Study: A microdose of LSD could alter a fundamental human experience

In large doses, lysergic acid diethylamide (LSD) can repair damaged neurons in the brain, and reveal new ways of seeing the world. In small doses, microdosers chase the effects of the drug on creativity or mood, without the full psychedelic experience.

However, a new study suggests that even a microdose might be able to change a powerful human sensation: pain.

Microdoses of LSD increased pain tolerance and decreased ratings of painfulness and unpleasantness. Here, a microdose was defined as about 20 micrograms.

Twenty-four college students were asked to plunge their hands into frigid 37-degree water and see how long they could handle the chill. Compared to a placebo, students on 20 micrograms of LSD could keep their hands in cold water about 20 percent longer and had lower ratings of unpleasantness and painfulness.

Greater increases in pain tolerance were "comparable" to what you might see with traditional pain-management drugs, like oxycodone or morphine during that same task, the authors note.

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The study was published Monday in The Journal of Psychopharmacology, and was partially supported by the Beckley Foundation, a non-profit that researches psychoactive substances and advocates for "evidence-based changes" in global drug policy.

The study's first author, Johannes Ramaekers, a professor at Maastricht University, suggests LSD could one day be an alternative to opioids, which are highly addictive.

"That would be of interest," he tells Inverse. "To see if low doses of LSD could actually replace an opioid and at least reduce the addiction potential, because LSD has no addiction potential."

While LSD does come with certain risks — a "bad trip" can lead to unpredictable behavior, it can possibly exacerbate certain psychotic disorders, and it's not recommended for people with severe cardiovascular disease — it does not entail physical dependence or cause withdrawal. People can become tolerant to LSD over time, meaning that they'll need higher doses to get the same effects.

It also exhibits very low physiological toxicity, even at very high doses. Taken together, its qualities make it an attractive alternative to pharmaceutical drugs to some scientists.

Microdosing and pain management – Research on the therapeutic potential of psychedelics is resurging after a drought between the 1970s and the 2000s. Ramaekers attributes the slowdown to the war on drugs. In 1970, psychedelics were placed into the most tightly regulated group (Schedule I) of The Controlled Substances Act).

Before the research landscape dried up, an influential study was conducted in 1964 on terminally ill patients who were suffering from extreme pain. They received LSD, and two opioids: meperidine and dihydromorphinone. LSD tended to produce longer and more powerful dampening of pain than the other drugs. The drawback was that the doses were so high, that the patients also experienced a psychedelic state.

"When those patients were asked, the next day or the next week, if they would like to have another dose to treat pain, there was a significant amount of patients that said, 'no thank you,' because of the strong, psychedelic experience," Ramaekers says.

"It's not really mind-altering or bringing hallucinations."

In this new study, Ramaekers and his colleagues tried to get that dosage just right: enough to improve pain tolerance, not enough to cause hallucinations.

The team tested three different dosages of LSD: 5 micrograms, 10 micrograms, and 20 micrograms.

"Anyone on any of these doses could sit behind a computer and do their work," Ramaeker says.

At five micrograms, the team found no significant differences in how long people could withstand the water challenge. At ten micrograms, they saw a small difference that approached significance, but random chance still couldn't be ruled out.

That 20 microgram dose was enough to produce significant effects on pain.

However, 20 is on the high-end of a microdose. You would be aware that you took a dose of LSD, says Ramaeker. Patients seemed to have more positive moods and were more attentive.

"It's not really mind-altering or bringing hallucinations," he says. "You may perceive colors, for example, as a little bit brighter."

How does it work? –  This study wasn't designed to illuminate why LSD seems to have an effect on pain, but Ramaekers proposes three ideas in the paper.

• LSD promotes "self-transcendence" that blunts the experience of pain. Psychedelics can cause "breakthrough experiences" that feel like entering another reality. As the paper puts it: "in essence: no self, no pain."
• Microdoses were linked to increases in the patient's blood pressure, and increases in blood pressure have been linked to increased pain tolerance before. However, as one 2013 study points out, this relationship may hold for acute pain (like a pinprick), but not chronic pain (that originates in the body).
• LSD can bind to two types of serotonin receptors that are present throughout the brain, body, and spinal cord, Ramaekers says. He suggests that "stimulation of these receptors inhibits the transduction of pain signals to your brain" but adds that there is still scant research on this in humans.

Ramaekers says it's possible the full explanation involves all three hypotheticals. He's less compelled by the transcendence idea because the psychedelic experiences reported by his patients were "almost nil" he says and feeling "dissociated" could only explain 6 percent of the variation in pain tolerance.

The blood pressure explanation could explain 14 percent of differences – a greater amount but not enough to suggest that's the whole story. However, data on serotonin in the brain wasn't collected, so how the third explanation interacts is still unclear.

For now, the study demonstrates that it might be possible to benefit from the pain-reducing aspects of LSD without having to commit to the drug's hallucinogenic side. In the future, Ramaekers hopes that we might be able to get a bit more specific with the dosage.

Microdosing may be the way forward, but just how "micro" that dose should be is up in the air.

Partial Abstract:

Methods: Twenty-four healthy volunteers received single doses of 5, 10 and 20μg LSD as well as placebo on separate occasions. A Cold Pressor Test was administered at 1.5 and 5h after treatment administration to assess pain tolerance to experimentally evoked pain. Ratings of dissociation and psychiatric symptoms as well as assessments of vital signs were included to monitor mental status as well as safety during treatments.

Results: LSD 20 μg significantly increased the time that participants were able to tolerate exposure to cold (3°C) water and decreased their subjective levels of experienced pain and unpleasantness. LSD elevated mean blood pressure within the normal range and slightly increased ratings of dissociation, anxiety and somatization.

Conclusion: The present study provides evidence of a protracted analgesic effect of LSD at a dose that is low enough to avoid a psychedelic experience. The present data warrant further research into the analgesic effects of low doses of LSD in patient populations.