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Cannabis and intractable chronic pain: An explorative retrospective analysis of Italian cohort of 614 patients

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Background Despite growing interest in the therapeutic use of cannabis to manage chronic pain, only limited data that address these issues are available. In recent years, a number of nations have introduced specific laws to allow patients to use cannabis preparations to treat a variety of medical conditions. In 2015, the Italian government authorized the use of cannabis to treat several diseases, including chronic pain generally, spasticity in multiple sclerosis, cachexia and anorexia among AIDS and cancer patients, glaucoma, Tourette syndrome, and certain types of epilepsy. We present the first snapshot of the Italian experience with cannabis use for chronic pain over the initial year of its use. Methods This is a retrospective case series analysis of all chronic pain patients treated with oral or vaporized cannabis in six hubs during the initial year following the approval of the new Italian law (December 2015 to November 2016). We evaluated routes of administration, types of cannabis products utilized, dosing, and effectiveness and safety of the treatment. Results As only one of the six centers has extensively used cannabinoids for intractable chronic pain (614 patients of 659), only the population from Azienda Ospedaliero Universitaria Pisana (Pisa) was considered. Cannabis tea was the primary mode of delivery, and in almost all cases, it was used in association with all the other pain treatments. Initial and follow-up cannabinoid concentrations were found to vary considerably. At initial follow-up, 76.2% of patients continued the treatment, and <15% stopped the treatment due to side effects (none of which were severe). Conclusion We present the first analysis of Italian clinical practice of the use of cannabinoids for a large variety of chronic pain syndromes. From this initial snapshot, we determined that the treatment seems to be effective and safe, although more data and subsequent trials are needed to better investigate its ideal clinical indication.
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ORIGINAL RESEARCH
open access to scientific and medical research
Open Access Full Text Article
http://dx.doi.org/10.2147/JPR.S132814
Cannabis and intractable chronic pain: an
explorative retrospective analysis of Italian
cohort of 614 patients
Guido Fanelli1,2
Giuliano De Carolis3
Claudio Leonardi4
Adele Longobardi5,6
Ennio Sarli7,8
Massimo Allegri1,2
Michael E Schatman9
1Anesthesia, Critical Care and
Pain Medicine Unit, Division of
Surgical Sciences, Department of
Medicine and Surgery, University
of Parma, 2Anesthesia, Intensive
Care and Pain Therapy Service,
Azienda Ospedaliero Universitaria
Parma, Parma, 3Pain Therapy Service,
Azienda Ospedaliero Universitaria
Pisana, Pisa, 4Department of Drug
Addiction Diseases, Local Public
Health of Rome, Rome, 5Department
of Neurosciences, Reproductive and
Odontostomatological Sciences,
University of Naples “Federico II”,
Naples, 6Young Against the Pain (YAP)
Group, Parma, 7Progetti Live Surgery,
8PinHub Group, Florence, Italy;
9Department of Public Health and
Community Medicine, Tufts University
School of Medicine, Boston, MA, USA
Background: Despite growing interest in the therapeutic use of cannabis to manage chronic
pain, only limited data that address these issues are available. In recent years, a number of nations
have introduced specific laws to allow patients to use cannabis preparations to treat a variety
of medical conditions. In 2015, the Italian government authorized the use of cannabis to treat
several diseases, including chronic pain generally, spasticity in multiple sclerosis, cachexia and
anorexia among AIDS and cancer patients, glaucoma, Tourette syndrome, and certain types of
epilepsy. We present the first snapshot of the Italian experience with cannabis use for chronic
pain over the initial year of its use.
Methods: This is a retrospective case series analysis of all chronic pain patients treated with
oral or vaporized cannabis in six hubs during the initial year following the approval of the new
Italian law (December 2015 to November 2016). We evaluated routes of administration, types
of cannabis products utilized, dosing, and effectiveness and safety of the treatment.
Results: As only one of the six centers has extensively used cannabinoids for intractable chronic
pain (614 patients of 659), only the population from Azienda Ospedaliero Universitaria Pisana
(Pisa) was considered. Cannabis tea was the primary mode of delivery, and in almost all cases,
it was used in association with all the other pain treatments. Initial and follow-up cannabinoid
concentrations were found to vary considerably. At initial follow-up, 76.2% of patients continued
the treatment, and <15% stopped the treatment due to side effects (none of which were severe).
