As if the political, bureaucratic, and moral issues weren’t enough to contend with, clinical trials involving cannabinoids are also struggling with significant placebo effect issues, says Ethan Russo, medical director at PHYTECS. “It’s an increasing challenge that requires the use of innovative trial designs,” he says.
There is a perception among the public that cannabis is a “wonder drug,” Russo explains. That’s a big part of the problem. Trial subjects receiving placebos can report anywhere from a 30% to 70% percent response rate. Typical result: Unsuccessful clinical trial.
It’s a thorny problem. However, Russo says there are some tools that can help researchers better sort out the effects of an active treatment versus a placebo in such trials:
- Start with a very low dose where the effects will be minor. Because cannabinoids enter the system so quickly after inhalation and impact the brain, he says administering them orally or via a spray in the mouth is possibly more effective because it slows the course of the drug’s effects.
- Leverage the situation by utilizing a randomized-withdrawal clinical trial design. Initially, all patients receive the test drug, unbeknownst to them. About a month into a trial, shift efforts to the portion of the subject group reporting significant alleviation of pain or whatever other problems are being examined. Only the responders continue into the randomization phase; half of them receive the same dose of the test drug taken previously, while the others receive the same “dose” of a look-alike placebo. After a time, it should become clearer that those still receiving the intended treatment are showing the most positive results, while the placebo group’s response rate should drop off.
It’s not easy, Russo warns. “I’ve seen this work in one trial and fail in a second,” he says. Still, these tools and others can improve the odds for a successful cannabinoid-related project.
Russo will address a bevy of unique challenges faced when setting up and running this kind of trial at his ACRP 2016 Meeting & Expo session, Cannabinoid Clinical Trials: Current Review, Problems, Pitfalls and Solutions.