Another less well-recognised factor in drug abuse is a desire of users for instant gratification. The kinetics of d- amphetamine when taken orally make it less rewarding pleasurable than cocaine or methamphetamine. Methamphetamine enters more slowly and its peak effects are delayed by 10—15 min compared with cocaine Fowler et al.
Although d- amphetamine sulphate has not been studied in an exactly comparable way, we can predict from its physico-chemical properties that after oral ingestion d- amphetamine would have even slower rate of uptake into the brain than methamphetamine. Having said that, the abuse of d- amphetamine is not a cause for complacency.
Although amphetamine abuse peaked in the s Rasmussen, , the misuse of amphetamine is a persistent social, legal and medical problem Das-Douglas et al. The intravenous use of d -amphetamine and other stimulants still pose major safety risks to the individuals indulging in this practice Charnaud and Griffiths, ; Das-Douglas et al.
Some of this intravenous abuse is derived from the diversion of ampoules of d- amphetamine, which are still occasionally prescribed in the UK for the control of severe narcolepsy and other disorders of excessive sedation. However, most intravenous d- amphetamine use is from local illicit production.
Some abusers will use solvents to extract the active ingredient from tablets or capsules, which can then be concentrated and injected intravenously.
The development of tamper-deterrent d- amphetamine formulations has been a major objective of the pharmaceutical industry to prevent this type of abuse. Several new once-daily d- amphetamine-containing prescription drugs have emerged that have a high degree of tamper deterrence, for example Adderall XR.
In addition, lisdexamfetamine as a prodrug of d- amphetamine, is a further advance in reducing diversion risk since it provides a more gradual increase in brain drug concentration, thereby further reducing the pleasurable effects of the d- amphetamine.
These topics will be revisited later in this review. Volkow and colleagues have performed an enormous body of research using PET and other brain imaging techniques to explore the relationship between DAT occupancy, synaptic dopamine concentration and dopamine D 2 receptor occupancy for psychostimulant drugs of abuse.
Although the dopamine release hypothesis of drug reinforcement proposed by Di Chiara and Imperato based on experiments performed in rats and then extended in humans by Volkow and colleagues , a has its limitations, it is now well accepted that euphoria, psychostimulation and reinforcement produced by stimulant drugs occur when there are rapid and substantial increases in the synaptic concentrations of dopamine in the basal striatum and mesolimbic system of the human brain.
Although d -amphetamine is a competitive substrate for DAT rather than a classical reuptake inhibitor, these same principles apply to its pharmacological action.
Thus, the rate and magnitude of neuronal dopamine release produced by amphetamine is absolutely dependent on the rate and concentration of drug that reaches DAT sites in the brain Heal et al. There has been little research conducted in humans on this kinetic course using brain imaging, but it seems likely that the same rules apply.
Consistent with the findings in microdialysis experiments, d -amphetamine has greater potency than l- amphetamine to evoke stimulant-like subjective effects in rats Schechter, and behavioural activation in primates Scraggs and Ridley, Both amphetamine isomers have been shown to serve as positive reinforcers in animals i. The same is true for human subjects Smith and Davis, ; Van Kammen and Murphy, , with the d -isomer once again being two to threefold more potent than the l -isomer Risner, ; Smith and Davis, ; Van Kammen and Murphy, ; Yokel and Pickens, As indicated above, it is the combination of the rapid rate of increase and magnitude of effect that accounts for the powerful stimulant effects of amphetamine.
Although l- amphetamine is the less potent of the two isomers, its pharmacological efficacy should not be underestimated. Cheetham et al. In contrast, the maximum increases in dopamine efflux achieved by classical dopamine reuptake inhibitors e. The importance of the rate of increase of synaptic dopamine concentrations to the induction of stimulation and euphoria is exemplified by the observation that bupropion and GBR were not experienced as stimulant or euphoriant by normal volunteers Hamilton et al.
In those bupropion and GBR trials where d -amphetamine was employed as the positive control, its stimulant, energising and reinforcing effects were unequivocally recognised by normal subjects and recreational drug users Hamilton et al. In previous reviews, we have extensively described the efficacy and safety of stimulant and non-stimulant drugs used in the management of ADHD and compared the relative merits of each Heal et al. This analysis has revealed that the stimulants, including amphetamine, are still accepted to be the most efficacious drugs available.
