Which pathologies benefit from Medical Cannabis?

• 1. Clinical uses of cm: the recommendations of the ministry of health
• 2. When is therapeutic cannabis refundable?
• 2.1 Multiple sclerosis, spinal cord lesions (pain and muscle spasticity)
• 2.2 Chronic, neurogenic pain (fibromyalgia or other pathologies in which treatment with non-steroid anti-inflammators or with cortisonic drugs or opiids has revened ineffective)
• 2.3 Nausea and vomiting (antikinetotic and antiemetic effect of chemotherapy, radiotherapy, hiv therapies)
• 2.4 Appetite and weight regulation (appetite stimulator in cachexia, anorexia, loss of appetite in oncology patients or with aids and in anorexia nervosa)
• 2.5 Intraocular pressure (hypotensive effect in glaucoma)
• 2.6 Involuntary body and facial movements (in gilles de la tourette syndrome)
• 3. Medical Cannabis in the italian regions
• 4. Cannabis and neurodegenerative diseases
• 5. Cannabis and epilepsy
• 6. Cannabis and eye diseases
• 7. Cannabis in dermatology
• 8. Cannabis and cardiovascular diseases
• 9. Cannabis and metabolic disorders
• 10. Cannabis and gastroinflammatory diseases
• 11. Cannabis and cancer patients
• 12. Cannabis and bone diseases
• 13. Cannabis and sleep disorders
• 14. Psychiatric patients: the pros and cons of cm-based therapy
• 14.1 The cons
• 14.1.1 Schizophrenia
• 14.1.2 Anxiety and depression
• 14.2 The pros
• 14.2.1 Anxiety and post traumatic stress disorder
• 14.2.2 CBD and psychosis
• 15. Diseases and medical cannabis: a final note
• 16. References

 

1. CLINICAL USES OF CM: THE RECOMMENDATIONS OF THE MINISTRY OF HEALTH

The Italian Ministry of Health states that "the medical use of cannabis cannot be considered a therapy as such, but rather a symptomatic treatment".

If we are talking about paid cannabis, Medicinal Cannabis (CM) can be prescribed for any pathology for which there is a minimum of accredited scientific literature.

 

2. WHEN IS THERAPEUTIC CANNABIS REFUNDABLE?

If we talk about cannabis paid for by the Regional Health System (SSR), the answer is "only for the therapeutic indications that the Region has accredited as recognised". Currently the uses (other than therapeutic indications) recognized by the Ministerial Decree 9/11/2015 for the free prescription paid by the SSR are:

• oncological and chronic pain,
• spasticity in multiple sclerosis,
• cachexia (in anorexia, HIV, chemotherapy),
• vomiting and loss of appetite due to chemotherapy,
• glaucoma,
• Tourette syndrome.

The medical use of cannabis in the above-mentioned conditions is recommended only if "Standard treatments have not produced the desired effects, or have caused intolerable side effects, or require dosage increases that could lead to the appearance of side effects."

Currently, each Italian region has independently legislated on the reimbursement of cannabis. For information on the provisions in force in your region, consult the general guide to Medical Cannabis and reimbursement region by region or consult the section How to take it and Laws of Cannabis Science where the legal situation of Medical Cannabis is analyzed region by region.

Let's analyze in more depth the symptoms for which the Ministry approves (and reimburses, through the SSR, in different ways in each region) the use of CM:

 

2.1 MULTIPLE SCLEROSIS, SPINAL CORD LESIONS (PAIN AND MUSCLE SPASTICITY)

As demonstrated by numerous clinical evidence, cannabinoids can help manage the main symptoms of Multiple Sclerosis. [1]

We have explored the topic in depth in a dedicated article: "Cannabis and Multiple Sclerosis: analysis of clinical studies"

In particular, CM is effective in treating:

• bladder incontinence,
• muscle stiffness,
• spasticity,
• chronic and neuropathic pain
• sleep disorders. [2] ; [3] ; [4]

 

2.2 CHRONIC, NEUROGENIC PAIN (FIBROMYALGIA OR OTHER PATHOLOGIES IN WHICH TREATMENT WITH NON-STEROID ANTI-INFLAMMATORS OR WITH CORTISONIC DRUGS OR OPIIDS HAS REVENED INEFFECTIVE)

Cannabis has been used to treat chronic pain for thousands of years. [5] Preclinical evidence obtained from well-characterized animal models with refractory pathological pain indicates that one of the most promising therapeutic uses of phytocannabinoids is as painkillers. [6]
The therapeutic benefit of medical cannabis has mainly been observed in studies on neuropathic pain.
Neuropathic pain is common, difficult to treat, and has limited treatment options. Consequently, even modest effects can be important for patients.

