Clinical research and schedule 1 drugs: is the issue about legal barriers or poor quality?

Dear Editor

Certainly, legal barriers to clinical research for schedule 1 drugs with therapeutic potential must be removed as pledged by King and colleagues.(1) However, we are concerned that the reviewers allowed them to claim “the misuse of controlled drugs intended for clinical use is extremely rare”.(1) How to ignore that fentanyl and other opioids fuel the worst drug crisis in the history of the United States? England is not spared (2) and opioids are only one among many misused medicines, an old, frequent and growing but unsettled issue yet, as with benzodiazepines.(3)

Similarly, the claim that “the placement of psilocybin in schedule 1 over 50 years ago was based on scant scientific evidence” (1) is a smokescreen: The federal government classified psilocybin as schedule I substances in 1971, after the Controlled Substance Act was signed into law by President Richard Nixon on October 27, 1970; this is several years after Sandoz Pharmaceutical’s wise decision to stop its production and dispensation, under the brand name indocybin®, in 1965. Indeed, harms are not limited to headaches or nausea, psilocybin is a hallucinogen, producing effects similar to LSD, reliably and dose-dependently inducing hallucinations, delusions and even psychosis.(5) In 1965 Sandoz also gave up LSD, discovered by Hoffman in 1943, 15 years before psilocybin.

In our opinion, the real challenge is about raising the bar of the quality of clinical research. Indeed, robust evidence for benefits and harms on clinically relevant outcomes vs appropriate comparators is needed. Presently, this is not the case yet, not to account for the numerous small trials of highly selected patients in particularly secure settings with little attention to safety issues and the lack of double blinding. The latter issue will need an innovative design.

References

1 King LA, Nutt DJ, Nichols DE. Remove barriers to clinical research for schedule 1 drugs with therapeutic potential. BMJ. 2023;381:p981. doi:10.1136/bmj.p981

2 Mahase E. Opioid related hospital admissions in England increased by nearly 50% in 10 years. BMJ. 2022;376:o299. doi:10.1136/bmj.o299

3 Hayhoe B, Lee-Davey J. Tackling benzodiazepine misuse. BMJ. 2018;362:k3208. doi:10.1136/bmj.k3208

4 Geiger HA, Wurst MG, Daniels RN. DARK Classics in Chemical Neuroscience: Psilocybin. ACS Chem Neurosci. 2018;9:2438-2447. doi:10.1021/acschemneuro.8b00186

5 Benjamin C. Persistent psychiatric symptoms after eating psilocybin mushrooms. BMJ. 1979;1:1319-1320. doi:10.1136/bmj.1.6174.1319