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Position Statement: A Pragmatic Approach for Medical Cannabis and Patients with Rheumatic Diseases

Authors:

Abstract

Objective Pain is one reason some rheumatology patients may consider use of medical cannabis, a product increasingly perceived as a safe and neglected natural treatment option for many conditions. Legalization of recreational cannabis in Canada will promote access to cannabis. Physicians must therefore provide patients with the best evidence-based information regarding the medicinal effects and harm of cannabis. Methods The Canadian Rheumatology Association (CRA) mandated the development of a position statement for medical cannabis and the rheumatology patient. The current literature regarding the effects of medical cannabis for rheumatology patients was assessed, and a pragmatic position statement to facilitate patient care was developed by the Therapeutics Committee of the CRA and approved by the CRA board. Results There are no clinical trials of medical cannabis in rheumatology patients. Evidence is insufficient about the benefit of pharmaceutical cannabinoids in fibromyalgia, osteoarthritis, rheumatoid arthritis, and back pain, but there is evidence of a high risk of harm. Extrapolating from other conditions, medical cannabis may provide some symptom relief for some patients. Short-term risks of psychomotor effects can be anticipated, but longterm risks have not been determined and are of concern. Conclusion Despite lack of evidence for use of medical cannabis in rheumatology patients, we acknowledge the need to provide empathetic and pragmatic guidance for patient care. This position statement aims to facilitate the dialogue between patients and healthcare professionals in a mutually respectful manner to ensure harm reduction for patients and society.
The Journal of Rheumatology
with Rheumatic Diseases
Position Statement: A Pragmatic Approach for Medical Cannabis and Patients
Canadian Rheumatology Association
Mary-Ann Fitzcharles, Omid Zahedi Niaki, Winfried Hauser, Glen Hazlewood and the
http://www.jrheum.org/content/early/2019/01/11/jrheum.181120
DOI: 10.3899/jrheum.181120
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Fitzcharles, et al: Medicinal cannabis in rheumatic disease
Pers onal non -com merc ial use only. The Journal of Rheumatology Copyright © 2019. All rights reserved.
Position Statement: A Pragmatic Approach for Medical
Cannabis and Patients with Rheumatic Diseases
Mary-Ann Fitzcharles, Omid Zahedi Niaki, Winfried Hauser, and Glen Hazlewood,
and the Canadian Rheumatology Association
ABSTRACT. Objective.Pain is one reason some rheumatology patients may consider use of medical cannabis, a
product increasingly perceived as a safe and neglected natural treatment option for many conditions.
Legalization of recreational cannabis in Canada will promote access to cannabis. Physicians must
therefore provide patients with the best evidence-based information regarding the medicinal effects
and harm of cannabis.
Methods.The Canadian Rheumatology Association (CRA) mandated the development of a position
statement for medical cannabis and the rheumatology patient. The current literature regarding the
effects of medical cannabis for rheumatology patients was assessed, and a pragmatic position
statement to facilitate patient care was developed by the Therapeutics Committee of the CRA and
approved by the CRA board.
Results.There are no clinical trials of medical cannabis in rheumatology patients. Evidence is insuf-
ficient about the benefit of pharmaceutical cannabinoids in fibromyalgia, osteoarthritis, rheumatoid
arthritis, and back pain, but there is evidence of a high risk of harm. Extrapolating from other condi-
tions, medical cannabis may provide some symptom relief for some patients. Short-term risks of
psychomotor effects can be anticipated, but longterm risks have not been determined and are of
concern.
Conclusion.Despite lack of evidence for use of medical cannabis in rheumatology patients, we
acknowledge the need to provide empathetic and pragmatic guidance for patient care. This position
statement aims to facilitate the dialogue between patients and healthcare professionals in a mutually
respectful manner to ensure harm reduction for patients and society. (J Rheumatol First Release
January 15 2019; doi:10.3899/jrheum.181120)
Key Indexing Terms:
RHEUMATIC DISEASE MEDICAL CANNABIS
From the Alan Edwards Pain Management Unit, and the Division of
Rheumatology, McGill University Health Centre, Montreal, Quebec;
Division of Rheumatology, University of Alberta, Calgary, Alberta,
Canada; Department Internal Medicine I, Klinikum Saarbrücken,
Saarbrücken; Department of Psychosomatic Medicine and Psychotherapy,
Technische Universität München, Munich, Germany.
M.A. Fitzcharles, MB ChB, Alan Edwards Pain Management Unit, and
Division of Rheumatology, McGill University Health Centre; O. Zahedi
Niaki, MD, Division of Rheumatology, McGill University Health Centre;
W. Hauser, Dr. med., Department Internal Medicine I, Klinikum
Saarbrücken, and Department of Psychosomatic Medicine and
Psychotherapy, Technische Universität München; G. Hazlewood, MD,
Division of Rheumatology, University of Alberta.
Address correspondence to Dr. M.A. Fitzcharles, Montreal General
Hospital, McGill University Health Centre, 1650 Cedar Ave., Montreal,
Quebec H3G 1A4, Canada. E-mail: mary-ann.fitzcharles@muhc.mcgill.ca
Accepted for publication November 27, 2018.
Persistent pain may cause some rheumatology patients to
explore treatment options outside mainstream medicine.
Cannabinoids may hold promise for attenuation of pain and
inflammation by modulating the endogenous endocan -
nabinoid system1. The popularized purported benefits of
herbal cannabis for many symptoms have catapulted cannabis
into the therapeutic arena. Specifically pertinent to rheumatic
diseases is the preclinical evidence for effect of cannabinoids
on immunological mechanisms with potential to modulate
inflammation and perhaps function as a disease modifier, but
with caution to emphasize that these concepts have not been
observed in patient populations2.
Herbal cannabis, the best-known natural source of
cannabinoids, is a genus of flowering plant in the family of
Cannabaceae, with the species Cannabis sativa most
commonly used therapeutically. The leaves and flowers
contain many molecules, of which Δ9-tetrahydrocannabinol
(THC) and cannabidiol (CBD) are the most studied. In
addition to THC and CBD, herbal cannabis contains many
noncannabinoid molecules, with physiologic effects that are
largely unknown. Medical cannabis refers to the whole plant
or extract thereof, used for medical purposes as dried flowers
and leaves or an oil extract, and may be administered by
smoking, inhalation through a vaporizer (heating to lower
temperatures than smoking), ingestion, or topical applica-
tions. Cannabinoids are also available as pharmaceutical-
quality preparations, either as plant extracts with specified
doses of THC and CBD, or synthesized products acting on
cannabinoid receptors.
Medical cannabis has been legally available to Canadians
Journal of Rheumatology The on January 19, 2019 - Published by www.jrheum.orgDownloaded from
since 2001. There are currently about 250,000 users regis-
tered with Health Canada, many of whom have muscu-
loskeletal complaints3. In contrast to this prevalent use,
rheumatologists are insecure about many aspects of this
treatment strategy. In a recent survey, over 80% of Canadian
rheumatologist respondents reported being asked at least
weekly about medical cannabis, but three-fourths reported
limited confidence in their knowledge of cannabinoids, or
their ability to effectively advise patients4. The need for
practical, patient-centered, evidence-based guidance will
increase with the legalization of recreational cannabis. In an
effort to reconcile these diverse and conflicting opinions,
unbiased and empathetic guidance is urgently required.
