|Summary sheet: Lisdexamfetamine|
|Common names||Lisdexamfetamine, Vyvanse|
|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 Literature
- 10 References
History and culture
This History and Culture section is a stub.
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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.
Peripheral effects (such as increased heart rate and higher body temperature) are reported to be less prominent than formulations that partly contain L-amphetamine, such as Adderall or the racemic amphetamine sulphate sold illicitly.
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.
- Stimulation - Lisdexamfetamine is reported to be very energetic and stimulating in a manner similar to amphetamine. It can encourage physical activities such as dancing, socializing, running, or cleaning. The particular style of stimulation which lisdexamfetamine produces can be described as forced. This means that, at higher dosages, it becomes difficult or impossible to keep still as jaw clenching, involuntary bodily shakes and vibrations become present, resulting in extreme shaking of the entire body, unsteadiness of the hands, and a general loss of fine motor control. This effect is replaced with mild fatigue and general exhaustion during the offset of the experience.
- Spontaneous bodily sensations - The "body high" of lisdexamphetamine can be described as a moderate euphoric tingling sensation that encompasses the entire body. This sensation maintains a consistent presence that steadily rises with the onset and hits its limit once the peak has been reached.
- Abnormal heartbeat
- Increased heart rate
- Increased blood pressure
- Appetite suppression - This effect is more pronounced compared to amphetamine, sometimes causing people to not eat for the entire duration of action. Lisdexamfetamine is sometimes prescribed to treat binge eating disorder due to its strong appetite suppressing effect.
- Dry mouth
- Frequent urination
- Increased bodily temperature
- Increased perspiration
- Nausea - This effect usually only occurs at heavy doses.
- Pupil dilation - This effect is more prominent on the offset of the experience.
- Stamina enhancement
- Teeth grinding - This component can be considered to be less intense when compared with that of MDMA.
- Temporary erectile dysfunction
The visual effects of lisdexamfetamine are usually less consistent and only mildly noticeable at higher dosages. They are somewhat comparable to the visual effects of deliriants and occur more readily in darker areas.
- Drifting (breathing and morphing) - This effect is usually subtle and only occurs at higher doses, after long periods of being awake, or when combined with cannabis. Commonly this consists of level 1-2 drifting.
- Brightness alteration - Lisdexamfetamine can make spaces seem brighter as a result of its pupil dilating effects.
- Transformations - This effect occurs very rarely, and typically only when the user has taken high doses, is coming down, or has been awake for unusually long periods. They are usually very mild when they do occur.
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
- Anxiety - This effect occurs more frequently on the offset phase of the experience.
- Creativity enhancement
- Ego inflation
- Emotion suppression - This effect is more commonly reported with lisdexamfetamine, in comparison to other amphetamines such as dextroamphetamine and methamphetamine. It is usually most intense at low and common doses.
- Focus enhancement
- Irritability - This effect occurs more frequently on the offset phase of the experience.
- Immersion enhancement
- Increased music appreciation
- Memory enhancement
- Motivation enhancement
- Increased libido or Decreased 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
- Hallucinations - Use of lisdexamfetamine and other amphetamines, at a strong or heavy dose, can occasionally cause mild auditory hallucinations. These hallucinations most commonly occur amongst a source of white noise, such as a fan, and typically consist of quiet phantom music or voices. Lisdexamfetamine may also cause auditory hallucinations in the form of stimulant psychosis.
- 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. The comedown produced by lisdexamfetamine, depending on the user, is often reported to be much less intense, or much more intense than its metabolite, dextroamphetamine, due to its extended release mechanism. 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.
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.
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.
Although many psychoactive substances are safe to use on their own, they can become dangerous or even life-threatening when taken with other substances. The list below contains some potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses but still increase the possibility of injury of death. Independent research should always be conducted 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/25x-NBOH - Members of the 25x family are highly stimulating and physically straining. Combinations with stimulants should be avoided due to the risk of excessive stimulation. This can result in panic attacks, thought loops, seizures, increased blood pressure, vasoconstriction, and heart failure in extreme cases.
- Alcohol - Alcohol can be dangerous to combine with stimulants due to the risk of accidental over-intoxication. Stimulants mask the sedative effects of alcohol, which is the main factor people use to assess their degree of intoxication. Once the stimulant wears off, the depressant effects of alcohol are left unopposed, which can result in blackouts and respiratory depression. If combined, one should strictly limit themselves to only drinking a certain amount of alcohol per hour.
- DXM - Combinations with DXM should be strictly avoided due to DXM's effects on serotonin and dopamine reuptake. This can lead to panic attacks, hypertensive crisis, or serotonin syndrome.
- MXE - Combinations with MXE may dangerously elevate blood pressure and increase the risk of psychosis.
- Tramadol - Tramadol lowers the seizure threshold. Combinations with stimulants may further increase this risk.
- 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, as well as other amphetamines, 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)
- Lisdexamfetamine (DrugBank)
- Dextroamphetamine and Amphetamine (Medicine Plus)
- Galli, A., Poulsen, N.W., Sulzer, D., & Sonders, M.S. (2005). Mechanisms of neurotransmitter release by amphetamines: a review. Progress in Neurobiology, 75 6, 406-33. https://doi.org/10.1016/j.pneurobio.2005.04.003
- Berman, S. M., Kuczenski, R., McCracken, J. T., & London, E. D. (2009). Potential adverse effects of amphetamine treatment on brain and behavior: a review. Molecular Psychiatry, 14(2), 123. https://doi.org/10.1038/mp.2008.90.
- 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
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