Evaluation Prospectively the Level of Reduction in Cognitive Functions of Cancer Patients Who Are on Active Oncology Treatments and Use Cannabis. The Second Goal is to Identify High-risk Groups for Cognitive Impairment Due to Cannabis Use.
Condition: 1- Cancer Patients During Chemotherapy Treatment; 2- Use of Cannabis Comparing to Control Without Cannabis Use
MeSH terms: Marijuana Abuse; Cognitive Dysfunction
Study type: Interventional

Summary: 
      Cannabis sativa is one of the most ancient psychotropic drugs known to humanity. Although
      most Western countries have outlawed the use of cannabis according to the UN Convention of
      Psychotropic Substances, an increasing number of states in the USA, Canada and several
      European countries allow the medicinal use of cannabis subject to a doctor's recommendation.
      In oncology, the beneficial effects of treatment with the plant or treatment with medicine
      produced from its components are related to symptoms of the disease: pain, nausea and
      vomiting, loss of appetite and weight loss. There is only partial clinical evidence of the
      efficacy of cannabis for these indications. In Israel, according to Ministry of Health
      regulations, permission to use medicinal cannabis for oncology patients can be given for two
      indications: to relieve disease-related symptoms in advanced disease or during chemotherapy
      treatment to reduce side effects. The indications are very wide and allow a great deal of
      freedom for the physician's decisions, but also cause high demands for cannabis from
      patients.

      The cannabis plant and the synthetic drugs based on the plant are considered to be medically
      safe. Most of the adverse effects are related to the fact that the plant and the drugs are
      psychoactive. Among the effects named were dizziness, euphoria, difficulty concentrating,
      disturbances in thinking, memory loss, and loss of coordination.

      Recently, we published the results of a prospective, observational study evaluating the
      medical necessity for medicinal cannabis treatment in cancer patients on supportive or
      palliative care. No significant side effects, except for memory lessening in patients with
      prolonged cannabis use (p=0.002), were noted.

      Chemotherapy-related cognitive impairment (CRCI) is a phenomenon of cognitive decline that
      patients may experience during or after chemotherapy. Memory loss and lack of concentration
      and attention are the most frequent symptoms encountered. Evidence suggests that CRCI is of
      significant concern to patients and has become a major quality-of-life issue for survivors,
      with estimates of its frequency ranging from 14-85% of patients. The influence of cannabis
      use on cognitive functions of oncology patients has never been tested. Theoretically, the
      combination of chemotherapy and cannabis can cause severe reduction in cognitive functions in
      additive or synergistic ways. However, this hypothesis, too, has never been tested, although
      the number of patients using cannabis during chemotherapy treatments in Israel and in other
      Western countries is growing.

      Goals of current research: The main goal of the study is to evaluate prospectively the level
      of reduction in cognitive function of cancer patients who are on active oncology treatments
      and use cannabis, comparing to a group of patients without cannabis treatment. The second
      goal is to identify high-risk groups for cognitive impairment due to cannabis use.

      Patients and Methods: The study will be comprised of a cannabis user group that will include
      patients who will come for guidance sessions before being issued with a cannabis license and
      a control group of patients on active oncology treatments, meeting the same inclusion and
      exclusion criteria (except for cannabis use), and willing to complete the same pack of
      questionnaires and cognitive tests at the same three time points. All patients will sign an
      informed consent form. The study includes questionnaires on quality of life (EORTC-Q30),
      anxiety, depression (HADS) and fatigue (BFI), and cognitive tests (MoCA, DSST, Digital Finger
      Tapping) administered by the nurses who give guidance on cannabis according to the patient's
      language (Hebrew, Russian or Arabic). The nurses will have a short guidance course on "how to
      do cognitive tests" and a monthly meeting with a neuropsychologist to test the quality of the
      cognitive tests. The questionnaires and cognitive tests will be done on the day of entering
      the study (T0) and after 3 (T3) and 6 months (T6). The patients will be asked not to use
      cannabis in the 12 hours before the interviews after 3 and 6 months.

      Sample size: The sample size was built to show a difference of 1.1 points in the MoCA test
      (half the SD for the normal population) between two groups after three months of cannabis
      use. The number of patients needed with a power of 80%, β≤0.05 and SD=3.1 (the SD for mild
      cognitive impairment in the MoCA test) is calculated at 42 patients in each group (total 84
      patients). Due to an expected drop-out of 20%, the number of patients to be included in the
      study is 101.
    

