Lisdexamfetamine

Standard Drug Panel Inclusion

Lisdexamfetamine is a prodrug of dextroamphetamine and will cause a positive result on standard 5-panel immunoassay drug screens for amphetamines. After oral ingestion, lisdexamfetamine is enzymatically cleaved in the blood by red blood cell aminopeptidases, releasing dextroamphetamine and L-lysine. The resulting dextroamphetamine is identical to that from any other amphetamine source and is fully detectable by all amphetamine immunoassays.

Urine Detection

Because lisdexamfetamine is converted to dextroamphetamine systemically, the urinary detection window mirrors that of dextroamphetamine: approximately 2 to 4 days after a single dose, extending to 5 to 7 days with chronic use. The primary urinary analyte is dextroamphetamine itself, along with its metabolites (4-hydroxyamphetamine, norephedrine, and deaminated products). Urinary pH affects the detection window as with all amphetamines.

Blood and Saliva Detection

Blood and oral fluid testing will detect dextroamphetamine (the active metabolite of lisdexamfetamine) for approximately 24 to 48 hours. The intact prodrug lisdexamfetamine has a very short plasma half-life and is rapidly converted, so parent compound detection is not clinically relevant. Oral fluid testing with a standard 25 ng/mL cutoff will detect use within 24 to 50 hours.

Hair Follicle Detection

Hair follicle analysis will detect dextroamphetamine from lisdexamfetamine use for up to 90 days. The incorporated analyte is dextroamphetamine. Chiral analysis will show predominantly d-amphetamine, consistent with a pharmaceutical source. All standard hair testing panels include amphetamines.

Confirmatory Testing

GC-MS and LC-MS/MS confirmation will identify dextroamphetamine as the primary analyte. Confirmatory testing cannot distinguish between lisdexamfetamine, dextroamphetamine, or mixed amphetamine salts as the source. A valid prescription for any of these medications, verified by a Medical Review Officer, can result in the positive test being reported as negative for non-prescribed use.

Reagent Testing

Lisdexamfetamine in its intact prodrug form (capsule powder) does not produce the same reagent reactions as free amphetamine, because the lysine conjugate alters the amine reactivity. Marquis reagent may produce a delayed or attenuated orange reaction. Once metabolized, the resulting dextroamphetamine produces standard amphetamine reagent reactions. For harm reduction identification of the capsule contents, Marquis remains the most informative reagent.

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

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 often require increasingly larger doses of the drug in order to achieve the same effect. Repeated use of lisdexamfetamine results 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.

• Psychosis

Using amphetamines in very high doses can result in stimulant psychosis which may include 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

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. It requires a special certificate while traveling within the Schengen Area, whic

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 often require increasingly larger doses of the drug in order to achieve the same effect. Repeated use of lisdexamfetamine results 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.

Psychosis

Using amphetamines in very high doses can result in stimulant psychosis which may include 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

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.

• Alcohol - Drinking alcohol on stimulants is considered risky because it reduces the sedative effects of the alcohol that the body uses to gauge drunkenness. This often leads to excessive drinking with greatly reduced inhibitions, increasing the risk of liver damage and increased dehydration. The effects of stimulants will also allow one to drink past a point where they might normally pass out, increasing the risk. If you do decide to do this then you should set a limit of how much you will drink each hour and stick to it, bearing in mind that you will feel the alcohol and the stimulant less.

• GHB/GBL - Stimulants increase respiration rate allowing a higher dose of sedatives. If the stimulant wears off first then the depressant effects of the GHB/GBL may overcome the user and cause respiratory arrest.

• Opioids - Stimulants increase respiration rate allowing a higher dose of opiates. If the stimulant wears off first then the opiate may overcome the patient and cause respiratory arrest.

