Cannabis and hemp have a long history of making their way into many different preparations that included teas and tinctures all the way through to lotions and poultices. Even as far back as Ancient Egypt, cannabis and hemp was being described in medical papyruses as a treatment for conditions as varied as the treatment of ingrown toenails to a remedy for inflammations of the vagina.
Yet, many scientists find it hard to believe that cannabis, hemp and in particular cannabinoids such as cannabidiol (CBD) can do so much, often chalking up the results to a placebo effect. However, as we enter 2025, the scientific landscape has dramatically changed, with hundreds of new clinical trials and sophisticated research methodologies providing unprecedented insights into CBD's true therapeutic potential.
What is a Placebo and the Placebo Effect?
In simple terms, a placebo is anything that seems to be a real medical treatment but doesn't actually contain any of the active ingredients that are meant to affect health.
Researchers use placebos as a control condition when studying the effects of pharmaceutical interventions to help them understand what the true effects of a new drug or other treatment might have on a particular condition. This allows them to then compare the effects of the drug and the placebo on the people in the study, determining the effectiveness of the new drug as well as checking for side effects.
However, scientists have noticed that during clinical trials, people can often times have a response to a placebo. For instance, the participant's symptoms may improve despite not receiving any active ingredients or the person may present with "side effects" from the "treatment". These responses are what is referred to as the "placebo effect."
How does the Placebo Effect Work?
Although scientists aren't exactly sure how the placebo effects works, one of the most widely accepted theory is that the placebo effect is due to a person's expectations. Basically, placebos are thought to work because brain processes related to perception and emotion shape and, ultimately, construct and modulate mental and physical health. In other words, because of the relationship between mind and body, when a person believes something will work, it's actually possible for the body's own chemistry to cause the effects the medication is expected to cause.
Ironically enough, the endocannabinoid system actually plays a major part in the placebo effect with the belief that a placebo capsule will help treat symptoms and ailments causing the brain to release the endocannabinoid anandamide, otherwise known as the bliss molecule. Anandamide has been shown to actually stimulate many of the desired effects of the expected treatment. This includes things like pain reduction, reducing inflammation and improving mood with the placebo effect accounting for much of the efficacy of pharmaceutical medications such as opioids and anti-depressants.
However, it is important to understand that the placebo effect is a very real thing. Just because it is tied to expectations, it doesn't mean it is imaginary or fake. In fact, there are studies that show that the changes that occur with a placebo effect are actual physical changes, often showing that the placebo effect is more effective than doing nothing at all.
Real-World Examples of Placebo Effects in CBD Studies
To illustrate this, let's look at some compelling examples from actual clinical trials.
For instance, in one randomised, double-blind study that assessed the effects of cannabinoids on multiple sclerosis (MS) symptoms, scientists used a Visual Analogue Scale (VAS) score for each patient's most troublesome symptom as a measure of how effective CBD is in reducing the symptoms of MS. Illustrating the power of the placebo effect, the scientists found that in the control group who only received the placebo, their symptom scores dropped from an average of 74.31 (12.5) to and average of 54.79 (26.3) points.
In another randomised, double-blind trial studying the efficacy of CBD in the treatment of Lennox-Gastaut syndrome, the researchers went so far as to actually include and account for the placebo effects in their hypothesis. And they were right. They found an astounding 21.8% drop in the monthly frequency of the participants' seizures even though they were giving nothing more than glucose.
Interestingly enough, in this same study, one participant in the placebo group also had to withdraw from the study because of "adverse events". So, it would seem that, just like people can sometimes experience an actual improvement in their symptoms because of the placebo effect, the opposite can also happen due to something called the nocebo effect.
What is the Nocebo Effect?
The term nocebo effect was coined to give a name to the negative equivalent of placebo and distinguish between desirable and undesirable effects of placebos. In other words, for some people this means that taking an inert pill or even just being informed of a pill or procedure's potential side effects, is enough to bring on real-life symptoms.
What this means in relation to CBD is that, interestingly enough, placebo and nocebo effects seem to be associated with the same dopaminergic and endogenous opioid pathways, but in opposite ways. So, the same way that people who think CBD is going to work for them may experience increased benefit, so too can people who do not believe in the effects of CBD end up feeling nothing, or even negative effects when using it.
The Scientific Revolution: What We've Learned Since 2019
Since our original article in 2019, the scientific understanding of CBD has advanced exponentially. We now have access to sophisticated clinical trial data, comprehensive meta-analyses, and a much deeper understanding of the endocannabinoid system's role in human health.
The Endocannabinoid System: Beyond the Basics
The discovery of the endocannabinoid system and the integral way in which it affects, regulates and modulates almost every system within the body is very real. Current research from 2024 shows that the endocannabinoid system (ECS) is now recognized as "critical for almost every aspect of our moment-to-moment functioning", regulating learning and memory, emotional processing, sleep, temperature control, pain control, inflammatory and immune responses, and eating.
Recent studies have identified that deficiencies in this system are now being thought to be responsible for a variety of pathophysiological patterns, symptoms, ailments and diseases that may be suitably treated with cannabinoids such as CBD. This concept, known as "Clinical Endocannabinoid Deficiency Syndrome" (CDS), provides a scientific framework for understanding why CBD might be effective for such a wide range of conditions.
2024-2025 Clinical Trial Evidence: Beyond Epilepsy
While CBD's efficacy in treating epilepsy remains the gold standard with FDA approval, recent clinical trials have expanded our understanding significantly:
Mental Health and Anxiety
A recent 2024 meta-analysis examining CBD's effects on performance found that while CBD showed minimal impact on cognitive function, it did have measurable effects on subjective ratings, particularly for anxiety and stress-related conditions. Multiple ongoing clinical trials at major institutions like UCSD and UCSF are examining CBD's efficacy in treating PTSD, social anxiety disorder, and early psychosis.
