Placebo-analgesic Neurotransmitters

The placebo effect caused by pre-administration of different painkillers can be formed with the participation of different neurotransmitters-substances that provide signal transmission between nerve cells. It hides not one, but several different mechanisms that reflect the General principles of the nervous system, but implemented in different ways.

A few years after experiments with stimulation, the main neurotransmitters of this phenomenon were found in laboratory rodents of the Central gray matter. They turned out to be endorphins, enkephalins, and a number of other substances called endogenous opioids. Their molecules have areas similar to those of the plant opioid morphine, so that all these substances can bind to opioid receptors, causing pain relief. Both short-term stress-induced pain relief and longer-term pain relief, which occur in response to almost any pain, are associated with activation of the Central gray matter and occur with the participation of endogenous opioids.

The suggestion that endogenous opioids are involved in the implementation of placebo pain relief was first made in 1978. This idea was suggested by the fact that the placebo effect is blocked by naloxone, a substance that suppresses the action of opioids. Subsequently, the hypothesis was criticized, but in the late 90’s the role of endorphins was confirmed: it was possible, first, to show an increase in their content in the cerebrospinal fluid against the background of the placebo effect, and secondly, to strengthen the placebo effect with the help of proglumid (which blocks cholecystokinin, which in turn blocks endorphins). It was also possible to block the placebo effect by stimulating receptors for cholecystokinin.

Another thing is that the opioid pathway is not the only one. If a patient is given the non-opioid analgesic Ketorolac, the subsequent placebo effect is not blocked by naloxone, which means it is not associated with endogenous opioids. But it is blocked by rimonabant, an inhibitory effect of endogenous cannabinoids. The latter include anandomide, 2-AG and other substances that are chemically similar to plant cannabinoids, which are found, for example, in hemp. Both endogenous and plant cannabinoids activate receptors in the brain’s cannabinoid system that regulate many important functions, such as appetite, memory, and mood. Endocannabinoids affect pain at the level of brain structures responsible for its emotional component.

In countries that allow medical use of cannabis and its products, they have high expectations. In particular, in Canada, an extract of a type Of cannabis sativa has recently entered the market, which is proposed to be used for the treatment of neuropathic pain, which is difficult to treat.

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