The Placebo Effect in MJ Therapy
The placebo effect is a well-studied phenomenon in science. Essentially, the term refers to the body’s psychological ability to respond to the act of treatment or taking medication, even if the actions or substances used have no real medical effect. In other words, a person’s health can improve simply because they believe the “medicine” should make them feel better. Scientists still cannot fully explain the mechanism behind this phenomenon, but often, a placebo—whether it’s a sugar pill or a fake surgery—can improve a patient’s mood and overall well-being. Observations show that placebos, even those without any psychoactive compounds or medications, can often lead to changes in brain activity and affect blood pressure and heart rate. Brain activity changes have been confirmed using tomography.
In 1955, Henry Beecher was the first physician to propose that placebos could have certain therapeutic properties. Later, neuroscientists discovered that taking a placebo activates the same neural pathways in the body as real treatments and actual medications. One notable effect is “placebo analgesia,” where a fake medicine can activate the same neural pathways responsible for reducing or suppressing pain.
In 1978, doctors found that the “placebo analgesia” effect stimulates the body’s natural release of endogenous opioids, in addition to activating neural pathways that affect biological pain relief mechanisms not related to opioid release. In 2011, Italian scientist Fabrizio Benedetti and his team found that, among other things, placebos partially activate the body’s endogenous cannabinoid receptors, producing a pain-relieving effect similar to that of anandamide and other endogenous cannabinoids. Their research shows that, for the most part, the placebo effect—outside of activating endogenous opioid receptors—acts on CB1 cannabinoid receptors, which are widespread in the brain and throughout the body, partially activating them and thus producing a noticeable pain-relieving and toning effect in patients. This is confirmed by the fact that when a CB1 receptor blocker (the synthetic drug SR141716) is used before a placebo, the analgesic effect disappears completely. At the same time, blocking CB1 does not affect the placebo’s ability to stimulate endogenous opioid release. “In other words, the placebo has a complex effect on the human body, activating several different biological systems at once to modulate bodily functions and suppress pain and discomfort,” the study concludes.
High Hopes for the Placebo Effect
Researchers studying the placebo effect note that its manifestation and ability to activate different biological systems for therapy can be effectively modulated by the power of suggestion. In simple terms, patients who took a placebo described as a psychostimulant reported increased heart rate, narrowed blood vessels, higher energy, and stimulated thinking, while another group taking the same placebo as a sedative experienced the opposite effects. Closer examination shows that such suggestion is a key factor in whether a fake medicine activates a particular bodily modulation system.
For example, a 2004 study found that a group of patients told they would receive morphine experienced a strong pain-relieving effect from an injection, similar to taking 6–8 mg of the opioid, even though the syringe only contained saline with no psychoactive ingredients. Many other studies over the past decade have shown that “priming” patients for a certain effect from a “medicine” can stimulate either endogenous opioid receptors (producing a sedative effect) or CB1 receptors (more associated with energizing and neurostimulating effects).
It’s also important to note that the placebo effect is not limited to fake medicines but also applies to real pharmaceuticals and therapy methods. In other words, if a patient believes in a drug’s effectiveness and trusts their doctor, the drug’s healing properties are somewhat enhanced by additional activation of certain receptors, supplementing therapy with endogenous neuromodulators and painkillers. Some doctors note that, in many cases, this belief in a medicine can produce up to twice the healing and pain-relieving effect compared to its “real” activity. This synergy has already been observed with various painkillers like morphine, ketorolac, tramadol, and metamizole. Additionally, up to 25% of the effect of pharmaceutical antidepressants may be linked to the therapeutic property of placebo analgesia.
Other placebo studies show that without the patient’s belief, the effectiveness of real medicine can decrease due to the lack of an analgesic effect. This theory is currently confirmed for painkillers, antidepressants, and sedatives. An experiment at the University of Turin with placebo pills and real Valium (a sedative) showed that patients who believed each pill was a placebo felt no relief from anxiety, even when they took the real drug.
Genetic Mechanisms of the Placebo Effect
Of course, the placebo effect does not work for every patient. Its strength can be influenced by certain genetic factors and the patient’s sex. For example, when expecting a saline injection, male patients regularly show a sharp increase in dopamine production linked to the placebo effect, while women do not show this reaction.
Under certain conditions, placebo analgesia is stronger and more frequent than under others. The lowest placebo effect is seen in patients with severe depression and anhedonia, possibly because they are less susceptible to being “primed” for a medicine’s effect than less emotionally suppressed people. Similarly, placebos rarely work in patients with neurodegenerative disorders like Alzheimer’s disease, since these illnesses directly affect brain areas responsible for hope and positive expectations.
