Lysergic acid diethylamide, better known as LSD, is one of the most potent psychedelics around. While it takes at least a couple grams of magic mushrooms are considered to be a proper dose, with acid, the average person only needs about 100 micrograms of acid (or 0.0001 grams) to trip.
But acid won’t seem all that powerful if you take it regularly. That’s because the human body is actually hardwired to develop a quick and strong tolerance to LSD in a short timespan.
What is LSD tolerance?
Tolerance refers to the body’s natural resistance to a drug’s effects. The human body resists some drugs completely. For instance, lisuride is a drug that, like LSD, is extracted from the ergot fungus, so it makes sense that it is also a hallucinogen—but only for rats. Humans don’t experience the same psychedelic effects of lisuride, which is why it’s commonly used as a treatment for people with Parkinson’s disease.
The human body can also develop a tolerance to substances like LSD over time due to frequent exposure. Like many psychedelics, acid loses its effect quickly if taken repeatedly over a short period of time. In other words, the more acid you drop, the less you’ll trip (unless you take a tolerance break).
LSD tolerance applies to both the psychological as well as some of the somatic (physical) effects of acid. While LSD is well known for inducing vivid visual, auditory, tactile, and even olfactory hallucinations, it may also cause some physical effects, such as dilated pupils, increased heart rate, increased blood pressure, and twitchiness.
Some of these physical side effects can also be reduced through frequent acid use—although this doesn’t mean you should take acid all the time as a solution (if LSD’s physical sensations bother you). The dilation of pupils, for instance, decreases 57 percent between the first and second day of doses, researchers say. That physical response can be restored by upping the dosage—but even then, if you hypothetically took that higher dose a few days in a row, it would also cease to have an effect on the pupils, and so on. (Researchers say there are not enough studies at this time to conclude if all of the other physical side effects will also disappear over time).
How long does it take to develop LSD tolerance?
The human body begins developing a tolerance to LSD within 24 hours of taking a dose. That means if you drop acid two days in a row, you will need to increase the dosage to get the same effect. Some people can develop a tolerance to LSD as early as three hours after taking a dose, so even reupping a trip on the same day can be difficult given the human body’s quick resistance to acid. Although, keep in mind that for most people, if you take another hit a few hours into your trip, you will likely have a more intense experience (so be careful when considering to do so).
Without increasing your intake, a dose that makes you vividly hallucinate one day probably won’t be half as trippy the next. That’s because the psychedelic effects of acid are reduced by 47 percent when the same dose is taken two days in a row, according to a 1956 study involving human participants. By day four of that study, the repeated dosage didn’t have any hallucinogenic effect at all for most participants. But researchers didn’t stop there. They continued giving the same dose to participants for another 10 straight days to see if the drug’s psychedelic effects would rebound over time, but none of the respondents reported a resurgence of hallucinations.
A followup study found that the average person will develop a total tolerance to acid’s psychedelic effects within seven days of taking daily doses (unless the dosage is increased).
While upping the dosage can have an impact in the short term, LSD tolerance catches up quickly according to another study from 1956, which saw participants take daily doses of LSD for 12 straight weeks. That’s 84 days of non-stop acid tests.
The researchers overseeing the extended experiment anticipated that participants would develop a tolerance to LSD over time, so they upped the dosage periodically. Despite those efforts, they noticed a steep decline in the effectiveness of acid by the end of the experiment’s first week. While regularly increasing the doses prevented the participants from developing a complete tolerance to LSD, they also stopped experiencing the full effect of acid after the first trip—even when the daily dose was doubled, tripled and even quadrupled as the weeks went on.
Can LSD tolerance be overcome?
Developing a tolerance to LSD seems inevitable based on current research, but there is one major caveat: No study has ever increased the daily dose beyond 500 micrograms, according to a 2016 review of LSD research. That means it is possible to combat tolerance with higher and higher intakes of acid.
However, grappling with your body’s tolerance comes with several risks. Taking higher doses of LSD puts you in danger of inducing a challenging experience that may cause severe distress (e.g. paranoia and panic attacks) or trigger underlying psychiatric disorders. (This is why those with a family or personal history of schizophrenia, psychosis, mania, or severe bipolar disorder, for instance need to exercise extreme caution if they want to take acid or other psychedelics.)
While no one has died directly from an LSD overdose to date, a number of people have experienced acute side effects from overdoing it on acid. In 1972, a group of eight adults were hospitalized after snorting powdered LSD, which they had mistaken for cocaine. Five were comatose upon arrival at the ER, and three had to be put on ventilators soon after admission. Other side effects included extreme vomiting, diarrhea and blood clots.
While all eight survived the ordeal, it’s possible that things could have ended worse if they had not received medical attention, or if they had snorted more of the powder before realizing their mistake. Blood tests suggested that each patient had between 1,000 to 7,000 micrograms per milliliter in their system. Researchers hypothesize that a lethal dose of LSD would probably be 14,000 micrograms, which is insanely high compared to the recommended dose of 100-200 micrograms.