Conclusion: We present the first analysis of Italian clinical practice of the use of cannabinoids
for a large variety of chronic pain syndromes. From this initial snapshot, we determined that the
treatment seems to be effective and safe, although more data and subsequent trials are needed
to better investigate its ideal clinical indication.
Keywords: cannabis, cannabinoids, chronic pain, safety, cannabidiol
Background
The past years have witnessed a growing interest in the therapeutic use of cannabis
and its constituents to manage chronic pain.1 Irrespective of the number of new trials
examining the use of cannabinoids for chronic pain, the evidence of its effectiveness
and its safety remains limited.2 The pharmacology of Cannabis sativa (the strain
generally used to treat chronic pain) is quite complex, as it contains ~100 distinct
cannabinoids,3 the relative levels of which largely determine their therapeutic effect.4
Of the numerous cannabinoids, 9-tetrahydrocannabinol (9-THC) is considered the
most psychoactive.5,6 The current definition of cannabinoids includes all endogenous
and exogenous compounds that act on cannabinoid receptors.7
Correspondence: Guido Fanelli
Department of Medicine and Surgery,
University of Parma, Via Gramsci, 43126
Parma, Italy
Tel +39 05 2170 3965
Email guido.fanelli@unipr.it
Journal name: Journal of Pain Research
Article Designation: ORIGINAL RESEARCH
Year: 2017
Volume: 10
Running head verso: Fanelli et al
Running head recto: Cannabis for the treatment of chronic pain
DOI: http://dx.doi.org/10.2147/JPR.S132814
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THC is not the only cannabinoid with therapeutic
effects8, as cannabidiol (CBD) is used in the treatment
of several different conditions. CBD is important not
only for its therapeutic effects but also for its ability to
mitigate euphoria and other side effects caused by THC,9
thereby increasing the potential therapeutic applications of
cannabis. A lack of standardized dosing and uncertainty
regarding the ideal ratio between THC and CBD continue
to limit the medicinal usage of marijuana.10 A review by
Koppel et al11 analyzed six different neurological disease
states and symptoms and a variety of THC/CBD ratios
and methods of administration (e.g., oral, oromucosal,
and inhaled) without obtaining clear evidence for specific
indications. As there are numerous products containing
myriad THC/CBD ratios, it remains extremely challenging
to draw reproducible data regarding their effectiveness in
the treatment of pain.10
There are several methods of administration of cannabi-
noids including smoking, orally (by infusion or by extraction
in oil, as well as through edible products), vaporizing, and
transdermally. While smoking remains the most common
form of administration, a recent study found that in jurisdic-
tions in which medical marijuana is legal, smoking is not
necessarily the preferred route of administration.12 However,
variance in routes of administration makes comparison of
results of different studies questionable. As a number of
different compounds and methods of administration exist,
thorough education of the physician (as well as the patient)
is imperative prior to prescribing or recommending these
compounds.13
The most comprehensive meta-analysis of inhaled can-
nabis for chronic pain to date14 has recently supported its
short-term effectiveness in treating neuropathic pain. The
authors also concluded that more studies are needed in
order to evaluate long-term effectiveness and safety. These
conclusions are consistent with those from Schatman’s
2015 comprehensive review.10 Regarding safety, Aggarwal15
opined that although “little data are available on the risks
associated with long-term medical use in published clinical
trials,” it can still be used to treat complex chronic pain
conditions. More recently, Ware et al16 published a 1-year
follow-up trial in order to better investigate the long-term
efficacy and safety. The median dose of cannabis was
2.5 g daily. The authors did not find differences in serious
adverse events between chronic pain patients treated with
or without cannabis. Nevertheless, a higher incidence of
mild adverse effects was registered among patients treated
with cannabis.
