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Placebo effect in focus

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Some scientists believe medical cannabis and CBD may have a placebo effect – although that’s not necessarily a bad thing.

The placebo effect has long fascinated scientists. Countless studies have shown that belief alone is enough to reduce pain, relieve irritable bowel syndrome symptoms, and help improve anxiety and depression, to name a few.

People think they’re getting a drug that works, and the body responds without the drug being applied.

Some scientists argue that the placebo effect could also be behind some of the health and wellbeing benefits of medical cannabis and CBD products.

Jürg Gertsch, deputy director at the University of Bern’s Institute of Biochemistry and Molecular Medicine, argues that the growing acceptance of medical cannabis as a legitimate therapy has been driven by trials that don’t pass the tests of good clinical practice.

It’s not that the effects of medical cannabis aren’t real, he believes, but that they might come from the placebo effect, rather than disease-related therapeutic effects, Gertsch tells Cannabis Health.

He says there’s a link between the endocannabinoid system – the biological system in our bodies that responds to cannabis – and the way we process the placebo effect.

This isn’t a controversial theory: studies have indicated that this is the case for the body’s endogenous opioid system, which react to morphine and heroin, and could help to mediate placebo effects.

Both this and the endocannabinoid system are linked to our perception of pain, including emotional pain and stress, Gertsch says.

Matthew Burke, cognitive neurologist and assistant professor at the University of Toronto, also argues that many of the perceived benefits of CBD might come from the placebo effect.

“When you have something that’s supposed to work for many different symptoms, especially symptoms shown to be a placebo response, including mood, pain, insomnia and fatigue, you have to ask how much the response to CBD is a result of the placebo effect.

“It’s not just an effect to be dismissed – it’s real, it meaningfully changes the brain in areas that are implicated in the path of physiology with these symptoms.”

In a patient with anxiety or pain, for example, there’s too much activity in the amygdala, and the placebo effect has shown to reduce activity here, Burke says.

“If a cannabinoid was able to directly activate the endocannabinoid system this would lead to broad palliative effect where the patient feels better, but you still see the same level of disease,” Gertsch says.

“I think there’s a big future for cannabis medicine, especially in palliative areas where you can’t cure the disease, but people feel they have better quality of life and sleep.”

However, Gertsch adds, these effects are dependent on getting the correct dose.

“The big question is about concentration and amount of dose of THC that each individual needs before the feel the effect, before it turns into the opposite,” he says.

“A low THC dose people often feel better, experience less fear, become more relaxed and sleep better, but in some patients, if they overdose they can experience anxiety and paranoia, and these things aren’t properly addressed when it comes to using cannabis as a medicine.”

Nevertheless, these placebo effects can be a strong motivation for people who use cannabis for medicinal purposes, who often don’t know what they’re buying when they go through unregulated sellers.

“Why do they use it? Everyone knows cannabis can get you high, that you have something very potent that could also be a medicine.”

“As scientists, we should be critical of these things,” Gertsch adds. “Cannabis seems to be a wonder drug. People expect it to cure cancer, pain, MS and neurodegenerative disease; they have extremely high expectations.”

On the benefits of CBD, Gertsch says: “In combination with antiepileptic drugs it improves rare forms of epilepsy in children, yet numerous anecdotes about CBD as broad-range therapeutic cannabinoid further increase the expectations, often also driven by sellers.

“CBD doesn’t have the same effects on cannabinoid receptors as THC. Thorough clinical randomised placebo-controlled trial with CBD as the only treatment showing efficacy are still lacking. Even though smaller trials look promising, I’m sceptical they stand the test with bigger trials.

“It’s unclear how CBD works. Doses used in published studies are very high, and most of the compound isn’t absorbed.”

Burke says the effectiveness of the placebo from CBD products could depend on social modelling.

“We trust reputation endorsements. If someone you respect and trust endorses this as working then that’s going to help,” he says.

“CBD can be expensive, but sometimes you need a high price point, and the fancy packaging and branding that comes with that price tag, to believe it will be effective.”

Burke believes a large proportion of CBD’s effects are due to placebo which, he says, ups the stakes of any undesirable side effects.

“You don’t want someone taking something that causes harm, if all they’re doing is expecting placebo effects for it,” he says.

“It’s not necessarily a bad thing that a large component of it is placebo, I’d much rather someone improves their symptoms through a placebo effect than resort to opioid based painkillers, but there are many ethical issues around consent, pricing, clearly there’s more that needs to be done.”

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