Cannabis and cannabinoids

Content

Introduction

There Cannabis sativa it is a very widespread shrub in areas with a temperate and tropical climate where it can grow spontaneously or be cultivated. From the 17th century to the mid-20th century it was widely used for its textile fiber. From the period of the Maritime Republics to the "advent of coal-fired ships, Italy had with Bologna and Ferrara one of the most important districts for the cultivation of Cannabis sativa, to become the first supplier of its fiber to the British Royal Navy in the era of colonization and the great seafaring conquests.

In the course of the twentieth century, to avoid the improper use of the plant in order to produce drugs, laws were introduced which, in fact, also opposed its widespread industrial use in the first post-war period, both in the textile and paper fields. .

The use of the Cannabis in medicine it has long been debated: in 1850, the substance was part of the British and US Pharmacopoeia and was then removed at the beginning of the twentieth century in favor of safer substances with less risk of being misused.

In Italy, since 2003, the use of the plant, in the form of masterful pharmaceutical preparations, is legal to alleviate the ailments of some serious diseases. However, the therapeutic use continues to be debated as the scientific evidence is extremely fragmented and not comparable data is available.In fact, most of the studies have a small number of people and a series of limitations regarding the method of conducting the studies themselves, such as, for example, the use of products of a different nature (sprays, capsules, decoctions, etc.). ), different routes of administration (and therefore a different absorption in the organism) and an unclear description of the long-term effects due to the lack of subsequent controls in most of them.

The difficulty in studying its therapeutic and toxic effects is also linked to the fact that the plant, used as such, produces a vast and diversified range of substances (almost 750 currently identified), defined secondary metabolites, which do not seem to have a direct function on growth and development but rather have as their main function the defense of the plant from predators and pathogens. More than 65 belong to the cannabinoid family, molecules that act on the human body by mimicking the effects of substances normally produced by the body (endocannabinoids) to adjust numerous functions such as, for example:

  • thought
  • memory
  • concentration
  • sensory perception
  • ache
  • movement
  • perception of time
  • appetite
  • brain development

The number of known substances contained in the Cannabis it is constantly increasing and the effect of some is not yet known.

There Cannabis is a pharmacologically active chemical substance, endowed with psychotropic action, i.e. capable of modifying the psycho-physical state of a person (perception, mood, consciousness, behavior, etc.) and has come to be the most consumed drug in Europe and in the world (more than 183 million adults in 2015).

It is estimated that around 10% of those who use it develop one Cannabis addiction syndrome, characterized by the "inability to stop using it despite the awareness of its negative effects (read the hoax).This proportion rises to 17% in the case of adolescents and to 25-50% if consumed daily.

The effects on mental processes (euphoria, relaxation, sedation), are mainly due to the main one phytocannabinoid present in the Cannabis, the Δ9-tetrahydrocannabinol (THC or Δ9-THC). Other important compounds present in the plant are the cannabinol (CBN) and the cannabidiol (CBD). The latter (CBD) has no psychoactive effects but acts together with THC, on a "wide variety of diseases, including the sense of nausea due to chemotherapy, chronic pain, muscle spasticity that affects people with multiple sclerosis, sleep disturbances, Tourette's syndrome and drastic weight loss in AIDS patients.

Among the psychological and neurological undesirable effects (side effects) that can occur following the intake of Cannabis we find:

  • reduced memory
  • decreased thinking ability and problem solving
  • reduction of reflections
  • impaired coordination of movements
  • alteration of the sense of time
  • altered perception of colors or sounds
  • mood changes
  • hallucinations and psychosis (for high doses)

The ability to drive or use machines may be impaired even 24 hours after smoking.

The long-term duration of the effects on the psycho-physical state of an individual (up to a real reduction in the intelligence quotient) is particularly pronounced if the substance is taken while the brain is developing, as occurs during the " adolescence.

Method of intake and metabolism

There Cannabis when used for narcotic use (also called marijuana if it is the leaves, flowers, stems and seeds that are dried and shredded, hashish if it is the resin, with higher THC content) it is generally smoked, vaporized or ingested.

When inhaled, the substance passes from the airways to the blood and in about 15 minutes reaches the brain where it generates the appearance of physical and psychological effects. They begin to diminish approximately 2-3 hours after consumption but the effects may occasionally persist for 12-24 hours following the slow release of psychoactive substances from the adipose tissue.