Even though the evidence is still weak and more studies
are needed, there is significantly increasing availability of
cannabis to treat chronic pain in several different countries,
especially in the US and Canada.17 Understanding of complex
policy and public health issues is imperative in order to fully
understand the distinction between medical vs. recreational
utilization of cannabis. Savage et al recently concluded that
there is a need not only for additional empirical investigation
but also for increased research funding to help us develop
a better understanding of how to make cannabinoids more
effective and safer.17
Questions have also been raised regarding the legitimacy
of dispensaries’ clientele.10 It has been demonstrated that
most dispensary customers had initiated marijuana use in
adolescence, with one-half presenting with indications of
risky alcohol use and 20% presenting with recent histories
of prescription medication or illicit drug abuse.15
Hence, many concerns are arising regarding the distinct
possibility that in the US and Canada, some of the same
problems that these nations have had with prescription opioid
abuse will potentially develop in relationship to “medical”
marijuana. Currently, the US is aggressively fighting its
opioid crisis while simultaneously liberalizing access to
cannabis – for both medical and recreational utilization.18
An Italian law approved in 201519 authorizes the use
of cannabis to treat chronic pain. The law allows for the
utilization of cannabis not only for neuropathic pain but
also for all chronic pain conditions, as well as for spasticity,
cachexia, and anorexia among AIDS and cancer patients,
ocular hypertension in glaucoma, the alleviation of spasms
in Tourette syndrome, and some types of epilepsy, reiterating
that cannabis-based drugs should be prescribed only “when
other available medications have proven to be ineffective or
inadequate to the therapeutic needs of the patient.”
In order to reduce the costs of cannabinoid products, the
Italian government in 2014 committed its Military Chemical-
Pharmaceutical Factory to cultivate cannabis to be distributed
to all pharmacies across the country (initial production is
scheduled for early in 2017). In the meantime, physicians can
legally prescribe different cannabis products (such as Bedrocan,
Bediol, and Bedrolite), with different THC and CBD concen-
trations; these drugs can be administered orally (e.g., through
infusions in olive oil) or via inhalation. Bedrocan’s constituents
are 22% THC and <1% CBD, while Bediol contains 6.5% THC
and 8% CBD and Bedrolite contains 9% CBD and 0.4% THC
and is accordingly considered “non-psychoactive.20
All patients treated with cannabinoids have to be regis-
tered through a Ministry of Health database. In recent months,
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Cannabis for the treatment of chronic pain
the society that includes all second-level (hubs) pain centers
(PinHub, www.pinhub.it) has received a directive to evaluate
all of these data among its centers.
This paper presents a retrospective analysis of a case
series of all chronic pain patients treated in one PinHub center
over the past year in order to provide a snapshot of the initial
Italian experience with legalized cannabis use for chronic
pain. The end point of this study has been the evaluation
and identification of clinical indications and dosages cur-
rently used in second-level center of pain therapy. Although
our intention was to include data from all six of the centers
initially involved in the study, a paucity of data from five of
the six centers precluded doing so.
Methods
Following the approval of the Italian law sanctioning the medi-
cal use of cannabis (2015), all patients who initiated the use of
medical cannabis have had to be registered, with their consent,
in a database to evaluate specific data (Figure 1). A retrospec-
tive group analysis of a case series of all chronic pain patients
treated in one of the second-level pain clinics affiliated with
the PinHub group in the first year following the approval
of the Italian law (December 2015 to November 2016) was
performed. The clinical centers intended to be involved in this
study were the pain therapy services of the following hospitals:
SS Antonio e Biagio Hospital (Alessandria), SS Annunziata
Hospital (Chieti), Monaldi Hospital (Naples), Verona Univer-
sity Hospital (Verona), Siena University Hospital (Siena), and
Azienda Ospedaliera Universitaria Pisana (Pisa).
Patients gave their permission to use their data when the
physician filled out the case report form (CRF). This research
did not require approval by the Institutional Review Boards
of the aforementioned clinical centers as we used only raw
data that was completely de-identified and anonymous. The
data were presented in accordance with the Strengthening
the Reporting of Observational Studies in Epidemiology
(STROBE) guidelines.21
This study evaluated all patients registered as they had
initiated treatment with cannabinoids for chronic pain based
upon the judgment of their pain therapists. In accordance with
the Italian law, all patients treated with cannabinoids have
had to be 18 years of age and determined to suffer from
refractory chronic pain. According to Italian law, cannabis
could be prescribed with only two routes of administration:
orally (infusion or extraction in olive oil) or through inhala-
tion. Smoking the cannabis is not permitted, so vaporiza-
tion was the technique used for inhalation. Currently, there
are no national guidelines to be followed by physicians.
Furthermore, comorbidities and their severity that might
preclude the treatment are not commonly predefined among
the centers that are using this treatment.
The primary end point of this study was to provide insight
into how the Italian second-level pain centers are utilizing
medical cannabinoids in terms of routes of administration.
Secondary end points included the determination of the
types of cannabis products most commonly utilized, as well
as dosing.