MATERIALS AND METHODS
This position statement was developed to provide information and practical
guidance for Canadian rheumatologists regarding medical cannabis in
rheumatology practice, and does not cover pharmaceutical cannabinoid
preparations. The target audience is rheumatologists, who will be required
to respond to patient requests for advice regarding medical cannabis and to
care for patients who may be self-medicating, or who may choose to
formally prescribe medical cannabis.
This document was developed by the Therapeutics Committee and the
Canadian Rheumatology Association (CRA). According to CRA policies,
position statements are designed as an immediate response to an emerging
or controversial topic, adhering to the standards of evidence-based literature
to support statements5.
The relevant literature was reviewed with special attention to the position
paper by the European Pain Federation, as well as a recent clinical practice
guideline published for Canadian family physicians6,7. This latter guideline
assessed use of all cannabinoids for various complaints and appended
summaries of provincial regulatory requirements. Using the GRADE
(Grading of Recommendations Assessment, Development, and Evaluation)
methodology, the results of 4 systematic reviews were used to support state-
ments8. This guideline was rated as high quality according to the Appraisal
of Guidelines Research and Evaluation (AGREE)-II instrument by 2
independent reviewers (GH, MAF). Relevant statements and supporting
evidence pertinent to rheumatic diseases from all publications were
reviewed, and a draft document was developed by the present authors; this
document was circulated to members of the Therapeutics Committee of the
CRA as well as an external expert, and was revised in an iterative fashion
based on feedback. The final document was reviewed and approved by the
CRA board, in accordance with CRA policy.
RESULTS
The recent Canadian guideline for prescribing medical
cannabinoids in primary care addressed the use of cannabi-
noids for pain associated with rheumatologic conditions6.
There were no randomized trials of medical cannabis in
rheumatic diseases6,9. Additionally, there was insufficient
evidence for the benefit of pharmaceutical preparations for
fibromyalgia, osteoarthritis, rheumatoid arthritis, and back
pain, but there was evidence of a high risk of harm10,11. In
evaluating the harm of medical cannabis reported for pain in
conditions other than rheumatic complaints, there was a high
rate of short-term harm, and the amount of longterm harm
was unknown. On the basis of the lack of evidence for
benefit, and the increased harm, the guideline group made a
strong recommendation against cannabinoids in general
(including pharmaceutical preparations) for rheumatic pain.
Further, in patients in whom cannabinoids were being
considered, there was a strong recommendation against
medical cannabis (particularly smoked) over pharmaceutical
cannabinoids. There is a high risk of bias in studies of smoked
cannabis, with unknown longterm consequences.
DISCUSSION
The reality of medical cannabis use in Canada. In accordance
with the lack of evidence for the effect of medical cannabis
in rheumatic diseases, the simplistic response, as endorsed
by others, is to recommend against use pending more
evidence6. The reality is that patients are requesting infor-
mation, may be considering use, or may be currently
self-medicating. Physicians may also have personal biases
regarding medical cannabis, either positive or negative.
Further, the Canadian legalization of recreational cannabis
allows freer access to cannabis by patients. Rheumatologists
therefore have an obligation to provide competent advice.
Physicians should understand the reason for consideration
of medical cannabis: relief of pain, sleep difficulties, or mood
disorders; poor effect of current treatments; perception of a
natural treatment; and encouragement by friends or family
members to use. Another prevailing argument is that medical
cannabis is safer than traditional analgesic drugs (i.e.,
opioids)12. Almost one-fifth of rheumatology patients are
currently using opioids, although not guideline-recommended
for rheumatic pain13,14. Considering fatalities associated with
opioids and absence of respiratory suppression by cannabi-
noids, medical cannabis may be a safer choice. Inserted into
this context must be the extensive media coverage of medical
cannabis, almost always favorable, and the constantly
associated anecdotes of outstanding effect. Subtle marketing
strategies buoyed by financial interests cannot be sufficiently
emphasized. In this highly charged climate, rheumatologists
must maintain an empathetic therapeutic relationship with
their patients, avoid personal biases, and ensure harm
reduction for both patients and society.
Position statement from the CRA for medical cannabis in
rheumatology patients. Given the lack of evidence for
medical cannabis for rheumatic complaints, but faced with
escalating access among patients, the CRA suggests the
following overarching principles (Table 1). Patients should be
informed that medical cannabis is not an alternative to
standard care for any rheumatic disease and that evidence for
the effect in rheumatic diseases is lacking. Short-term adverse
events including immediate psychomotor effects, dizziness,
appetite changes, effect on mood, and the rare serious side
effects of disorientation and psychosis are high, and longterm
risks are not yet known. Rheumatologists should adhere to
current treatment standards and guidelines for rheumatic
disease management and should maintain an empathetic thera-
peutic relationship with their patients, avoid personal biases,
and ensure harm reduction for both patients and society.
2The Journal of Rheumatology 2019; 46:doi:10.3899/jrheum.181120
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Putting principles into practice. Treatment principles to
reduce harm are outlined in Table 2. In line with good
medical practice, physicians must adhere to standard of care
when prescribing medical cannabis15. Beginning with a clear
understanding of the symptoms requiring treatment, attention
should be given to previous treatment trials, including
nonpharmacologic measures. Standard therapeutic options
should be accessed prior to consideration of medical
cannabis.
A prescription should only be provided by a physician
who is fully knowledgeable of the patient and is responsible
for patient care. Cannabis should not be prescribed following
online consultation or by those who project themselves as
“cannabis experts” focusing only on prescription of cannabis
without attention to global patient care. A formal distance
consultation requested by, and in collaboration with, the
treating physician may be considered for patients in distant
locations. The medical encounter must include documen-
tation of the medical condition, reason for medical cannabis
consideration, associated comorbidities, current medications,
and previous treatment trials. A psychosocial history must
include an assessment of mental health status, including past
or present psychosis or substance use disorder. A treatment
trial with a pharmaceutical product before consideration of
medical cannabis, although recommended, is often not a
practical consideration owing to difficulties with access and
cost.
Following consideration of potential benefits versus harm,
and when a decision is made to initiate a treatment trial, the
prescribing physician must assume responsibility for
followup. The goals of treatment should be clearly specified
and be realistic [e.g., a 30% symptom relief (pain, sleep, and
mood problems) and/or individually defined relevant
improvement of daily functioning]. Some physicians may
choose to complete a written treatment contract. Followup
should be within 4–8 weeks to evaluate efficacy and side
effects. Treatment should be initiated slowly, beginning with
a nighttime dose, and not exceeding 3 g/day, the maximum
average dose reported by medical cannabis users16. Cannabis
should be obtained legally from a registered grower
following submission of a prescription with known molecular
content of THC and CBD, and patients and physicians must
adhere to the legal requirements in their geographic region.
