We employ a five-step risk scale with values ranging from "very low" to "very high" within six categories: Acute toxicity, Long-term toxicity, Dependence, Cognitive problems, Unpleasant events, and Interactions.
These values are based on qualitative reviews of available knowledge, and should only be viewed as guidelines. They are also relative, so a score of "very low risk" does not mean the substance is risk-free. The scale assumes users are normal, healthy individuals; beware that even drugs which are well-tolerated by most people may nevertheless be harmful to some users. It also assumes normal use patterns; that is, if a given drug is only harmful when used in a certain way, yet is almost never used in that way, then the drug will be considered less harmful compared to a similar drug which is commonly used in a harmful way.
⦿⦾⦾⦾⦾ (Very low risk)
Lethal overdoses of methylphenidate are exceedingly rare. Between 2000–2005, the US Toxic Exposure Surveillance System only registered two deaths attributed to methylphenidate, despite also registering more than 8000 cases of methylphenidate poisoning in 2004 alone . Testing on rats indicates that medically significant overheating – a typical indication of overdose – due to methylphenidate begins to occur at serum concentrations twice as high as for amphetamine . LONG-TERM TOXICITY
⦿⦿⦾⦾⦾ (Low risk)
Methylphenidate appears not to be neurotoxic, although excessive doses can indirectly cause brain damage through overheating. There is also reason to believe that frequent use of methylphenidate at high doses can put too much strain on the heart, as with amphetamine, but it is unclear whether long-term methylphenidate use increases one's risk of cardiovascular disease. Although one study of adults before and after commencing methylphenidate treatment found a 1.8-fold increase in heart attack risk, another (larger) study did not find any increased risk [8, 9]. Methylphenidate treatment does, however, appear capable of triggering heart attacks in some especially vulnerable patients . DEPENDENCE
⦿⦿⦿⦾⦾ (Moderate risk)
Methylphenidate bears a strong resemblance to cocaine in its mechanism of action, and lab animals have been shown to self-administer the two drugs at comparable rates. Nevertheless, methylphenidate is assumed to carry a lower risk of addiction than cocaine and amphetamine in humans, and humans tend to self-administer the drug at low to moderate rates in similar clinical trials . This may be due to methylphenidate's negligible effect on the brain's serotonin system, or possibly the fact that it is broken down in the brain more slowly than is cocaine . Some users also experience more bodily discomfort and unpleasant side-effects from methylphenidate than cocaine, which might contribute to a lower prevalence of excessive use among methylphenidate users . COGNITIVE PROBLEMS
⦿⦿⦾⦾⦾ (Low risk)
Use of methylphenidate in humans, at therapeutic doses and over long periods of time, is not associated with any of the structural changes in the brain that normally indicate brain damage. Experiments on mice have found a certain toxic effect on the brain's dopamine system, but it is unclear whether or to what extent this effect translates into humans . Excessive methylphenidate use can nevertheless cause transient cognitive problems following cessation of use, due to tolerance build-up. There is no observed link between methylphenidate use and increased risk of psychosis, even in individuals with a history of psychosis. However, overdose and/or several-day "binge" use of any stimulant (including methylphenidate) can lead to stimulant psychosis
, a transient state of psychosis resulting from severe and acute sleep deprivation .
Researchers used to believe that methylphenidate had the opposite effect on individuals with and without ADHD, but this has since been disproven, and it is now known that the drug enhances cognitive performance in both groups at therapeutic doses. The effect is, however, more significant in those whose performance level is lower to begin with, which in turn levels out the observed group differences to some extent . UNDESIREABLE EVENTS
⦿⦿⦾⦾⦾ (Low risk)
Some find it tempting to use methylphenidate for day-to-day performance enhancement. This often leads to users exceeding their daily work capacity and de-prioritizing sleep, increasing one's risk of burnout in the long run. Moreover, chronic sleep deprivation reliably and rapidly impairs cognitive performance, which on average cancels out any performance-enhancing effects caused by the methylphenidate itself. Thus, people who frequently or regularly use methylphenidate for performance enhancement should ideally make sure to get more sleep and rest than they would otherwise need, as well as take longer breaks from the drug on a regular basis in order to recover fully and avoid developing a tolerance. Methylphenidate tends to boost feelings of accomplishment and mastery by activating the brain's reward system. Especially at higher doses, this can lead to poor judgement and impulsive decision-making, in addition to making users less attentive to their own and others' needs. In general, for daily users of methylphenidate (whether for medical or performance-enhancing purposes), feelings of unusual satisfaction or euphoria should be taken as a sign that one's dosage is too
high; if so, the dosage should be decreased to a point where only the desired medical or performance-enhancing effects are noticeable. Given that a normal prescribed dose is intended for daily users (who have developed a tolerance to the drug's effects), those who only use methylphenidate occasionally or sporadically should avoid taking more than half of a normal prescribed dose at a time. INTERACTIONS
⦿⦿⦾⦾⦾ (Low risk)
Methylphenidate should, like all central nervous stimulants, never be used in combination with any monoamine oxidase-inhibiting drugs or medications, known as MAOIs. This includes recreational drugs such as ayahuasca, changa, and psychedelics in the 2C-T-series, atypical antidepressants such as phenelzine and moclobemide, and anti-Parkinsons drugs such as rasagiline and selegiline. Taking methylphenidate at the same time as (or soon after) a strong MAOI can result in dangerously high blood pressure; in the worst case, it can lead to serotonin syndrome, a potentially life-threatening medical emergency.
Combining methylphenidate with tramadol in large doses of either drug significantly increases one's risk of seizures, and is thus strongly discouraged. (15) It is also best to avoid combining methylphenidate with other strong central nervous stimulants, as this can lead to dangerously high blood pressure and overheating. Combinations with central nervous depressants can effectively delay a depressant overdose until the methylphenidate wears off, at which point the overdose effects set in rapidly, often with little to no perceived warning. Anyone using methylphenidate and CNS depressants together should thus be extra cautious about their depressant intake.
Combining methylphenidate with SSRI-based antidepressants can increase the serotonin reuptake-inhibiting effects of the latter, and may also increase one's risk of becoming addicted to methylphenidate. (19)
Combining methylphenidate and cannabis can lead to short-term confusion and anxiety, and likely also increases the risk of psychosis associated with cannabis use. It can also increase one's heart rate to a significant degree, and should thus be avoided by users with heart problems.
Methylphenidate in combination with psychedelics or dissociatives does not appear to carry much risk, so long as one is normally able handle each drug on its own. Users with known cardiovascular problems should nevertheless be careful with such combinations, as the central nervous stimulant effects of each drug is often mutually reinforcing, potentially causing a rapid rise in heart rate and blood pressure. Taking psychedelics on the "way down" from methylphenidate can negatively affect the psychedelic experience, and is thus discouraged.
For a detailed list of medications known to interact with methylphenidate, see Felleskatalogen