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CBD for Pain Relief is More Than the Placebo Effect, Study Finds

By Alexander Beadle

Published: Apr 28, 2021   
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Outside of general wellness, one of the most frequently reported motivations for using CBD is to address feelings of pain or chronic pain. But how does CBD actually affect pain?

In new research published in the journal Experimental and Clinical Psychopharmacology, scientists at Syracuse University have demonstrated for the first time that CBD’s effects on pain are two-fold; users benefit both from the psychological expectation of thinking they are taking CBD and the real pharmacological effects of the drug. Notably, these modes of action both appeared to affect pain perception in different ways.

Further research using larger trial groups could help to confirm these results, the researchers say. However these findings do warrant further research into the psychological and pharmacological mechanisms underlying CBD’s use.

CBD pain relief driven by both psychological and pharmacological action

While there are many observational studies in the literature linking CBD use with effective pain relief, until recently, there had not yet been any experimental studies designed to assess whether CBD is any more effective than a placebo at tackling pain.

“For science and the public at large the question remained, is the pain relief that CBD users claim to experience due to pharmacological effects or placebo effects,” study author Martin De Vita, a researcher in the psychology department at Syracuse University, said in a statement.

“That’s a fair question because we know that simply telling someone that a substance has the ability to relieve their pain can actually cause robust changes in their pain sensitivity. These are called expectancy effects.”

To untangle the effects of expectation from the actual effects of the drug, the researchers enrolled fifteen participants into the first human experimental study of CBD for pain.

The study used special equipment that allowed the researchers to apply controlled heat pain and measure the participants’ nervous system responses. Participants went through a total of four sessions using this apparatus, all at least a week apart.

During each session, participants were sublingually given either a dose of CBD isolate or a small amount of inert coconut oil placebo. Participants were told at the beginning of the session that they were about to receive either a placebo or the active CBD. However, on half of the occasions this information was manipulated so that the participants were told they were given a placebo when actually given the CBD, and vice versa. Across the four sessions, each participant went through each possible combination of drug and verbal instruction once.

“That way we could parse out whether it was the drug that relieved the pain, or whether it was the expectation that they had received the drug that reduced their pain,” explained De Vita.

“We hypothesized that we would primarily detect expectancy-induced placebo analgesia (pain relief). What we found though after measuring several different pain outcomes is that it’s actually a little bit of both. That is, we found improvements in pain measures caused by the pharmacological effects of CBD and the psychological effects of just expecting that they had gotten CBD. It was pretty remarkable and surprising,” De Vita added.

CBD changes perception of pain unpleasantness, rather than intensity

In a previous review and meta-analysis, the same Syracuse University group found that the use of cannabinoid drugs did not appear to reduce the intensity of any ongoing pain. Instead, the drugs were associated with modest increases in pain threshold and tolerance, as well as a reduction in the perceived unpleasantness of the pain.

“It’s not sunshine and rainbows pleasant, but something slightly less bothersome,” explained De Vita. “We replicated that in this study and found that CBD and expectancies didn’t significantly reduce the volume of the pain, but they did make it less unpleasant – it didn’t bother them as much.”

By looking at pain in terms of this more complex model, the researchers were able to observe that CBD and the expectancy of CBD led to reductions in pain unpleasantness, both separately and when combined.

“It’s not just pain, yes or no, but there are these other dimensions of pain, and it would be interesting to see which ones are being targeted,” said De Vita. “We found that sometimes pharmacological effects of CBD brought down some of those, but the expectancies did not. Sometimes they both did it. Sometimes it was just the expectancy. And so, we were going into this thinking we were going to primarily detect the expectancy-induced pain relief but what we found out was way more complex than that and that’s exciting.”

What does this mean for CBD and treating pain?

It is still unclear why CBD and its expectancy effect are both able to effectively reduce the unpleasantness of pain. From further examination of two dynamic pain measures used in the study –conditioned pain modulation and offset analgesia – the researchers hypothesize that CBD and its expectancy are both able to enhance central nervous system processes that inhibit pain. 

Specifically, they suggest that both CBD and CBD expectancy can individually enhance endogenous pain inhibition systems mediated by spatial pain processing, while CBD expectancy can also exclusively enhance endogenous inhibition mediated by temporal processing. This is important as many chronic pain conditions, including fibromyalgia, chronic tension headache, and complex regional pain syndrome, are all characterized by deficiencies in endogenous pain inhibition.

“The data is exciting but pretty complex in that different pain measures responded differently to the drug effect, to the expectancy, or both the drug and expectancy combined – so we’re still trying to figure out what is behind the differential data with different kinds of pain measures,” said co-author Stephen Maisto, research professor and professor emeritus of psychology at Syracuse University.

“The next step is studying the mechanisms underlying these findings and figuring out why giving instructions or CBD itself causes certain reactions to a pain stimulus.”


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