Participating physicians were able to choose among infu-
sion or inhalation via vaporization of the following types of
cannabinoid products: pure Bediol, Bediol combined with
Bedrocan, pure Bedrocan and Bedrolite, and oil infused with
Bedrocan. As ~92% of the patients in the study used the high-
THC, low-CBD Bedrocan, it was unable to assess differences
in efficacy and adverse events between the strains utilized in
this preliminary investigation (Figure 1).
Furthermore, the study evaluated effectiveness and
safety through the analysis of patients who had at least one
follow-up subsequent to initial prescription based on the data
provided by the CRFs defined by the Italian Health Ministry.
Through the data requested by the Italian Health Minis-
try for follow-up purposes, the study evaluated the dosages
utilized, whether the therapy has been continued, clinical effi-
cacy (determined by patient-reported levels of pain severity),
and the reason for discontinuing treatment (pain worsened,
pain not clinically improved, or presence of intolerable side
effects). Although assessing other outcomes such as function-
ality would have been useful, the Italian Health Ministry has
requested the provision only of data pertaining to pain relief.
Data have been obtained by the CRF requested by the
Italian Health Ministry that has to be filled whenever patients
initiated the therapy or had subsequent contact with the pain
center at which they were being treated.
Statistical analysis
The sample size was not calculated a priori as this study
was an explorative retrospective analysis of all patients
treated with cannabinoids for a year in second-level centers
in Italy after the approval of the law that legalized their use
for chronic pain.
All data are presented with percentages or means, as well
as standard deviations. As this initial study is a case series,
it is not surprising that the data are quite heterogeneous.
However, the authors chose not to formally evaluate any
statistical differences between the different treatments, as
there were insufficient number of subjects using any product
besides Bedrocan.
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Fanelli et al
Pilot project for Italian production of cannabis and its derivatives
Case record form for cannabis-based therapies
Region Hospital
PRESCRIBER
PATIENT
PRESCRIPTION
Weight of cannabis dose
Administration method
THERAPY
Use of medical cannabis Replacement of conventional treaments Integration therapy
First prescription
Continuation of therap
yImproved symptoms Symptoms unchanged
Side effects Symptoms unchangedWorsening symptoms
Date of interruption
Interruption of therap
y
Continuation therapy Interruption of therapy
Indications for use
Spasticity associated pain (multiple sclerosis, spinal cord injury) resistant to conventional therapies
Neuropathic chronic pain resistant to conventional therapies
Nausea and vomiting associated with cancer chemotherapeutic agents, radiation therapy, HIV therapy
Cachexia, anorexia in patients with cancer, AIDS, and anorexia nervosa
Glaucoma
Gilles de Ia Tourette syndrome motor and phonic tics
Other
Oral Inhalation
Other
Name
Telephone
Surname
Alphanumeric code Age Gender MF
Cannabis FM2 Cannabis FM19 Imported
Treatment plan date Duration (days)
Daily dose
Number of daily administrations
(Following law 94/98 article 5 comma 3)
Hospital doctor / specialist Primary care physician
specialty
Mailing address
Figure 1 (Continued)
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Cannabis for the treatment of chronic pain
Results
Of the 659 patients who initiated treatment with oral cannabis
at all of the facilities originally intending to participate in the
study, the study included only the subjects from the Azienda
Ospedaliero Universitaria Pisana (Pisa) for the analysis of
data. As only 6% of the patients came from the other five
facilities, a comparison of inter-facility data would not have
been possible. On a positive note, utilizing only the data from
the Azienda Ospedaliero Universitaria Pisana also allowed
for a more homogeneous evaluation of current treatment. Of
all the subjects, 181 were male and 422 were female, and data
on gender were missing for 11 subjects. The average age of
subjects was 61.33 (±15.29) years. Of 614 patients whose
data were used, 341 (55.5%) had at least one follow-up at
Figure 1 Case report form, approved by the Italian Health Ministry, used by clinicians who prescribed cannabis to patients.
Note: This is an English translation of the original version of the form, which was presented in Italian. FM2 and FM19 are specic varieties of cannabis preparations made by
the Italian Military Pharmacy. FM2 contains THC 6% and cannabidiol 6–9%; FM19 contains only THC 19%.
