Answer: An active placebo is a substance that induces some physiological reaction that is given as a control medication in experiments.
The placebo effect is an often observed phenomenon in human medication pharmacology studies. A person being treated with a substance may often times experience an improvement in their symptoms, even if the substance they are receiving is chemically inert. Often times, the placebo given is simply a starch pill. In order to demonstrate the effectiveness of a new medication, it must be shown that that medicine provides a significant improvement of symptoms compared to the effect of the placebo.
One problem with the standard placebo is that there are no physiological reactions to the placebo, whereas many medical treatments cause some somatic reactions, such as a quickening of heart rate or a dilation of blood vessels. By noticing a lack of physiological effects, a patient undergoing treatment by placebo may be aware that their treatment is an inactive substance.
The way to get around this confound is to administer an active placebo, which is a substance that induces some physiological reaction that is similar to the side effects of the experimental substance being evaluated.
Active placebos are also called a concealed placebo, or an active control substance. In most cases, the active control is chosen because it mimics the side effects without inducing any effect on the intended measure.
Examples of active placebo in neuroscience research
In research studies, especially when psychoactive substances are being tested, good design must include an active placebo group as the comparison.
Active placebos in pain research
Morphine is a potent painkiller. Among the side effects of morphine use are sleepiness and dizziness. In testing its efficacy as a pain killer, an active placebo such as lorazepam (brand name Ativan) may be a more reliable substance better than a starch pill, because lorazepam causes sleepiness and dizziness without affecting pain sensation. Lorazepam is a benzodiazepine drug that interacts with the GABA receptors.
As another example, using opioid analgesics during major surgery carries risks of adverse side effects, such as addiction potential. Different opioid drugs have different properties, which have different risk profiles. When testing between two opioid drugs, it is important to also include a non-opioid pain blocking drug along with the treatment regimen. For example, in the study Duration of postoperative analgesia with Nalbuphine vs Butorphanol as an adjunct to spinal anesthesia for lower limb orthopedic surgeries: A randomized double-blind active control trial, the researchers also gave bupivacaine as the active control. Bupivacaine has a similar mechanism of action as lidocaine; they are both potent voltage-gated sodium channel blocker that prevents the passing of sensory signals towards the central nervous system.
Active placebos in psychedelic research
In the Good Friday Experiment at Marsh chapel, experimenters Timothy Leary and Walter Pahnke from the Harvard Psilocybin Project chose niacin as an active placebo for studying the effects of psilocybin as an entheogen. Niacin can produce similar physiological responses as psilocybin, such as facial flushing, but has no psychological effects. In modern psilocybin administration experiments, another active placebo may be diphenhydramine (brand name Benadryl), which is an antihistamine drug with anticholinergic activity. The drug may produce an increased heart rate, which people may perceive as being due to the psilocybin (Psilocybin for alcohol use disorder: Rationale and design considerations for a randomized controlled trial).