption or onset.
Unlike other amphetamine formulations such as racemic street "speed" or Adderall, lisdexamfetamine, once it is converted into its active form, is pure dextroamphetamine. Dextroamphetamine is known to produce stronger central and weaker peripheral nervous system effects relative to its opposite enantiomer, levoamphetamine. For this reason, it is commonly used both illicitly as a study drug and for recreational purposes due to the euphoria and prosocial effects it can produce at higher doses.
Despite the marketed anti-abuse design of the drug, lisdexamfetamine is commonly reported to be capable of producing dependence and addiction like other euphoria-producing stimulants, particularly when it is taken above the recommended dosage. For this reason, it is highly advised to use harm reduction practices if choosing to use this drug.
- 1 History and culture
- 2 Chemistry
- 3 Pharmacology
- 4 Subjective effects
- 5 Toxicity and Harm Potential
- 6 Legal status
- 7 See also
- 8 External links
- 9 References
History and culture
This History and Culture section is a stub.
As such, it may contain incomplete or wrong information. You can help by expanding it.
Lisdexamphetamine consists of the dextro-rotary stereoisomer of amphetamine bonded to the essential amino acid L-Lysine. Amphetamine is comprised of a phenethylamine core featuring a phenyl ring bound to an amino (NH2) group through an ethyl chain with an additional methyl substitution at Rα. It can be referred to as a methyl homologue of phenethylamine as it has the same general formula, differing only in the addition of one methyl group.
Lisdexamfetamine was developed with the goal of providing a long duration of effect that is consistent throughout the day, with reduced potential for abuse. The attachment of the amino acid lysine slows down the relative amount of dextroamphetamine that is released into the bloodstream. Because no free dextroamphetamine is present in lisdexamfetamine capsules, dextroamphetamine does not become available through mechanical manipulation, such as crushing or simple extraction. There is, therefore, no way to speed up absorption via alternate routes of administration, such as via insufflation, vaporization, or injection, making the drug theoretically less abusable.
A relatively sophisticated biochemical process is needed to produce dextroamphetamine from lisdexamfetamine. While amphetamine sulphate contains 50% L-amphetamine, and the ADHD medication Adderall contains a mix of four amphetamine salts totaling 75% D-amphetamine and 25% L-amphetamine, lisdexamfetamine is a single enantiomer formulation, and a prodrug to one of the least common forms of pharmaceutical amphetamines, dextroamphetamine (trade-name "Dexedrine" among many others).
As a prodrug, lisdexamfetamine is inactive in the form administered. Once ingested, it is enzymatically cleaved into two parts: L-lysine, a naturally occurring essential amino acid, and D-amphetamine, a central nervous system stimulant. Thus lisdexamfetamine functions as an extended release version of dexamphetamine. Because D-amphetamine needs to be liberated from lysine via contact with red blood cells, effects are independent of route of administration. Conversion of lisdexamfetamine into active D-amphetamine is enzymatically rate-limited, slowing down the time to achieve peak concentrations and decreasing its magnitude and dampening consequent striatal dopamine release, which is thought to be responsible for its euphoric and compulsive redosing effects.
Amphetamine is a full agonist of the trace amine-associated receptor 1 (TAAR1), which is a key regulator of common and trace brain monoamines such as dopamine, serotonin and noradrenaline. The agonism of this set of receptors results in the release of increased concentrations of dopamine, serotonin and noradrenaline in the synaptic cleft. This leads to cognitive and physical stimulation within the user.
D-amphetamine's affinity for the TAAR1 receptor is twice that of L-amphetamine. As a result, D-amphetamine produces three to four times as much central nervous system (CNS) stimulation as L-amphetamine. L-amphetamine, on the other hand, has stronger cardiovascular and peripheral effects.
Roughly 1/3 of the mass of lisdexamfetamine is dexamphetamine, such that a dose of 70mg lisdexamfetamine is equivalent to 21mg dexamfetamine. The subjective experience will differ due to the slower, more steady release of active substance in the prodrug. An equivalent dose of dexamphetamine will have a higher peak plasma concentration and shorter duration.
While the subjective effects are almost identical to that of amphetamine, lisdexamfetamine is significantly longer in its duration and more consistent in its intensity due to the slow release metabolism. Although this drug is rate-limited in its metabolism, sufficiently high doses are comparable to its instant release counterparts once the peak has been reached.
The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.
Peripheral effects (such as increased heart rate and higher body temperature) are less intense than formulations that partly contain L-amphetamine, such as Adderall or the racemic amphetamine sulphate sold illicitly.
- Spontaneous physical sensations - The "body high" of lisdexamfetamine can be described as a moderate euphoric tingling sensation that encompasses the entire body, radiating from the core. This sensation maintains a consistent presence that steadily rises with the onset and hits its limit once the peak has been reached.
- Physical euphoria
- Bodily control enhancement
- Increased heart rate
- Pupil dilation
- Tactile enhancement - Feelings of enhanced tactile sensation are consistently present at mild to moderate levels proportional to dosage.
- Teeth grinding
- Appetite suppression
Lisdexamfetamine shares most of its cognitive effects with other amphetamines, although it is less forceful in its come up due to the slow release mechanism. It produces a variety of cognitive enhancements associated with stimulants. However, during the latter part of the duration, these cognitive enhancements may compete with or be nullified by the accumulated dopamine depletion and its effects.