Some authors have suggested a maximum of 9% THC
concentration17. The treatment trial for a period of about 4–12
weeks may result in discontinuation of the product if
ineffective or if there are unwanted side effects.
Cannabis should not be smoked because of the toxic
products of combustion. Inhalation through a vaporizer is
preferred because less intensive heating reduces release of
toxic combustion products. Inhaled cannabis, through a
vaporizer, will give effects within a few minutes, with effects
3
Fitzcharles, et al: Medicinal cannabis in rheumatic disease
Pers onal non -com merc ial use only. The Journal of Rheumatology Copyright © 2019. All rights reserved.
Table 1. Overarching principles for medical cannabis in rheumatology patients.
1. Medical cannabis is not an alternative to standard care for any rheumatic disease, and rheumatologists should adhere to current treatment standards and
guidelines for rheumatic disease management.
2. There are no published studies of the effects of medical cannabis in patients with rheumatic diseases, and the few studies examining cannabinoid pharma-
ceutical products report limited benefits and high risk of adverse events.
3. Medical cannabis should not be used in rheumatology patients under the age of 25 years.
4. It is acknowledged that rheumatic disease patients may seek advice regarding use of medical cannabis, may currently be self-medicating with medical
cannabis, or may request a prescription for medical cannabis.
5. Common reasons that patients may consider use of medical cannabis are for pain relief and/or sleep promotion.
6. Current treatment strategies for pain relief and sleep promotion including non-pharmacologic treatments must be tried before consideration of use of
medical cannabis.
7. Medical cannabis may provide symptom relief for some patients with rheumatic diseases.
8. Short-term adverse events (including immediate psychomotor effects, dizziness, appetite changes, and effect on mood, and the rare serious side effects
of disorientation and psychosis) are frequent with the use of medical cannabis and are likely to be similar to those reported for other disease populations.
9. The longterm risks associated with medical cannabis use in patients with rheumatic diseases are unknown.
10. Despite a patient’s understanding of the lack of any scientific evidence to support a benefit, and the increased risk of harm, some patients may prefer a
trial of medical cannabis over other options, including opioids.
11. Rheumatologists must endeavor to maintain an empathetic therapeutic relationship with their patients, avoid personal biases, and ensure harm reduction
for both patients and society.
12. There is an urgent need for further research regarding the effects of medical cannabis in rheumatic diseases.
Table 2. Treatment principles to reduce harm.
Prior to starting medical herbal cannabis
Treatment goals and objectives should be realistic and clearly specified.
An assessment for substance use disorder must be documented.
Patients should be well informed about the adverse effects associated
with cannabis use.
Drug preparations, route of administration, and dosing
Inhalation through a vaporizer has a rapid therapeutic effect, whereas
oral ingestion has a slower but more sustained effect. Both routes of
administration are preferred over smoked cannabis.
Cannabis with a low THC content (maximum 9%) and higher CBD
content is preferable.
Total daily dose should not exceed 3 g.
The drug can be used regularly or on demand.
Assessment of side effects and efficacy
Followup 4–8 weeks after initiating the drug
Followup every 3 months thereafter
THC: Δ9-tetrahydrocannabinol; CBD: cannabidiol.
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lasting up to a few hours, although the psychoactive and
motor effects may last for over 24 h16. The effects of ingested
cannabis will occur more slowly and be more prolonged, and
may be the preferred method of administration for a treatment
regimen. Although there is no evidence to support the thera-
peutic effect of various concentrations of THC and CBD in
the herbal product, cannabis with a low THC content and
higher CBD content is preferable because there will be fewer
and less severe THC-induced psychoactive effects. Studies
to date have reported on THC content up to 12.5%, but with
a high rate of adverse events at this concentration18.
The ideal dosing schedule for medical cannabis is
unknown, with no dose-finding studies to examine optimal
daily amount or specific molecular concentrations of THC
and CBD6. Some patients may choose “on-demand” use
rather than regular use, but there is no evidence to support
this method. It is conceivable that ingested cannabis could
provide a more sustained effect, and that on-demand
inhalation could be used as a breakthrough measure.
However, on-demand use could lead to progressive increased
use and misuse.
Patients reporting benefit should be followed at least every
3 months, with assessment of efficacy as well as need for
continued treatment. Medical cannabis is ideally not a
lifetime treatment, and at each visit justification for continued
treatment must be documented. Physicians may choose to
request a urine drug screen for patients taking continuous
cannabis treatment as a caution to ensure that cannabis is not
being used as a concomitant recreational product, or that the
prescribed cannabis is not being diverted if there is
reimbursement for the medical product.
Risks applicable to all rheumatic disease patients using
medical cannabis. The risks associated with medical cannabis
have not been specifically examined in patients with
rheumatic diseases. Extrapolation from risks reported for
other medical conditions as well as from recreational users
is currently the only reasonable means to help inform clinical
care.
1. Smoking of herbal cannabis
Cannabis should not be smoked. Inhalation of combustible
products carries a risk of bronchial irritation19. Attenuation
of the protective respiratory tract mucosa will promote entry
of foreign antigens that have immunological effects that
influence the expression of inflammatory arthritis20. Similar
to the smoking of cigarettes, smoked cannabis may adversely
affect rheumatic diseases, but remains to be examined. The
risk for lung cancer and smoked cannabis remains unclear21.
2. Psychomotor effects
Psychomotor function is affected by cannabis in young recre-
ational users for up to 5 h after use22. This effect may be
prolonged for as long as 24 h when cannabis is ingested.
Driving after cannabis use is a risk for a collision, with risk
increased with dose of cannabis and further increased when
combined with alcohol23. In a metaanalysis of 9 studies
(49,411 subjects), Asbridge and colleagues reported a pooled
motor vehicle collision risk of 1.92 (95% CI 1.35–2.73,
p = 0.0003)24. Therefore, in line with recommendations of
Health Canada, patients using medical cannabis should be
warned not to drive or operate machinery for at least 24 h
after consumption, with possible effects prolonged in the
presence of other agents affecting psychomotor function such
as tranquilizers, antidepressants, anti-epileptic drugs, and
opioids16. Self-report that a patient experiences no
psychomotor effects is not sufficient reason to ignore this risk
and requires formal evaluation (e.g., a formal test of driving
ability).
3. Risks of addiction
Cannabis is an addictive substance25. Regular recreational
cannabis use is associated with a risk of addiction estimated
to be about 9% for all users, but with increased rates for
younger age of onset of use, regular daily use, and likely
increased concentration of THC. Addiction risk is not known
for medical cannabis use but is unlikely to be different from
that observed for recreational users. It is prudent to reflect on
the evolution of the 1980s concept that opioid treatment for
chronic pain would not be associated with addiction; that
concept is now completely overturned26.
4. Interactions of cannabinoids with other medications
Information regarding interactions of herbal cannabis and
other drugs is limited. It can be anticipated that the
psychomotor effects of drugs, such as tranquilizers, anti -
depressants, anticonvulsants, and also alcohol, will be
augmented with cannabis and should be avoided or used with
caution. In a study of smoked cannabis in patients with
chronic pain, with almost two-thirds of the subjects treated
concomitantly with opioids, the rate of serious adverse events
was over 20 per 100 patient-years, an alarmingly high rate
that is greater than many rheumatology drug treatments18.
