By Roger Chriss, PNN Columnist

Recent news that a small pilot study found LSD has a “protracted analgesic effect” at low doses garnered a lot of enthusiasm and hype. Headlines declared that LSD “could replace opiates” and be a “potent weapon against pain.”

The study looked at two dozen healthy volunteers given low doses of LSD or a placebo and then subjected them to a “cold pressor test” – immersing a hand in near-freezing water. Researchers found that 20 micrograms of LSD “significantly increased the time that participants were able to tolerate exposure to cold (3°C) water.”

Despite this, LSD has a clear problem: Its therapeutic index is very low.

The therapeutic index is a measure of the relative safety of a drug, computed by dividing the toxic dose by the dose needed for a therapeutic response. A toxic dose represents a threshold beyond which undesirable side effects or adverse events become common.

A high therapeutic index is better. It signifies a broader range of possible doses, letting clinicians adjust a dose precisely for a specific patient. Body weight, age, gender and metabolic status all influence drug metabolism and a high therapeutic index improves clinical safety.

A high therapeutic index also means that the drug can be given in multiple doses. If an initial dose is inadequate, a second dose can be given. Or a dose of another medication from the same class can be given. Or the drug can be given repeatedly over a short time without risky cumulative effects. All of this is important, because acute pain associated with trauma, injury or surgery may last for days.

The therapeutic dose of LSD in the simulated pain study was 20 micrograms (lower doses were ineffective). In general, a hallucinogenic dose starts at 25 micrograms. This suggests that LSD’s therapeutic index is 1.25.

Other measures of drug safety look even worse. The measure known as the margin of safety looks at how a dose may be toxic for 1% of people while being clinically effective for the other 99 percent. This accounts for variations in dose-response curves. Since some people experience LSD’s psychoactive effects at well below the standard 25 microgram threshold, LSD’s margin of safety is also very low.

LSD probably has little future as an over-the-counter analgesic or in a standard clinical setting for acute or chronic pain. It may instead have potential as a narrow therapeutic index (NTI) drug, which the FDA defines as a drug “where small differences in dose or blood concentration may lead to serious therapeutic failures and/or adverse drug reactions that are life-threatening or result in persistent or significant disability or incapacity.”

Current NTI drugs include lithium and methotrexate, which are used to treat serious conditions such as bipolar disorder and rheumatoid arthritis in carefully selected patients under close medical supervision. LSD could wind up being designated as an NTI drug, but only if clinical trials demonstrate safety and efficacy in the management of specific types of pain.

In general, however, LSD is unlikely to be a broadly useful analgesic. Pain relievers need to have a wide therapeutic index in order to succeed, and there seems to be no practical way to do this with LSD.

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.