Nowadays, the use of medical cannabis is already a reality. For some diseases, such as epilepsy and autism, it is considered one of the first-line treatments, being extremely safe and effective. Based on this scenario, its use for other pathological conditions has been studied [1].

Patients in palliative care are terminally ill, in which the cure can no longer be met. Therefore, the main objective of medical teams should provide the best possible quality of life [2]. They need to deal with an extensive debilitating number of symptoms, such as pain, nausea, vomiting, anorexia, and depression [3].

A portion of these symptoms can be aggravated or worsened by treatments and medicines used such as chemotherapies, prolonged use of high opioids, neuroleptic agents, benzodiazepines, and certain antiemetic substances doses [3] [4], which promote neurotoxicity and bad side effects.

In this scenario, medical cannabis is a possible treatment. It can be used in a complementary way to traditional practices already applied to patients or alternatives, being used only the plant substances [5].

The results for the improvement of symptoms and the quality of life of palliative patients is excellent, with an improvement in adverse effects, anxiolytic, antitumor, antiemetic and analgesic with synergism with opioids, actions, increased appetite, improved sleep, and significant reduction of the drug load of these patients [2] [3] [6] [7] [8] [9].

However, cannabis administration involves numerous variables, such as composition, form, possibility of acquisition, drug interaction management [1] and socioeconomic and political issues surrounding cannabis spp. Thus, this review seeks knowledge on the subject and determination as a search for the area.

Understand the endocannabinoid system and its influence on different physiological systems. From this, understand the most prevalent complaints of patients in palliative care and, thus, the feasibility and benefits of using medical cannabis for this group.

Data Sources and Search Strategy

This systematic literature review adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) recommendations and assesses the use of medicinal cannabis for palliative care patients.

A broad electronic search was performed using the Virtual Health Library (VHL), which included Lilacs, SciELO, Medline, PubMed, and Cochrane, using the descriptors: Cancer, Cannabis and Palliative Care. These search terms were used individually and in varying combinations.

To ensure the contemporary relevance of the data, the search was limited to articles written in English and Portuguese, published between the years 2013 and 2022.

Eligibility Criteria

Initially, 139 articles were found, which underwent a relevance test consisting of the inclusion criteria: 1) Reference to the term medical cannabis; 2) Assessment of palliative patient’s condition and the main factors that worsen their quality of life; 3) Association of cannabis use in this patients profile; 4) publication in selected languages and periods.

After a detailed analysis, 73 articles were excluded due to duplication and failure to present the proposed criteria. After reading the abstracts, 23 articles were excluded for not presenting the full text and the proposed theme; and finally, after reading the articles in full, 19 articles were excluded for not presenting the proposed criteria. Thus, this review is based on the remaining 24 articles that met the pre-established eligibility criteria for the analysis, as shown in (Figure 1).

Data Extraction and Statistical Analysis

Studies that met the inclusion criteria were divided among the authors and data were independently extracted into a standardized spreadsheet. The articles were evaluated by the researchers and any discrepancies were resolved by consensus.

In summary, a narrative synthesis was applied to approach the collected data, and a descriptive statistical analysis was performed using the Office 2021 Excel program for Mac.

After eliminating duplicates and selecting publications, the articles were read in full, from which the parameters proposed in the analytical matrix of the present study were analysed.

This systematic literature review analysed 24 scientific studies that rigorously met the previously established characteristics in the sample selection. Of this total of articles, 3 were quantitative/qualitative studies, 4 were quantitative study and 17 were qualitative.

The synthesis of these selected scientific articles is presented below, converting the following aspects: author/year of publication, article title, objective, type of study and database (Table 1).

Source: Elaborate by the authors.

Patients in palliative care are those with diseases in terminal stages, in which the physician’s role is to manage the symptoms in order to promote a more comfortable death with less suffering. In this way, the focus is on the physical, emotional and psychological aspects that most hinder quality of life [2].

Several treatments are proposed and tested for these patients. However, there are many adverse effects, which makes new approaches to be considered. Complementary or alternative treatments can be performed aiming at the best management of these effects, according to the patient’s conditions [5] [10].