Contraindications and cautions for medical cannabis use.
Attention should be given to the use of medical cannabis for
certain patient populations (Table 3).
4The Journal of Rheumatology 2019; 46:doi:10.3899/jrheum.181120
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Table 3. Contraindications and cautions for medical cannabis.
Populations in which medical cannabis should not be used
Rheumatology patients under the age of 25 years
Patients with allergic reactions to cannabinoid products
Women who are pregnant or breastfeeding
Patients with a history of a psychotic illness, substance abuse disorder,
previous suicide attempts, or suicidal ideation
Populations in which medical cannabis should be used with caution
Elderly patients
Patients with unstable mental health disease
Patients with a history of current moderate or severe cardiovascular or
pulmonary disease
Patients working in settings requiring high levels of concentration,
optimal executive functioning, and alertness
Patients receiving concomitant therapy with sedative-hypnotics or other
psychoactive drugs
Journal of Rheumatology The on January 19, 2019 - Published by www.jrheum.orgDownloaded from
1. Young persons
Herbal cannabis should not be used by patients under the age
of 25 years, in line with the Canadian Paediatric
Association17,27. Brain development continues until the early
20s, with the cannabinoid system playing a critical role28.
Cannabis use at a young age adversely affects psychosocial
development, academic and social attainment, and is a risk
for mental health disease29,30. There are no studies examining
the above effects related to various concentrations of THC
and CBD in the herbal product, although concentration of
THC in street cannabis has increased exponentially in the last
2 decades, from 3% to a current 25–30%31,32. Young patients
self-medicating with a recreationally acquired product should
be cautioned about this increased concentration of THC and
the associated increased risk of cognitive and psychoactive
effects. Microbial contamination of the street product is also
a risk for patients who may be immunocompromised.
2. Pregnant and lactating women
Cannabis should be avoided in women during pregnancy and
lactation. The endocannabinoid system is critical in normal
brain development, although effect on the human fetus is
unclear. THC crosses the placenta in rat studies, with appre-
ciable levels measured in the pups, and associated transient
and permanent behavioral effects33. There is transfer of
cannabinoids into breast milk, with cannabinoid metabolites
excreted by both animal and human offspring34.
3. Those hypersensitive to cannabis
Allergic sensitization with the development of specific
immunoglobulin E can occur through inhalation, oral
ingestion, or cutaneous contact with cannabis. Depending on
the route of exposure, hypersensitivity reactions can vary
widely and range from mild cutaneous or respiratory
symptoms to angioedema and anaphylaxis35. Because of the
potential for life-threatening reactions, strict avoidance
measures should be enforced for patients with suspected or
confirmed cannabis allergy36.
4. Older persons
Medical cannabis has had limited study in the elderly. In an
Israeli study of patients over 65 years, with one-third of the
original 2736 persons followed for 6 months, there was
reduction of pain and discontinuation or reduction of opioid
doses in 18%37. The potential risks associated with medical
cannabis in the elderly include effects on cognitive function
and motor coordination, risk of confusion, and falls and
injury. Psychomotor impairment is well described in young
recreational users, but although not evaluated in the elderly,
is likely to be at least similar but probably more
pronounced22. Impairments in reaction time, selective
attention, short-term memory, and motor control will criti-
cally affect the well-being of older persons. Additional
potential risks not yet examined are the effects of drug inter-
actions and comorbid illnesses, especially cardiac and
pulmonary diseases. Drug interactions can reasonably be
expected to be compounded by cannabis, especially those
affecting cognition, motor control, or mood. Therefore,
extreme caution should be exercised when an elderly patient
anticipates use of medical cannabis.
5. The working patient
Cannabis has psychoactive properties and affects motor
function; therefore, competence in the work environment is
critical. Higher concentrations of THC are associated with
greater effect on cognition and psychomotor activity,
although even a low concentration may have appreciable
effects for some22. Patient self-report of competence is
unreliable. In the absence of any formal standard of testing,
patients should be informed that cognitive function will likely
be impaired, although perhaps not perceptibly, and that any
use of cannabinoids should be avoided in settings requiring
concentration, optimal executive functioning, and alertness.
This is particularly true for settings where impairment of
cognition may pose a threat to others.
6. Those with comorbid illness
a. Mental health disease
Cannabis should generally be avoided in persons with a
history of mental health disease, with an absolute contraindi-
cation for persons with a personal or family history of a
psychotic illness, a history of substance abuse disorder,
previous suicide attempts, or suicidal ideation38. According
to the comprehensive publication on the health effects of
cannabis and cannabinoids by The National Academies of
Sciences, Engineering, and Medicine, there is an absence of
evidence to support or refute cannabis-induced changes in
the course of depressive disorders, but moderate evidence for
increased suicidal ideation, suicide attempts, and suicide
completion38. For anxiety, there is limited evidence of an
association of daily cannabis use and development of any
type of anxiety disorder, except social anxiety, and limited
evidence for increased symptoms of anxiety in those with a
previous anxiety state38. Therefore in this context of uncer-
tainty, it is prudent to be cautious when counseling patients
with mental health disorders on the use of cannabis, and in a
case of uncertainty, referral for psychiatric evaluation should
be considered. Therefore, the CRA suggests a relative
contraindication in persons with mental health disorders
including anxiety and depression, with a warning that mood
disorders may be aggravated by cannabis. Although cannabis
is mostly anxiolytic, paradoxically anxiety may be increased
and depressive symptoms aggravated. Although cannabis is
widely advocated for effect on posttraumatic stress disorder,
the current evidence is limited to anecdotes, case reports, and
observational studies39. Clinical judgment should be used to
assess the risk of medical cannabis in current recreational
users. There should be an assessment of addiction risk and
severity of symptoms requiring treatment, and as much as
possible, distinction made between recreational and
medicinal use. If medical cannabis is used, treatment should
ideally be in collaboration with a psychiatrist.
b. Cardiovascular disease and pulmonary disease
5
Fitzcharles, et al: Medicinal cannabis in rheumatic disease
Pers onal non -com merc ial use only. The Journal of Rheumatology Copyright © 2019. All rights reserved.
Journal of Rheumatology The on January 19, 2019 - Published by www.jrheum.orgDownloaded from
Cannabis should not be used in patients with moderate or
severe cardiovascular or pulmonary disease40,41. Because
cannabis increases heart rate, blood pressure, and myocardial
oxygen demand, use may aggravate stable angina or trigger
myocardial infarction. Daily cannabis use increases the
annual risk of myocardial infarction from 1.5% to 3% per
year. Cardiovascular events, including sudden cardiac death,
vascular events (coronary, cerebral, and peripheral), and
arrhythmias are increasingly reported in young recreational
users without other risk factors, suggesting that older persons
with preexisting disease are at even greater risk42. Smoked
cannabis is associated with chronic bronchitis symptoms, but
case-controlled studies have not identified an association with
lung cancer40.
