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Exploring the Use of Medical Marijuana for Supportive Care of Oncology Patients


Abstract and Figures

Medical marijuana, also known as cannabis, is being sought by patients and survivors to alleviate common symptoms of cancer and its treatments that affect their quality of life. The National Academy of Sciences (2017) reports conclusive or substantial evidence that cannabis is successful in treating chronic cancer pain and chemotherapy-induced nausea and vomiting, moderate evidence that cannabinoids are beneficial for sleep disorders that accompany chronic illnesses, and limited evidence supporting use for appetite stimulation and anxiety. However, due to the fact that cannabis is classified as a Schedule I controlled substance, there is an absence of rigorous, scientific evidence to guide health-care professionals. In addition, the Schedule I designation makes it illegal for health-care professionals in the United States to prescribe, administer, or directly distribute these drugs. Legislation has outpaced research in this area. Therefore, the National Council of State Boards of Nursing (NCSBN) appointed a medical marijuana guideline committee to create guidelines for the nursing care of patients using medical marijuana, marijuana education in nursing programs, and guidelines for advanced practice registered nurses (APRNs) certifying a patient for the use of medical marijuana (The NCSBN Medical Marijuana Guidelines Committee, 2018). Six states/districts authorize APRNs to recommend the use of medical marijuana to patients with qualifying conditions (Kaplan, 2015). As of March 2021, 35 states plus the District of Columbia have authorized the use of medical marijuana (DISA Global Solutions, 2021). Therefore, APRNs will be caring for these patients and need to know the medical, pharmacological, and legal issues surrounding medical cannabis use.
Content may be subject to copyright.
J Adv Pract Oncol
Section Editor: Denice Economou
Exploring the Use of Medical
Marijuana for Supportive Care of
Oncology Patients
From 1Sarasota Memorial Hospital, Sarasota,
Florida; 2Florida State University College of
Medicine, Tallahassee, Florida
Authors’ disclosures of conflicts of interest are
found at the end of this article.
Correspondence to: Deena Damsky Dell, MSN,
APRN, AOCN®, LNC, Sarasota Memorial Hospital,
1700 South Tamiami Trail, Sarasota, FL 34238.
© 2021 Harborside
Medical marijuana, also known as cannabis, is being sought by patients
and survivors to alleviate common symptoms of cancer and its treat-
es (2017) reports conclusive or substantial evidence that cannabis is
successful in treating chronic cancer pain and chemotherapy-induced
nausea and vomiting, moderate evidence that cannabinoids are ben-
eficial for sleep disorders that accompany chronic illnesses, and limited
evidence supporting use for appetite stimulation and anxiety. However,
due to the fact that cannabis is classified as a Schedule I controlled
substance, there is an absence of rigorous, scientific evidence to guide
health-care professionals. In addition, the Schedule I designation makes
it illegal for health-care professionals in the United States to prescribe,
administer, or directly distribute these drugs. Legislation has outpaced
research in this area. Therefore, the National Council of State Boards
of Nursing (NCSBN) appointed a medical marijuana guideline commit-
tee to create guidelines for the nursing care of patients using medical
marijuana, marijuana education in nursing programs, and guidelines for
advanced practice registered nurses (APRNs) certifying a patient for
the use of medical marijuana (The NCSBN Medical Marijuana Guide-
lines Committee, 2018). Six states/districts authorize APRNs to recom-
mend the use of medical marijuana to patients with qualifying condi-
tions (Kaplan, 2015). As of March 2021, 35 states plus the District of
Columbia have authorized the use of medical marijuana (DISA Global
Solutions, 2021). Therefore, APRNs will be caring for these patients and
need to know the medical, pharmacological, and legal issues surround-
ing medical cannabis use.
plaining of increased pain in his spine. He also reports loss of appetite
and a 12-lb weight loss over the past 2 weeks. MR has a history of pros-
J Adv Pract Oncol 2021;12(2):188–201
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189 Vol 12 No 2 Mar 2021
tate cancer metastatic to the bone diagnosed in
2018. He is status post treatment with docetaxel
and intensity-modulated radiation therapy. He
was started on radium-223 dichloride and re-
ceived the fourth of 6 doses 1 month ago. He
is currently on leuprolide and denosumab. His
pain was previously controlled on a 100 µg fen-
tanyl patch with 15 mg oxycodone orally for
breakthrough pain.
In his support group, he heard anecdotal
stories of patients using cannabis to relieve
pain, as well as insomnia, nausea, anxiety, and
loss of appetite, and wants to know if this is an
option for him. He lives in one of the six states
that allow advanced practice registered nurses
(APRNs) to certify patients for use of medical
marijuana. A review is performed of MR’s cur-
rent and past treatments for chronic cancer pain
and anorexia, which are qualifying conditions in
this state. MR does not want more opioids due
to the adverse eects of sedation and constipa-
tion. He previously tried a course of gabapentin
with no relief. He is unable to take nonsteroi-
dal anti-inflammatory drugs due to renal insuf-
ficiency. Acupuncture and meditation provide
only momentary relief.
A clinical assessment reveals no conditions
that would prevent the use of medical marijuana.
MR has no history of alcohol or substance abuse,
psychosis, schizophrenia, or bipolar manic dis-
order. A review of his medications is conducted
to assess for any potential drug interactions. It
is known that medical marijuana is metabolized
by cytochrome P450 (CYP) enzymes, in partic-
ular, CYP3A4, CYP2C19, and CYP2C9 (see Table
1 for drug interactions). Serum drug levels may
increase with concomitant administration of en-
zyme inhibiters and decrease with concomitant
administration of enzyme inducers (MacCallum
& Russo, 2018). None of his cancer drugs are
metabolized by the CYP system. However, can-
nabis does work synergistically with opioids to
decrease pain (Abrams et al., 2011). A dose re-
duction may be possible in the future (The NC-
SBN Medical Marijuana Guidelines Committee,
2018). Also, medical marijuana has an added
central nervous system depressant eect with
benzodiazepines, so his alprazolam dose may
need to be decreased. Following a thorough re-
view, MR is then registered in the state medical
marijuana program for treatment of the chronic
pain of cancer and anorexia.
An assessment of MR’s prior experience with
medical marijuana and a discussion of his prefer-
ences, needs, and knowledge is conducted. MR
reports recreational use of marijuana in the 1970s
but has had no exposure since then. He is open
to smoking flower, vaping, or edibles. There is
no recommended dosage of medical marijuana
since it is not a U.S. Food & Drug Administration
(FDA)-approved drug. In addition, there is a wide
range of medical marijuana concentrations in dif-
ferent products. Based on the assessment and
MR’s desires, a recommendation is made to start
with a low dose and slowly titrate up in order to
Table 1. Drug Interactions
It is possible that THC may decrease serum
concentrations and pharmacologic eect of CYP1A2
substrates such as clozapine, duloxetine, naproxen,
cyclobenzaprine, olanzapine, haloperidol, or
Substrates that are CYP2C9, 2C19, and 3A4 inhibitors
may increase the eects of THC.
CBD may increase serum concentrations
of macrolides, calcium channel blockers,
benzodiazepines, cyclosporine, sildenafil, and
other PDE5 inhibitors, antihistamines, haloperidol,
antiretroviral, and some statins (atorvastatin and
CYP2D6 metabolizes many antidepressants, so
CBD may increase serum concentrations of SSRIs,
tricyclic antidepressants, antipsychotics, beta
blockers, and opioids.
THC and CBD increase warfarin levels.
Cannabis-infused tea has no eect on docetaxel
or irinotecan.
Alcohol may increase THC levels.
Smoked cannabis can decrease theophylline levels.
Smoked cannabis had no eect on indinavir or
CBD increased clobazam levels in children treated
for epilepsy.
Cannabis during treatment with immunotherapy
(nivolumab) decreased response rate but not
progression-free or overall survival in one small
retrospective study.
Note. CYP enzyme interactions occur mostly in the liver
with oral cannabis administration. Smoking or topical
administration of cannabis bypass the liver. Patients
with liver cancer have a greatly reduced ability to
metabolize cannabis. THC = tetrahydrocannabinol; CBD
= cannabidiol; PDE5 = phosphodiesterase type 5; SSRI
= selective serotonin reuptake inhibitors. Information
from Alsherbiny & Li (2019); Government of District of
Columbia Department of Health (2015); Kleckner et al.
(2019); LeClair et al. (2019); Taha et al. (2019).
J Adv Pract Oncol
reach an optimal dose while avoiding undesir-
able side eects (see Table 2 for dosing strate-
gies). The recommendation is to start with a 30
mL sublingual tincture of 1:1 cannabinoid (CBD)
300 mg to delta-9-tetrahydrocannabinol (THC)
300 mg. He is instructed to take 1 to 2 drops in
the morning and evening for 5 days then increase
it to 3 times a day for 5 days. This formulation
provides 0.5 mg of THC and 0.5 mg of CBD per
drop. A 1:1 formulation was chosen because THC
contributes analgesic and anti-inflammatory ef-
fects, while CBD can counteract the psychoac-
tive eects of THC and adds anxiolytic eects
(LeClair et al., 2019). MR can then increase the
dose by 1 to 2 drops every 2 days until he obtains
relief or experiences side eects. This may take
at least 1 to 2 weeks. For sleep, the recommenda-
tion is 1 to 2 pus of THC medical marijuana vape
pen (2 mg per pu) of an indica strain, which can
be repeated if necessary after 15 minutes.