Pain is an important aspect present in most of these individuals, regardless of the disease they have. In order to improve this situation, many opioids are administered, generating several side effects—nausea, vomiting, anorexia, in which more drugs are needed [3].

In this context, medical cannabis gains space. The endocannabinoid system has aroused increasing interest in research. Currently, its ability to modulate the immune, autonomic nervous, gastrointestinal, endocrine and cardiovascular systems is known [11]. Medicinal substances such as terpenes, flavonoids and cannabinoids, more than 140 different ones, the most studied being 9-tetrahydrocannabinol (THC) and cannabidiol (CBD) found in the flowers and bracts of cannabis spp [3] [6] [11] [12].

The endocannabinoid system has CB1 and CB2 as its main receptors and its two most studied neurotransmitters are anandamide (AEA) and 2-arachidonylglycerol (2-AG) [7].

CB1 and CB2 are G protein-coupled receptors that associate with adenylate cyclase and MAPK (mitogen-activated protein kinase). When CB1 activation occurs, some results are observed, such as: decrease in cAMP and, consequently, in PKA; closure of Ca²⁺ and K⁺ channels; stimulation of MAPK (it has effects on synaptic plasticity and cell migration); and influence on the release of neurotransmitters, such as GABA and glutamate—CB1 agonists decrease the release of glutamate, resulting in an increase in dopamine [7].

CB1 is quite present in the brain, especially in sensory and motor regions, indicating its participation in motivation, cognition and pain modulation [3] [7]. CB2, on the other hand, is usually found in cells and tissues of the immune system, especially in microglia.

As for neurotransmitters, AEA is located in the brain and 2-AG in peripheral tissues. When compared with other neurotransmitters, they have some particularities, such as being produced according to demand, not being stored in vesicles [7]. In addition, they act mainly on the presynaptic membrane (after being synthesized in the postsynaptic membrane, they rapidly target receptors on the presynaptic membrane and inhibit both excitatory and inhibitory stimuli) [3] [7].

In this context, THC and CBD, which are derived from cannabis sativa, act on these receptors, triggering the beneficial effects of this process, similar to endocannabinoids. THC is associated with analgesic effects due to its action as an agonist at both CB1 and CB2 receptors [3] [6], and may have different effects depending on the dose [7]. CBD, on the other hand, is more associated with CB2, which explains its atoxicity [13], reduced psychotropic effects of THC [3] [6] and potent anti-inflammatory role [7].

In this scenario, several studies have been carried out to analyze the effects of medical cannabis on the symptoms of palliative patients.

As for pain, the improvement observed in patients is undeniable [1] [2] [3] [6] [8] [9] [11] [14] [15] [16]. Those who have an oncological condition, in which the pain is often mixed, neuropathic and nociceptive, being generated not only by the presence of the tumor, but also by the effects of chemotherapy and radiotherapy [17], an integrative approach becomes essential. According to one study, patients undergoing cancer treatment who used 10 mg of THC experienced pain reduction proportional to 60 mg of codeine and compared to sedation with 120 mg of codeine [3]. This improvement is mostly associated with combating neuropathic pain. In addition, the interaction of cannabinoids with opioids was evaluated, which showed synergistic effects. It has been shown that, with the association, there is a lower risk of tolerance to opioids and, when this already exists, there is the possibility of rekindling previously ineffective opioid analgesia [2].

Another very common symptom in these patients is nausea and vomiting. The positive effect on its improvement has been demonstrated, especially of THC [2] [3] [5] [6] [11] [16] [18]. Cannabinoids have been shown to be more effective than various antiemetics, such as prochlorperazine, metaclopramide, chlorpromazine, thiethylperazine, domperidone, and alizapride [2] [11].

Not restricted to just these occurrences, CBD and THC present good results in cases of anorexia, fatigue and constipation [1] [2] [3] [5] [9] [11] [16] [18] [19], and weight gain was observed in patients who administered 3 mg of THC 1 hour after meals [2] [19]. In addition, its antitumor effect has been verified, mainly for astrocytomas and glioblastomas [2] [6] [16] [18].