Much remains unknown regarding medical cannabis use
in rheumatic diseases, including true efficacy as well as risks
(Table 4). Rheumatologists can play an important role in (1)
ensuring patients are educated regarding what is currently
known concerning potential risks versus benefits of medical
cannabis, and (2) providing patient-centered counseling for
those who are taking or planning to take cannabis, with a goal
toward harm reduction. Whether medical cannabis will
finally emerge as a standard treatment option for our patients
remains to be seen.
ACKNOWLEDGMENT
The authors thank the Canadian Rheumatology Association Therapeutics
Committee members: Kenneth Blocka, Claire Bombardier, Sasha Bernatsky,
Jeff Gong, Adam Huber, Michelle Jung, Janet Pope, Rosie Scuccimarri,
J. Carter Thorne, Peter Tugwell, and Michael Wodkowski.
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[Internet. Accessed November 29, 2018.] Available from:
www.canada.ca/en/health-canada/services/drugs-health-products/
medical-use-marijuana/licensed-producers/market-data.html
4. Therapeutics. Survey results on medical marijuana. CRAJ
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6. Allan GM, Ramji J, Perry D, Ton J, Beahm NP, Crisp N, et al.
Simplified guideline for prescribing medical cannabinoids in
primary care. Can Fam Physician 2018;64:111-20.
7. Hauser W, Finn DP, Kalso E, Krcevski-Skvarc N, Kress HG,
Morlion B, et al. European Pain Federation (EFIC) position paper
on appropriate use of cannabis-based medicines and medical
cannabis for chronic pain management. Eur J Pain 2018;
22:1547-64.
8. Allan GM, Finley CR, Ton J, Perry D, Ramji J, Crawford K, et al.
Systematic review of systematic reviews for medical cannabinoids:
pain, nausea and vomiting, spasticity, and harms. Can Fam
Physician 2018;64:e78-94.
9. Hauser W, Petzke F, Fitzcharles MA. Efficacy, tolerability and
safety of cannabis-based medicines for chronic pain management -
an overview of systematic reviews. Eur J Pain 2018;22:455-70.
10. Fitzcharles MA, Baerwald C, Ablin J, Hauser W. Efficacy,
tolerability and safety of cannabinoids in chronic pain associated
with rheumatic diseases (fibromyalgia syndrome, back pain,
osteoarthritis, rheumatoid arthritis): a systematic review of
randomized controlled trials. Schmerz 2016;30:47-61.
11. Fitzcharles MA, Ste-Marie PA, Hauser W, Clauw DJ, Jamal S,
Karsh J, et al. Efficacy, tolerability, and safety of cannabinoid
treatments in the rheumatic diseases: a systematic review of
randomized controlled trials. Arthritis Care Res 2016;68:681-8.
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JM 3rd, Matteson EL. Opioid use in patients with rheumatoid
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14. Ste-Marie PA, Shir Y, Rampakakis E, Sampalis JS, Karellis A,
Cohen M, et al. Survey of herbal cannabis (marijuana) use in
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diagnosis. Pain 2016;157:2792-7.
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Pers onal non -com merc ial use only. The Journal of Rheumatology Copyright © 2019. All rights reserved.
Table 4. Key points associated with use of medical cannabis.
Medical cannabis is defined as the leaves and flowers of the plant family
Cannabaceae.
Cannabis comprises many molecules, of which Δ9-tetrahydrocannabinol
(THC) and cannabidiol (CBD) are the most studied for therapeutic effect.
THC is associated with psychoactive effects whereas CBD is likely to have
pain- and inflammatory-modulating effects.
Herbal cannabis has THC content varying from < 1% to 24% and CBD
content from < 1% to 13%.
There are no studies examining the efficacy of whole plant herbal cannabis
(i.e., medical cannabis) in patients with rheumatic disease.
Studies examining cannabinoid pharmaceutical products reveal limited
benefits and high risk of adverse events.
Patients considering use of medical cannabis should be warned not to drive
or operate machinery for at least 24 h after consumption.
Patients should be warned that their function may be compromised when
working in settings requiring high levels of concentration, optimal executive
functioning, and alertness.
Regular recreational cannabis use is associated with a risk of addiction, but
this risk has not been assessed in medical cannabis users.
Concomitant use of medical cannabis and tranquilizers, antidepressants,
anticonvulsants, or alcohol should be avoided.
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consumption and motor vehicle collision risk: systematic review of
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27. Grant CN, Belanger RE. Cannabis and Canada’s children and youth.
Paediatr Child Health 2017;22:98-102.
28. Harkany T, Keimpema E, Barabas K, Mulder J. Endocannabinoid
functions controlling neuronal specification during brain
development. Mol Cell Endocrinol 2008;1-2 Suppl 1:S84-90.
29. Meier MH, Caspi A, Ambler A, Harrington H, Houts R, Keefe RS,
et al. Persistent cannabis users show neuropsychological decline
from childhood to midlife. Proc Natl Acad Sci U S A
2012;109:E2657-64.
30. Jager G, Ramsey NF. Long-term consequences of adolescent
cannabis exposure on the development of cognition, brain structure
and function: an overview of animal and human research. Curr Drug
Abuse Rev 2008;1:114-23.
31. Mehmedic Z, Chandra S, Slade D, Denham H, Foster S, Patel AS, et
al. Potency trends of ∆9-THC and other cannabinoids in confiscated
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2010;55:1209-17.
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Changes in cannabis potency over the last 2 decades (1995-2014):
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2016;79:613-9.
33. Vardaris RM, Weisz DJ, Fazel A, Rawitch AB. Chronic
administration of delta-9-tetrahydrocannabinol to pregnant rats:
studies of pup behavior and placental transfer. Pharmacol Biochem
Behav 1976;4:249-54.
34. Mourh J, Rowe H. Marijuana and breastfeeding: applicability of the
current literature to clinical practice. Breastfeed Med 2017;
12:582-96.
35. Decuyper I, Ryckebosch H, Van Gasse AL, Sabato V, Faber M,
Bridts CH, et al. Cannabis allergy: what do we know anno 2015.
Arch Immunol Ther Exp 2015;63:327-32.
36. Decuyper I, Van Gasse AL, Cop N, Sabato V, Faber MA, Mertens C,
et al. Cannabis sativa allergy: looking through the fog. Allergy
2017;72:201-6.
37. Abuhasira R, Schleider LB, Mechoulam R, Novack V.
Epidemiological characteristics, safety and efficacy of medical
cannabis in the elderly. Eur J Intern Med 2018;49:44-50.
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health effects of cannabis and cannabinoids: The current state of
evidence and recommendations for research. Washington, DC: The
National Academies Press; 2017.
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marijuana for the treatment of posttraumatic stress disorder: real
symptom re-leaf or just high hopes? Ment Health Clin 2018;
8:86-94.
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Cardiol Rev 2016;24:158-62.
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Cardiovascular complications of marijuana and related substances:
A review. Cardiol Ther 2018 Jun;7:45-59.
7
Fitzcharles, et al: Medicinal cannabis in rheumatic disease
Pers onal non -com merc ial use only. The Journal of Rheumatology Copyright © 2019. All rights reserved.
