1- Cancer Patients During Chemotherapy Treatment Clinical Trial
Official title:
Cannabis-related Cognitive Impairment: Prospective Evaluation of Possible Influences in Cancer Patients During Active Oncology Treatment
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.
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.
;