However, as already mentioned, the main objective of the physician is to promote the best possible quality of life for these patients. Thus, the psychological aspect cannot be ignored. Given the condition to which they are subjected, in which there are no more technical resources to progress with the treatment, sleep disorders, anxiety and depression are conditions that will be inserted in the context. And cannabis also acts in these aspects [1] [2] [3] [4] [6] [9] [11] [13] [15] [16] [18]. No work was found that elucidated the mechanisms by which cannabinoids improve anxiety and depression, but it is recognized that the endocannabinoid system influences mood regulation, and an improvement in these symptoms is theoretically expected. There is some promising research that demonstrates the positive impact of using CBD on rodents [20]. However, Israeli research has shown that 80% of patients believed that cannabis relieved physical and psychological stresses, improving the way they deal with the situation [18].

From this aspect, it is worth highlighting a point that makes advances involving cannabis very difficult. Marijuana is a drug used for centuries by different peoples, and most of its use is associated with illegality, youth and addiction. However, it is essential to make it clear that plant smoke, often mixed with tobacco and other substances [21], is absolutely different from its medicinal use, in which a strict control of the administered substances is carried out. Thus, there are reliable studies that show the harm associated with the recreational use of cannabis [22], not with its use as a treatment. On the contrary, it is proven that, unlike most drugs, cannabinoids do not have significant side effects, which facilitates adherence and maintenance of treatment [4] [15] [16] [18]. Likewise, much is said about dependence on marijuana smoking, but no study demonstrates that the administration of cannabinoids generates any degree of dependence.

Regarding the supply of cannabis, it can be made in different ways, such as sachets, gels, sprays, oils and tablets [3], presenting different pharmacokinetics depending on the technique applied in the management of the plant [12]. In addition, there can be several combinations, both of THC with CBD, and with conventional treatments. Most of the positive results were due to these associations [9] [13].

In this way, it is remarkable that medical cannabis can bring many beneficial effects to patients in palliative care, greatly improving their quality of life. However, due to the lack of sufficient studies to understand its entire mechanism of action and the effects of the drug interaction with the numerous drugs used by these individuals [16] [23], the administration of cannabis must be done with care. There are studies that argue that its adverse effects are minimal when compared to the improvement of the condition [3] and, especially, of the effects of opioids, and its administration is considered safer [4]. On the other hand, there are studies showing that its use can cause changes in liver function and a possible reduction in the effectiveness of chemotherapy [11], and its use should be restricted to only patients admitted to the hospice [24].

Finally, the lack of regulation of the use of medical cannabis, its substitution of opioids and its use as an alternative treatment rectifies the association of therapy with recreational use, which makes studies difficult and, consequently, the most appropriate prescription [16].

The use of medical cannabis and its action and efficacy under the endocannabinoid system in palliative patients is undeniable. There is a significant improvement in the main debilitating symptoms of these individuals, such as pain, nausea, vomiting, anxiety and depression. However, there are several challenges involved in prescribing this drug. The formulation and the ideal moment to start the association with conventional treatment, as well as doubts about the mechanism of action and the interaction with the various highly toxic therapies used by these individuals are some of the difficulties. Associated with them, beliefs and prejudices still plague people when it comes to cannabis. Due to all this, currently, the use of medical cannabis is still chosen, maintaining conventional treatment—whether chemotherapy or any other medication, with the exception of hospice, where there may be a total replacement, depending on the patient`s condition [24].

In this sense, more double-blind randomized studies are needed to validate the information that has been seen in medical practice. In this way, it will be possible to fully understand its action, which will make your prescription more assertive, improving the quality of life, comfort and treatment offered to patients. By this means, trust and the demystification of the treatment will be gained.

The authors declare no conflicts of interest regarding the publication of this paper.

da Costa, V.F.D.D. and de Carvalho, W.S.R. (2022) Use of Medicinal Cannabis for Palliative Care Patients: A Systematic Review. Journal of Biosciences and Medicines, 10, 242-252. https://doi.org/10.4236/jbm.2022.109017