ONLY FOR FIRST PRESCRIPTION
Conventional therapy
Patient already treated with cannabis
If you notice unexpected side effects, please note it
Previous treatment has no side effects
Product
Dose
Observations
Signature
Place Date
Last intake of cannabis
Treatment duration < 6 months 6–12 months > 12 months
Unchanged symptoms
Side effects
Improved symptoms
Worsening symptoms
Previous treatment has side effect
Treatment requiring doses that could be harmful
Other
1.0%
5.7%
0.2%
91.9%
0.7%
0.7%
Data missing
Bediol
Bediol Bedrocan
Bedrocan
Bedrocan in olive oil
Bedrolite
0.0% 20.0% 40.0%
Cannabinoid type prescribed (%)
60.0% 80.0%
100.0%
Figure 2 Type of cannabinoids prescribed.
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Fanelli et al
98.42 (±144.66) days. Figure 2 illustrates the type of cannabis
product used, by percentage. Figure 3 indicates the specific
symptoms for which physicians initiated cannabis treatment.
In 89.2% of patients, cannabis was prescribed without
discontinuing their previous analgesic therapy. At initial
follow-up, 76.2% patients continued the cannabinoid therapy
(of whom 64.7% reported an improvement associated with
the therapy, while 34.1% reported neither an improvement
nor a worsening), and 23.8% discontinued treatment (3.7%
due to a worsening of their pain, 61.7% due to side effects,
29.6% due to an unsatisfactory change of their clinical condi-
tion; for 4.9% of patients, the data were missing). There were
no complaints of severe side effects, even though this may
not have been directly assessed at follow-up visits. Figure 4
illustrates the dosages (mg/day) of Bedrocan and Bediol at
the initiation of the study and at initial follow-up, respectively.
Discussion
Over the past year, a dramatic increase in the use of can-
nabis to treat chronic intractable pain has been witnessed.11
Nevertheless, specific guidelines are still missing, and there is
considerable heterogeneity in the use of this drug throughout
the world. In Italy, cannabis was approved legally 18 months
ago for its use for several indications, including treatment
of intractable pain (not specifically neuropathic pain). All
patients who initiated treatment with cannabis had been
required to be registered in a specific national database in
order to evaluate the clinical effectiveness and safety of can-
nabis in the 2 years immediately following its legalization.
Hence, a retrospective analysis of a case series of patients
treated in a second-level pain clinic that is a part of the
PinHub society was performed. This analysis attempted to
provide an initial snapshot of how cannabinoids are used in
Italy in order to understand how cannabis is currently used
for chronic pain treatments and its implications for clinical
practices.
The initial data that were obtained are those only from
one of the six centers that have extensively used canna-
binoids for intractable chronic pain. It was observed that
cannabinoid treatment is not yet common, even though the
10.6
91
2.3
2.9
61.7
0102030
Reason for cannabinoid prescription (%)
40 50 60 70 80 90 10
0
Pain in diseases with spasticity (i.e., multiple sclerosis)
Chronic pain (especially neuropathic) not responsive
Nausea and vomiting after chemotherapy or in HIV
Cachexia
Other
Figure 3 Reasons for which cannabinoids have been prescribed.
69.52
Bediol
Initiation of the study and initial follow-up: Bedron and Bedrocan mean dosages
SD
76.22
SD
44.3 SD
58.75
SD
45.54
Mean at the initiation of the study
Mean at initial follow-up
58.29
67.02
Bedrocan
56.69
Dosages (mg/day)
50
54
58
62
66
70
74
78
82
Figure 4 Mean of dosages (mg/day) of Bediol and Bedrocan at the rst visit and at the rst follow-up.
Abbreviation: SD, standard deviation.
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Cannabis for the treatment of chronic pain
new law has been approved. This situation could be com-
pared to a similar situation observed in Italy several years
ago with regard to opioids; despite the passage of legisla-
tion intended to facilitate opioid prescription, several years
passed prior to the initiation of an appropriate increase in
opioid prescription.