MR is requested to keep a diary of doses
and eects and to set up a follow-up appoint-
ment to monitor his response and any side ef-
fects. Documentation of provider assessment,
including how the patient qualifies for medical
marijuana, goals of treatment, plans to evalu-
ate patient response, and patient education
provided must be done (see Table 3 for patient
resources). MR is cautioned to only buy medi-
cal marijuana at a state-regulated dispensary,
as products from other sources may be diluted
with toxic substances (such as vitamin E ac-
etate), and flower may be contaminated with
fungus or pesticides, which pose a particular
risk to immunocompromised patients.
State-regulated dispensaries should be able
to provide a Certificate of Analysis (CoA), a doc-
ument from a third party that lists the product’s
cannabinoid and terpene profile as well as the
presence of any pesticide, heavy metal, or mi-
crobial contaminant residue. A review of which
dispensaries carry the recommended product
is conducted with MR, as each dispensary car-
ries dierent products. He is also instructed to
include medical marijuana on the list of medica-
tions he provides his health-care providers so
that they can monitor any drug interactions or
adverse eects that may occur. In the case of
MR’s hospitalization, his health-care providers
will need to provide substitutes for symptom
management, as most hospitals do not allow
use on site.
Table 2. Dosing Strategies
Start low and go slow.
Determine delivery system(s). Long-acting oral preparations are best for chronic conditions. However, an immediate
acting preparation should be available for symptom breakthrough relief.
Determine if the patient desires a product rich in CBD, THC, or a more equal ratio.
Caution prior recreational users that THC concentrations in cannabis plants have increased from about 4% in the
early 1990s to more than 15% in 2018.
If a patient is cannabis naive, it is best to start with CBD preparations of 15–20 mg 2 to 3 time a day. If THC is
needed, add in 1.5–2.5 mg increments. THC-dominant preparations should first be used at bedtime to limit adverse
For inhalation, patients should start with 1 pu, wait 10–15 minutes, then increase by 1 pu every 15–30 minutes until
symptom relief is obtained.
If symptom relief is not obtained, adjust the dose up or down in small increments or try a dierent product.
With edibles, it is best to wait until the next day to increase dose to avoid overmedicating.
Cannabis therapeutic doses are individually determined.
Symptom control can be obtained without euphoric eects if desired with the use of CBD to balance THC side
eects, especially for daytime use or the need to drive.
If THC tolerance develops, this can be annulled with a drug vacation of at least 48 hours.
Typical oral dose can range from 2–60 mg per day.
If improvement is not seen after 8–16 weeks, consider stopping treatment or referral to a cannabinoid specialist.
Example of a THC titration regimen
»Days 1–2: 1–2.5 mg once a day at bedtime (consider lower doses in the elderly, children, or those with other
»Days 3–4: If previous dose is well tolerated, increase by 1.25–2.5 mg at bedtime.
»Days 5–6: Increase by 1.25–2.5 mg at bedtime and initiate daytime doses.
»Increase as needed to a maximum of 15 mg in divided doses every 2 days until relief is obtained or side eects are
not tolerated.
Note. Information from Dolce & Chin (2018); Kleckner et al. (2019); MacCallum & Russo (2018); NIDA (2020).
191 Vol 12 No 2 Mar 2021
The term medical marijuana refers to the
leaves or flowers of the Cannabis sativa
plant. The words marijuana and can-
nabis are often used interchangeably.
Marijuana was in fact listed in the US Dispensary
from 1850 to 1924 (Ryan & Sharts-Harpko, 2017).
It was used to treat a variety of illness, including
asthma, anorexia, insomnia, seizures, nausea and
vomiting, and sexual dysfunction. At the end of al-
cohol prohibition, the Marihuana Tax Act of 1937
was passed. Under this act, importation, cultiva-
tion, possession, or distribution was regulated, and
importers were required to pay an annual tax. The
act was opposed by the American Medical Asso-
ciation. Marijuana was ocially removed from the
United States Pharmacopoeia in 1942. The Con-
trolled Substances Act of 1970 classified marijuana
as a Schedule I controlled substance (Bridgeman &
Abazia, 2017; Ryan & Sharts-Hopko, 2017; The NC-
SBN Medical Marijuana Guidelines Committee,
2018). The classification not only prevents health-
care providers from prescribing medical mari-
juana, but it also makes research very challenging.
Additionally, many studies are small, retrospec-
tive, lack a control group, use a comparator that is
no longer a standard treatment, and incorporate a
variety of synthetic and plant-based products.
Marijuana was first legalized for medical use
by the voters in California in 1996. The federal
government opposed this proposition and threat-
ened to revoke the privileges of anyone who pre-
scribed it. In 2000, a group of physicians chal-
lenged this policy and the United States District
Court made the decision to allow physicians to
recommend, but not prescribe, medical marijua-
na (The NCSBN Medical Marijuana Guidelines
Committee, 2018).
To this day, the use of medical marijuana, even
through authorized state medical marijuana pro-
grams (MMPs), conflicts with federal law. The fed-
eral government has issued position papers from
the Department of Justice (DOJ) on prosecuting
people who recommend or use medical marijua-
na for medical purposes in compliance with state
laws. These position papers change with each ad-
ministration. Under Obama, the Cole Memo (2014)
discouraged federal prosecutors from prosecuting
those in compliance under local law. However, this
guidance was rescinded in 2018 with the Trump ad-
ministration when the DOJ suggested the prosecu-
tion weigh all relevant considerations including im-
pact of the crime on the community when deciding
whom to prosecute (Sessions, 2018; The NCSBN
Medical Marijuana Guidelines Committee, 2018).
What Are Medical Marijuana Programs?
Medical marijuana programs provide the specif-
ics of each state’s medical marijuana legislation.
Since all MMPs dier, APRNs need to know ex-
actly what their state laws say. (Links to the leg-
islation of each state can be found at
aspx.) However, the state laws share some com-
mon features (Kaplan, 2015; The NCSBN Medical
Marijuana Guidelines Committee, 2018):
A definition of which health-care providers
may authorize patients to use marijuana as
well as specific courses or training required.
A list of qualifying conditions. Often, the
conditions must be deemed terminal, de-
bilitating, and/or not relieved by standard
A definition of the required type of provid-
er-patient relationship. Some states require
a previous relationship to be up to 6 months.
Table 3. Patient Resources
Name Link
National Cancer Institute
National Center for Complementary and
Integrative Health
Americans for Safe Access
National Institute on Drug Abuse
Neurology of Cannabis
J Adv Pract Oncol
Forms of marijuana permitted and any limi-
tations on the amount that can distributed.
How patients with a certified condition can
be registered with the MMP.
Rules regarding designated caregivers.
Legal protections for patients, designated
caregivers, and health-care providers.
The Endocannabinoid System
The endocannabinoid system (ECS) consists of
endocannabinoids (eCBs), cannabinoid receptors,
endogenous ligands, and enzymes used for their
production and degradation. eCBs are also referred
to as endogenous cannabinoids. Arachidonoyl-
ethanolamide (AEA), also known as anandamide
(named after the Sanskrit word for bliss), and 2-ar-
achidonoylglycerol (2-AG) are eCBs produced by
both humans and animals (except for insects). They
are lipophilic molecules synthesized mainly in the
postsynaptic membranes of the brain. They serve as
primary messengers across nerve synapses and are
synthesized on demand (Bridgeman & Abazia, 2017;
Di Marzo et al., 1998; Nahtigal et al., 2016; Pacher et
al., 2020; Sarfaraz et al., 2008; see Figure 1).
Two endogenous cannabinoid receptors have
been identified: CB1 and CB2. The CB1 recep-
tors are found mostly in the brain (specifically the
basal ganglia and limbic system but also the hip-
pocampus and cerebellum), peripheral nervous
system, as well as in the liver, stomach, heart, and
in male and female reproductive systems. Notably,
they do not exist in the brain stem area controlling
respiration, so lethal overdoses due to respiratory
depression do not occur.
The CB2 receptors are found mostly in the im-
mune system, particularly the spleen. Simulation
of eCBs is thought to promote homeostasis of five
key functions: eating, sleeping, relaxing, forget-
ting, and protecting (Bridgeman & Abazia, 2017;
Di Marzo et al., 1998; Nahtigal et al., 2016; Pacher
et al., 2020; Sarfaraz et al., 2008).