• Cocaine - The rewarding effects of cocaine are mediated by DAT inhibition, and an increase of exocytosis of dopamine through the cell membrane. Amphetamine reverses the direction of DAT and the direction vesicular transports within the cell by a pH mediated mechanism of displacement, thus excludes the regular mechanism of dopamine release through means of exocytosis because the effects Na+/K+ ATPase are inhibited. You will find cardiac effects with the combination of cocaine and amphetamine due to a SERT mediated mechanism from the subsequent activation of 5-HT2B, which is an effect of serotonin-related valvulopathy. Amphetamines generally cause hypertension in models of abuse, and this combination can increase the chances of syncope due to turbulent blood flow during valve operation. The rewarding mechanisms of cocaine are reversed by administration of amphetamine.

• Cannabis - Stimulants increase anxiety levels and the risk of thought loops and paranoia which can lead to negative experiences.

• Caffeine - This combination of stimulants is generally considered unnecessary and may increase strain on the heart, as well as potentially causing anxiety and physical discomfort.

• Tramadol - Tramadol and stimulants both increase the risk of seizures.

• DXM - Both substances raise heart rate, in extreme cases, panic attacks caused by these substances have led to more serious heart issues.

• Ketamine - Combining amphetamine and ketamine may result in psychoses that resemble schizophrenia, but not worse than the psychoses produced by either substance alone, but this is debatable. This is due to amphetamines ability to attenuated the disruption of working memory caused by ketamine. Amphetamine alone may result in grandiosity, paranoia, or somatic delusions with little to no effect on negative symptoms. Ketamine, however, will result in thought disorders, disruption of executive functioning, and delusions due to a modification of conception. These mechanisms are due to an increase of dopaminergic activity in the mesolimbic pathway caused by amphetamine due to its pharmacology effecting dopamine, and due to a disruption of dopaminergic functioning in the mesocortical pathways via NMDA antagonism effects of ketamine. Combining the two, you may expect mainly thought disorder along with positive symptoms.

• PCP - Increases risk of tachycardia, hypertension, and manic states.

• Methoxetamine - Increases risk of tachycardia, hypertension, and manic states.

• Psychedelics (e.g. LSD, mescaline, psilocybin) - Increases risk of anxiety, paranoia, and thought loops.

• 25x-NBOMe - Amphetamines and NBOMes both provide considerable stimulation that when combined they can result in tachycardia, hypertension, vasoconstriction and, in extreme cases, heart failure. The anxiogenic and focusing effects of stimulants are also not good in combination with psychedelics as they can lead to unpleasant thought loops. NBOMes are known to cause seizures and stimulants can increase this risk.

• 2C-T-x - Suspected of mild MAOI properties. May increase the risk of hypertensive crisis.

• 5-MeO-xxT - Suspected of mild MAOI properties. May increase the risk of hypertensive crisis.

• DOx

• aMT - aMT has MAOI properties which may interact unfavorably with amphetamines.

• MAOIs - MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably. MAO-A inhibitors with amphetamine can lead to hypertensive crises.

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. It requires a special certificate while traveling within the Schengen Area, which covers most of Europe, but not the United Kingdom.

• Australia: It is a Schedule 8 drug.

• Canada: Lisdexamfetamine, as well as other amphetamines, is a Schedule I drug.

• Germany: Lisdexamfetamine is controlled under Anlage III BtMG (Narcotics Act, Schedule III) as of July 17, 2013. It can only be prescribed on a narcotic prescription form.

• 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 övervakning" (extended surveillance).

• Switzerland: Lisdexamphetamine is a controlled substance as of October 1, 2014 specifically named under Verzeichnis A. Medicinal use is permitted.

• United Kingdom: Lisdexamfetamine is a Schedule II, Class B controlled drug.

• United States: Lisdexamfetamine is a Schedule II controlled drug.

• Responsible use

• Stimulants

• Amphetamine

• Methylphenidate

• Lisdexamfetamine (Wikipedia)

• Lisdexamfetamine (Isomer Design)

• Lisdexamfetamine (DrugBank)

• Lisdexamfetamine (Drugs.com)

• Dextroamphetamine and Amphetamine (MedicinePlus)

• 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.