The population in this investigation that was treated was
similar to that generally observed in pain clinics (average
age of 61 years, and majority being female). Regarding
the type of cannabinoid and modality of administration,
almost all patients received infusions of Bedrocan, while
administration of the extract of cannabinoids in olive oil or
vaporization was quite uncommon. Hence, as these data are
quite discrepant from those from Canada and the US, it is
extremely difficult to compare the effectiveness and safety
of the treatment to those data from studies performed in
other nations. This heterogeneity currently limits the pos-
sibility of developing guidelines available and useful on an
international basis. Although the method of administration
in this study was relatively homogeneous, a large variety (as
demonstrated through a large standard deviation) of concen-
trations (especially for Bediol) used both at the initiation
of treatment and (even more so) at the first follow-up was
observed. Furthermore, in Italy, a formidable variety of indi-
cations for the prescription of cannabinoids. Several types of
chronic pain syndromes have been treated. In order to obtain
more reproducible data, in the near future, the authors intend
to better focalize indications for specific pain syndromes,
such as intractable neuropathic pain. That a low rate (22%)
of discontinuation of cannabinoids (certainly compared to
discontinuation rates of opioid analgesics) was observed is
clearly encouraging, particularly given that the iatrogeneses
of cannabinoids in pain treatment are likely less substantial
than those of opioids.
This study has several important limitations. First, it is a
retrospective analysis of only one center, and unfortunately,
we are compelled to acknowledge that this somewhat limits
our understanding of the efficacy of medical cannabinoids for
chronic pain. Accordingly, we will continue to collect data
from the five hospitals other than the Azienda Ospedaliero
Universitaria Pisana and intend to publish data that will
address inter-facility variance in outcomes. Second, future
investigation will analyze the impact of concomitant treat-
ments, which will require a sufficient number of subjects for
the performance of analyses of covariance. Thus, we expect to
move toward a better understanding of whether cannabinoid
products are more effective as a monotherapeutic approach
to chronic pain treatment as opposed to a component of
multimodal care. Finally, as the vast majority of patients
enrolled in the study used the high-THC Bedrocan, we
were unable to assess the difference between cannabinoid
treatments with different ratios of THC and CBD. Future
investigation will certainly look at this issue, as questions
regarding the medical benefits and safety of high-THC, low-
CBD cannabis have arisen.10
Conclusion
An initial analysis of the Italian clinical practice of the use
of cannabinoids for chronic pain syndromes in a reasonably
large population is presented. Even with the heterogeneity
of the sample size and the limited data available, it can be
stated that the treatment seems to be effective and safe in the
majority of patients, even though the safety and effectiveness
data should be confirmed in a trial better designed to assess
them. Nevertheless, additional data from a variety of types of
trials are needed in order to better understand the benefits of
cannabinoids to chronic pain sufferers. It is important for the
Italian and other European pain societies to more thoroughly
investigate this topic in order to provide clearer and more
useful guidelines, which will more adequately guide physi-
cians in the use of this drug in the treatment of chronic pain.
Disclosure
The authors report no conflicts of interest in this work.
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... Tipo Os dois estudos retrospetivos de série de casos incluídos nesta revisão (Tabela 5) utilizaram amostras de doentes com dor crónica de diferentes etiologias, nos quais foram utilizados canabinoides em diferentes proporções e com diferentes formas de administração, excluindo a via inalatória. [23][24] Bellnier e colaboradores obtiveram resultados de diminuição de dor de média de 6,76 para 2,04 em escala de avaliação da dor (p<0,0001) (NE 3). 23 No estudo de Fanelli e colaboradores, os doentes foram submetidos a tratamento com canabinoides de administração oral com concentrações variáveis de THC e CBD. ...
... 23 No estudo de Fanelli e colaboradores, os doentes foram submetidos a tratamento com canabinoides de administração oral com concentrações variáveis de THC e CBD. 24 Dos 76,2% dos doentes que não descontinuaram a terapêutica até à primeira consulta de reavaliação, 64,7% referiram melhoria sintomática, não tendo sido utilizada nenhuma escala validada. Dos 23,8% que descontinuaram, 3,7% fizeram-no por agravamento das queixas e 61,7% por efeitos adversos não graves (NE 3). ...
... 17 Relativamente a efeitos adversos, a incidência destes parece estar relacionada com formulações com maior concentração de THC relativamente a CBD, tendo-se verificado heterogeneidade entre os estudos no que respeita às formulações utilizadas. 24 O NNH obtido no trabalho de Stockings e colaboradores 11 foi de seis, valor inferior ao de outros fármacos, como a pregabalina (NNH 13,9). 26 A dor crónica, pelo impacto que apresenta na qualidade de vida dos doentes e, muitas vezes, pelo seu caráter incurável, constitui um desafio para os clínicos. ...