Prof Livio Luongo has explored the topic in depth in this article by him: "Pain and endocannabinoids: a word from the neuropharmacologist"

The main cannabinoids in cannabis are effective against neuropathic pain. Tetrahydrocannabinol (THC) is able to relieve various types of pain, such as diabetic neuropathy [7], while cannabidiol (CBD) prevents the onset of peripheral neuropathies in diabetic patients. [8]

Patient preference studies indicate that the side effects of cannabinoids are better tolerated than opioid-based medications. Additionally, much research shows that even low doses of THC can enhance the analgesic effects of morphine and codeine. A combined therapy of opioids and cannabinoids produces long-term pain-relieving effects, both in acute and chronic pain models, in doses low enough to be free of substantial side effects and thus avoiding inducing those neuronal biochemical changes that would then lead to tolerance. [9] ; [10] ; [11] ; [12]

In contrast, studies measuring the effects of isolated CBD in acute pain (post-operative for example) do not demonstrate beneficial effects. [13] ; [14] CBD is in fact not effective against acute pain but is effective against pathological pain (such as neuropathic pain). CBD has good analgesic activity against inflammatory conditions [15], and can be used medicinally to treat chronic inflammatory and neuropathic pain. [16]

Cannabigerol (CBG) is a minor cannabinoid with analgesic properties against inflammatory pain; it acts by increasing the endocannabinoid tone (decreasing the reuptake of Anandamide, therefore allowing this endocannabinoid to act for longer) and to synergistically increase the pain-relieving effects of THC. [17] ; [18]

These properties are also found in Cannabichromene (CBC), which similarly enhances the pain-relieving effects of THC and blocks the reuptake of Anandamide. [19] ; [20]

 

2.3 NAUSEA AND VOMITING (ANTIKINETOTIC AND ANTIEMETIC EFFECT OF CHEMOTHERAPY, RADIOTHERAPY, HIV THERAPIES)

 Among the first recognized medicinal benefits of cannabis is its usefulness in combating nausea and vomiting.[21]
THC acts effectively against nausea and vomiting in patients undergoing chemotherapy.
CBD, on the other hand, produces biphasic effects (when in isolated form): at low doses it suppresses the vomiting reflex induced by chemotherapy and radiotherapy, but at high doses it does not provide beneficial effects and can aggravate the condition. [22] ; [23] ; [24]

When tested in a combined formulation, THC and CBD (e.g. in the nabiximols spray mixture), reduce the incidence of nausea and vomiting in patients undergoing chemotherapy, compared to those who used a placebo (as demonstrated by a clinical study conducted in a double blind manner). [25]

Other non-psychotropic phytocannabinoids such as CBDA, THCA, THCV, CBDV and CBG are also effective in producing similar antiemetic effects. [21]

 

2.4 APPETITE AND WEIGHT REGULATION (APPETITE STIMULATOR IN CACHEXIA, ANOREXIA, LOSS OF APPETITE IN ONCOLOGY PATIENTS OR WITH AIDS AND IN ANOREXIA NERVOSA)

The ability of Cannabis-based preparations to stimulate the appetite, especially for palatable foods, has been documented as far back as 300 BC. [26]

The hyperphagic action of THC (and its degradation product Cannabinol or CBN) is mediated by the stimulation of the cannabinoid CB1 receptors, which promote caloric assimilation by amplifying the pleasure of food, and is revealed in the decrease in the interval time to start a meal. new meal. [27]

In other words, phytocannabinoids, by stimulating the CB1 cannabinoid receptors, generate a series of biochemical changes within our bodies that lead us to remember how good we feel when we eat and, therefore, how interesting it would be not to wait until the next meal, and have a snack beforehand.

Therapeutic appetite stimulation using THC or cannabis has been studied for many decades, especially in relation to cancer-associated cachexia, acquired immunodeficiency syndrome (AIDS), and anorexia nervosa.

Cachexia is a term that derives from the Greek “kakos” (evil) and “hexis” (condition), and describes the progressive loss of adipose tissue and body mass following numerous chronic debilitating pathologies. [27]
Anorexia, on the other hand, is the loss of the desire to eat despite caloric deprivation and, unlike anorexia nervosa, is frequently observed with patients with chronic diseases in advanced states.

It is also possible that patients may lose pleasure or interest in food due to changes in flavor perception generated by chemotherapy, or through the acquisition of taste aversions following nausea or vomiting accompanied by a series of radical treatments. [28] ; [29]
Furthermore, in the elderly, debilitating phenomena are accompanied by a decrease in the perception of taste and smell.