Phytocannabinoids are plant-derived can-
nabinoids such as THC and CBD and are found
in the marijuana plant Cannabis sativa L. More
than 140 cannabinoids have been isolated, and
there are thousands of medical marijuana strains
referred to as “chemovars.” Each chemovar has
varying concentrations of cannabinoids and oth-
er components. THC is the primary cannabinoid
responsible for the psychotropic and intoxicat-
ing effects of medical marijuana. THC-domi-
nant sativa strains produce uplifting, energizing
cerebral effects; THC-dominant indica strains
have sedating, relaxing cerebral effects; and hy-
brid chemovars fall in between. CBD has mild
mood-altering psychotropic activity but does
not cause intoxication. CBD binds to receptors
adjacent to THC, thus modulating its effects. To
take advantage of this, medicinal preparation
with specific CBD to THC ratios are produced
by licensed companies and medical marijuana
growers. Other phytocannabinoids, including
cannabinol (CBN), cannabigerol (CBG), and
cannabichromene (CBC), also appear to have
biological effects and are being investigated for
therapeutic use. Additionally, more than 200
terpenoids or terpenes have been found in spe-
cialized structures called trichomes, which are
epidermal projections on the medical marijuana
plant. Terpenes are the main component of the
essential oils of plants and flowers. They work
synergistically with cannabinoids, creating what
is referred to as the “entourage effect.” This re-
fers to the idea that plants as a whole can be bet-
ter drugs than individual compounds derived
from them. Some terpenes found in many medi-
Figure 1. Cannabinoids. Anandamide and 2-AG
are the two major endocannabinoids produced
endogenously in the body. Reprinted with
permission from
193 Vol 12 No 2 Mar 2021
cal marijuana plants are (The NCSBN Medical
Marijuana Guidelines Committee, 2018; Pacher
et al., 2020; Sarfaraz et al., 2008):
Limonene, which has anxiolytic and antide-
pressant eects.
Myrcene, which has anti-inflammatory, an-
algesic, and sedative eects.
α-pinene, which has anti-inflammatory,
antibacterial and bronchodilator eects, as
well as the ability to counteract short-term
memory defects induced by too much THC.
Linalool, which has anxiolytic eects.
β-caryophyllene, which has gastroprotec-
tive and anti-inflammatory eects.
Ocimene, which has possibilities as an an-
Terpinolene which, in preclinical studies,
has potential as an antibiotic and may have
antitumor activity.
Patients who want medical marijuana to treat
a particular condition can utilize the terpene pro-
file in the CoA to aid in finding the right product.
Synthetic cannabinoids are those developed
in the laboratory. Dronabinol (used to treat
chemotherapy-induced nausea and vomiting
[CINV] and decreased appetite) and nabilone
(used to treat severe CINV) are synthetic prepa-
rations of THC.
The cannabidiol oral solution, Epidiolex, is a
purified plant-derived preparation of CBD used
to treat seizures associated with Lennox-Gastaut
syndrome, Dravet syndrome, or tuberous sclerosis
complex in patients who are 1 year old or older.
THC and cannabidiol (Sativex), also a plant-de-
rived preparation, is a CBD to THC 1:1 ratio oral
mucosal spray used for muscle spasms associated
with multiple sclerosis. It is not approved in the
United States (Kleckner et al., 2019).
The pharmacokinetics (PK) of medical marijuana
vary with the method of administration (see Table
4 for a quick guide to PK). The PK of THC in hu-
mans has been evaluated after inhalation (smok-
ing or vaporization) and ingestion. The onset, rate
of absorption, and bioavailability are increased
after inhalation. THC has been detected in the
plasma after the first inhalation, and peak plasma
concentrations are achieved after 5 to 10 min-
utes. Bioavailability of inhaled THC ranges from
2% to 56%. It is thought that up to 50% of the in-
haled dose is lost due to pyrolysis and side stream
smoke. Factors aecting PK of inhaled THC are
the volume of each pu, the duration of time that
the pu is held, and the temperature of the vapor-
izer. Recommended temperatures for vaporizers
range from 350°F to 400°F. Temperatures above
400°F may cause the release of the carcinogenic
agent benzene and other toxins. Duration of action
of inhaled THC is 2 to 4 hours. The rapid action
of inhaled medical marijuana makes it ideal for
acute or episodic symptoms. Chronic use is asso-
ciated with respiratory symptoms such as cough,
phlegm, and bronchitis, but not lung cancer or
chronic obstructive pulmonary disease (COPD)
unless patients also use tobacco (Tashkin, 2013).
It is felt that vaporization produces less harmful
byproducts than smoking and produces decreased
pulmonary symptoms (Bridgeman & Abazia, 2017;
MacCallum & Russo, 2018; Nahtigal et al., 2016;
National Academy of Sciences, 2017). Patients
should wait 10 to 15 minutes between pus to
avoid overconsumption and unwanted eects.
Oral consumption and metabolism of medi-
cal marijuana “edibles” is much slower and less
predictable. The onset of action may be 30 to 90
minutes, with peak levels between 1 to 6 hours and
Table 4. Quick Guide to Pharmacokinetics
smoke or vapor
drops or sprays Capsules/edibles Transdermals Suppositories
Onset 5 sec–10 min 15–45 min 30–90 min 1–15 min 10–15 min
Peak eect 5–10 min 1–2 hr 1–6 hr 90 min 2–8 hr
Duration 2–4 hr 6–8 hr 4–8 hr Up to 48 hr Up to 8 hr
Note Good for acute
symptoms; can
cause bronchial
Good for acute
symptoms; easy
to titrate dose
Good for chronic
conditions; dicult to
titrate dose
Must be placed
1–1.5 in from anal
J Adv Pract Oncol
a duration of 4 to 10 hours. Bioavailability after in-
gestion is 4% to 20%. Oral medical marijuana un-
dergoes significant first-pass hepatic metabolism
by the CYP450 gene where delta-9-THC is con-
verted to 11-hydroxy-THC, which is a longer-last-
ing and more potent cannabinoid. Cannabinoids
are lipophilic so are best absorbed in the presence
of fats, oils, or polar solvents. Therefore, recent
meals may aect absorption. Oral routes are pop-
ular due to convenience, more accurate dosing,
and are good for chronic symptoms; however, they
are more dicult to titrate (Bridgeman & Abazia,
2017; Dolce & Chin, 2018; MacCallum & Russo,
2018; Nahtigal et al., 2016).
Oral mucosal preparations have on onset of 15
to 45 minutes if held sublingually and last 3 to 4
hours; the onset is 90 minutes if swallowed and
lasts 6 to 8 hours. Topical preparations such as
salves are used for local pain such as that from der-
matologic or arthritic conditions and have a vari-
able onset of action and duration. Newer trans-
dermals using nanoparticles or ionized particles
may have enhanced and time-released absorption.
Their onset is usually within 15 minutes and may
last up to 48 hours depending on dose.
A less popular form of medical marijuana is
suppositories. THC-hemisuccinate is the form of
THC that has the best rectal absorption. Supposi-
tories could be helpful for palliative care, patients
who cannot swallow, gastrointestinal illnesses,
and for healing skin damaged by rectal radiation.
Onset of action is about 15 minutes and the eect
may last up to 12 hours (Backes, 2017; Dolce &
Chin, 2018; MacCallum & Russo, 2018; see Table 2
for dosing strategies and Table 4 for a guide to PK).
Adverse Eects of Medical Marijuana
In general, medical marijuana is considered safe
and well tolerated (Bar-Lev Schleider et al., 2018;
Kleckner et al., 2019; MacCallum & Russo, 2018;
Ware al., 2015). An Israeli study of 2,970 cancer
patients found that 30% of patients reported at
least one side eect from medical marijuana at 6
months, but that the side eects were relatively
minor: dizziness, dry mouth, increased appetite,
sleepiness, and psychoactive eects. Most patients
reported fewer side eects as well as less severe
side eects than with their prescription medica-
tions (Bar-Lev Schleider et al., 2018). Ware and
colleagues (2015) prospectively studied safety
issues using a standardized medical marijuana
product (12.5% THC) in patients who did not have
cancer but were being managed in chronic pain
clinics. Patients could choose the route of admin-
istration. The patients were compared with pa-
tients in the same clinics who did not use medi-
cal marijuana and were followed for 1 year. They
found no significant dierence in the occurrence
of serious adverse eects.
Adverse eects are related primarily to THC and
are dose dependent. THC administered with CBD
reduces psychoactive side eects. Side eects of
THC such as fatigue, tachycardia, and dizziness are
often avoidable when the starting dose is low and ti-
tration is slow. Slow titration also decreases the inci-
dence of psychoactive side eects. There have been
no reported deaths due to overdose due to the lack
of CB1 receptors in the cardiorespiratory centers of
the brainstem (MacCallum & Russo, 2018).