One particularly noteworthy 2022 study published in Communications Medicine showed that patients with moderate-to-severe anxiety experienced significant improvements not only in anxiety symptoms but also in mood, sleep, quality of life, and cognitive function, specifically executive function, after four weeks of CBD treatment.
Pain Management
A comprehensive 2024 systematic review of CBD in pain treatment analyzed 40 studies, including 11 human clinical trials. The evidence shows that CBD has demonstrable analgesic effects beyond what can be attributed to placebo, particularly for neuropathic pain and inflammatory conditions.
Cannabis Use Disorder
Perhaps most remarkably, ongoing Phase III clinical trials are examining CBD's potential to treat cannabis use disorder itself. A large-scale Australian study involving 250 participants has shown preliminary evidence that CBD can reduce cannabis use in people with cannabis use disorder, suggesting real pharmacological effects rather than placebo.
The Placebo Problem in Cannabis Research
A 2022 meta-analysis specifically examined "Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain." This study revealed important insights about how media attention and public expectations can influence trial outcomes, but also confirmed that well-designed studies continue to show effects beyond placebo.
So, Is CBD Oil a Placebo?
The answer in 2025 is definitively more nuanced than it was in 2019. While many scientists previously believed that we did not have enough scientific data to make definitive claims about the true effects and therapeutic efficacy of CBD, we now have substantial evidence from multiple sources:
Established Therapeutic Effects
Conditions for which CBD has been shown to be effective beyond what can purely be due to placebo now include:
- Epilepsy: FDA-approved Epidiolex has demonstrated clear efficacy in multiple controlled trials
- Pain: Both neuropathic and inflammatory pain conditions show measurable improvements
- Anxiety: Multiple controlled studies show statistically significant improvements
- Sleep disorders: Clinical evidence supports CBD's role in improving sleep quality
- Inflammation: Both preclinical and clinical studies demonstrate anti-inflammatory effects
- Neurodegenerative disorders: Emerging evidence for conditions like Parkinson's disease
- Substance use disorders: Including promising results for cannabis use disorder treatment
The Quality of Evidence Has Improved Dramatically
Unlike in 2019, we now have:
- Multiple Phase III randomized controlled trials
- Large-scale meta-analyses including hundreds of studies
- Standardized, pharmaceutical-grade CBD products for research
- Sophisticated biomarker analyses
- Long-term safety data
Why Do Some Still Think CBD Is A Placebo?
Despite the mounting evidence, several factors continue to fuel skepticism:
Too Good to be True
Unfortunately, CBD's reputation as being a panacea for so many different symptoms and diseases continues to work against it. The broad therapeutic potential of the endocannabinoid system, while scientifically sound, can appear implausible to those unfamiliar with the research.
Individual Variation
CBD should be viewed as only one weapon in an arsenal that for some may be a great adjunct therapy to use with their traditional pharmaceutical drugs, while for others, it might work perfectly on its own. Recent research has identified genetic polymorphisms in enzymes like FAAH (fatty acid amide hydrolase) that can significantly affect individual responses to CBD.
It Works Over Time
Another issue that causes many people to think that CBD is a placebo is because, unlike its cousin cannabinoid, tetrahydrocannabinol (THC) which produces immediate effects, CBD simply doesn't do that. Add to that the fact that CBD tends to work over time, it's easy to understand why many still consider CBD to be a placebo.
Poor Quality Products
A significant factor that wasn't as prominent in 2019 is the quality control issue. Studies have shown that up to 69% of commercially available CBD products are mislabeled, and 21% contain significant amounts of THC. This variability can lead to inconsistent results and reinforces placebo attributions.
The 2025 Perspective: Moving Beyond the Placebo Debate
As we move through 2025, the scientific community has largely moved beyond the simple "CBD vs. placebo" debate. The current focus is on:
Precision Medicine Approaches
Research is now focusing on identifying which patients are most likely to benefit from CBD, based on genetic markers, endocannabinoid tone, and specific biomarkers.
Optimal Dosing and Delivery
Studies are examining the "inverted U-shaped" dose-response curve that CBD often exhibits, where moderate doses are more effective than either very low or very high doses.
Combination Therapies
Research is increasingly examining CBD as part of combination treatments rather than as a standalone therapy.
Final Thoughts
It is no longer reasonable to dismiss CBD as merely a placebo effect. While skepticism was understandable in 2019 given the limited high-quality evidence available at the time, the scientific landscape has fundamentally changed.
We now have:
- FDA-approved CBD medications with demonstrated efficacy
- Hundreds of peer-reviewed studies showing measurable biological effects
- Sophisticated understanding of the endocannabinoid system's role in health and disease
- Multiple ongoing Phase III clinical trials for various conditions
- Standardized research methodologies that account for placebo effects
However, CBD is by no means a cure-all, and the ever-growing body of scientific research and evidence from clinical trials show that CBD has real, measurable effects in the body and that its benefits are genuine and distinct from placebo effects. The key, just like with any other medication or therapeutic agent, is to use pharmaceutical-grade products, understand appropriate dosing, work with healthcare providers when appropriate, and have realistic expectations about therapeutic outcomes.
The placebo effect remains an important consideration in CBD research and clinical practice, but it no longer serves as a reasonable explanation for the totality of CBD's therapeutic effects. As we continue to develop our understanding of personalized cannabinoid medicine, the focus has rightfully shifted from "Is it real?" to "How can we optimize its therapeutic potential for individual patients?"