When it is ingested, the onset of effect is more delayed (30-90 minutes) and the peak can also occur 3 or 4 hours after taking the drug. This can suggest that you have not taken enough and lead to consuming larger quantities with the consequent onset of intoxication. The effects last 6-8 hours but the consequences on the ability to concentrate can persist much longer.

The masterful preparations of Cannabis for medical use they can be taken as a decoction, oil or inhaled through a special vaporizer.

The elimination of the substance through the urine is very slow, so much so that cannabinoids can be detected (positivity) even after a week of their consumption, in the occasional smoker, and after a month in the chronic consumer.

Mechanism of action

There Cannabis and its derivatives act on the brain and other organs by mimicking the action of substances naturally produced by the organism, the endocannabinoids. Both the latter and cannabis and derivatives are able to influence many physiological processes, including motor control, memory and learning, pain perception, the immune system, regulation of energy balance and certain behaviors such as taking of food.

The effects of the Cannabis on the Central Nervous System and on mental functions are mainly due to the presence of the Δ9-tetrahydrocannabinol (THC, Δ9-THC). The concentration of THC varies a great deal from one strain to another Cannabis depending not only on the type of crop, but also on soil conditions, the presence of contaminants and many other environmental factors. Tetrahydrocannabinol (THC) is responsible for the psychoactive effects of Cannabis thanks to its action on the cannabinoid receptor CB1. Other actions of THC (such as pain relieving, anti-nausea, anti-vomiting, stimulating appetite) also depend on the involvement of other receptors and other targets.

Both the Δ9-tetrahydrocannabinol (THC, Δ9-THC) that the cannabidiol (CBD, another important active substance found in cannabis) they also act on other organs and tissues such as muscles, heart and blood vessels, the gastrointestinal tract, liver, kidneys, skin, immune system and reproductive system.

Effects

There Cannabis produces intense and rapid (acute) effects causing long-term health risks.

In the short term euphoria, uncontrollable laughter, alterations in the notion of time and in the perception of sounds and colors, change in mood, detachment from reality appear. Later, feelings of relaxation, introspective experiences, unnatural sleep appear. remembering or concentrating becomes difficult and the ability to move may also be impaired.In high doses, intense anxiety, depression, hallucinations, delusions and psychosis may occur.

Immediately after its consumption, an increase in heart rate (rapid pulse) and blood pressure appears, which can overload the heart. Some studies also suggest an increased risk of ischemic stroke.

The continued consumption of Cannabis it can damage the ability to coordinate movements, attention, learning ability, memory and reaction time. All of this also occurs in adults but is much more evident and lasting if consumption started in adolescence, when the brain is still developing.The duration of these effects and the possibility that some changes may be permanent are still being studied.

Substance abuse is also associated with the appearance of psychological problems such as anxiety, depression, suicidal thoughts in adolescents or typical disorders of schizophrenia (such as hallucinations and detachment from reality). These disorders can be transient but the Cannabis it can worsen the progress of a mental illness or anticipate its onset in already predisposed people.

The chronic smoker of Cannabis may be prone to many of the same respiratory problems that affect tobacco smokers such as habitual coughing and phlegm production, high frequency of acute respiratory disease, high risk of lung infections and a tendency to suffer from obstruction of the airways . To smoke Cannabis it can also favor the onset of forms of respiratory tract tumors.

Negative effects on fertility have also been documented.

The assumption of Cannabis during pregnancy it can interfere with the normal development of the unborn baby's brain. Children exposed to Cannabis while they are in the maternal uterus, they have an increased risk of suffering from reduced attention, memory and learning ability as well as behavioral problems.

Despite the Cannabis has, in general, the effect of counteracting vomiting, the cannabinoid hyperemetic syndrome characterized by repeated vomiting, nausea and abdominal pain, ailments that can be relieved by hot showers and baths and that are resolved by stopping the consumption of Cannabis.

THE withdrawal disorders they are frequent and precocious in habitual consumers (read the Bufala).They include anxiety, irritability, depression, restlessness, insomnia, loss of appetite, nausea and vomiting but also convulsions, palpitations, feeling of difficulty in breathing, chest pain, headache and heavy sweating may occur. Psychic disorders usually prevail. with a maximum intensity of 2 to 6 days after the last intake, and a duration of approximately 2 or 3 weeks.