The most common adverse eects reported are
drowsiness and fatigue, dizziness, dry mouth, anx-
iety, nausea, cognitive eects (alteration in percep-
tion, time distortion, memory and attention), and
cough or bronchitis if smoked. Euphoria, blurred
vision, and headache are also common. Rare side
eects are orthostatic hypotension, paranoia, tox-
ic psychosis, depression, ataxia, tachycardia, di-
arrhea, and medical marijuana hyperemesis syn-
drome (Kleckner et al., 2019; MacCallum & Russo,
2018). Medical marijuana hyperemesis syndrome
is most often seen in patients under 50 years old
with a long history of marijuana use. These pa-
tients present with severe, cyclic nausea and vom-
iting. Cessation of marijuana, long, hot showers or
baths, and capsaicin applied to the abdomen are
recommended to relieve the symptoms (Lapoint,
2014; The NCSBN Medical Marijuana Guidelines
Committee, 2018). Allergies to cannabis have also
been reported. They are immunoglobulin E (IgE)
mediated and vary depending on the route of ad-
ministration (Kleckner et al., 2019).
Cannabis use disorder (CUD) is a term used
when medical marijuana use leads to significant
impairment or distress. Long-term medical mari-
juana use can lead to addiction; 9% of users are at
risk (The NCSBN Medical Marijuana Guidelines
Committee, 2018). Adolescents are at greater risk,
as are persons with persistent negative emotions
195 Vol 12 No 2 Mar 2021
and psychological distress (The NCSBN Medical
Marijuana Guidelines Committee, 2018). Medical
marijuana withdrawal syndrome is usually seen in
patients with heavy, prolonged use. Symptoms may
include insomnia, lack of appetite, restlessness,
anxiety, irritability, anger, depression, physical
discomfort, and unpleasant dreams (The NCSBN
Medical Marijuana Guidelines Committee, 2018).
Pregnancy, lactation, and psychosis are consid-
ered to be contraindications for cannabis use. Care
should be taken in patients with unstable cardiac
conditions due to tachycardia and possible hypo-
tension. There is no evidence of QTc prolonga-
tion. Medical marijuana use in children and teens
is controversial. There is felt to be an increased
risk of schizophrenia and psychosis-related disor-
ders in those with a predisposition to these disor-
ders. According to the National Institute on Drug
Abuse (NIDA, 2020), people who use marijuana,
especially during adolescence, and carry the AKT
serine/threonine kinase 1 (AKT1) C/C gene vari-
ant or the Val variant of the catechol-O-methyl-
transferase (COMT) gene have an increased risk
of developing psychosis. Marijuana use also seems
to worsen the course of the illness in those who
already have schizophrenia. Additionally, regu-
lar use of medical marijuana under the age of 18
has been associated with lower IQ and changes
in brain regions critical to memory and learning.
In one study of 1,037 persons from birth to age 38,
the frequent use of marijuana starting in adoles-
cents was associated with a loss of an average of
6 to 8 IQ points. There was no decline seen when
use started as an adult (Bridgeman & Abazia, 2017;
Government of District of Columbia Department
of Health, 2015; Meier et al., 2012; The NCSBN
Medical Marijuan Guidelines Committee, 2018).
Smoking as a route of administration should
be avoided in patients with COPD or chronic
bronchitis. Medical marijuana may increase
symptoms of poor balance in patients with dys-
kinetic disorders and thus increase the risk of
falls. Patients should be cautioned not to drive
or operate heavy machinery when using medical
marijuana, as impaired attention and psychomo-
tor performance may occur (Bridgeman & Aba-
zia, 2017; Government of District of Columbia
Department of Health, 2015; National Academy
of Sciences, 2017; The NCSBN Medical Marijuan
Guidelines Committee, 2018).
Lack of high-quality data and randomized con-
trolled trials due to government restrictions has
impeded the accumulation of high-quality evi-
dence. Evidence thus has been derived mostly
from clinical and basic science research. There-
fore, the NCSBN recommends that medical can-
nabis is best used when current first- and second-
line medications or therapies have failed or been
insucient and for patients who might benefit
from complementary use (The NCSBN Medical
Marijuana Guidelines Committee, 2018).
Preclinical research indicates that cannabi-
noids have more anticancer than procancer ef-
fects. Cannabinoids have been shown to inhibit
some cancer cell types by modulating signaling
pathways that lead to cell death and the inhibi-
tion of angiogenesis (Abrams & Guzman, 2014;
Ghasemiesfe et al., 2019). Medical marijuana has
also demonstrated anti-inflammatory and anti-
oxidant eects. A meta-analysis published in 2019
concluded there is low-strength evidence that
regular use of marijuana for 10 years is associated
with the development of testicular germ cell tu-
mors but insucient evidence to associate mari-
juana use with lung, head and neck, oral squa-
mous cell cancers, and lung cancer (Ghasemiesfe
et al., 2019; National Academy of Sciences, 2017).
However, the possibility exists that medical mari-
juana could interact with cancer treatments such
as chemotherapy or immunotherapy (see Table
1 on drug interactions). One small, retrospective
Israeli study of 140 patients on nivolumab for ad-
vanced malignancies showed a reduced response
rate to the immunotherapy (although there was no
change in progression-free or overall survival) in
the 51 patients who used medical marijuana dur-
ing treatment (Taha et al., 2019).
Chronic Pain
Pain is one of the most common symptoms in pa-
tients with cancer and has a negative impact on
patients’ activities of daily living and quality of
J Adv Pract Oncol
life. Pain is reported in up to 60% of patients be-
ing actively treated for cancer and up to 90% of
those with advanced disease (Boland et al., 2020).
There is evidence that cannabis aects both sen-
sation and perception of pain. CB1 receptors are
located on nociceptors, allowing medical mari-
juana to have a direct eect on nociceptors in the
periphery. CB1 and CB2 receptors in the nervous
and immune systems allow for additional modu-
lation of pain sensation (Kleckner et al., 2019).
Additionally, medical marijuana is known to have
a euphoric eect, so it may increase a subjective
sense of well-being that may decrease the percep-
tion of pain.
Various systematic reviews arrive at conflict-
ing opinions on the helpfulness of medical mari-
juana in reducing pain. The National Academy of
Sciences concluded that there is substantial evi-
dence that medical marijuana is an eective treat-
ment for chronic pain in adults (National Academy
of Sciences, 2017). Another systematic review and
meta-analysis of 28 studies using various formu-
lations of medical marijuana demonstrated a non-
significant improvement in pain control (Whiting
et al., 2015). Davis (2016) looked at multiple stud-
ies of low to moderate quality and reported a mod-
est reduction in cancer pain. Ware and colleagues
(2015) compared outcomes for over a year in a
study of 215 patients with chronic noncancer pain
who used a standardized preparation of medical
marijuana administered by whatever route the pa-
tient chose. There was a comparison group of 216
patients with chronic noncancer pain who did not
use medical marijuana. They found a significant
reduction in pain intensity reported on the 0 to
10 numerical rating scale, as well as an improve-
ment in physical function in the medical marijua-
na group but not in the control group. However,
Boland and colleagues (2020) reported in their
systematic review and meta-analysis that the ad-
dition of medical marijuana to opiates in patients
with advanced cancer did not decrease pain.
Two recent studies showed significant relief
in pain. Bar-Lev Schleider and colleagues (2018)
assessed pain intensity and quality of life in more
than 1,000 patients and demonstrated a significant
reduction in pain in those using medical mari-
juana. Prior to use, 52.9% of the patients reported
their pain to be between 8 to 10 on a 0 to 10 pain
scale where 0 is no pain and 10 is intense pain; af-
ter 6 months, only 4.6% of patients reported pain
at this intensity. Patients also said their quality of
life improved; 18.7% reported a good quality of life
before starting medical marijuana, while 69.5%
reported a good quality of life 6 months later (Bar-
Lev Schleider et al., 2018). Another retrospective
study of 244 patients reported a decrease in opioid
use of 64%, less drug-related side eects, and an
improved quality of life (Kleckner et al., 2019).
The exact pathway in which medical mari-
juana acts to relieve the symptoms of chemother-
apy-induced peripheral neuropathy (CIPN) is not
known. However, preclinical studies in rats have
presented evidence that CBD plays a role in reduc-
ing neuropathic pain. Studies in rats have shown
that a CB1/CB2 receptor agonist both reduced
paclitaxel-induced thermal hyperalgesia and tac-
tile allodynia by activating CB1 and CB2 recep-
tors. The same agonist also prevented vincristine-
induced neuropathy (Kleckner et al., 2019).
Placebo-controlled trials in patients with
chronic neuropathic pain from various etiologies
other than cancer have been conducted. Patients
reported that smoking medical marijuana signifi-
cantly decreased neuropathic pain when com-
pared with placebo (Kleckner et al., 2019).
Nausea and Vomiting
Chemotherapy-induced nausea and vomiting is
highly prevalent. Although modern regimens are
eective at preventing vomiting, 40% to 75% of
patients still report nausea when highly or mod-
erately emetogenic chemotherapies are admin-
istered (Bar-Lev Schleider et al., 2018; Kleckner
et al., 2019). Dronabinol and nabilone are FDA-
approved for the treatment of CINV in patients
who have not responded adequately to conven-
tional antiemetic therapy, and the National Com-
prehensive Cancer Network (NCCN) Guidelines
on antiemesis (2020) list dronabinol and nabi-
lone as agents that can be added for breakthrough
treatment of CINV.
