The dependence potential of psychostimulants is well established. For many years the dependence was considered to be entirely 'psychological' (Senate Standing Committee on Social Welfare, 1977). However, the existence of a withdrawal syndrome is now well recognised. The literature pertaining to psychostimulant withdrawal is inconsistent and of mixed quality. Similarly, despite an exhaustive search, no studies that describe the natural history of methamphetamine withdrawal among dependent individuals could be located and as a result that particular process is still poorly understood.
In spite of this, there is some agreement that the psychostimulant withdrawal syndrome is unlike the withdrawal syndromes that occur in people who are dependent on CNS depressant drugs such as opioids or alcohol, the features of which are the opposite to those of the acute pharmacological effects of these drugs. In contrast, several features of the psychostimulant withdrawal syndrome actually mimic those of intoxication, particularly agitation and hyper-arousal.
'Crash' periodIt is important to note that many users of psychostimulants will experience what is commonly called a 'crash' or brief period of recovery that may last for a few days following binge use. This recovery period may be planned or unplanned, but does not in itself constitute a clinically significant withdrawal syndrome (although it may herald it in some cases). Rather it is a process of recovery from a period of CNS over-stimulation and is usually characterised by excessive sleeping and eating and irritability of mood.
Such a recovery period may be compared to the experience of a 'hangover' from alcohol characterised by irritability, tiredness, headache and nausea, which is widely recognised as time-limited and not a withdrawal syndrome in itself. A withdrawal syndrome, therefore, manifests as a cluster of symptoms, enduring for a meaningful duration (according to drug class and severity of withdrawal), which impairs the functioning of an individual to a clinically significant degree. The key features of intoxication and withdrawal from heroin, alcohol and psychostimulants are compared Table 13.
Table 13: Comparison of key features of intoxication versus withdrawal from heroin, alcohol and psychostimulants (includes cocaine and amphetamines)Table 13 is presented as text in this HTML version for accessibility reasons.Top of page
- Intoxication - Relaxation, sociability, euphoria, disinhibition, reduced motor coordination, reduced respiratory rate, sleepiness/sedation (respiratory arrest in toxicity state).
- Withdrawal - Tremulousness, agitation, anxiety perspiration, insomnia, sleep disturbance, increased blood pressure, pulse and temperature, nausea, vomiting and diarrhoea (seizures and delirium tremens in complicated withdrawal). Onset 6–24 hours after last drink, peaks day 2–3, resolves by day 5 (may last up to 10–14 days if complicated withdrawal).
- Intoxication - Intense euphoria, extreme relaxation, calmness, sleepiness, constricted pupils, dulled responses, potent pain relief, constipation and reduced respiratory rate (respiratory arrest in toxicity state).
- Withdrawal - Restlessness, insomnia, agitation, irritability, dilated pupils, piloerection (gooseflesh), hot and cold flushes, watering eyes and nose, perspiration, muscle aches, leg cramps, joint pain, abdominal cramps, diarrhoea, nausea, vomiting and craving to use. Onset 8–12 hours after last dose, peaks day 2–3, usually resolves by day 5.
- Intoxication - Increased confidence, anxiety, agitation, motor hyperactivity, insomnia, excitement, talkativeness and rapid speech, irritability, hypervigilance, muscle twitches, hand tremor, sweating, rapid heart rate, elevated blood pressure, heart palpitations, poor appetite, dilated pupils, increased body temperature, dry mouth and jaw clenching (psychosis, hyperthermia and seizures in toxicity state).
- Withdrawal - Following a possible initial 'crash' period: dysphoria, depression, slowing of physical movements, poor concentration, agitation, insomnia, irritability, lethargy, exhaustion, craving to use, anxiety, variable (often increased) appetite and anhedonia. Onset and duration variable according to type of stimulant used: amphetamine sulphate withdrawal may last up to 4 weeks, some symptoms of methamphetamine withdrawal may last for many months.
Clinical pictureUnfortunately, the number of individuals who are dependent on psychostimulants and are likely to experience a withdrawal syndrome following cessation or reduction in use is not yet able to be estimated, although the presence of a withdrawal syndrome is not necessary for a person to meet criteria for dependence (which includes psychological factors). Similarly, the roles that tolerance (neuroadaptation) and acute toxicity play in long-term withdrawal are also unclear (Davidson et al., 2001). Having said this, the incidence, severity, course and subjective experience of the withdrawal syndrome are likely to be influenced by:
- the severity of dependence;
- duration of use;
- frequency of psychostimulant use (irregular use versus regular, daily use);
- potency of psychostimulant used (e.g. methamphetamine versus amphetamine sulphate);
- duration of action of psychostimulant (e.g. cocaine versus methamphetamine);
- the presence of other physical or psychiatric disorders; and
- psychosocial factors (e.g. physical environment, fears and expectations).
At least two mechanisms may be involved with this. The first is the depletion of monoamine neurotransmitter stores, specifically of serotonin, norepinephrine and dopamine that affect mood regulation (Cho & Melega, 2002). The second involves alteration in brain structure identified by brain imaging studies of current and past methamphetamine users, particularly the loss of dopamine transporters, the effect of which is slowed motor function and impaired memory (Volkow, Chang, Wang, Fowler et al., 2001).
The onset of withdrawal following cessation of high-level, regular use varies between the subgroups of psychostimulants according to their half-lives and route of administration.