The tolerance and withdrawal criteria are not considered to be met if the stimulant is used only under appropriate medical supervision. Participating in a 12-step treatment program and getting individual counseling may reduce your chances of relapse and improve your chances for recovery. Treatment aims to help a person stop misusing drugs and improve their relationships with family, work, and society.
Amphetamine
There are some suggested pharmacological medications for treating amphetamines abuse 4 which may be used alone or in combination with long-term behavioral interventions 5, 6. However, using long-term behavioral interventions with pharmacological treatments has several important operational barriers to implementation 7. Firstly, such behavioural interventions remain unaffordable for most patients 8.
Treatment for amphetamine withdrawal
After administration of equivalent doses of lisdexamfetamine and IR d-amphetamine (1.5 mg/kg ip as d-amphetamine base), the observed plasma PK profiles for the pharmacologically active moiety, d-amphetamine, were very different. The AUC0-480 min values were identical, but the maximum concentration reached in plasma (the Cmax) was 50% lower after administration of lisdexamfetamine and the time to Cmax (the tmax) was doubled (Jackson et al., 2011). 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).
Amphetamines can be Addictive
Amphetamine’s diverse pharmacological actions translate not only into therapeutic efficacy, but also Amphetamine Addiction into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine’s distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed.
- However, this result was based on data of one study (Cruickshank 2008), as the mirtazapine study by Kongsakon 2005 met criteria for inclusion, but their data could not be included due to differences in study methodology.
- The second study examined buprenorphine (8 mg SL OD) versus methadone (40 mg po OD) over 17 days, with 20 participants in each study arm.
- These differences in the PK and PD characteristics of IR d-amphetamine and lisdexamfetamine observed in humans by Jasinski and Krishnan (2009b) are very similar to the results from the rat PK/PD study that are described earlier in this review (Jackson et al., 2011; Rowley et al., 2011).
- Although this mechanism is often discounted because amphetamine is a relatively weak inhibitor of MAO, in the situation where amphetamine is concentrated in presynaptic nerve terminals, shown in Figure 3, it is probable that some inhibition of this enzyme would occur.
- Acute amphetamine use with resultant psychosis can present like a sympathomimetic toxidrome.
- In addition, the data collected by both reviewers can be located in its entirety in the Supplementary Data (see ESM).
- Amphetamines rank as a schedule II/IIN controlled substance (2/2N), which means that there is a high potential for the drug to cause physical dependence (addiction).
- The PK parameters for plasma d-amphetamine observed after oral versus intravenous administration of lisdexamfetamine (50 mg) are also summarised in Table 4.
- “Addiction” is the term for long-term behavioral, physical, and social changes a person may experience as a result of substance misuse.
Despite a relative lack of short-term consequences (most patients recover fully), there are legitimate concerns that chronic use may lead to eventual permanent cognitive deterioration. Hyperthermia often requires close monitoring and pharmacotherapy appropriate to an intensive care setting. Tachycardia, hyperthermia, volume depletion, agitation, seizures, and rhabdomyolysis are sentinel findings. Diagnosis is facilitated by a high index of suspicion and urine amphetamine screening. Displacement was determined in vitro at a lisdexamfetamine concentration of 10μM.
Furthermore, presence of the study drug/metabolite does not necessarily indicate adherent consumption of the study drug, and authors varied in their assessments in that regard (i.e. present or not versus present at a defined level). Studies relying on pill count or self-report lacked critical appraisal of the results. For example, in one study where no participant returned un-used study drug, 100% adherence was inferred as opposed to examining if there were other reasons (e.g. discarding drug). The titles and abstracts of the studies identified by the search strategy were evaluated by two reviewers (KS and LA) independently. Divergent selection of publications was discussed among the investigators until a consensus was obtained, and if required a third reviewer (NE) resolved disputes. Data were managed in Covidence 23 up to the point of data extraction; due to the large variation in outcome measures, data extraction was completed on identical spreadsheets by the two reviewers and compared for consistency.
Amphetamines
When used illegally, pure amphetamines may be mixed with other substances—such as sugar, glucose, or bi-carb soda—that can be poisonous. This may cause collapsed veins, tetanus, abscesses, and damage to the heart, lungs, liver, and brain. Amphetamine users may also use other drugs inappropriately to manage the side effects of amphetamines. Benzodiazepines, for example, are anti-anxiety agents that may be used to help an individual sleep, but that can also be addictive.
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. One of the additional benefits of these new formulations is their tamper deterrence, making it difficult for abusers to extract amphetamine for self-administration by hazardous routes, such as smoking, ‘snorting’ or intravenous injection. Examples of once-daily amphetamine medications include MES-amphetamine XR and the d-amphetamine prodrug, lisdexamfetamine. The effects of BCBT alone or in combination with pharmacological treatments were sustained between two and 12 months 20–23. Furthermore, high rates of treatment retention were reported at six-month and 12-month follow-ups 20–23. These findings demonstrate the efficacy of the two treatments as well as patient engagement in the treatment.
Importantly, only three studies reviewed here (7%) provided information on adverse events/serious adverse events, despite the standard reporting format adopted by most publishers (CONSORT 83) including a minimum standard of harm reporting. This limits the capacity to appropriately assess the risk versus benefit of the pharmacotherapies reviewed here. We elected to include studies in this review irrespective of safety reporting, to provide a comprehensive review of the current status of research. 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 D2 receptor occupancy for psychostimulant drugs of abuse. These researchers have also demonstrated that the rate of DAT occupancy by drugs such as cocaine and methylphenidate is critical to their ability to produce ‘highs’ in human subjects (Volkow and Swanson, 2003; Volkow et al., 1996a,b, 1997, 1999a,b).