It is hypothesized that cannabinoids, specifi-
cally CBD, exert their antiemetic eect through
modulation of the 5-HT3 and 5-HT1A receptors. Ad-
ditionally, cannabinoids modulated the release of
substance P in preclinical studies (Kleckner et al.,
2019). The National Academy of Sciences (2017)
197 Vol 12 No 2 Mar 2021
decided that there is conclusive evidence that
oral cannabinoids are eective antiemetics for the
treatment of CINV (National Academy of Sciences,
2017). In his systematic review, Davis (2016) con-
cluded that nabilone was a better antiemetic than
the older drugs domperidone, chlorperazine, and
alizapride, but noted there were no comparisons
between medical marijuana and the serotonin re-
ceptor antagonists. He also pointed out that there
have been no direct comparisons to olanzapine
and aprepitant, which are both eective drugs for
breakthrough nausea and vomiting. Whiting and
colleagues (2015) assessed 28 studies comparing
medical marijuana with a variety of antiemetics
including ondansetron. They found that the aver-
age number of patients showing a complete nausea
and vomiting response was greater with medical
marijuana than with placebo and that there was a
nonsignificant greater benefit of medical marijua-
na compared with the other active comparators.
There is also evidence that nabilone is somewhat
eective in managing nausea and vomiting related
to radiation therapy and anesthesia after abdomi-
nal surgery (Abrams & Guzman, 2014).
More recent clinical evidence supports pa-
tient claims that cannabis relieves CINV. Bar-Lev
Schleider and colleagues (2018) reported that
1,662 patients in their study used medical mari-
juana (as an oil or flower, capsules, or cigarettes)
for CINV. At 6 months, 36.3% of patients report-
ed no more nausea or vomiting, 54.7% claimed
symptom improvement, and 9% reported no
change (Bar-Lev Schleider et al., 2018). A study
by Reblin and colleagues (2019) looked at medical
marijuana use in patients with gliomas treated at
a comprehensive cancer center in Florida. Thir-
teen patients used medical marijuana (smoked or
ingested THC, CBD only, or THC and CBD oil)
for the treatment of nausea; 12 reported symp-
tom relief and 1 reported no eect (Reblin et al,
2019). A study of patients enrolled in Minnesota’s
medical marijuana program (which allows vapes,
capsules, oral solutions, and topical agents) re-
vealed that 40.5% of patients complaining of
nausea achieved 30% or greater improvement in
symptoms within 4 months and that 49.8% of pa-
tients complaining of vomiting achieved a 30% or
greater improvement of symptoms in 4 months
(Anderson et al., 2019).
The route of delivery must be considered
when using medical marijuana for treating nausea
and vomiting. A nonoral route is preferred so that
the drug has more opportunity to be retained (not
expelled) and to reach the target site.
Anorexia and Decreased Appetite
Anorexia and weight loss in cancer patients lead to
a poorer quality of life and decreased survival. Dys-
geusia is also a common complaint among patients
undergoing chemotherapy as well as those with
advanced cancer. It is possible that CB1 receptors
in the hypothalamus, hindbrain, limbic system, in-
testinal system, and adipose tissue modulate pep-
tides involved in appetite regulation (Kleckner et
al., 2019). Thus, it is possible that medical cannabis
may stimulate the orosensory reward pathway and
increase the enjoyment of food.
The National Academy of Sciences (2017) did
not find enough evidence to support or refute the
use of cannabis as a treatment for decreased ap-
petite or anorexia-cachexia syndrome in cancer
patients. However, they did conclude that there
is limited evidence supporting its use in increas-
ing appetite and decreasing weight loss in patients
with human immunodeficiency virus/acquired im-
munodeficiency syndrome (HIV/AIDS; National
Academy of Sciences, 2017). Davis (2016) reports
two small trials and a small case series with medi-
cal marijuana where appetite was improved and
weight loss was slowed in patients with cancer.
However, a large, randomized trial revealed meges-
trol as superior to dronabinol in increasing appe-
tite (Davis, 2016). There are also animal studies
that show that THC and other cannabinoids stimu-
late appetite and increase food intake. For example,
anandamide enhanced appetite in mice and rats.
However, there is some clinical evidence show-
ing that medical marijuana can help increase ap-
petite and improve dysgeusia in adult cancer pa-
tients. In 2011, Brisbois and colleagues reported on
a randomized trial comparing oral tetrahydrocan-
nabinol to oral placebo. They found the tetrahydro-
cannabinol significantly heightened chemosensory
perception of food resulting in the perception that
food “tasted better.” Also, premeal appetite and
the number of calories eaten as protein increased.
Bar-Lev Schleider and colleagues (2018) reported
that 1,453 patients in their study utilized medical
J Adv Pract Oncol
marijuana for lack of appetite. 25.8% said the symp-
tom disappeared at 6 months, 62.1% reported im-
provement, and 12.1% reported no change (Bar-Lev
Schleider et al., 2018). Reblin and colleagues (2017)
reported on 12 patients who used medical mari-
juana as an appetite stimulant, and all reported
symptom relief. In the Minnesota study by Ander-
son and colleagues (2019), 1,000 patients reported
a lack of appetite, and 38.8% achieved a 30% or
greater improvement in appetite within 4 months
of initiating the use of medical marijuana. In ad-
dition, a randomized study of 47 patients from the
National Cancer Institute of Canada found that, af-
ter 8 weeks, patients who were given nabilone had
a significantly increased caloric intake compared
with those given placebo (Turcot et al., 2018).
Medical marijuana may be a good option for
cancer patients to try, because the recommended
drugs (megestrol acetate, metoclopramide, and
steroids) are only recommended for short-term
use due to side eects. Dronabinol use is not lim-
ited. It is important to note that although medical
marijuana may increase appetite and caloric in-
take, it may not necessarily reverse the cancer ca-
chexia related to energy wasting (Abrams & Guz-
man., 2014; Kleckner et al., 2019).
Sleep Disorders and Fatigue
Sleep disorders (insomnia, dicultly falling and
staying asleep, or unrestful sleep) are complaints
of approximately 80% of patients with cancer. Ad-
ditionally, patients with cancer-related fatigue have
a high incidence of sleep disorders. Animal studies
have shown that endogenous cannabinoids regu-
late the circadian rhythm; for example, there is
evidence in rats that 2-AG level is highest during
the light phase of the dark-light cycle, while AEA is
higher during the dark phase (Kleckner et al., 2019).
There is moderate evidence that medical mar-
ijuana helps sleep disorders due to chronic illness
(National Academy of Sciences, 2017). The evi-
dence that assesses medical marijuana’s eect on
sleep and fatigue derives from studies of patients
with other chronic disorders: irritable bowel dis-
ease, fibromyalgia, Crohn disease, Parkinson dis-
ease, multiple sclerosis, and post-traumatic stress
syndrome. These patients reported less fatigue
and sleep disturbances than patients not using
medical marijuana (Kleckner et al., 2019).
Studies in patients with cancer have evalu-
ated the eect on sleep and fatigue as secondary
outcomes. Turcott and colleagues (2018) studied
the eect of nabilone on appetite in a randomized
controlled trial and found that patients using nabi-
lone reported a significant decrease in insomnia. In
the Bar-Lev Schleider and colleagues study (2018),
2,329 patients used medical marijuana for sleep
problems: The sleep problem went away in only
16.7% of patients, but 70.8% reported improvement,
while 12.3% reported no relief. In the same study,
2,160 patients used medical marijuana for weakness
and fatigue. Only 10.9% reported the symptoms
went away, while 55.9% reported improvement and
33.2% reported no improvement (Bar-Lev Schleider
et al., 2018). In a study by Anderson and colleagues
(2019) in Minnesota, it was reported that of 1,073
patients with disturbed sleep, 41.8% claimed a 30%
or more improvement within the first 4 months.
In this same study, of the 1,113 patients reporting
fatigue, only 27% had an improvement of 30% or
more after 4 months. Reblin and colleagues (2019)
had only 2 patients using cannabis as a sleep aid, but
both found relief from medical marijuana.
Gastrointestinal Distress
Gastrointestinal (GI) distress (abdominal pain,
bloating, cramps, constipation, diarrhea, or flatu-
lence) are common in patients with cancer, par-
ticularly in those undergoing chemotherapy and
with advanced cancer. However, there is not a lot
known about how medical marijuana may modu-
late GI symptoms or its ecacy in treating them.
It is hypothesized that medical marijuana moder-
ates the inflammatory cytokines produced by can-
cer and chemotherapy or via a direct eect on the
endocannabinoid systems that helps regulate gut
motility and peristalsis (Kleckner et al., 2019). A
study by Bar-Lev Schleider and colleagues (2018)
evaluated the 1,918 patients who complained of
digestive problems. After 6 months of medical
marijuana use, the problems disappeared in 26.7%
of the patients, improved in 50.3% of the patients,
and did not help 23% of the patients.
