By Roger Chriss, PNN Columnist

The well-known hallucinogen LSD may have a new use. A new study published in the Journal of Psychopharmacology found evidence that LSD exerts a “protracted analgesic effect” at low doses.

The study was performed in The Netherlands on 24 healthy volunteers. Three low doses of LSD or placebo were given to the participants, who immersed a hand in near freezing water 90 minutes and five hours after dosing to assess their pain tolerance.

Results from the “Cold Pressor Test” showed that 20 micrograms of LSD “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.”

It is not clear how or why LSD increased tolerance to cold water. The study authors speculate about LSD’s various actions on serotonin receptors, but also note that “an additional or alternative explanation for the analgesic effects of LSD could be hypertension-associated hypoalgesia.”

There were side effects from LSD, even at low doses. LSD slightly raised blood pressure and increased feelings of dissociation, anxiety and somatization in the volunteers. Psychological and cognitive effects were described as “very mild.”

The study has other important limitations. The Cold Pressor Test is not a good analog for real-world acute pain. And healthy volunteers in such studies tend not to be typical of the population at large. They skew young, male, and often have prior experience with the substance being evaluated that most people do not have.

Also, these studies tend not to translate to real-world use. Recent work on LSD microdosing has found “few benefits and significant downsides.”

Findings Hyped

Unfortunately, this preliminary study has already led to hype about the analgesic potential of LSD. New Atlas called it  “an incredible, first-of-its kind trial” and Futurism reported that LSD microdoses were “as effective as opioids at treating pain.”  Interesting Engineering predicted “there could be possible applications of LSD as a non-addictive pain medication.”

The Beckley Foundation, which funded the study, fed the hype with a news release that claimed the analgesic effects of LSD were “remarkably” similar to oxycodone and morphine, but without the risk of addiction.

“The present data suggests low doses of LSD could constitute a useful pain management treatment option that is not only effective in patients but is also devoid of the problematic consequences associated with current mainstay drugs, such as opioids,” said Amanda Feilding, Founder and Director of the Beckley Foundation. “We must continue to explore this with the aim of providing safer, non-addictive alternatives to pain management, and to bring people in pain a step closer to living happier, healthier and fully expressed lives.”

Misunderstanding Pain Research

The Cold Pressor Test is a standard way to assess pain threshold and tolerance. But results in the test vary significantly with water temperature, and the test is not seen as a precise analog with real-world pain. As a 2016 review noted, “No single experimental model can mimic the complex nature of clinical pain.”

Pain is a biopsychosocial phenomenon involving a long chain of interactions that start with peripheral sensory nerve endings and manifest in the conscious mind. Analgesic effect can be achieved locally in nerve endings, as seen with lidocaine injections; or intermediately in the spinal cord, as seen with radio frequency ablation or spinal cord simulators; or centrally in the brain, as seen with psychoactive drugs.

Therefore, comparing analgesic efficacy is far more complex than just looking at outcomes in a simple lab-induced pain model in a handful of healthy people. The LSD study did not test its subjects with multiple substances or combinations of substances.

Further, analgesics have to be safe and effective. Safety includes understanding possible drug-drug interactions. A 2008 review noted that “lithium and some tricyclic antidepressants have also been reported to increase the effects of LSD.”

A 2019 study describes several important biochemical pathways and gene polymorphisms in LSD metabolism, possibly affecting pharmacokinetics and pharmacodynamics. The article concludes that “drug-drug interaction studies in humans are required to further assess the clinical relevance of these findings.”

Analgesics like acetaminophen have relatively few drug-drug interactions. Opioids have a number of important ones, but these are well-understood and can be controlled. By contrast, cannabis is messy. Drugs.com lists 24 major and 353 moderate interactions for cannabis. There is no such list for LSD.

Pain medication needs to be effective as well as safe and reliable. Demonstrating efficacy requires far more than a handful of willing subjects being subjected to a simulated pain experience in a laboratory setting. Demonstrating safety and reliability will require extensive testing, pharmacodynamic studies, and research on drug-drug interactions. LSD may have taken the first step toward becoming an analgesic, but there is a long road ahead.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.