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Clinical Psychopharmacology of Amphetamine and Related Compounds
Published in John Caldwell, S. Joseph Mulé, Amphetamines and Related Stimulants: Chemical, Biological, Clinical, and Sociological Aspects, 2019
Narcolepsy was one of the first conditions to be treated successfully with amphetamine3 and remains one of the few (some would say the only) clinical indications for its use. While the required oral dose of dextroamphetamine (Dexedrine®) ranges from 5 to 120 mg/day, most patients respond to 10 mg two to four times daily. The most frequently reported side effects include irritability, insomnia, palpitations, muscle jerking, and sweating; dextramphetamine can also at times lead to a sustained increase in blood pressure.59 Some patients fail to respond at all, and about a third develop tolerance to the drug and require progressively larger doses. The closely related compound methylphenidate (Ritalin®), 20 mg two to four times daily, has been shown to be as effective as dextroamphetamine but with less likelihood of causing side effects.61 The same is true of levoamphetamine.62
Misuse, Recreational Use, and Addiction in Relation to Prescription Medicines
Published in Ornella Corazza, Andres Roman-Urrestarazu, Handbook of Novel Psychoactive Substances, 2018
Francesco S. Bersani, Claudio Imperatori
Amphetamine derivatives are a wide range of medications whose chemical structure is similar to that of amphetamine, a potent CNS stimulant (Hernandez & Nelson, 2010). Overall, all the medications of this class act as ‘stimulants’, i.e., they are able to enhance alertness by increasing circulating catecholamines, particularly dopamine, norepinephrine, and, at higher doses, serotonin (Hernandez & Nelson, 2010); amphetamine enantiomers (dextroamphetamine and levoamphetamine), both ingredients of commonly prescribed medications, bind to the same biological targets although with different binding affinities and therefore may have different degrees of CNS stimulation (Lewin, Miller, & Gilmour, 2011; R. C. Smith & Davis, 1977). Methylphenidate is a CNS stimulant of the phenethylamine and piperidine classes; its proposed mechanism of action is the release and increase of CNS dopamine, secondary to its effect on the dopamine transport mechanism, which results in an increased amount of postsynaptic dopamine (Morton & Stockton, 2000). Both classes of medications (amphetamines and methylphenidate) are mainly used for the treatment of attention deficit/hyperactivity disorder (ADHD) and have a strong potential of misuse (Hernandez & Nelson, 2010; Morton & Stockton, 2000).
Stimulants and psychedelics
Published in Ilana B. Crome, Richard Williams, Roger Bloor, Xenofon Sgouros, Substance Misuse and Young People, 2019
Amphetamine (α-methylphenethylamine), and its two enantiomers Levo-amphetamine and Dextro-amphetamine (dexamphetamine), are potent central nervous system stimulants that are related to the naturally occurring trace amine neuro-modulators phenethylamine and N-methylphenethylamine. Properly applied, the term amphetamine refers to a specific chemical, which is equal parts of the two enantiomers. However, it is frequently used informally to refer to any combinations of the two enantiomers, or to either of them alone. Amphetamine was first discovered in 1887, but its stimulant properties were largely unknown until 1927 when it was independently re-synthesised and reported to have sympathomimetic properties (Sulzer et al., 2005). It had no pharmacological use until 1932 when Smith, Kline and French developed it as an over-the-counter decongestant inhaler under the trade name of Benzedrine (Rasmussen, 2006). During the Second World War, amphetamine was used extensively for its stimulant and performance-enhancing properties (Defalque and Wright, 2011; Rasmussen, 2011). Its recreational use expanded in the 1950s and the 1960s, when it was used as a euphoriant and aphrodisiac, especially by the beatnik and mod generations. It became a Schedule II controlled substance during the early 1970s, when its addictive properties and significant adverse health effects were recognised. Amphetamine is occasionally used today in treating patients who have narcolepsy and refractory attention deficit hyperactivity disorder (ADHD). It is also used off-label in treating people who are obese or have treatment-resistant depression, and as a performance and cognitive enhancer. Pharmaceutical amphetamine in the UK is prescribed as dexamphetamine or lisdexamphetamine mesilate, a pro-drug of amphetamine. The British National Formulary states: Amphetamines have very few indications and in particular, should not be used for the treatment of depression, obesity, senility, debility, or for relief of fatigue. They should be prescribed for children with severe and persistent symptoms of ADHD, only when the diagnosis has been confirmed by a specialist.(Joint Formulary Committee, 2019)
