The half-life of a drug refers to how long it takes for it to become 50 percent less active in (or eliminated from) the bloodstream. For example, a drug with a half-life of four hours will be half as effective at the four-hour mark, and its effects will continue to slowly decrease after that, becoming largely inactive around eight hours after it was taken.

A drug will keep activating receptors and interacting with the brain’s chemical messengers during its active period. This reduction in activity is called the elimination half-life of a drug. Plasma half-life is different and refers to the rate of time it takes for a drug to no longer be in the bloodstream at all. So a drug may still show up on a drug test (as it still remains in the plasma of the blood) after it is no longer active in the body.

What Affects the Half-Lives of Drugs?

Half-lives of drugs are estimates and not specifics since there are many variables that can impact how long it takes the body to process a drug. A person’s specific metabolism can play a role, for example, as can kidney and liver functions since these organs are vital in drug metabolism and blood filtration.

How a person takes a drug can affect how quickly it starts working and how long it takes to process out as well. For instance, smoking, snorting, and injecting drugs tends to send it more rapidly into the bloodstream while ingesting them results in a slower onset of action. Half-lives of drugs are therefore generalizations and not exact.

Shorter half-life drugs tend to take action quickly, and their effects may wear off rapidly as well. This may encourage a person who is abusing a short half-life drug to take more of it in a binge pattern, following doses on top of each other to prolong the effects. A long half-life drug, on the other hand, may stay in the body for longer than a person wants it to as the effects can be prolonged.

Drugs with longer half-lives can be beneficial in the case of medicinal necessity; for instance, if a person only has to take a medication once daily and it remains active for 12-24 hours, this can be helpful instead of having to take more doses more often. Many prescription drugs are also available in both immediate-release (IR) and extended-release (ER) formulations. The ER versions dole out the dosage in a controlled manner over a set period of time, thus extending the active period of the drug.

Examples of drugs with a short half-life

  • Cocaine: Cocaine has a very short half-life of less than an hour. The illegal drug cocaine takes effect quickly and wears off quickly, the National Highway Traffic Safety Association (NHTSA) reports.
  • Heroin: The Drug Enforcement Administration (DEA) publishes that heroin is the most rapidly acting of all the opioid drugs, taking effect almost immediately. It has a short half-life of around 30 minutes.
  • Tylenol (acetaminophen): An over-the-counter (OTC) pain reliever, Tylenol has a short half-life of around two hours, which is why it is recommended to take a dose every 4-6 hours as needed for pain relief.
  • Marijuana: Marijuana is an illegal plant-based drug that is often smoked or eaten in the form of edibles. The active component of marijuana, THC (delta-9-tetrahydrocannabinol) typically remains active in the bloodstream for about 2-4 hours, NHTSA
  • OxyContin (oxycodone): A relatively short-acting prescription opioid designed for the management of acute to moderate pain, the manufacturers of OxyContin, Purdue Pharma, report its half-life is 3-5 hours. The controlled-release version (OxyContin CR) remains active in the body for closer to 12 hours, as it is designed to be taken only once or twice a day for around-the-clock pain management.
  • Valium (diazepam): Considered a short-acting benzodiazepine (benzo) sedative and hypnotic drug prescribed for the short-term relief of anxiety or panic disorders, Valium has a short elimination half-life of 2-4 hours but a much longer plasma half-life; therefore, it can remain detectable in urine for several days, per the S. Food and Drug Administration (FDA) prescribing information.
  • LSD (lysergic acid): An illegal hallucinogenic drug, LSD only remains in blood plasma for 2-4 hours, NHTSA reports, but a “trip” may last 6-8 hours or even longer in some cases.
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Drugs that have a long half-life include