Cognitive Impairment
Cognitive impairment is a common complaint in pa-
tients with cancer. Kleckner and colleagues (2019)
reported that up to 30% of patients report cognitive
199 Vol 12 No 2 Mar 2021
impairment before treatment even starts, and that
number increases to 75% during treatment. Unfor-
tunately, research is lacking on the eect of medi-
cal marijuana and cognitive impairment. Patients
have reported that moderate to large doses of medi-
cal marijuana cause acute impairment in memory
and attention, but it appears these eects are tem-
porary. In fact, the study by Ware and colleagues
(2015) on the safety of using medical marijuana as a
treatment for pain found that neurocognitive tests
showed significant improvement after 6 and 12
months both in the group using medical marijuana
and the group that did not. There is also some pre-
clinical evidence that CBD can reverse age-related
cognitive impairment in rats; and, in older mice,
low dose THC restored learning and improved spa-
tial learning and memory (Kleckner et al., 2019).
Anxiety and Depression
Anxiety and depression are very common emo-
tions in patients with cancer; approximately one
third of patients experience severe reactions.
Preclinical studies of anxiety and depression are
lacking; however, the endocannabinoid system is
known to be involved in mood regulation, so there
is a possibility medical marijuana could modulate
mood disorders by binding with cannabinoid re-
ceptors in the brain area that influences pleasure.
A decrease in generalized anxiety disorder has
been demonstrated in mice (Kleckner et al., 2019).
In a study by Bar-Lev Schleider and colleagues
(2018), 1,694 patients used medical marijuana for
anxiety and depression. At 6 months, the symptoms
disappeared in 10.1% but were improved in 74.1%,
and 15.8% reported no change. A study by Ander-
son and colleagues (2019) in Minnesota found that
990 patients used cannabis for depression and that
44.5% reported a 30% or greater improvement in
depression within 4 months. Reblin and colleagues
(2019) reported 10 patients used medical marijua-
na for “ability to cope emotionally” and 9 of the 10
reported symptom relief. Quality of life and emo-
tional functioning demonstrated significant in-
creases in Turcott and colleagues’ (2018) study of
nabilone use in lung cancer patients.
In the illustrative case, MR reported pain relief
without side eects by using six drops of 1:1 CBD
to THC three times a day. For convenience, he
switched to 10 mg 1:1 CBD to THC capsules once
in the morning and once in the late afternoon. He
reported that 1 to 2 pus of indica THC at bedtime
helped him fall asleep but not stay asleep, so a 5 mg
indica THC capsule was added at bedtime. He was
reminded to make sure to store his medical mari-
juana in an area out of reach of children and non-
registered individuals and to dispose of any unused
products in a collection receptacle indicated by the
Drug Enforcement Administration (DEA), which
can be located by calling the DEA at 800-882-9539.
He was also told that his medical marijuana card
was only good in the state in which it was issued
and that it is illegal to take the drug over state lines.
Evidence for medical marijuana use is limited
by inadequate research and legal availability. How-
ever, medical marijuana has a safety profile supe-
rior to many other medications and has no report-
ed deaths due to overdoses. Individuals are using
medical marijuana and health-care providers will
see them in their practices. Health-care providers
need to have knowledge of the current legal stat-
utes regarding both medicinal and recreational
medical marijuana, as well as the jurisdiction of
the MMP where they practice. They also need to
have an understanding of the endocannabinoid
system, medical marijuana pharmacology, and
safety considerations for patient use. In addition,
health-care providers need to practice shared de-
cision-making and not judge patients’ choices for
treatment of chronic pain and other symptoms. l
The authors have no conflicts of interest to disclose.
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... Our study population's attitude towards MC had a fair mean percentage of 69.78 ± 15.47, but almost half of the participants (53.3%) had a good attitude concerning the demand for MC use. This result is similar to the results of a previous study that investigated the attitudes related to the intention to use MC for cancer patients in Thailand by As with the previous study by Dell and Stein (2021), we see that cannabis successfully treats chronic cancer pain and chemotherapy-induced nausea and vomiting. ...
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Objective: Cannabis is therapeutic for numerous medical conditions. The demand for medical cannabis (MC) use in cancer patients is increasing, even with many patients lacking proper knowledge about MC. Therefore, this study aimed to describe the attitudes and beliefs of cancer patients demanding MC use in northern Thailand. Methods: This cross-sectional study administered multistage random sampling to recruit 565 cancer patients who indicated that they demand MC use in northern Thailand. These patients responded to a self-administered structured questionnaire about their feelings on MC. We used descriptive statistics, including frequency and percentage, to describe categorical data, whereas we used mean and standard deviation for continuous data. Results: Out of a total of 565 participants, 59.7% were female, 40.3% were male, and 46.4% were middle-aged adults, with a mean age of 58.3 ± 13.0 years. Of these participants who demanded the use of MC, the top three most common types of cancers were breast cancer (27.8%), colorectal cancer (21.4%), and lung cancer (10.6%). Most of the participants (51.2%) had early-stage cancer, and 46.5% received chemotherapy. We found that patients who demanded MC use had a generally positive attitude (53.3%). Among the patients who required MC use, 55.4% believed that it would help relieve side effects caused by modern treatments, cure cancer (38.8%), relieve suffering from cancer symptoms (30.6%), and cause one to live longer and to improve their health (16.3%). Most patients' decisions regarding MC use (45.3%) demanded MC use after receiving modern treatments, and 95.6% demanded MC use with modern treatment. Overall, these patients (65.3%) needed MC from the MC clinic in the Government Hospital. Conclusions: This study highlights the attitudes and beliefs towards MC use among cancer patients, their positive expectations of the outcome, and the need for MC use.
... Aside from recreational use, marijuana and other Cannabis sativa L. products have been purported to have multiple medicinal benefits [13,14]. These include pain management [15], the treatment of Inflammatory Bowel Disease [16] and epilepsy [17], decreased nausea associated with some cancer medications [18], and potential protection from diabetes [19][20][21][22][23]. The latter claim is based on large epidemiological studies reporting on decreased incidence of diabetes in habitual and former marijuana users. ...
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The purpose of the study was to describe and compare the pharmacokinetics of five commercial edible marijuana products, determine the influence of body composition on pharmacokinetics, and, in light of epidemiology suggesting marijuana may offer diabetes protection, explore the influence of edible marijuana on glucose tolerance. Seven regular users of marijuana self-administered five edible products in a randomized crossover design; each product contained 10 mg of delta-9-tetrahydrocannabinol (THC). Thirty minutes following marijuana ingestion, participants imbibed a 75 g glucose beverage. Time-to-peak plasma THC concentration ranged between 35 and 90 min; maximal plasma THC concentration (Cmax) ranged between 3.2 and 5.5 ng/mL. Differences between products in plasma THC concentration during the first 20-30 min were detected (p = 0.019). Relations were identified between body composition and pharmacokinetic parameters for some products; however, none of these body composition characteristics were consistently related to pharmacokinetics across all five of the products. Edible marijuana had no effect on oral glucose tolerance compared with a marijuana-free control (Matsuda Index; p > 0.395). Commercially available edible marijuana products evoke different plasma THC concentrations shortly after ingestion, but do not appear to influence acute glucose regulation. These data may allow recreational marijuana users to make informed decisions pertaining to rates of edible marijuana ingestion and avoid overdose.
... Aside from recreational use, marijuana and other Cannabis sativa L. products have been purported to have multiple medicinal benefits [13,14]. These include pain management [15], the treatment of Inflammatory Bowel Disease [16] and epilepsy [17], decreased nausea associated with some cancer medications [18], and potential protection from diabetes [19][20][21][22][23]. The latter claim is based on large epidemiological studies reporting on decreased incidence of diabetes in habitual and former marijuana users. ...
The purpose of the study was to describe and compare the pharmacokinetics of five commercial edible marijuana products, determine the influence of body composition on pharmacokinetics, and, in light of epidemiology suggesting marijuana may offer diabetes protection, explore the influence of edible marijuana on glucose tolerance. Seven regular users of marijuana self-administered five edible products in a randomized crossover design; each product contained 10mg of delta-9-tetrahydrocannabinol (THC). 30-minutes following marijuana ingestion, participants imbibed a 75g glucose beverage. Time-to-peak plasma THC concentration ranged between 35 and 90 minutes; maximal plasma THC concentration (Cmax) ranged between 3.2 and 5.5 ng/mL. Differences between products in plasma THC concentration during the first 20-to-30 minutes were detected (P=0.019). Relations were identified between body composition and pharmacokinetic parameters for some products; however, none of these body composition characteristics were consistently related to pharmacokinetics across all five of the products. Edible marijuana had no effect on oral glucose tolerance compared with a marijuana-free control (Matsuda Index; P>0.395). Commercially available edible marijuana products evoke different plasma THC concentrations shortly after ingestion, but do not appear to influence acute glucose regulation. These data may allow marijuana users to make informed decisions pertaining to rates of edible marijuana ingestion and avoid overdose.