Detailed description: 
      Cannabis sativa is one of the most ancient psychotropic drugs known to humanity. Evidence of
      the use of cannabis for medicinal and ceremonial purposes goes back 4000 years. In 1854, the
      plant appeared in the United States Dispensatory and was sold freely in pharmacies in Western
      countries. It also appeared in the British Pharmacopoeia as an extract and tincture for over
      100 years. In 1942, cannabis was removed from the United States Pharmacopoeia and, with that,
      its legal medicinal use was stopped. Only in 1971 did Britain and most of the European
      countries outlaw the use of cannabis according to the UN Convention of Psychotropic
      Substances [1]. Regardless, a rising number of states in the USA, Canada and several European
      countries allow medicinal use of cannabis subject to a doctor's recommendation. Along with
      the popularity of the cannabis plant as an effective treatment for disease symptoms in
      oncology patients and for various medicinal indications unrelated to cancer patients, there
      is growing evidence to demonstrate interest in the use of cannabinoids in medicine, although
      high quality studies are still missing. In oncology, the beneficial effects of treatment with
      the plant, or treatment with medicine produced from its components, are related to symptoms
      of the disease: pain, nausea and vomiting, loss of appetite and weight loss. The clinical
      evidence of the efficacy of cannabis for these indications is only partial. Improvement in
      mood swings and sleep disorders has also been reported, although these were not goals of the
      research [2].

      There is a basic difficulty in conducting randomized, double-blind statistical power research
      in products that are extracted from plants. This difficulty arises from the lack of a driving
      economic source and from difficulty in reaching set standards regarding the product and its
      quality over time, the method of consumption, and the diversity of the population. In Israel,
      according to Ministry of Health regulations, permission to use medicinal cannabis for
      oncology patients can be given for two indications: to relieve disease-related symptoms in
      advanced disease or during chemotherapy treatment in order to reduce side effects. The
      indications are very wide and allow a great deal of freedom for the physician's decisions,
      but also cause high demands for cannabis from patients.

      The cannabis plant and the synthetic drugs based on the plant are considered to be medically
      safe. The main reason for this is the lack of cannabis receptors in the brain stem, a fact
      that prevents life-threatening side effects which exist, for example, in morphine-based
      drugs. The side effects can be divided into acute and chronic, and are a result of prolonged
      use of cannabis. As cannabinoid receptors are present in other tissues throughout the body,
      adverse effects include redness of the eyes, tachycardia, bronchodilation, muscle relaxation,
      and decreased gastrointestinal motility [3]. Most of the adverse effects are related to the
      fact that the plant and the drugs are psychoactive, mostly depending on their concentration
      and on the THC dosage. Among the effects named were dizziness, euphoria, difficulty
      concentrating, disturbances in thinking, memory loss, and loss of coordination [4].

      Recently, we published the results of a prospective, observational study evaluating the
      medical necessity for medicinal cannabis treatment in cancer patients on supportive or
      palliative care. Of the 211 patients who had a first interview, only 131 had the second
      interview, 25 of whom stopped treatment after less than a week. All cancer- or anti-cancer
      treatment-related symptoms showed significant improvement (p<0.001). No significant side
      effects, except for memory lessening in patients with prolonged cannabis use (p=0.002), were
      noted [5].

      Chemotherapy-related cognitive impairment (CRCI) is a phenomenon of cognitive decline that
      patients may experience during or after chemotherapy [6]. Memory loss and lack of
      concentration and attention are the most frequent symptoms encountered [7]. Other complaints
      include difficulties with multi-tasking, organizing and planning, as well as difficulty in
      thinking and other subtle cognitive changes [8]. CRCI is now one of the most common
      post-treatment symptoms reported by breast cancer survivors and may also represent the most
      troublesome symptom [9]. Evidence suggests that CRCI is of significant concern to patients
      and has become a major quality-of-life issue for survivors, and estimates of its frequency
      range from 14% to 85% of patients [10]. For some cancer survivors, the cognitive effects of
      chemotherapy linger on for years after treatment, and even mild impairment may impact the
      survivors' ability to function, both at home and at work [9,10].

      The influences of cannabis use on cognitive functions of oncology patients have never been
      tested. Theoretically, the combination of chemotherapy and cannabis can cause severe
      reduction in cognitive functions in additive or synergistic ways. However, this hypothesis
      has never been tested, although the number of patients using cannabis during chemotherapy
      treatments in Israel and in other Western countries is growing.
    

Intervention name(s): cannabis
Intervention type(s): Drug
Intervention description(s): use of cannabis oil or cigarets
Other intervention name(s): use of cannabis oil or cigarets
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other