How long does LSD tolerance last?
Luckily for avid psychonauts, LSD tolerance disappears almost as quickly as it develops.
Researchers have found that the body’s tolerance to acid goes back to normal after three to six days of abstaining from LSD. Even the participants who took increasing doses of acid for 84 days straight found that their enhanced tolerance disappeared after three days of abstention.
So if you ever end up developing a tolerance, even then you won’t have to take a long sabbatical from acid before being able to enjoy another trip—on a regular dose. And while tolerance is common, developing a resistance to LSD won’t make you permanently immune to its psychedelic effects. Even a few of those eight people who snorted way too much acid back in 1972 say they still enjoy tripping now and then.
Giving acid a rest shouldn’t be too hard for most people: Acid has no withdrawal effects and a very low liability for addiction.
What causes LSD tolerance?
Scientists aren’t entirely sure why we develop such a quick and strong tolerance to LSD. Many believe that tolerance arises from temporary changes in the brain caused by exposure to acid.
LSD works by attaching itself to certain parts of the brain—especially serotonin receptors in the prefrontal cortex. Some scientists believe that those receptors become desensitized immediately after coming into contact with acid. Others think the density of those receptors decreases temporarily in response to an acid trip, which suggests that a followup dose won’t have the same effect until those receptors have been replenished.
However, researchers can’t be certain about the cause of LSD tolerance until further research has been conducted. Most of our knowledge on the subject comes from preliminary studies on human subjects from the 1950s and 60s. In order to fully understand LSD tolerance and other ways in which acid interacts with the human body, psychedelic researchers need the freedom to study psychedelics without the severe restraints that have been imposed on their work by the War on Drugs.
Are there any side effects of LSD tolerance?
There are no serious side effects of LSD tolerance, but the phenomenon can be frustrating for psychonauts. That’s because acid tolerance can also reduce the effectiveness of psilocybin, mescaline, MDMA, and other psychedelics.
Scientists aren’t sure why cross-tolerance is common with psychedelics. Some believe that since most of these substances interact with the same serotonin receptors, when the brain develops a tolerance for one type of psychedelic, its tolerance for the others increases, as well.
The one major exception to that rule is DMT. The human body does not appear to develop any tolerance for DMT, regardless of how much or how often people take it on its own or along with other psychedelics.
Can everyone develop a tolerance to acid?
Yes, developing a tolerance to LSD is very common—and not just in humans. Researchers have found that animals also develop a quick tolerance to acid.
When given LSD, animal test subjects (including rats, cats, and mice) demonstrate a number of common symptoms: They groom themselves excessively, flick their tails and paws more than usual, stare off as if in a trance, and twitch much like humans do while tripping. But when given acid regularly, cats and rats develop a resistance to twitching and flicking within a few hours. That resistance subsides after three days for cats and one day for rats.
However, there’s no way of knowing if cats and rats also experience a decrease in hallucinations (or if they can hallucinate at all) since, of course, neither animal can describe their acid trips to researchers.
LSD tolerance could be a medical breakthrough in disguise.
LSD tolerance doesn’t mean that the drug is ineffective. In fact, tolerance has an upside for patients who could benefit from other psychological effects of acid.
In a 1970 study, American neuropsychiatrist Luaretta Bender gave 150 micrograms of LSD to children with autism and schizophrenia for several months and found that the drug “improved the well-being and the psychosocial adjustment of her patients.” That might sound strange given the hallucinogenic effects of acid, but Bender says those wore off quickly. The children developed a strong resistance to the “perceptual effects” of LSD by the second day of the experiment, but the clinical benefits persisted for months. (Again, however, keep in mind that this was a clinical setting and attempting to self-medicate autism or schizophrenia on your own might reap different effects, and could be more challenging.)
Read: How LSD is Made
Other research has also proven the benefits of LSD for a variety of mental health conditions. In a 2014 study, researchers noted that LSD could benefit patients with migraines, eating disorders, depression, bipolar disorder, anxiety, panic attacks, and substance-use disorders. For many, a one-time dose or infrequent use of LSD can work wonders—with the right set and setting. But if you are considering whether to take acid often enough (multiple times a week, or even multiple times a month) to cause a tolerance, first ask yourself about your intentions for doing so. LSD is a powerful psychedelic and can be both transformative, but also challenging—especially if you have underlying mental health issues.
A note about microdosing: According to the most popular microdosing regimens, consumers take one small, subperceptible dose every three to four days. This intermittent style helps people avoid developing a tolerance.
James McClure is a journalist, playwright and scholar based in Saint John, New Brunswick, Canada who specializes in cannabis culture, international drug policy, hockey and English literature. His work has appeared in Civilized, Mental Floss and other publications.