Cannabis for medical use

Since 2006 in Italy, doctors have been able to prescribe preparations based on Cannabis for medical use. These preparations, called magistral, can be prepared by the pharmacist using the active substance obtained from the inflorescences of the Cannabis (grown with permission from a state organization for Cannabis), dried and ground, to be taken in the form of a decoction or by inhalation with a special vaporizer.

Since 2013 in Italy a product registered as a medicine based on extracts of Cannabis to reduce painful spasms in multiple sclerosis.

From 9 November 2015 (GU General Series n.279 of 30-11-2015) the Ministry of Health has issued a decree regulating national production and preparations of vegetable origin based on Cannabis with a THC percentage higher than 0.2%.

Since 2016, Italy has therefore started a national production of Cannabis for medical use at the Military Pharmaceutical Chemical Plant of Florence (SCFM), thanks to the collaboration between the Ministry of Health and the Ministry of Defense, in order to guarantee access to such therapies at adequate costs and in a safe way. matter (referred to as FM-2) is the first active substance based on Cannabis produced in compliance with the European directives on medicines (EU - GMP) on a production process, deposited and controlled, in a pharmaceutical workshop authorized by the AIFA and whose distribution is authorized by the state body for the Cannabis at the Ministry of Health. Since July 2018, the FM-1 cannabis variety has also been available, which contains different amounts of active ingredients.

Other medicines based on are also available Cannabis marketed in other states. To order these medicinal specialties from abroad, the procedure required by art. 2 of the Ministerial Decree 11-2-1997 In particular, products authorized by the Dutch Ministry of Health, Welfare and Sport (Bedrocan, Bedrobinol, Bediol, Bedica and Bedrolite) are imported into Italy.

In consideration of the scientific evidence produced up to now and updated every two years, it can be stated that the "medical use of Cannabis it cannot be considered a therapy proper, but a symptomatic supportive treatment to the standard ones where the latter have not produced the desired effects, have caused intolerable side effects, require dose increases that could lead to the onset of undesirable effects (effects collateral).

The uses of Cannabis for medical use concern:

  • pain relief (analgesia), in diseases involving spasticity associated with pain resistant to conventional therapies such as multiple sclerosis or spinal cord injury
  • analgesia in chronic pain, with particular reference to neurogenic pain
  • anti-nausea and anti-vomiting effect, which cannot be achieved with traditional treatments in chemotherapy, radiotherapy and HIV therapies
  • stimulating effect on appetite, which cannot be obtained with traditional treatments, in physical wasting and loss of appetite in cancer patients or AIDS patients, in anorexia and anorexia nervosa and in glaucoma resistant to conventional therapies
  • reduction of involuntary movements of the body and face, which cannot be achieved with traditional treatments in Gilles de la Tourette syndrome

In the United States of America (USA), two drugs based on Cannabis. One of them is used for weight loss and appetite loss in people with AIDS as well as in the treatment of unresponsive nausea and vomiting in cancer patients receiving chemotherapy; the second is used for severe forms of epilepsy linked to Lennox-Gastaut and Dravet syndrome. The latter is currently under review by the European Medicines Agency (EMA) and is expected to be distributed in Europe from 2019.

Bibliography

Cartabellotta A, Iacono C. Therapeutic use of cannabis in chronic pain: efficacy and adverse effects. Evidence. 2017; 9: 1-12

Pacifici R, Marchei E, Salvatore F, Guandalini L, Busardò FP, Pichini S. Evaluation of long-term stability of cannabinoids in standardized preparations of cannabis flowering tops and cannabis oil by ultra-high-performance liquid chromatography tandem mass spectrometry. [Synthesis] Clinical Chemistry and Laboratory Medicine. 2018; 56: 94-96

Pacifici R, Marchei E, Salvatore F, Guandalini L, Busardò FP, Pichini S. Evaluation of cannabinoids concentration and stability in standardized preparations of cannabis tea and cannabis oil by ultra-high performance liquid chromatography tandem mass spectrometry. [Synthesis] Clinical Chemistry and Laboratory Medicine 2017; 55: 1555-1563

In-depth link

World Health Organization (WHO). Essential Medicine and health products (English)

Ministry of Health. Medical use of cannabis

Presidency of the Council of Ministers, Department of Drug Policies.National Early Warning System. Variants of Cannabis Plants and Damage to Health. Rome, 2014

National Institute on Drug Abuse. Marijuana (English)

National Institute on Drug Abuse. Syntetic Cannabinoids (K2 / Spice) (English)

National Institute on Drug Abuse. Marijuana as Medicine (English)

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