Cannabinoid-based preparations stimulate appetite by increasing the attraction to the pleasure of food, or reducing the negative effects on eating habits caused by other therapeutic interventions. [30]

To delve deeper into the conversation on the regulation of hedonic hunger, you can consult the article written by Dr. Fabio Turco, neuro-gastro-cannabinologist: “The Endocannabinoid System in the Gastrointestinal Tract”

THCV and CBD, on the contrary, have an opposite effect on CB1 receptors, decreasing food consumption.
To treat cachexia or anorexia, preparations that contain both CBD and THC should therefore maintain a higher proportion of THC to allow the activation of CB1 receptors (and not 1:1, as for example in nabiximols).

In the case of anorexia nervosa, it is hypothesized that the Endocannabinoid System is dysregulated and that the use of CBD-based preparations can help reduce the anxiety associated with food consumption itself. [30]

 

2.5 INTRAOCULAR PRESSURE (HYPOTENSIVE EFFECT IN GLAUCOMA)

The treatment of glaucoma represented the first medical use of cannabis since prohibition banned its use worldwide. Already in 1971, a 25-30% decrease in intra-ocular pressure due to smoking cannabis was reported [31], confirmed by other studies on glaucoma patients. [32] Furthermore, numerous studies have documented the neuroprotective properties of cannabinoids towards the retina. [33]

To minimize systemic effects and possible side effects and maximize the dose at the site of action, topical administration into the eye would be ideal for this type of pathology. To obtain this type of preparations, microemulsions and cyclodextrins improve the corneal penetration of cannabinoids, which is one of the major obstacles (being lipophilic molecules, with difficulty in passing the hydrophilic tear film).

 

2.6 INVOLUNTARY BODY AND FACIAL MOVEMENTS (IN GILLES DE LA TOURETTE SYNDROME)

Oral doses of dronabinol (synthetic THC) in patients with Gilles de la Tourette Syndrome have been shown to reduce the frequency of tics over a 6-week period. These results were confirmed by another more recent clinical study. [34]

 

 

 

Numerous evidence, both preclinical and clinical, suggests that, among others, the activation of CB1 receptors contributes to the development of diabetes and its main complications; the use of cannabinoids that activate CB1 receptors (such as THC) should be weighed very carefully in diabetic patients and in complications of diabetes, including neuropathic pain resulting from diabetes. [52]

In contrast, CBD appears to demonstrate excellent therapeutic potential for these pathologies.
CBD has been studied in type I diabetes, showing that it reduces the incidence of autoimmune diabetes. [53] Furthermore, CBD, administered after the onset of the initial symptoms of hereditary diabetes, halts the progression of the disease in non-obese mice. [54]

The researchers also demonstrated that in a model of type II diabetes (induced in animals with a high-fat diet), all control mice developed diabetes in an average of 17 weeks, while most treated with CBD remains free from diabetes until the 26th week; these results coincide with less inflammation in the pancreatic islets that produce insulin and a lower total weight compared to their untreated rodent cousins. [55]

Tetrahydrocannabivarin (THCV), a component of cannabis, by blocking CB1 receptors causes hypophagia while activating CB2 receptors, considered protective for obesity and metabolic diseases. [56] It has in fact been shown that THCV produces an increase in the body's energy expenditure, while reducing glucose intolerance and improving insulin sensitivity. [57]

 

THC has also been shown to attenuate the severity of the immune response and glycemia in type I diabetes (in animals). [58] ; [59]

Similarly, continuous exposure to THC leads to decreased weight, lower food intake, and reduction in fat reserves in animals (during the period of exposure to the drug). [60] In parallel, data collected cross-sectionally in humans for 6 years at the National Health and Nutrition Examination Survey (NHANES), indicate that Cannabis use is associated with a lower prevalence of Diabetes Mellitus compared to the non-user population. [61]

In light of the demonstrated ability of cannabis (used acutely) to induce insulin resistance, taken together the above data may reflect peripheral desensitization of CB1 receptors resulting from chronic cannabis use. [62] A similar mechanism could contribute to the lower prevalence of obesity among cannabis users compared to non-users, an effect that is also found after adjusting the statistical data for tobacco use, gender, age and hereditary family history. . [63]

 

 

Cannabinoids decrease the secretion of gastric acids in animals through the activation of CB1 receptors. [64] This activation is protective in animal models of gastric ulcers induced by aspirin and stress. [65] ; [66]

THC induces a marked reduction in gastric ulcers, without modifying the quiescent production of acid in animals, but only that induced by histamine (pathological). [67]

Furthermore, cannabinoids that activate CB1 receptors decrease gastric, small intestine and colon motility. [68] They also decrease intestinal smooth muscle contractions and peristalsis. [69]

THC and CBN, therefore, decrease the speed of intestinal transit and gastric emptying.