Research into single nucleotide polymorphisms (SNPs) suggests a closer link between CB1 receptor activity and the therapeutic placebo effect than previously thought. According to a 2014 study in the journal “Molecular Psychiatry,” so-called fatty acid amide hydrolases (FAAH)—complex organic enzymes involved in many endocannabinoid system mechanisms—also play a role in activating and modulating the processes that produce placebo analgesia. In simple terms, it’s possible that this class of compounds, which are directly involved in synthesizing anandamide and other endogenous cannabinoids, also has variants that can stimulate serotonin and cannabinoid receptors when a placebo is taken.
Later, a team from the University of Michigan found that a missense mutation in the gene encoding FAAH compounds is responsible for the manifestation of placebo analgesia. This mutation makes the body’s receptors that release anandamide and other neuromodulators more active and sensitive to stress from external or internal factors, while suppressing the release of FAAH molecules responsible for metabolizing these endocannabinoids. In other words, this mutation can enhance the natural placebo effect, as the body will process a higher concentration of endogenous painkillers and modulators more slowly.
The Negative Impact of Negative Thinking
Some readers may wonder: “If positive thinking about a ‘medicine’ can greatly enhance its real therapeutic effect, does the opposite phenomenon exist—where pessimism weakens the qualities of real medicine or therapy?” In short, yes. This “opposite” effect is known as the “nocebo” effect, and available data show it is indeed linked to a negative psychological attitude toward treatment effectiveness.
Unfortunately, this phenomenon is seen in medicine almost as often as placebo analgesia. The previously mentioned Italian research group led by Dr. Benedetti, while studying placebo mechanisms, also investigated the nocebo effect. They found that this effect, associated with negative thinking, physiologically manifests as increased levels of prostaglandins—molecules responsible for stimulating inflammatory responses in body tissues. Both psychological effects use the same neural pathways, but while the positive placebo effect suppresses prostaglandin production, the nocebo effect increases it.
The most vivid example of the nocebo effect is chemotherapy—specifically, the strong pessimism and fear patients feel about this cancer treatment, expecting prolonged discomfort and severe nausea from the toxins. Doctors note that nausea and vomiting usually occur in patients who have already undergone several rounds of therapy, as their experience and anticipation of repetition trigger a negative psychological reaction, making the body more sensitive to treatment stress. For this reason, oncologists always recommend starting anti-nausea medications, including MJ or its extracts, during the first therapy session to reduce the negative impact of the nocebo effect later on.
Researchers at the University of Guelph, Canada, report that THC, CBD, and CBC are highly effective in suppressing nausea caused by the nocebo effect, thanks to their ability to reduce stress and panic in patients. These findings have been confirmed not only in animals but also in human volunteers, who report that the overall toning effect of MJ on the body and mind significantly reduces discomfort during chemotherapy sessions.
Placebo: Obstacle or New Opportunity for Medicine?
Unfortunately, as practical experience and many studies by doctors and psychologists show, the placebo/nocebo effect can be extremely unpredictable and uncontrollable. Sometimes, simply being around friends and family or eating favorite foods can improve a patient’s mood before therapy, thereby increasing its effectiveness. Other times, complications can arise during treatment of a mild illness simply because the patient was in a bad mood or tired. Some doctors even note that just informing a patient about possible side effects of a treatment or medication can psychologically predispose them to experience those complications. For this reason, doctors cannot say with 100% certainty whether the effect of suggestion is a blessing or a curse for modern medicine.
Historically, doctors and scientists have considered these effects to be random and undesirable factors in experiments, statistically distorting drug effectiveness and increasing the risk of unwanted side effects. Many doctors still believe that both placebo and nocebo effects are more of an obstacle in developing and testing new therapies than a natural factor that could be used to improve patient health.
On the other hand, psychologists studying the phenomenon do not deny that the psychological component of medicine and its “healing rituals” are just as important in treating diseases as identifying symptoms and selecting pharmaceuticals. Specialists note that the so-called “distorting” psychological factor often explains why “folk” and “ritual” medicine can be more effective for some people. The power of belief in healing stimulates the brain to produce various substances like dopamine, endorphins, and endogenous cannabinoids, which have many therapeutic and neuromodulating effects. In other words, proponents of using placebos in medicine believe that a positive attitude toward treatment allows the body to produce many healing substances on its own, without needing external agents to activate the cells and receptors that make them.
Finally, it’s important to note that using a placebo does not necessarily mean deceiving the patient. According to Dr. Benedetti, even if patients know or suspect they have taken a placebo, their psychological attitude and belief that the treatment could have a healing effect allow the placebo effect to manifest fully. Overall, the doctor does not recommend that his colleagues completely abandon experimental placebo therapy, and suggests the following guidelines to enhance the overall positive effect of this type of treatment: “Talk about the therapy method in a positive way, avoid listing possible risks; establish personal contact and gain the patient’s trust; support the patient in moments of doubt; respect the patient’s freedom and individuality; and don’t forget the importance of the treatment ritual—show your effort in their healing,” he advises.