Article
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Objetivo: Avaliar a evidência existente relativa à eficácia de canabinoides no tratamento da dor crónica. Fontes de dados: MEDLINE/PubMed, Cochrane Library, TRIP Database, National Guideline Clearing House, Canadian Medical Association Practice Guidelines. Métodos de revisão: Utilizando os termos MeSH cannabis e chronic pain fez-se, em agosto de 2019, uma pesquisa de meta-análises (MA), revisões sistemáticas (RS), estudos observacionais (EO), ensaios clínicos (EC) e guidelines, publicados em português e inglês, sem limite temporal. Incluíram-se estudos realizados em adultos com dor crónica, independentemente da causa, submetidos a terapêutica com canabinoides, excluindo-se aqueles com intervenção em dor aguda. Utilizou-se a escala Strength of Recommendation Taxonomy, da American Academy of Family Physicians, para atribuir níveis de evidência (NE) e força de recomendação (FR). Resultados: Dos 244 artigos encontrados, 16 cumpriram os critérios de inclusão: nove RS, quatro EC duplo-cegos aleatorizados e controlados com placebo, dois estudos retrospetivos de série de casos e um estudo prospetivo de série de casos. Todos os estudos selecionados abordavam dor crónica, mas de etiologia diversa (oncológica, neuropática, reumatológica, visceral). Os resultados entre os estudos não foram consistentes. Parece haver algum benefício na dor neuropática e na dor oncológica, embora haja consenso pelas revisões de que serão necessários estudos de maior dimensão e duração para que a utilização de canabinoides tenha evidência robusta. Podem verificar-se efeitos adversos gastrointestinais e nas funções cognitiva e motora, sobretudo com as preparações contendo maior dosagem de tetrahidrocanabinol. Não há evidência para utilização em dor de origem reumatológica ou visceral. Não se atribuiu NE 1 a qualquer estudo. Conclusões: A utilização de canabinoides, embora promissora e com eventual benefício identificado em pequenos estudos para alguns tipos de dor crónica (sobretudo a neuropática), tem evidência limitada (FR B) e requer a realização de ensaios de maior qualidade e dimensão. Devem ser considerados a eficácia e os possíveis efeitos secundários a longo prazo em estudos de maior duração, algo que poderá ser alcançado com a crescente utilização dos fármacos na prática clínica. Com base na evidência disponível, os canabinoides poderão ser uma solução de última linha em casos de dor refratária neuropática e oncológica.
... Cannabinoid prescriptions in Italy [2][3][4][5] are allowed for chronic pain and pain associated to multiple sclerosis, as well as other indications (i.e., HIV and cancer) [6][7][8]. However, therapy with medical cannabis would also be insufficient to control chronic pain or would cause collateral effects such as sleep problems, anxiety, or stress [9,10]. ...
... However, due to side effects and a low efficacy, the pain intensity remains of considerable clinical importance. e discovery of the crucial role of the endocannabinoid system in pain opened new therapeutic perspectives [20,21], and the introduction of cannabis therapy for chronic pain has been successful [3,22], as demonstrated by several studies [23][24][25][26]. Medical cannabis products were recently well-summarized by Brunetti et al. [5], with the rationale to help doctors with dosing and titration strategies for THC and CBD preparations. ...
Article
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Background: Chronic pain is a condition where pain persists for months or even years. Nowadays, several drugs comprising of medical cannabis are utilized for chronic pain relief. Even if there are some associated side effects, the use of supplements can widen the reliable tools available for improving an individual's quality of life. Objective: The aim of the present study was to evaluate the efficacy in terms of pain intensity, psychological well-being, and quality of life of a new dietary supplement in chronic pain subjects under current treatment with medical cannabis. Methods: In this pilot study, 48 medical cannabis-treated subjects were supplemented with a dietary supplement containing a combination of standardized Zingiber officinalis and Acmella oleracea extracts in phytosome (Mitidol), coenzyme Q10 phytosome (Ubiqsome), and group B vitamins (B1, B6, and B12), twice daily for 90 days. In order to explore the benefits of the product as an adjuvant supplementation for pain relief, the pain intensity, measured by the visual analogue scale (VAS), the pain type, and quality, evaluated by the Italian Pain Questionnaire (QUID) and the possible reduction of therapeutic and/or painkiller doses were recorded. Results: After 90 days, significant pain relief was detected in almost 70% of the subjects receiving the new dietary supplement, with sensory, emotional, and pain amelioration in one-third of them. A reduction in both tetrahydrocannabinol (THC) and cannabidiol (CBD) doses was also observed after 3 months of supplementation. These findings demonstrate new perspectives for the use of an innovative dietary supplement that combines Acmella and Zingiber extracts, Coenzyme Q10, and group B vitamins resulting in a beneficial long-term adjuvant in cannabis-treated pain subjects.