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... In the absence of RCTs for use of MC and cannabis-based medicines, development of guidelines is problematic leading some medical groups to propose position statements. The Canadian Rheumatology Association (CRA) published a statement in 2019 on MC use in patients with rheumatic diseases, which includes FM [62]. They concluded that there was insufficient evidence about the benefits of cannabinoids but there was evidence of harm. ...
... For all other patients (including FM patients) both statements recommend that cannabinoids may be considered as an individual therapeutic trial, and that the patient be informed concerning the evidence of risks and benefits. Furthermore, treatment must be discontinued if there is lack of efficacy or adverse effects [62,63]. Widespread media coverage has been influential in prompting patients with chronic pain to try herbal cannabis as a therapy. ...
... Pragmatic guidance for prescription use of MC has been provided by the CRA and outlined in Table 2 [62]. Physicians must strive to maintain an empathetic and trusting relationship with patients and be free of bias when there is discussion of cannabis-based medicines. ...
Article
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Nociplastic pain is defined as pain due to sensitization of the nervous system, without a sufficient underlying anatomical abnormality to explain the severity of pain. Nociplastic pain may be manifest in various organ systems, is often perceived as being more widespread rather than localized and is commonly associated with central nervous system symptoms of fatigue, difficulties with cognition and sleep, and other somatic symptoms; all features that contribute to considerable suffering. Exemplified by fibromyalgia, nociplastic conditions also include chronic visceral pain, chronic headaches and facial pain, and chronic musculoskeletal pain. It has been theorized that dysfunction of the endocannabinoid system may contribute to persistent pain in these conditions. As traditional treatments for chronic pain in general and nociplastic pain in particular are imperfect, there is a need to identify other treatment options. Cannabis-based medicines and medical cannabis (MC) may hold promise and have been actively promoted by the media and advocacy. The medical community must be knowledgeable of the current evidence in this regard to be able to competently advise patients. This review will briefly explain the understanding of nociplastic pain, examine the evidence for the effect of cannabinoids in these conditions, and provide simplified guidance for healthcare providers who may consider prescribing cannabinoids for these conditions.
... Cannabis use disorder and withdrawal syndromes also occur [115]. Medicinal cannabis use is not recommended in people under age 25 or who are pregnant or breastfeeding [111,116]. ...
... There are no clinical guidelines for medicinal cannabis available in the USA to date, likely because of the contradictory legal status and highly limited evidence available. Based on our experience, the evidence that does exist, and guidance from the Canadian Rheumatology Association, which incorporates patient perspectives [116], we suggest the following points for clinicians. ...
Article
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Purpose of Review Changing attitudes about marijuana have led to an increase in use of medicinal marijuana, especially for painful chronic conditions. Patients ask rheumatologists for guidance on this topic. This review provides up-to-date information on the safety and efficacy of medicinal cannabis for rheumatic disease pain. Recent Findings The number of publications related to rheumatic disease and cannabis has increased, but recent literature skews heavily toward reviews vs primary research. Data supporting a role for cannabinoids in rheumatic disease continue to grow. Observational and survey studies show increased use of medicinal cannabis, both by people with rheumatic disease and the general population, and suggest that patients find these treatments beneficial. Prospective studies, however, including randomized controlled clinical trials, are rare and sorely needed. Summary As medicinal cannabis use for rheumatic diseases rises, despite lack of evidence, we review the sparse data available and provide tips for conversations about medicinal cannabis for rheumatologists.
Chapter
Cannabis has been well known for centuries due to its medicinal properties. In recent decades, the inclination of researchers towards its important phytoconstituents as a potential therapeutic alternative has been propounded due to the discovery of its major active constituent, i.e., Δ9-tetrahydrocannabinol (Δ9-THC). Besides this, the presence of other phytoproducts, including cannabidiol (CBD), cannabigerol (CBG), cannabichromene (CBC), etc., also contribute towards its medicinal importance. Interestingly, due to the effectiveness of cannabis against various pathological conditions, its use for medicinal purposes has been revolutionized worldwide. Despite these facts, it has become obligatory to explore synergistic interactions and mode of action of its phytoconstituents involving various biological pathways. Current advancements have allowed medical practitioners to better understand cannabis-derived products as a pharmacological choice in several conditions, including pain treatment, stress, anxiety, neurodegenerative disorders, and cancer. However, there exists a lacuna in the literature regarding its beneficial doses. Since medicinal exploration and the legalization of cannabis depend upon various factors, the present review deals with the important phytocannabinoids, their biogenesis, types of drugs obtained, mode of action, therapeutic implications, and new approaches for supporting this plant as a critical therapeutic agent for pharmaceutical drugs. Overall, this may provide an insight into the role of cannabis as a potent candidate for future drug discovery and generate efficient products for human welfare.
Chapter
Bhanga (Cannabis) has been reported with numerous therapeutic, traditional, commercial, and sacred uses in India and across the globe. Its uses are deeply rooted in the cultural, social, and economic lives of the people. The inclusion of Cannabis under ‘Scheduled E1’ drugs in India restricts its use. However, being a crop of economic and medicinal importance, the pharmaceutical and various other sectors are showing much interest in the plant. The present review article delineates traditional, culinary, cosmetic, ritual, social, spiritual, recreational, economic, and therapeutic uses of Cannabis. The review illustrates various uses of Cannabis across the globe; noted from articles, publications, and books providing description of various parts, viz. leaves and seeds (Bhanga), flowering and fruiting tops (Ganja), resin (Charas), extract, tincture, and whole plant, stalks (Fibers). The review may be helpful to researchers, clinicians, and pharmaceutical companies to carry out further research for developing cost-effective healthcare options.
Article
Objectives: Cannabinoids have gained popularity recently with special emphasis on their use for chronic pain. Although NICE guidelines advise against their usage for management of chronic pain, almost all rheumatologists encounter a few patients in their daily practice who either use them or are curious about them. We reviewed the mechanism of action of cannabinoids, current knowledge about their role in rheumatology and potential drug interactions with common drugs used in Rheumatology. We attempted to answer the question "If cannabinoids are friend, foe or just a mere bystander?" Methods: We adhered to a search strategy for writing narrative reviews as per available guidelines. We searched PubMed with the search terms "Cannabinoids", "Rheumatology" and "Chronic pain" for published articles and retrieved 613 articles. The abstracts and titles of these articles were screened to identify relevant studies focusing on mechanism of actions, adverse effects and drug interactions. We also availed the services of a musculoskeletal librarian. Results: Despite the NHS guidelines against the usage of cannabinoids and associated significant stigma, cannabinoids are increasingly used for the management of pain in rheumatology without prescription. Cannabinoids act through two major receptors CB1 and CB2, which are important modulators of the stress response with potential analgesic effects. Their role in various rheumatological diseases including Rheumatoid arthritis, Osteoarthritis and Fibromyalgia have been explored with some benefits. However, in addition to the adverse effects, cannabinoids also have some potential interactions with common drugs used in rheumatology, which many users are unaware of. Conclusion: While the current studies and patient reported outcomes suggest cannabinoids to be a "friend" of rheumatology, their adverse events and drug interactions prove to be a "Foe". We were unable to arrive at a definite answer for our question posed, however on the balance of probabilities we can conclude cannabinoids to be a "foe". Under these circumstances, a disease and drug focussed research is need of the hour to answer the unresolved question.