Introduction: Glioblastoma (GBM) is the most common invasive brain tumor composed of diverse cell types with poor prognosis. The highly complex tumor microenvironment (TME) and its interaction with tumor cells play important roles in the development, progression, and durability of GBM. Angiogenic and immune factors are two major components of TME of GBM; their interplay is a major determinant of tumor vascularization, immune profile, as well as immune unresponsiveness of GBM. Given the ineffectiveness of current standard therapies (surgery, radiotherapy, and concomitant chemotherapy) in managing patients with GBM, it is necessary to develop new ways of treating these lethal brain tumors. Targeting TME, altering tumor ecosystem may be a viable therapeutic strategy with beneficial effects for patients in their fight against GBM. Materials and Methods: Given the potential therapeutic effects of cannabidiol (CBD) in a wide spectrum of diseases, including malignancies, we tested, for the first time, whether inhalant CBD can inhibit GBM tumor growth using a well-established orthotopic murine model. Optical imaging, histology, immunohistochemistry, and flow cytometry were employed to describe the outcomes such as tumor progression, cancer cell signaling pathways, and the TME. Results: Our findings showed that inhalation of CBD was able to not only limit the tumor growth but also to alter the dynamics of TME by repressing P-selectin, apelin, and interleukin (IL)-8, as well as blocking a key immune checkpoint-indoleamine 2,3-dioxygenase (IDO). In addition, CBD enhanced the cluster of differentiation (CD) 103 expression, indicating improved antigen presentation, promoted CD8 immune responses, and reduced innate Lymphoid Cells within the tumor. Conclusion: Overall, our novel findings support the possible therapeutic role of inhaled CBD as an effective, relatively safe, and easy to administer treatment adjunct for GBM with significant impacts on the cellular and molecular signaling of TME, warranting further research.
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Importance Marijuana use is common and growing in the United States amid a trend toward legalization. Exposure to tobacco smoke is a well-described preventable cause of many cancers; the association of marijuana use with the development of cancer is not clear. Objective To assess the association of marijuana use with cancer development. Data Sources A search of PubMed, Embase, PsycINFO, MEDLINE, and the Cochrane Library was conducted on June 11, 2018, and updated on April 30, 2019. A systematic review and meta-analysis of studies published from January 1, 1973, to April 30, 2019, and references of included studies were performed, with data analyzed from January 2 through October 4, 2019. Study Selection English-language studies involving adult marijuana users and reporting cancer development. The search strategy contained the following 2 concepts linked together with the AND operator: marijuana OR marihuana OR tetrahydrocannabinol OR cannabinoid OR cannabis; AND cancer OR malignancy OR carcinoma OR tumor OR neoplasm. Data Extraction and Synthesis Two reviewers independently reviewed titles, abstracts, and full-text articles; 3 reviewers independently assessed study characteristics and graded evidence strength by consensus. Main Outcomes and Measures Rates of cancer in marijuana users, with ever use defined as at least 1 joint-year exposure (equivalent to 1 joint per day for 1 year), compared with nonusers. Meta-analysis was conducted if there were at least 2 studies of the same design addressing the same cancer without high risk of bias when heterogeneity was low to moderate for the following 4 cancers: lung, head and neck squamous cell carcinoma, oral squamous cell carcinoma, and testicular germ cell tumor (TGCT), with comparisons expressed as odds ratios (ORs) with 95% CIs. Results Twenty-five English-language studies (19 case-control, 5 cohort, and 1 cross-sectional) were included; few studies (n = 2) were at low risk of bias. In pooled analysis of case-control studies, ever use of marijuana was not associated with head and neck squamous cell carcinoma or oral cancer. In pooled analysis of 3 case-control studies, more than 10 years of marijuana use (joint-years not reported) was associated with TGCT (OR, 1.36; 95% CI, 1.03-1.81; P = .03; I² = 0%) and nonseminoma TGCT (OR, 1.85; 95% CI, 1.10-3.11; P = .04; I² = 0%). Evaluations of ever use generally found no association with cancers, but exposure levels were low and poorly defined. Findings for lung cancer were mixed, confounded by few marijuana-only smokers, poor exposure assessment, and inadequate adjustment; meta-analysis was not performed for several outcomes. Conclusions and Relevance Low-strength evidence suggests that smoking marijuana is associated with developing TGCT; its association with other cancers and the consequences of higher levels of use are unclear. Long-term studies in marijuana-only smokers would improve understanding of marijuana’s association with lung, oral, and other cancers. Trial Registration PROSPERO identifier: CRD42018102457
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Cannabis has the potential to modulate some of the most common and debilitating symptoms of cancer and its treatments, including nausea and vomiting, loss of appetite, and pain. However, the dearth of scientific evidence for the effectiveness of cannabis in treating these symptoms in patients with cancer poses a challenge to clinicians in discussing this option with their patients. A review was performed using keywords related to cannabis and important symptoms of cancer and its treatments. Literature was qualitatively reviewed from preclinical models to clinical trials in the fields of cancer, human immunodeficiency virus (HIV), multiple sclerosis, inflammatory bowel disease, post-traumatic stress disorder (PTSD), and others, to prudently inform the use of cannabis in supportive and palliative care in cancer. There is a reasonable amount of evidence to consider cannabis for nausea and vomiting, loss of appetite, and pain as a supplement to first-line treatments. There is promising evidence to treat chemotherapy-induced peripheral neuropathy, gastrointestinal distress, and sleep disorders, but the literature is thus far too limited to recommend cannabis for these symptoms. Scant, yet more controversial, evidence exists in regard to cannabis for cancer- and treatment-related cognitive impairment, anxiety, depression, and fatigue. Adverse effects of cannabis are documented but tend to be mild. Cannabis has multifaceted potential bioactive benefits that appear to outweigh its risks in many situations. Further research is required to elucidate its mechanisms of action and efficacy and to optimize cannabis preparations and doses for specific populations affected by cancer.
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Background: There has been a significant increase in the use of immunotherapy and cannabis recently, two modalities that have immunomodulatory effects and may have possible interaction. We evaluated the influence of cannabis use during immunotherapy treatment on response rate (RR), progression-free survival (PFS), and overall survival (OS). Subjects, materials, and methods: In this retrospective, observational study, data were collected from the files of patients treated with nivolumab in the years 2015-2016 at our hospital, and cannabis from six cannabis-supplying companies. Included were 140 patients (89 nivolumab alone, 51 nivolumab plus cannabis) with advanced melanoma, non-small cell lung cancer, and renal clear cell carcinoma. The groups were homogenous regarding demographic and disease characteristics. A comparison between the two arms was made. Results: In a multivariate model, cannabis was the only significant factor that reduced RR to immunotherapy (37.5% RR in nivolumab alone compared with 15.9% in the nivolumab-cannabis group (p = .016, odds ratio = 3.13, 95% confidence interval 1.24-8.1). Cannabis use was not a significant factor for PFS or OS. Factors affecting PFS and OS were smoking (adjusted hazard ratio [HR] = 2.41 and 2.41, respectively (and brain metastases (adjusted HR = 2.04 and 2.83, respectively). Low performance status (adjusted HR = 2.83) affected OS alone. Tetrahydrocannabinol and cannabidiol percentages did not affect RR in any group (p = .393 and .116, respectively). Conclusion: In this retrospective analysis, the use of cannabis during immunotherapy treatment decreased RR, without affecting PFS or OS and without relation to cannabis composition. Considering the limitations of the study, further prospective clinical study is needed to investigate possible interaction. Implications for practice: Although the data are retrospective and a relation to cannabis composition was not detected, this information can be critical for cannabis users and indicates that caution is required when starting immunotherapy.
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The endocannabinoids system (ECS) has garnered considerable interest as a potential therapeutic target in various carcinomas and cancer-related conditions alongside neurodegenerative diseases. Cannabinoids are implemented in several physiological processes such as appetite stimulation, energy balance, pain modulation and the control of chemotherapy-induced nausea and vomiting (CINV). However, pharmacokinetics and pharmacodynamics interactions could be perceived in drug combinations, so in this short review we tried to shed light on the potential drug interactions of medicinal cannabis. Hitherto, few data have been provided to the healthcare practitioners about the drug-drug interactions of cannabinoids with other prescription medications. In general, cannabinoids are usually well tolerated, but bidirectional effects may be expected with concomitant administered agents via affected membrane transporters (Glycoprotein p, breast cancer resistance proteins, and multidrug resistance proteins) and metabolizing enzymes (Cytochrome P450 and UDP-glucuronosyltransferases). Caution should be undertaken to closely monitor the responses of cannabis users with certain drugs to guard their safety, especially for the elderly and people with chronic diseases or kidney and liver conditions.