The most prominent of these cognitive effects generally include:
- Analysis enhancement
- Creativity enhancement
- Ego inflation
- Focus enhancement
- Immersion enhancement
- Increased music appreciation
- Memory enhancement
- Motivation enhancement
- Novelty enhancement
- Increased libido
- Novelty enhancement
- Personal bias suppression
- Time distortion - This can be described as the experience of time speeding up and passing much quicker than it usually would when sober.
- Thought acceleration
- Thought organization
- Time distortion
- Cognitive euphoria
- Depersonalization - This drug is commonly reported to induce depersonalization on the second half of the duration due to an accumulation of dopamine depletion mixed with the residual stimulation of the substance.
- 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:
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
Toxicity and Harm Potential
In rodents and primates, sufficiently high doses of amphetamine cause dopaminergic neurotoxicity, or damage to dopamine neurons, which is characterized by reduced transporter and receptor function. There is no evidence that amphetamine is directly neurotoxic in humans. However, large doses of amphetamine may cause indirect neurotoxicity as a result of increased oxidative stress from reactive oxygen species and autoxidation of dopamine.
A severe amphetamine overdose can result in a stimulant psychosis that may involve a variety of symptoms, such as paranoia, delusions, and hallucinations, including the infamous Shadow people. A Cochrane Collaboration review on treatment for amphetamine, dextroamphetamine, and methamphetamine psychosis states that about 5–15% of users fail to recover completely. According to the same review, there is at least one trial that shows antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis. Psychosis very rarely arises from therapeutic use. The combination of prolonged use of high doses combined with sleep deprivation significantly increases the risk of stimulant psychosis.
It is strongly recommended that one use harm reduction practices when using this drug.
Tolerance and addiction potential
Addiction is a serious risk with heavy recreational amphetamine use but is unlikely to arise from typical long-term medical use at therapeutic doses. Lisdexamfetamine has been posited to have less potential for abuse and addiction than other pharmaceutical amphetamines due to the slower onset and the self-limiting metabolism, which puts a cap on the maximum peak plasma concentration and consequent dopamine release. Caution is nonetheless advised, as with other drugs in the amphetamine class.
Tolerance develops rapidly in amphetamine abuse (i.e. a recreational amphetamine overdose), so periods of extended use require increasingly larger doses of the drug in order to achieve the same effect. Repeated use of lisdexamfetamine will result in a gradual tolerance proportional to the dosage taken. Patients prescribed this drug often must increase their dosage after a time to maintain its efficacy.
Although many psychoactive substances are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.
- Stimulants - Amphetamine can be potentially dangerous in combination with other stimulants as it can increase one's heart rate and blood pressure to dangerous levels.
- Tricyclic antidepressants - Amphetamine may increase the effects of tricyclic antidepressants to dangerous levels.
- 25x-NBOMe - Both the NBOMe series and this compound induce powerful stimulation and their interaction may cause severe side effects. These can include thought loops, seizures, increased blood pressure, vasoconstriction, increased heart rate, and heart failure (in extreme cases).
- Alcohol - It is dangerous to combine alcohol, a depressant, with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of alcohol which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of alcohol will be significantly increased, leading to intensified disinhibition as well as respiratory depression. If combined, one should strictly limit themselves to only drinking a certain amount of alcohol per hour.
- DXM - This combination may cause increased heart rate and panic attacks.
- MXE - Increased heart rate and blood pressure may occur.
- Tramadol - This combination can increase the risk of seizures.
- MDMA - The neurotoxic effects of MDMA may be increased when combined with amphetamines.
- MAOIs - This combination may increase the amount of neurotransmitters such as dopamine to dangerous or even fatal levels. Examples include syrian rue, banisteriopsis caapi, 2C-T-2, 2C-T-7, αMT, and some antidepressants.
- Cocaine - This combination may increase strain on the heart to dangerous levels.
Lisdexamphetamine is approved for medical use with a doctor's prescription, but in most countries it is illegal to sell or possess without a prescription.
- Australia: It is a Schedule 8 drug.
- Germany: Lisdexamfetamine is scheduled in Anlage III.
- Canada: Lisdexamfetamine is a Schedule I drug.
- Norway: Lisdexamfetamine is a Class A drug under particularly strict control.
- Sweden: Lisdexamfetamine is a Class II narcotic, with strict requirements for prescription. It has been placed under "utökad övervåkande" (extended surveillance).
- Schengen Area: Lisdexamphetamine requires a special certificate while traveling within the Schengen Area, which covers most of Europe, but not the United Kingdom.
- United Kingdom: Lisdexamfetamine is a Class B scheduled drug.
- United States: Lisdexamfetamine is a Schedule II controlled drug.
- Lisdexamfetamine (Wikipedia)
- Lisdexamfetamine (Isomer Design)
- Potential Adverse Effects of Amphetamine Treatment on Brain and Behavior: A Review
- Dextroamphetamine and Amphetamine (Medicine Plus)
- The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005101/
- Drug banks amphetamine targets | http://www.drugbank.ca/drugs/DB00182#targets
- TA1 receptor | http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=364
- Adderall Prescription info | http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf
- Gillman, P. K. (2005). Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia, 95(4), 434-441. https://doi.org/10.1093/bja/aei210