Article
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Background: Medical cannabis has been legal in Canada since 2001, and recreational cannabis was legalized in October 2018, which has led to a widespread increase in the accessibility of cannabis products. Aims: This study aimed to estimate the prevalence of cannabis use among adults living with chronic pain (CP) and investigate the relationship between age and cannabis use for CP management. Methods: A cross-sectional analysis of the COPE Cohort data set, a large Quebec sample of 1935 adults living with CP, was conducted. Participants completed a web-based questionnaire in 2019 that contained three yes/no questions about past-year use of cannabis (i.e., for pain management, management of other health-related conditions, recreational purposes). Results: Among the 1344 participants who completed the cannabis use section of the questionnaire, the overall prevalence of cannabis use for pain management was 30.1% (95% confidence interval 27.7-32.7). Differences were found between age groups, with the highest prevalence among participants aged ≤26 years (36.5%) and lowest for those aged ≥74 years (8.8%). A multivariable logistic model revealed that age, region of residence, generalized pain, use of medications or nonpharmacological approaches for pain management, alcohol/drug consumption, and smoking were associated with the likelihood of using cannabis for pain management. Conclusions: Cannabis is a common treatment for the management of CP, especially in younger generations. The high prevalence of use emphasizes the importance of better knowledge translation for people living with CP, rapidly generating evidence regarding the safety and efficacy of cannabis, and clinicians' involvement in supporting people who use cannabis for pain management.
Chapter
Rheumatic diseases include inflammatory arthritis of which rheumatoid arthritis is the most common, as well as degenerative arthritis including peripheral and spinal osteoarthritis and the spectrum of soft tissue rheumatic complaints of tendonitis and bursitis. The Pain Management Task Force of the American College of Rheumatology has acknowledged pain management as a critical aspect of the medical management of patients with rheumatic diseases. The major stimulus initiating pain in an active inflammatory process is the outpouring of inflammatory molecules at the local tissue site. Pain management must be tailored to the individual patient, taking into account age, comorbidity, specific rheumatic process, involved pain mechanisms and personal beliefs of the patient. Any pain management strategy must begin with non‐pharmacologic management. Patients with rheumatic pain use herbal products and dietary interventions extensively.
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Neuropathic pain represents a broad category of pain syndromes that include a wide variety of peripheral and central disorders. The overall prevalence of neuropathic pain in the general population is reported to be between 7 and 10%. Management of neuropathic pain presents an unmet clinical need, with less than 50% of patients achieving substantial pain relief with medications currently recommended such as pregabalin, gabapentin, duloxetine and various tricyclic antidepressants. It has been suggested that cannabis-based medicines (CbMs) and medical cannabis (MC) may be a treatment option for those with chronic neuropathic pain. CbMs/MC are available in different forms: licensed medications or medical products (plant-derived and/or synthetic products such as tetrahydrocannabinol or cannabidiol); magistral preparations of cannabis plant derivatives with defined molecular content such as dronabinol (tetrahydrocannabinol); and herbal cannabis with a defined content of tetrahydrocannabinol and/or cannabidiol, together with other active ingredients (phytocannabinoids other than cannabidiol/tetrahydrocannabinol, terpenes and flavonoids). The availability of different types of CbMs/MC varies between countries worldwide. Systematic reviews of available randomised controlled trials have stated low-quality evidence for CbMs and MC for chronic neuropathic pain. Depending on the studies included in the various quantitative syntheses, authors have reached divergent conclusions on the efficacy of CbMs/MC for chronic neuropathic pain (from not effective to a clinically meaningful benefit). Clinically relevant side effects of CbMs/MC, especially for central nervous system and psychiatric disorders, have been reported by some systematic reviews. Recommendations for the use of CbMs/MC for chronic neuropathic pain by various medical associations also differ, from negative recommendations, no recommendation possible, recommended as third-line therapy, or recommended as an alternative in selected cases failing standard therapies within a multimodal concept. After reading this paper, readers are invited to formulate their own conclusions regarding the potential benefits and harms of CbMs/MC for the treatment of chronic neuropathic pain.
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Under the Access to Cannabis for Medical Purposes (ACMPR)1 section of Canada’s cannabis regulations, which came into effect with the Cannabis Act on October 17, 2018, access to medical cannabis is authorized by a physician who signs a medical document. Authorized patients may purchase cannabis from a federally licensed producer, designate another person to produce it for them, or register to produce it themselves.2 Physicians do not prescribe cannabis since it is not a Health Canada–registered medication with a Drug Identification Number. The ACMPR medical document is an authorization for the use of cannabis for medical purposes, and, while the authorizing physician is encouraged to offer guidance on the form, strength, and dose, the dispensed form, dose, and titration are ultimately determined by the licensed producer. Under the Cannabis Act 2018, the use of cannabis for recreational purposes became legal (except for edible cannabis, cannabis extracts, and cannabis topicals, which became lawfully produced and sold as of October 17, 2019; see Table 1). Cannabis for recreational purposes differs from cannabis for medical purposes in that Health Canada does not regulate recreational cannabis production, possession, and distribution in the same way it does for cannabis for medical purposes. The basic facts and advice on safe consumption of recreational cannabis are summarized in the Government of Canada fact sheet.3 Provinces differ in their guidance and regulatory oversight for cannabis use.4 Provincial medical colleges, in the absence of regulatory oversight and approval, issued statements and guidance to comply with federal and provincial regulations (see the list of regulators provided under Recommendation 6). The Cannabis Act legalized recreational cannabis use and proposed a framework for the use of medical cannabis in Canada. However, it remains illegal to carry any cannabis with you when entering or leaving Canada, whether it is for medical or recreational purposes. Before cannabis use legalization, little research had been conducted on its therapeutic use, safety, or efficacy. This situation puts family physicians in a difficult position, as they are asked to authorize their patients’ access to a product with little evidence to support its use. To address this predicament, this document offers family physicians guidance on authorizing cannabis use for some specific conditions. Although the old Access to Cannabis for Medical Purposes regulations spoke only of use for medical purposes without specifying any diagnoses, the writing group chose chronic pain and anxiety as the original clinical areas of focus because they are the most common conditions for which a patient requests authorization. Since the original 2014 version was released, we have updated the document, added content, and broadened the scope of discussion beyond chronic pain and anxiety. Cannabis is the raw plant material, composed of hundreds of different compounds, that serves as the source for non-pharmaceutically produced medical cannabis, including material for smoking and vaping as well as for edibles and concentrates. The two chemicals from the cannabis plant discussed are tetrahydrocannabinol (THC) and cannabidiol (CBD).Research shows that cannabis could be a potent psychoactive substance with a risk of acute and chronic adverse effects of varying severity. Its most common acute effects include perceptual distortions, cognitive impairment, euphoria, and anxiety.5 Chronic use of cannabis may be associated with persistent neuropsychological deficits, even after a period of abstinence.6, 7 The frequency and intensity vary based on the proportional content of psychoactive ingredients and on other factors including extent of use, age of first use, and length of abstinence.8 Medium- and long-term therapeutic and adverse effects of medical and recreational cannabis have not been sufficiently studied. Products containing THC have a known abuse and dependence potential (liability). It is recommended that family physicians consider the anticipated therapeutic benefits versus potential harms for a patient’s health condition before authorizing initial or continuing cannabis use. As with any other therapeutic approach, continuing cannabis use is warranted only if the authorizing physician is satisfied that there has been improvement in the patient’s presenting symptoms (e.g., pain level), function, and/or quality of life; the risk of cannabis use disorder has been reassessed; and the benefits outweigh potential harms.