On the other hand, the innovations in formulation technology and drug delivery systems have made significant strides forward in improving the clinical management of ADHD. All of the stimulants have biological half-lives that require at least twice-daily dosing to deliver efficacy over 12—14 h. ADHD is characterised by inattention, distractibility, working memory deficits and impulsivity, and as such, subjects with this disorder are particularly unsuited to compliance with rigid dosing schedules.
Examples of once-daily amphetamine medications include MES-amphetamine XR and the d- amphetamine prodrug, lisdexamfetamine. As briefly discussed earlier in the review, lisdexamfetamine is the first amphetamine prodrug to have been approved for use in treating ADHD. This profile is consistent with lisdexamfetamine being pharmacologically inactive. Although there is no definitive information on the subject, the large molecular size and polar characteristics of lisdexamfetamine predict that the parent molecule is unlikely to cross the blood—brain barrier.
In vitro experiments revealed that the metabolism of lisdexamfetamine to d -amphetamine occurs in red blood cells by rate-limited enzymatic hydrolysis Pennick, Lack of affinity of lisdexamfetamine for a portfolio of abuse-related molecular targets. The locomotor activity of the rats was also simultaneously monitored. After administration of equivalent doses of lisdexamfetamine and IR d- amphetamine 1. These observations are entirely consistent with the postulated rate-limited enzymatic conversion of lisdexamfetamine to d- amphetamine.
This difference in PK characteristics had a profound impact on the pharmacological effects of these two compounds in rats Figure 5. Lisdexamfetamine produced a gradual and sustained increase in striatal dopamine efflux, whereas the increase produced by IR d- amphetamine was faster in onset, reaching a peak at 30 min, and it subsequently declined more rapidly Figure 5. In the case of lisdexamfetamine, the more gradual and sustained increase in dopamine efflux was associated with a much smaller and visibly delayed locomotor response.
Using the hysteresis analysis in a more conventional way to explore the relationship between the plasma concentration of d- amphetamine and the functional response, there was a clear difference between the two compounds with an anticlockwise hysteresis for lisdexamfetamine and no hysteresis for IR d- amphetamine Rowley et al. The anticlockwise hysteresis shows that the functional effect of lisdexamfetamine was greater as the plasma concentration of d- amphetamine was falling, whilst the lack of hysteresis with IR d- amphetamine demonstrates that as soon as the plasma concentration of the drug starts to decline, so does its pharmacological effect.
The clinical importance of these findings will be discussed in the following section. The efficacy of lisdexamfetamine has been demonstrated in a number of randomised, double-blind, placebo-controlled clinical trials in ADHD in children, adolescents Biederman et al.
Since lisdexamfetamine has been the subject of several reviews Dew and Kollins, ; Heal et al. Biederman et al. Following a 3-week, open-label run-in period where the dose of MES-amphetamine XR was optimised to 10, 20 or 30 mg once a day, subjects were then randomised into a 3-way double-blind, placebo-controlled crossover trial.
They received their optimal dose of MES-amphetamine XR, an equivalent dose of lisdexamfetamine in terms of d- amphetamine base, or placebo. On the primary and secondary efficacy variables of behaviour, attention and problem solving, lisdexamfetamine delivered equivalent or better efficacy than MES-amphetamine XR with both drugs being maximally effective at 2 h post-dose Biederman et al.
However, on the problem-solving endpoints, it was also evident that lisdexamfetamine maintained its maximum effect for at least 12 h, whereas the effect of MES-amphetamine XR showed a clear decline after 6—8 h Biederman et al. An exceptionally long duration of effect of lisdexamfetamine was observed by Wigal et al.
A post-hoc analysis of the data also showed that the sex and age of the subjects had no significant influence on the efficacy of lisdexamfetamine Wigal et al. These observations fit well with the PD profile of lisdexamfetamine in the microdialysis experiments. Another way to produce a more gentle increase of brain dopamine is to bind d -amphetamine to a support. Another factor that almost certainly contributes to the consistently high level of therapeutic efficacy observed with lisdexamfetamine treatment is the very low inter- and intra-subject variability in the plasma concentration of d -amphetamine observed after administration of the prodrug compared with traditionally formulated stimulants, including beaded and osmotic-release formulations.
Once again, the reproducible pharmacokinetics of its active metabolite, d -amphetamine, are probably due to the rate-limited, enzymatic cleavage of the precursor molecule that occurs primarily in red blood cells Ermer et al.