Stimulant storm – state health department psychostimulant age-adjusted mortality rate correlates with psychostimulant-based Michigan Poison Center case exposures over time
Published in Clinical Toxicology, 2021
Varun Vohra, Andrew King, Sydney Daviskiba, Brian Reed, Sarah Rockhill, Perri Kern, Diana Dean
Reporting to the MDHHS database is mandatory. The ME determines, using post-mortem confirmatory toxicology testing, clinical information, patient history, and scene investigation to determine contributing factors to the cause of death. The MDHHS data do not contain autopsy information beyond what is captured in the underlying and related causes of death. We performed the MDHHS database query on a timeline spanning between February 25, 2020 and March 27, 2020. We recorded manner of death (i.e., intentional, unintentional, other, undetermined) in each MDHHS case; a distinction being that “intentional” was defined as death resulting from “self-harm” in contrast to “unintentional”, involving unanticipated fatal consequences. Psychostimulants included in MDHHS reports were methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), dextroamphetamine, levoamphetamine, caffeine, and methylphenidate (Figure 1). Based on how MDHHS Vital Statistics are collected and aggregated, codified by International Classification of Disease – Tenth Revision (ICD-10) diagnoses, we were unable to identify which type of psychostimulant(s) were a contributing cause of death or perform separate analyses by substance.
A randomized, double-blind, 3-way crossover, analog classroom study of SHP465 mixed amphetamine salts extended-release in adolescents with ADHD
Published in Postgraduate Medicine, 2019
Sharon Wigal, Frank Lopez, Glen Frick, Brian Yan, Brigitte Robertson, Manisha Madhoo
SHP465 mixed amphetamine salts (SHP465 MAS) extended-release is a once-daily, single-entity MAS product for oral administration approved in the United States for the treatment of ADHD in patients 13 years and older [8]. It contains equal amounts (by weight) of four salts: dextroamphetamine sulfate, amphetamine sulfate, dextroamphetamine saccharate, and amphetamine aspartate monohydrate. This results in a 3:1 mixture of dextro- to levoamphetamine base equivalent. Each capsule contains three types of drug-releasing beads, an immediate-release bead and two different types of delayed-release beads. The efficacy and tolerability of SHP465 MAS in individuals with ADHD has been demonstrated in four phase three efficacy studies: three conducted in adults [9–11] and one in children and adolescents [12]. Across all short-term efficacy studies, dose-optimized and fixed-dose SHP465 MAS met the primary efficacy endpoint of significant reductions in ADHD Rating Scale (ADHD-RS) total score from baseline versus placebo [9–12]. SHP465 MAS has also been shown to have a safety and tolerability profile consistent with other long-acting stimulants [13–15].
A randomized, double-blind study of SHP465 mixed amphetamine salts extended-release in adults with ADHD using a simulated adult workplace design
Published in Postgraduate Medicine, 2018
Timothy Wigal, Matthew Brams, Glen Frick, Brian Yan, Manisha Madhoo
SHP465 mixed amphetamine salts (MAS) extended-release is a once-daily, single-entity MAS product for oral administration approved in the United States for the treatment of ADHD in patients 13 years and older. It contains equal amounts (by weight) of four salts: dextroamphetamine sulfate, amphetamine sulfate, dextroamphetamine saccharate, and amphetamine aspartate monohydrate. This results in a 3:1 mixture of dextro- to levo-amphetamine base equivalent. Each capsule contains three types of drug-releasing beads, an immediate-release bead, and two different types of delayed-release beads. The efficacy, safety, and tolerability of SHP465 MAS in adults with ADHD have been described in several 4- to 7-week randomized, placebo-controlled phase 3 studies [9–11] and in a 52-week, open-label, safety extension study [12].