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Cannabis‐based medicines are being approved for pain management in an increasing number of European countries. There are uncertainties and controversies on the role and appropriate use of cannabis‐based medicines for the management of chronic pain. EFIC convened a European group of experts, drawn from a diverse range of basic science and relevant clinical disciplines, to prepare a position paper to empower and inform specialist and non‐specialist prescribers on appropriate use of cannabis‐based medicines for chronic pain. The expert panel reviewed the available literature and harnessed the clinical experience to produce these series of recommendations. Therapy with cannabis‐based medicines should only be considered by experienced clinicians as part of a multidisciplinary treatment and preferably as adjunctive medication if guideline‐recommended first and second line therapies have not provided sufficient efficacy or tolerability. The quantity and quality of evidence are such that cannabis‐based medicines may be reasonably considered for chronic neuropathic pain. For all other chronic pain conditions (cancer,non‐neuropathic non‐cancer pain), the use of cannabis‐based medicines should be regarded as an individual therapeutic trial. Realistic goals of therapy have to be defined. All patients must be kept under close clinical surveillance. As with any other medical therapy, if the treatment fails to reach the predefined goals and/or the patient is additionally burdened by an unacceptable level of adverse effects and/or there are signs of abuse and misuse of the drug by the patient, therapy with cannabis‐based medicines should be terminated. This article is protected by copyright. All rights reserved.
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Introduction: The incidence of posttraumatic stress disorder (PTSD) is common within the population and even more so among veterans. Current medication treatment is limited primarily to antidepressants. Such medicines have shown to produce low remission rates and may require 9 patients to be treated for 1 to have a response. Aside from the Veterans Affairs/Department of Defense guidelines, other guidelines do not recommend pharmacotherapy as a first-line option, particularly in the veteran population. Marijuana has been evaluated as an alternative and novel treatment option with 16 states legalizing its use for PTSD. Methods: A systematic search was conducted to evaluate the evidence for the use of marijuana for PTSD. Studies for the review were included based on a literature search from Ovid MEDLINE and Google Scholar. Results: Five studies were identified that evaluated the use of marijuana for PTSD. One trial was conducted in Israel and actively used marijuana. Three studies did not use marijuana in the treatment arm but instead evaluated the effects postuse. A retrospective chart review from New Mexico relied on patients to recall their change in PTSD symptoms when using marijuana. Three studies concluded there might be a benefit, but two discouraged its use. Although the two negative studies show a statistical difference in worse PTSD outcomes, clinical significance is unclear. Discussion: Conflicting data exist for the use of marijuana for PTSD; however, current evidence is limited to anecdotal experiences, case reports, and observational studies, making it difficult to make clinical recommendations.
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Objective: To determine the effects of medical cannabinoids on pain, spasticity, and nausea and vomiting, and to identify adverse events. Data sources: MEDLINE, the Cochrane Database, and the references of included studies were searched. Study selection: Systematic reviews with 2 or more randomized controlled trials (RCTs) that focused on medical cannabinoids for pain, spasticity, or nausea and vomiting were included. For adverse events, any meta-analysis for the conditions listed or of adverse events of cannabinoids was included. Synthesis: From 1085 articles, 31 relevant systematic reviews were identified including 23 for pain, 5 for spasticity, 6 for nausea and vomiting, and 12 for adverse events. Meta-analysis of 15 RCTs found more patients taking cannabinoids attained at least a 30% pain reduction: risk ratio (RR) of 1.37 (95% CI 1.14 to 1.64), number needed to treat (NNT) of 11. Sensitivity analysis found study size and duration affected findings (subgroup differences,P≤ .03), with larger and longer RCTs finding no benefit. Meta-analysis of 4 RCTs found a positive global impression of change in spasticity (RR = 1.45, 95% CI 1.08 to 1.95, NNT = 7). Other results were not consistently statistically significant, but when positive, a 30% or more improvement in spasticity had an NNT of 10. Meta-analysis of 7 RCTs for control of nausea and vomiting after chemotherapy found an RR of 3.60 (95% CI 2.55 to 5.09) with an NNT of 3. Adverse effects caused more patients to stop treatment (number needed to harm [NNH] of 8 to 22). Individual adverse events were very common, including dizziness (NNH = 5), sedation (NNH = 5), confusion (NNH = 15), and dissociation (NNH = 20). "Feeling high" was reported in 35% to 70% of users. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) evaluation reduced evidence ratings of benefit to low or very low. Conclusion: There is reasonable evidence that cannabinoids improve nausea and vomiting after chemotherapy. They might improve spasticity (primarily in multiple sclerosis). There is some uncertainty about whether cannabinoids improve pain, but if they do, it is neuropathic pain and the benefit is likely small. Adverse effects are very common, meaning benefits would need to be considerable to warrant trials of therapy.
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Objective: To develop a clinical practice guideline for a simplified approach to medical cannabinoid use in primary care; the focus was on primary care application, with a strong emphasis on best available evidence and a promotion of shared, informed decision making. Methods: The Evidence Review Group performed a detailed systematic review of 4 clinical areas with the best evidence around cannabinoids: pain, nausea and vomiting, spasticity, and adverse events. Nine health professionals (2 generalist family physicians, 2 pain management-focused family physicians, 1 inner-city family physician, 1 neurologist, 1 oncologist, 1 nurse practitioner, and 1 pharmacist) and a patient representative comprised the Prescribing Guideline Committee (PGC), along with 2 nonvoting members (pharmacist project managers). Member selection was based on profession, practice setting, location, and lack of financial conflicts of interest. The guideline process was iterative through content distribution, evidence review, and telephone and online meetings. The PGC directed the Evidence Review Group to address and provide evidence for additional questions as needed. The key recommendations were derived through consensus of the PGC. The guideline was drafted, refined, and distributed to a group of clinicians and patients for feedback, then refined again and finalized by the PGC. Recommendations: Recommendations include limiting medical cannabinoid use in general, but also outline potential restricted use in a small subset of medical conditions for which there is some evidence (neuropathic pain, palliative and end-of-life pain, chemotherapy-induced nausea and vomiting, and spasticity due to multiple sclerosis or spinal cord injury). Other important considerations regarding prescribing are reviewed in detail, and content is offered to support shared, informed decision making. Conclusion: This simplified medical cannabinoid prescribing guideline provides practical recommendations for the use of medical cannabinoids in primary care. All recommendations are intended to assist with, not dictate, decision making in conjunction with patients.
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