Recently, CBD and CBC, both non-psychotropic molecules, are considered capable of modulating intestinal motility without decreasing transit (like most antidiarrheal agents which can cause constipation) and normalizing it following inflammation, thanks also to their antispasmodic effect. [70]

Both THC, CBD, CBC and CBG have all been shown to provide benefits in so-called Chronic Intestinal Diseases (IBD). [71]

Some clinical trials have evaluated the use of medical cannabis in Crohn's disease with improvements in quality of life, weight gain, ability to work and social interactions, decreased pain and depression. [72]

 

 

Cannabinoids are recognized to exert palliative effects in cancer patients. [73] The major use is in the inhibition of nausea and vomiting induced by chemotherapy and to control pain associated with cancer. Another potential palliative use of cannabinoids in oncology, supported by Phase 3 clinical trials, includes appetite stimulation and decreased debilitation (cachexia). [74]

Apart from these uses, the application of cannabinoids in oncology may not be limited only to the palliative actions mentioned above.

Numerous studies have indicated that THC and other cannabinoids exhibit antitumor effects across a wide range of animal cancer models. [75] These observations led to the development of a pilot clinical trial to investigate the anticancer effects of THC in glioma patients. [76] A combined administration of CBD and THC increases the anti-tumor activity of THC and reduces the doses of THC necessary to induce inhibitory effects on tumor growth. [77] ; [78]

Thus, in animal studies cannabinoids induce tumor cell death and inhibit angiogenesis (aberrant creation of new capillaries that the tumor needs to enlarge and metastasize) and tumor invasion, and there are indications that cannabinoids exert the same effects also on patients with Glioblastoma Multiforme (brain tumor). [74]

 

 

Following the discovery of a skeletal cannabinoid system, much attention from the scientific community has been directed towards this sector. [79]

At the moment, CB2 receptors seem to have the most promising role. CBD (but not THC) appears to improve fracture healing. [80]

In the future, it is hoped that THCV and B-caryophyllene, (the terpene contained in the essential oil of black pepper and, of course, cannabis) both activators of CB2 receptors, can be studied more thoroughly for the treatment of osteoporosis. [81]

 

 

Cannabinoids have a high therapeutic potential for the treatment of insomnia but also drowsiness.
THC induces sleep, while CBD improves sleep in insomniac patients. [82]
In particular, CBD is a factor that promotes awakening, increasing alertness and increasing extracellular levels of dopamine when taken in low doses, but at high doses CBD can block sleep suppression induced by anxiety states (therefore facilitate rest). [83]

Patients suffering from post-traumatic stress (PTSD), fibromyalgia, and chronic pain demonstrate significant improvements in sleep duration and quality when treated with a synthetic drug similar to THC, called nabilone. [84] ; [85]

 

 

It is important to consider that massive use of cannabis in adolescence and young adults is correlated with a double increase in the probability of being diagnosed with psychosis. [87]

The reason why cannabis causes such effects is still a hotly debated topic today. Evidence reports that although the majority of people who consume cannabis do not develop schizophrenia, chronic consumption of THC causes lowering of Anandamide levels and the decrease in this endocannabinoid in the cerebrospinal fluid is directly related to an increased likelihood of psychosis. [88] ; [89] ; [90]

Furthermore, it is likely that young people who make heavy chronic use of cannabis (as opposed to medicinal use) are precisely those who, due to environmental and/or genetic risk factors, are most vulnerable to psychosis, and that this use leads them to suffer their first psychiatric episode approximately two years earlier than if they had not used cannabis. [91]

 

 

There is also evidence that associates chronic cannabis use with changes in mental health and well-being indices. [90]
Meta-analyses have suggested a link between heavy cannabis use and depression, and a direct correlation between THC levels in the hair of young chronic users with levels of anxiety and depression. [ninety two] ; [93]
However, a 2013 epidemiological study suggests that the increase in depression that can occur with improper use of cannabis is not long-term and no real associations have been found between adolescent use and depression in their 30s, if not that the same factors that predispose people to cannabis use may increase the risk for common mental illnesses such as anxiety and depression. [94]

In this regard, it may be interesting to consult the report of a patient who, by adding a direct administration of CBD to her high % THC variety, was able to control the state of anxiety induced by cannabis therapy.

