Comedown (drugs)

The comedown, or crashing (also called feeling "down", "low", “drained”), or occasionally referred to by its more technical neurobiological term; synaptic fatigue, is a temporary phase consisting of neurochemical imbalances that symptomatically result in a deterioration in feelings of mood and energy levels for individuals that commonly occurs shortly after the administration of certain types of psychoactive drugs (typically stimulants). This essentially leads to a transient biological state of endocytosis by (often substantially), increasing levels of neurotransmitters in the brain; initially producing desirable effects before a subsequent postsynaptic-based negative feedback loop which leads leads to subjectively perceivable negative symptoms by the user due to a subsequently comparable decrease in the presence of these same pleasurable and euphoric neurotransmitters. This is then followed by a homeostatic recovery phase known as synaptic stabilization, which can depend on many factors but typically directly in relation to dosage and degree or length of use. This stabilization period, in addition to the drugs clearance rate from the plasma levels in the bloodstream eventually leads to a typically drastic decrease in negative symptoms within a number of hours, but can persist to a lower form sometimes for days or in more extreme cases of chronic usage; possibly months. It however, is distinct from withdrawal syndrome and even drug rebound, but may have some crossover mechanisms such as receptor-down regulation. It is not however, especially in the case of CNS stimulants; in any way a form of drug dependence or withdrawal and is instead more related (if not entirely synonymous) to the phenomenon of most drug “hangovers” in general, albeit with the exception of alcohol which actually appears to be a somewhat of a combination of both the rebound effect, and a genuine “crash” as a result of various factors such as toxicity, dehydration, but still some level of neurotransmitter depletion.

The phasic improvement and deterioration of mood (euphoria and dysphoria) are represented in the cognitive schema as high and low elevations; thus, after the drug has elevated the mood (a state known as a high), there follows a period of coming back down, which often has a distinct character from withdrawal, with the former (comedowns/crashes) being uniquely prevalent and/or intense with stimulant substances compared to the “crashes“ of other substances. Generally, a comedown is an ordinary occurrence with even casual drug experimentation and can happen to anyone as a short-term period of symptoms, however in people who further attempt to administer the drug; oftentimes in an attempt to try and counteract the negative symptoms of comedowns in addition to also repeating the desirable effects (sometimes even with polysubstance use), this can; not uncommonly lead to cyclic patterns of further use leading to habits and even eventually become tangible drug addictions or even dependencies. This kind of repeated behavior can therefore truly result in genuine withdrawal and thus, can be followed by the presence and/or recurrence of both syndromes; continuous cycles of concurrent comedowns as well as periods of withdrawal, depending on the drug. Many repetitive instances of withdrawal in particular, may even lead to a “kindling” effect overtime, meaning progressively worsening and more intense withdrawal syndromes with each additional, or set of additional attempts at detoxification; even when tapering. Acute or multiplicastic problems like these make extensive or regular periods and breaks between use of such substances a vital and practical harm reduction strategy for avoiding substance use disorders and their related physical, psychological and socials detrimental consequences.

Various drug classes, most especially stimulants and, to a lesser degree, opioids and sedatives, are subject to comedowns.[1] A milder analogous mood cycle can happen even with blood sugar levels (thus sugar highs and sugar lows), which is especially relevant to people with diabetes mellitus and to parents and teachers managing children's behavior, as well as in adults with ADHD, although the notion of a "sugar high" has not been verified in scientific studies and appears to be a form of confirmation bias or placebo effect. The use of caffeine may also be subject to periods of low energy and mood following its effects. Stimulant comedowns are unique in that they often appear very abruptly after a period of focus or high, and are typically the more intensely dysphoric phase of withdrawal than that following complete elimination from the bloodstream. Besides general dysphoria, this phase can be marked by frustration, anger, anhedonia, social withdrawal, and other symptoms characteristic to a milder mixed episode in bipolar disorder. Alertness and other general stimulant effects are still present.