  • Xanax (alprazolam): A longer-acting benzodiazepine, Xanax has a plasma-elimination half-life of around 11 hours. Librium (chlordiazepoxide) is an even longer-acting benzodiazepine drug.
  • MDMA (3,4-methylenedioxymethamphetamine): A recreational synthetic drug that often goes by the names ecstasy or Molly, MDMA is a stimulant and hallucinogenic drug with a half-life of around seven hours, per NHTSA. The high may last only a few hours; however, residual effects can linger for up to 24 hours.
  • Methamphetamine (meth): With an average half-life of around 12 hours, a meth “high” can be prolonged, lasting 4-8 hours on average (with residual effects lasting longer) and causing lasting impairment, NHTSA Prescription stimulants like Adderall (amphetamine/dextroamphetamine) and Ritalin (methylphenidate) also have relatively long half-lives.
  • Methadone: One of the longest-acting opioid drugs, the prescription drug methadone has an elimination half-life of 8-59 hours and a vastly different analgesic duration of action of about 4-8 hours, the FDA
  • PCP (phencyclidine): An illegal hallucinogenic drug with an average half-life of 21 hours, the effects of a PCP trip can last up to an entire day, NHTSA

Variables in Abusing Drugs with Short or Long Half-Lives

A drug with a short half-life usually rapidly crosses the blood-brain barrier and can have near-instant effects. Extended-release formulations of drugs that are crushed and then snorted, smoked, or injected, or chewed up and swallowed, bypass the drug’s controlled-release mechanism, which sends the whole dosage into the bloodstream at once and causes it to have a rapid and potentially dangerous impact on the body. The “rush” of a short half-life drug can be quickly followed by a “crash,” which often has the exact opposite effect of the high. Low energy, fatigue, trouble focusing, increased appetite, and depression often accompany a cocaine crash, for instance, which is the opposite of the stimulant, euphoric, and energy-producing high. Individuals may then take these drugs in a binge pattern, which can amplify and prolong the drug’s effects and increase the potential rate of addiction and risk for a life-threatening overdose.

Short-acting drugs tend to be more highly addictive, as individuals will likely take higher doses more often to keep feeling the desired effects. This practice can easily lead to drug dependence and compulsive drug-seeking and using behaviors. Studies have shown that short half-life benzodiazepines can have a greater risk of dependence than longer ones, the American Journal of Public Health reports. This indicates that drugs with short half-lives may more quickly lead to drug dependence and potentially addiction.

Drugs with long half-lives can have unwanted residual effects. Someone under the influence of meth or a hallucinogen like PCP may be aggressive and hostile, and suffer from psychotic symptoms for several hours. These drugs can be unpredictable, and once a trip has started, there is nothing a person can do except wait for the effects to wear off. Accidents, injuries, and violence are potential side effects of a bad trip from a long-acting drug with possible psychotic side effects.

A drug with a long half-life may also take longer to start working, which may cause a person to feel the need to take more of it (or add another drug or alcohol to the mix). This practice can be highly dangerous and possibly result in a fatal overdose or other negative complications.

Replacing Short Half-Life Drugs with Long Half-Life Drugs during Detox

Many drugs, such as opioids and benzodiazepines, have dangerous and serious withdrawal symptoms when a person who has developed physical and psychological dependence attempts to stop taking them. These drugs will then need to be carefully, and often slowly, tapered during a medical detox program in order to safely process them out of the bloodstream.

Much of the time, drugs with long half-lives are used to replace drugs with shorter half-lives during medical detox. Someone who abuses Valium may replace it with Librium, Klonopin (clonazepam), or Xanax, for instance. Short-acting opioids like heroin, oxycodone, or Vicodin (hydrocodone/acetaminophen) may be replaced with the longer-acting methadone or buprenorphine during medical detox. Buprenorphine is only a partial opioid agonist as well, so in addition to having a longer half-life, it also doesn’t fully activate opioid receptors in the same way as heroin or prescription painkillers, making it potentially less of a target for abuse.

Drugs with longer half-lives remain the bloodstream for longer, helping to keep cravings and withdrawal symptoms to a minimum with fewer doses given less often. These medications can then be tapered down until dependence and addiction are managed, and physical dependence is stabilized. A medical detox protocol will set up a tapering schedule that is optimal for each individual person.

Prescription Drug Categories

Other medications may be useful during medical detox to control symptoms of withdrawal, and supportive measures can also help to smooth out the entire withdrawal process. Medical detox is performed under direct medical and mental health supervision in a specialized facility. It should then be closely followed with a comprehensive addiction treatment program.