In two earlier published studies, Jasinski and Krishnan compared the subjective effects of lisdexamfetamine and IR d -amphetamine in drug-experienced human volunteers when these compounds were administered intravenously Jasinski and Krishnan, a and orally Jasinski and Krishnan, b. In the trial where they compared these compounds after oral administration, IR d -amphetamine 40 mg However, the peak effect of the higher dose of lisdexamfetamine was even more delayed, at 4. Both compounds yielded equivalent AUC h values, but compared with the equivalent dose of IR d -amphetamine, the C max for plasma d- amphetamine was threefold smaller for lisdexamfetamine and the t max was threefold greater Jasinski and Krishnan, b.
From these results, it can be concluded that although in terms of d- amphetamine base equivalents lisdexamfetamine is clearly less potent than IR d -amphetamine, it does nonetheless produce d -amphetamine-like subjective effects in man. Although increasing the dose of lisdexamfetamine enhanced its efficacy, it also progressively delayed its time of peak effect.
Furthermore, switching to the intravenous route for lisdexamfetamine appeared to have relatively little influence on the abuse potential of the prodrug. To explore this possibility further, we performed a post-hoc analysis on the data in the original clinical study reports Jasinski, , NRP A02; Jasinski, , NRP A03 to compare pharmacodynamics and pharmacokinetics of lisdexamfetamine when given by the clinical route oral versus one of those favoured by recreational abusers intravenous.
This topic is of particular importance because lisdexamfetamine has very high aqueous solubility, making the prodrug very easy to extract.
This result shows that the subjective effects of lisdexamfetamine were not enhanced when the drug was given intravenously. Blood pressure measurements are useful objective measures of the PD effects of sympathomimetic drugs. Compared with placebo, 50 mg lisdexamfetamine significantly increased the peak systolic blood pressure when administered both orally and intravenously and diastolic blood pressure when given orally Figure 6.
What is also evident from the data in Figure 6 is that the magnitude of increases in systolic and diastolic blood pressures was not statistically different after oral or intravenous administration of lisdexamfetamine.
A comparison of the pharmacodynamics and pharmacokinetics of orally versus intravenously administered 50 mg lisdexamfetamine. A comparison of the mean peak increases in systolic and diastolic blood pressure produced by intravenous versus oral administration of 50 mg lisdexamfetamine. Means are adjusted for differences between the treatment groups at baseline.
Drugs in this class are usually considered the first choice of medications for treating ADHD. Other stimulants that are options for treating ADHD include:. Some people also use herbs and dietary supplements to treat ADHD. For most of these supplements, there is very little research showing that they work, or research findings are inconsistent. Examples of these supplements include:. Despite these similarities, there are some differences between the drugs that might make you prefer one over the other.
Vyvanse is approved for treating ADHD and binge eating disorder. Vyvanse is also used off-label to treat narcolepsy. Adderall comes in two forms: an immediate-release tablet Adderall and an extended-release capsule Adderall XR. Vyvanse is available as a delayed-release capsule and a chewable tablet, both of which are taken once daily.
The chewable tablet may be a good option for those who have a hard time swallowing pills. However, individual people may respond better to one over the other.
Because Adderall and Vyvanse are very similar medications, they also have similar side effects and drug interactions. Both medications can cause psychological and physical dependence and can be misused or abused. However, Vyvanse may be less likely to be misused. This is because Adderall has a more immediate and intense effect when taken, which might be attractive to people who want to misuse it.
The costs of brand-name versions of Adderall and Vyvanse are similar. However, Adderall is also available in a generic form, while Vyvanse is not. The FDA has determined that the patent for Vyvanse is valid until It will be at least until then before a generic for Vyvanse is available.
Generic drugs are typically less expensive than brand-name drugs. But in some cases, the brand-name drug and the generic version may be available in different forms and strengths. However, there are some differences that might make you prefer one over the other. The Adderall tablet is taken one to three times daily. Adderall XR is taken just once daily.
Like Adderall, Ritalin also comes in two forms: an immediate-release Ritalin tablet and an extended-release capsule Ritalin LA. Ritalin tablet is taken two to three times daily, and Ritalin LA is taken once daily. Generic versions of Ritalin also come in other dosage forms, including a chewable tablet and an oral liquid solution. These forms may be a good option for people who have a hard time swallowing pills. However, individual people may respond better to one than the other.
Ritalin tablets may work slightly faster than Adderall. However, Adderall works for a slightly longer period of time than Ritalin:. Adderall and Ritalin are very similar medications. They also have similar side effects and drug interactions. The cost of brand-name versions of Adderall and Ritalin are similar. The actual amount you pay will vary depending on your health insurance plan.
