FOCUS Hemp heals

For what? Scientists once bred mice lacking CB1 - one type of receptor for our "inner marijuana". It turned out that rodents modified in this way function worse than the "normal" ones: they have problems with memory, are more prone to diseases and live shorter.

Young mammals get their first dose of cannabinoids right after birth - in their mother's milk. They stimulate appetite in newborns, help them develop the sucking reflex, and at the same time probably relieve the stress of coming into the world. Later, they play an important role in the development of the nervous system, among other things. Even in brains of adult individuals, endocannabinoids control the process of neurogenesis, i.e. creation of new neuron cells, as well as healing of damage, e.g. after a stroke or trauma.

Professor Robert Melamede of the University of Colorado says that the endocannabinoid system is the body's damage-reduction system, a kind of emergency room. It is possible that the "internal cannabis" is necessary for us to maintain so-called homeostasis. If a disturbance occurs, cannabinoids spring into action to restore balance.

What are we missing?

The endocannabinoid system was not discovered until 1990. It was then that it turned out that there are receptors in the human brain to which one of the components of marijuana - tetrahydrocannabinol (THC) - "attaches". Subsequent research showed that our body itself produces chemical compounds with similar effects: anandamide and 2AG. Today we know that there are two types of receptors in our body. CB1 are typical of nerve cells. They can be found in the spinal cord and almost all of the brain. The exception is the brain stem - the part of the brain where, among other things, the centers that control breathing and heart function are located. This is why taking even the largest dose of marijuana is not life-threatening. To put it another way: unlike other psychoactive substances, it is virtually impossible to overdose on marijuana. CB2 receptors, on the other hand, are most commonly found in cells classified as part of the immune system.

It's not hard to imagine what a "dysregulation" of the system that takes care of the balance in such key places can lead to. Scientists have called this clinical endocannabinoid deficiency. Shaped millions of years ago, this system is unable to adapt to the rapid changes occurring in our environment. This condition can cause a multitude of pathologies: from migraines to fibromyalgia, from lack of appetite to glaucoma, from depressive states to irritable bowel syndrome.

This also explains the great popularity of marijuana among patients suffering from chronic conditions such as neuropathic pain, multiple sclerosis, epilepsy, Huntington's or Parkinson's disease. Their bodies lack natural cannabinoids, so they supply it with those derived from cannabis.

For migraines

Increased levels of endocannabinoids (our "internal cannabis") have been found in the brains of people after mechanical head trauma. This is how the body tries to reduce the effects of the injury. Conversely, lower-than-normal levels of these substances have been detected in people suffering from chronic migraines and headaches. Perhaps the cause of these complaints - at least in some of them - is precisely a deficiency of endocannabinoids.

"Regularly taking small doses of marijuana could strengthen our endocannabinoid system," says Dr. Sulak. Researchers believe this reduces the risk of diseases such as stroke, Alzheimer's and Parkinson's.

The question is, would it be safe? To date, there is not a single known case of death that can be directly attributed to marijuana. Something like that cannot be said not only about alcohol, for example, but also about most drugs sold in pharmacies. The problem, however, is that scientists still don't have solid, reliable studies in hand on the long-term effects of marijuana on humans. The data available today often comes from animal experiments, isolated cases, or even outside the scientific world. The people who have used marijuana for many years on their own have mostly used it recreationally, which means in large doses and often in combination with other drugs such as cigarettes, alcohol or "hard" drugs. Thus, it is difficult to determine what the negative effects of plant cannabinoids are.

That such effects exist is virtually certain. Every drug causes some side effects in some patients. There is no reason why it should be any different with marijuana. An example? Marijuana's ability to reduce pain is well known, but in some people it does not work at all, and in some cases it even makes the pain worse. Without solid research, it will be impossible to determine why this is so and how to protect patients from complications. The same is true of the relationship between marijuana and schizophrenia. It is possible that cannabinoid use could trigger mental problems in some people, especially those with a genetic disposition to the disease. However, we still don't know how often this happens.

Herbal prevention?

This is where the controversy comes in, of course. Marijuana is considered a drug in many countries - including Poland. Its production and possession is punishable. Meanwhile, some scientists believe that this plant should even be a dietary supplement.

Many studies have shown that cannabinoids can be a strong antioxidant and anti-inflammatory agent, and their relaxing effect effectively reduces stress. The theory of clinical endocannabinoid deprivation suggests that the use of these substances may have a preventative effect.

The endocannabinoid system

CB1 receptors are found in all nerve cells. They are most abundant in the brain. It is estimated that their concentration is 10-50 times higher than, for example, opioid or dopamine receptors.

Outside the brain, a high concentration of CB1 receptors is found in the spinal cord. They can also be found outside the nervous system, including in the pituitary gland, thyroid gland, liver, muscle tissue and gastrointestinal tract, as well as in cells of the reproductive system. The most important site for CB2 receptors is the immune system. They are in the spleen, tonsils, thymus, and in white blood cells (lymphocytes, leukocytes, macrophages) that travel with the blood. CB2 has also been found in cells of the gastrointestinal tract and peripheral nervous system, as well as in the brain, although in much smaller amounts than CB1. There are also tissues in whose cells both types of receptors are found.

Plant-based versus synthetic

We may be about to find out, however. The pharmaceutical industry - emboldened by relaxed regulations in some countries - is increasingly eager to get involved in marijuana research. And this means that scientists will get more objective, reliable data on how it works.

A pioneer in this area is the British company GW Pharmaceuticals. It was the first to receive a license to legally grow marijuana for research purposes. The result - a drug called Sativex, which went on sale in 2010. It's an orally administered spray containing a marijuana extract with specific purity and parameters. It is currently approved for use in 24 countries (including Poland) as a means of reducing spasticity - muscle stiffness that is a symptom of multiple sclerosis. "This is an example of how patient experience can inspire scientific research. We knew that many multiple sclerosis sufferers were being accused of having marijuana. Patients defended themselves by claiming that they were relieving the symptoms of the disease in this way. And they were right!" - says Stephen Wright of GW Pharmaceuticals. The company is working with market giants Bayer and Novartis to distribute the drug. And it is testing another formulation called Epidiolex to help epilepsy patients.

Other companies are focusing on the individual ingredients found in marijuana. The plant contains as many as 108 different cannabinoids, but only two of them - THC and CBD - have been fairly reliably studied so far. As research with marijuana continues to be hampered, some laboratories are trying to create synthetic equivalents of the natural substances. There are already two such drugs on foreign markets - dronabinol and nabilone. Both reduce nausea that occurs in cancer patients undergoing chemotherapy.

"The therapeutic potential of marijuana, the cannabinoids it contains and synthetic drugs with similar structures is enormous. Equally enormous, though unjustified, is the public fear and resistance to tapping into this inexpensive natural source of potentially wonderful and inexpensive drugs." - believes Professor Jerzy Vetulani from the Institute of Pharmacology of the Polish Academy of Sciences. Unfortunately, as long as fear prevails, official medicine will not reach for new substances. And patients like Jakub will have to treat themselves in secret. Possession of even small amounts of cannabis in Poland can still lead to three years in prison

collaboration: Jan Stradowski