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Background: Over one half of the patients diagnosed with advanced lung cancer experience anorexia. In addition to its high incidence, cancer-induced anorexia promotes the development of the anorexia-cachexia syndrome, which is related to poor clinical outcomes. Recently, drugs derived from cannabinoids, such as Nabilone, have been recognized for their appetite improvement properties; however, clinical trials to support their use in cancer patients are necessary. Methods: This is a randomized, double-blind, placebo-controlled clinical trial to assess the effect of Nabilone vs. placebo on the appetite, nutritional status, and quality of life in patients diagnosed with advanced Non-small cell lung cancer (NSCLC) (NCT02802540). Results: A total of 65 patients from the outpatient clinic at the National Institute of Cancer (INCan) were assessed for eligibility and 47 were randomized to receive Nabilone (0.5 mg/2 weeks followed by 1.0 mg/6 weeks) or placebo. After 8 weeks of treatment, patients who received Nabilone increased their caloric intake (342-kcal) and had a significantly higher intake of carbohydrates (64 g) compared to patients receiving placebo (p = 0.040). Quality of life also showed significant improvements in patients in the experimental arm of the trial, particularly in role functioning (p = 0.030), emotional functioning (p = 0.018), social functioning (p = 0.036), pain (p = 0.06), and insomnia (p = 0.020). No significant change in these scales was seen in the control group. Conclusion: Nabilone is an adequate and safe therapeutic option to aid in the treatment of patients diagnosed with anorexia. Larger trials are necessary in order to draw robust conclusions in regard to its efficacy in lung cancer patients.
Objectives There is increased interest in cannabinoids for cancer pain management and legislative changes are in progress in many countries. This study aims to determine the beneficial and adverse effects of cannabis/cannabinoids compared with placebo/other active agents for the treatment of cancer-related pain in adults. Methods Systematic review and meta-analysis to identify randomised controlled trials of cannabinoids compared with placebo/other active agents for the treatment of cancer-related pain in adults to determine the effect on pain intensity (primary outcome) and adverse effects, including dropouts. Searches included Embase, MEDLINE, PsycINFO, Web of Science,, Cochrane and grey literature. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Results We identified 2805 unique records, of which six randomised controlled trials were included in this systematic review (n=1460 participants). Five studies were included in the meta-analysis (1442 participants). All had a low risk of bias. There was no difference between cannabinoids and placebo for the difference in the change in average Numeric Rating Scale pain scores (mean difference −0.21 (−0.48 to 0.07, p=0.14)); this remained when only phase III studies were meta-analysed: mean difference −0.02 (−0.21 to 0.16, p=0.80). Cannabinoids had a higher risk of adverse events when compared with placebo, especially somnolence (OR 2.69 (1.54 to 4.71), p<0.001) and dizziness (OR 1.58 (0.99 to 2.51), p=0.05). No treatment-related deaths were reported. Dropouts and mortality rates were high. Conclusions Studies with a low risk of bias showed that for adults with advanced cancer, the addition of cannabinoids to opioids did not reduce cancer pain. Trial registration number CRD42018107662.
Purpose Medical marijuana is often used as adjuvant therapy in cancer patients for symptom management, although limited evidence-based studies evaluating its efficacy or safety exist. Similar to over-the-counter medications, supplements, or herbal products, documentation of medical marijuana is important to monitor efficacy, potential adverse effects, or interactions. The objective of this quality improvement study was to improve the consistency of medical marijuana documentation in cancer patients by assessing current practices; educating healthcare team members about the importance of documentation and newly established documentation process; and evaluating the new documentation process. Methods This three-part quality improvement study was approved by the Institutional Review Board. In part I, a voluntary survey was sent via email to Cancer Center healthcare personnel to assess the current documentation process of medical marijuana. In part II, a best practice process for documenting medical marijuana in the electronic medical record was established. Medical marijuana was to be listed as a historical medication in the medication list. In-person and electronic education sessions were offered to Cancer Center clinical staff. The education emphasized the importance of documenting medical marijuana use and provided a detailed process for electronic medical record documentation. A pre- and post-test to assess understanding was also included. Part III was a retrospective chart review to evaluate documentation practices of certified medical marijuana users in the Cancer Center. Patients included in the study were greater than 18 years old and certified for medical marijuana use on or after 1 January 2018. Department of Corrections patients were excluded. Descriptive statistics were used for data analysis. Results The survey results in part I demonstrated a lack of consistency in the documentation of medical marijuana in the Cancer Center. The pre- and post-test scores measured in part II showed a significant improvement in understanding after education was provided. The average pre-test score was a 61 and post-test score was 88, indicating an average increase of 27 points. A larger increase in test scores was observed in those attending the in-person education than the online sessions ( p < 0.002). The results of the retrospective chart review in part III revealed 56 patients who met inclusion criteria, but only 39 patients were alive and evaluated at the time of the retrospective chart review. Of the 39 patients, 22 never completed the patient registration process and therefore, would never have been able to obtain medical marijuana. Seven patients had medical marijuana properly documented in their medication list and 10 patients were missing documentation in the medication list, showing room for improvement in documentation practices. Conclusions This quality improvement study led to the implementation of medical marijuana documentation in the medication list. Education increased healthcare team members understanding of medical marijuana utilization and the importance of documentation.
Research in the cannabinoid field, namely on phytocannabinoids, the endogenous cannabinoids anandamide and 2-arachidonoyl glycerol and their metabolizing and synthetic enzymes, the cannabinoid receptors, and anandamide-like cannabinoid compounds, has expanded tremendously over the last few years. Numerous endocannabinoid-like compounds have been discovered. The Cannabis plant constituent cannabidiol (CBD) was found to exert beneficial effects in many preclinical disease models ranging from epilepsy, cardiovascular disease, inflammation, and autoimmunity to neurodegenerative and kidney diseases and cancer. CBD was recently approved in the United States for the treatment of rare forms of childhood epilepsy. This has triggered the development of many CBD-based products for human use, often with overstated claims regarding their therapeutic effects. In this article, the recently published research on the chemistry and biological effects of plant cannabinoids (specifically CBD), endocannabinoids, certain long-chain fatty acid amides, and the variety of relevant receptors is critically reviewed. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 60 is January 6, 2020. Please see for revised estimates.
Background: Glioma is a devastating primary tumor of the central nervous system with difficult-to-manage symptoms. Cannabis products have been postulated to potentially benefit glioma patients. Recent state legalization allowed investigators an opportunity to study glioma patients' adoption of medical marijuana (MM). Objective: Our goals were to: (1) determine the prevalence of marijuana use, both through physician recommendation and self-medication, and (2) evaluate its perceived risks and benefits in glioma patients. Design: Self-report data were collected and descriptive analyses were conducted. Setting/Subjects: Participants were adult, English-speaking patients undergoing treatment for primary non-recurrent malignant glioma in neuro-oncology clinics at an NCI-designated Comprehensive Cancer Center. Measurements: The survey on MM was adapted from previous research and included questions on knowledge and attitudes toward MM; use, frequency, type, and sourcing of MM; and reasons for use of MM and perceived symptom relief among users. Results: A total of 73 patients were surveyed. The majority of participants were aware that MM was legal in the state, and most reported learning of this through the media. Over 70% of participants reported having considered using MM, and a third reported using marijuana products after their diagnosis. Most received recommendations from friends/family rather than a medical provider, and only half of the users had obtained a physician's recommendation. Users generally reported benefits. Conclusions: With the increasing national conversation that accompanies legalization, glioma patients are pursuing marijuana for the treatment for their symptoms. More research and education is needed to bring health care providers into the conversation.
Purpose: Minnesota's medical cannabis program is unique, in that it routinely collects patient-reported scores on symptoms. This article focuses on changes in symptom severity reported by patients with cancer during their first 4 months of program participation. Materials and methods: Patients with cancer in Minnesota's medical cannabis program reported symptoms (anxiety, lack of appetite, depression, disturbed sleep, fatigue, nausea, pain, and vomiting) at their worst over the last 24 hours before each medical cannabis purchase. Baseline scores on each of the eight symptoms were statistically compared with the average symptom scores reported in the first 4 months of program participation. Symptom scores were also calculated as percent change from baseline, with patients achieving and maintaining at least a 30% reduction in symptoms reported in this article. Patients also reported intensity of adverse effects. Results: A significant reduction in scores was found across all symptoms when comparing baseline scores with the average score submitted within the first 4 months of program participation (all Ps < .001). The proportion of patients achieving 30% or greater symptom reduction within the first 4 months of program participation varied from 27% (fatigue) to 50% (vomiting), with a smaller proportion both achieving and maintaining those improvements. Adverse effects were reported in a small proportion of patients (10.5%). Conclusion: Patients with cancer enrolled in Minnesota's medical cannabis program showed significant reduction across all eight symptoms assessed within 4 months of program participation. Medical cannabis was well tolerated, and some patients attained clinically meaningful and lasting levels of improvement.