Adderall and Ritalin are both available in generic forms. The generic name for Ritalin is methylphenidate. Adderall and Concerta methylphenidate extended-release are medications that are commonly used for ADHD.
They are both stimulant medications and work in a similar way. There are some differences that might make you prefer one over the other.
Adderall is also approved for narcolepsy, but Concerta is not. Concerta is used off-label to treat narcolepsy. Adderall comes in two forms: an immediate-release Adderall tablet and an extended-release capsule Adderall XR. One difference between the drugs is how fast they work and how long they last.
Adderall may work slightly faster, but Concerta lasts longer:. Adderall and Concerta are very similar medications. Both medications can cause psychological and physical dependence, and can be misused or abused. Both Adderall and Concerta are brand-name drugs. The generic name of Concerta is methylphenidate extended-release. Adderall and modafinil, a generic drug, are both stimulant medications, but they affect the brain in slightly different ways. Modafinil increases wakefulness and alertness.
Adderall can also stimulate wakefulness and, in people with ADHD, can produce feelings of calm and focus. Modafinil is approved to treat narcolepsy, shift-work sleep disorder, and sleep apnea. Modafinil is used off-label to treat ADHD. Both Adderall and modafinil are effective treatment options for daytime sleepiness in people who have narcolepsy.
Adderall is considered a first-choice medication for treating symptoms of ADHD. Adderall and modafinil are both stimulants and have some similar side effects.
However, Adderall is more likely to cause side effects than modafinil. Both Adderall and modafinil can cause physical and psychological dependence leading to misuse or abuse. However, dependence appears to be more common with Adderall than modafinil. Due to these differences in side effect risk, modafinil is often preferred over Adderall for treating narcolepsy. Adderall and modafinil are both available in brand-name and generic versions.
The brand name of modafinil is Provigil. The generic versions of medications typically cost less. But in some cases, they may not be available in all strengths or forms as the brand-name drug. The generic version and the brand-name version Provigil of modafinil usually cost more than the brand-name and generic versions of Adderall. Adderall is a stimulant medication that increases norepinephrine and dopamine in the brain and produces calm and focus in people with ADHD.
It works as a selective norepinephrine reuptake inhibitor and increases the amount of norepinephrine in parts of the brain. Norepinephrine is a neurotransmitter, a chemical that sends messages between cells. Adderall, a stimulant, is considered a first-choice treatment for ADHD. Stimulants are the best studied and most effective treatments for ADHD. Adderall and Strattera are both available in brand-name and generic versions. The generic name of Strattera is atomoxetine. The brand and generic versions of Strattera usually cost more than the brand and generic versions of Adderall.
Adderall and methylphenidate are both commonly used to treat ADHD. Both are also used off-label for treating similar conditions, such as depression and anxiety, in combination with other medications. The chewable and solution forms of methylphenidate may be good options for those who have trouble swallowing pills. As a result, patients should alert their doctors if they have a history of heart disease, heart rhythm disorder, coronary artery disease or heart attacks, according to the NIH.
Doctors should also be alerted if the patient has a history of high blood pressure , mental illness, peripheral vascular disease or seizure disorders. Adults ages 65 and older should usually not take Adderall because it is not as safe as other medications for this age group, the NIH says. Some drug interactions could be harmful.
The NIH says that people should not take Adderall if they have taken a monoamine oxidase inhibitor MAOI , a type of antidepressant, in the last two weeks. For children with ADHD , or hyperactive-impulsive or inattentive symptoms that cause impairment and appear before the age of 7, Adderall can be considered part of a total treatment program.
ADHD must be diagnosed through a series of tests that rule out other mental disorders. Other treatment measures will include psychological, educational and social aspects — drug treatments may not even be necessary.
For children with narcolepsy, the drug is approved for those ages 12 and older. Adderall is not intended for use in children who exhibit symptoms that are secondary to environmental factors or exhibit symptoms that indicate other psychiatric disorders, such as psychosis, according to the Food and Drug Administration FDA. There is evidence that Adderall may slow a child's growth or weight gain, so doctors should monitor children's growth carefully while they are on the medication, the NIH says.
What is the chemistry of Adderall? What are the side effects of Adderall? How was Adderall intended to be used? How is Adderall abused? What are the signs and symptoms of Adderall abuse? Questions about starting treatment? Find a Recovery Centers of America location near you. Make the call that changes everything. Call Now!
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