 

 

 

Pazienti che soffrono di stress-post traumatico (PTSD) trovano sollievo dai continui flashback traumatici diurni e dai frequenti incubi notturni quando trattati con il nabilone, un composto sintetico che agisce in maniera simile (ma più potente) al THC, e comunemente usato in medicina come anti-emetico ed analgesico. [95]

Report clinici hanno confermato i benefici della Cannabis proprio nel ridurre la severità dei sintomi del disturbo da Stress Post-Traumatico. In generale, i risultati ottenuti nella pratica clinica sono consistenti con gli studi condotti sugli animali, ove la regolazione del Sistema Endocannabinoide è stata individuata come direttamente collegata all’estinzione delle risposte di paura che seguono esperienze traumatiche. [96]

Infatti, l’attivazione dei recettori CB1 induce l’estinzione delle memorie di traumi/paure, mentre la riduzione dell’attività dei CB1 (per esempio, bloccando tali recettori), previene la possibilità di eliminare comportamenti che riflettono paure condizionate. [97] ; [98] ; [99] ; [100]

Il CBD invece sembrerebbe essere una molecola molto utile come ansiolitico.
Il CBD è un cannabinoide considerato pleiotropico, ovvero che agisce tramite diverse vie, cioè non interagisce con un’unica tipologia di recettori. Molti studi, condotti sia su animali che su umani, hanno dimostrato che il CBD riduce l’ansia tramite l’interazione nel cervello con i recettori della serotonina 5-HT1A, aiutando sia pazienti che soffrono di ansia, sia la popolazione sana sottoposta a stress (ad esempio parlare in pubblico). [101] ; [102]

 

 

 

CBD may attenuate the psychotomimetic effects associated with THC and exert antipsychotic effects. [103] In '95, Zuardi and his collaborators found a significant improvement during treatment with CBD in a young 19-year-old woman who had serious side effects with conventional antipsychotics. No side effects have been reported with CBD.

More recently (in 2006) Zuardi, however, did not find that CBD monotherapy was effective with schizophrenic patients resistant to therapy. [104] ; [105]
CBD therefore appears to have antipsychotic effects in healthy subjects or in patients with non-refractory schizophrenia.

Several clinical studies have compared CBD to atypical antipsychotics and the effects obtained were similar or better for CBD, especially in controlling the "negative" symptoms of schizophrenia (depression, withdrawal into oneself, etc.); CBD has been defined as a safe and tolerable medicine with significantly fewer side effects than traditional drugs used as antipsychotics. [106]

CBD has also demonstrated effectiveness in treating psychotic symptoms associated with Parkinson's disease; in part this may depend on CBD's ability to increase serum Anandamide levels. [107]

CBD demonstrates a similar profile to atypical antipsychotics but its use is associated with fewer side effects. [108]

 

 

 

Dear reader, if you have made it this far I thank you from the bottom of my heart, the time to read seems to get shorter every day in increasingly hectic lives, and I am honored to have had a space in those clippings.

There is a lot that can be written about the interactions of medical cannabis with various different health problems. Above I have chosen to start writing a small guide, which can introduce you to the medicinal (or laboratory) uses of this plant.
Don't blame me if the topics haven't all been particularly in-depth; if I didn't mention uses in oncology outside the brain, and I certainly could have explored the use in heart-related pathologies more (possibly with a pro and con, as in the last chapter).
Realistically, though, I'm just a neuroscientist, and I prefer to leave some fields of medicine to those who know them much better than I do. (If you're the one reading this, send your application as an author here)

I hope you found the necessary information; if not, (I'm not offended) 🙂 just scroll down and you will find an entire library of the original studies used to write this article, which you can click on and read directly from the researchers and remove any doubts about the what and how.

I believe it is important to give you the opportunity to come into direct contact with the source: we are all very tired of the waves of "fake news" and sensationalism that are spreading on the web and in newspapers on medical-scientific topics.
Scientific literature articles, papers, play a very important role in conveying and evaluating medical-scientific information, but, alas, not only are they often quite expensive (making them accessible to the elite), but they use boring words, such as antinociceptive or prodromal, and mostly in English ... the Cannabiscienza articles will not only always be accessible, downloadable and shareable (upon request, if you are a media publisher), but they will contain understandable translations from hard core science to Italian 🙂

 

 

 

16. References

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   Pain, In Handbook of cannabis: Edited by Roger G. Pertwee.
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16. Costa, B., Trovato, A. E., Comelli, F., Giagnoni, G., & Colleoni, M. (2007).
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