... Adherence to cannabis treatment was 77.7%, similar to the treatment withdrawal of 23.8% that was found in a retrospective cohort study on medical cannabis patients with a mean age similar to the patients' ages in our study (33). ...
Article
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Background Despite the absence of rigorous prospective studies, there has been an increase in the use of cannabis-based medicinal products. During the study period, the use of medical cannabis in Israel was tightly regulated by national policy. Through a prospective study of approximately 10,000 patients, we aimed to characterize the medical cannabis patient population as well as to identify treatment adherence, safety, and effectiveness. Methods and Findings In this study of prescribed medical cannabis patients, adherence, safety, and effectiveness were assessed at 6 months. Treatment adherence was assessed by the proportion of patients purchasing the medication out of the total number of patients (excluding deceased cases and patients transferred to another cannabis clinic). Safety was assessed by the frequency of the side-effects, while effectiveness was defined as at least moderate improvement in the patient condition without treatment cessation or serious side-effects. The most frequent primary indications requiring therapy were cancer (49.1%), followed by non-specific pain (29.3%). The average age was 54.6 ± 20.9 years, 51.1% males; 30.2% of the patients reported prior experience with cannabis. During the study follow-up, 1,938 patients died (19.4%) and 1,735 stopped treatment (17.3%). Common side-effects, reported by 1,675 patients (34.2%), were: dizziness (8.2%), dry mouth (6.7%), increased appetite (4.7%), sleepiness (4.4%), and psychoactive effect (4.3%). Overall, 70.6% patients had treatment success at 6 months. Multivariable logistic regression analysis revealed that the following factors were associated with treatment success: cigarette smoking, prior experience with cannabis, active driving, working, and a young age. The main limitation of this study was the lack of data on safety and effectiveness of the treatment for patients who refused to undergo medical assessment even at baseline or died within the first 6 months. Conclusions We observed that supervised medical-cannabis treatment is associated with high adherence, improvement in quality of life, and a decrease in pain level with a low incidence of serious adverse events.
... Na Itália, em uma análise retrospectiva de 614 casos de pacientes com dor crônica tratados com Cannabis oral ou vaporizada, verificou-se que o tratamento demonstra ser eficaz e seguro, apesar de ainda serem necessários mais estudos para melhor analisar e definir os critérios e protocolos de prescrição. Nesta pesquisa, 76,2% dos participantes continuaram o tratamento com Cannabis, e 64,7% destes relataram melhoras associadas à terapia (FANELLI et al., 2017). E, no Reino Unido, o uso de Cannabis foi relatado por pacientes com dor crônica, esclerose múltipla, artrite, neuropatia e depressão (WARE et al., 2005). ...
... Among all included studies, only two examined the prevalence of cannabis use exclusively among patients suffering from CMP (Ste-Marie et al., 2016). Most of the studies focused on mixed samples that included patients with CMP (between 2 and 91% of participants) (31 studies) (Swift et al., 2005;Aggarwal et al., 2009;Ilgen et al., 2013;Aggarwal et al., 2013a;Aggarwal et al., 2013b;Belle-Isle et al., 2014;Bottorff et al., 2011;Bruce et al., 2018;Coomber et al., 2003;Degenhardt et al., 2015;Erkens et al., 2005;Gorter et al., 2005;Haroutounian et al., 2016;Harris et al., 2000;Hoffman et al., 2017;Kilcher et al., 2017;Lucas & Walsh, 2017;Lynch et al., 2006;Nunberg et al., 2011;Ogborne et al., 2000;Pedersen & Sandberg, 2013;Piper et al., 2017;Reinarman et al., 2011;Schnelle et al., 1999;Sexton et al., 2016;Shiplo et al., 2016;Ste-Marie et al., 2012;Troutt & DiDonato, 2015;Walsh et al., 2013;Ware et al., 2003) or experiencing unspecified chronic non-cancer pain (between 24 and 97% of participants) (17 studies) (Boehnke et al., 2016;Perron et al., 2015;Alexandre, 2011;Bonn-Miller et al., 2014;Brunt et al., 2014;Corroon Jr. et al., 2017;Cranford et al., 2016;Crowell, 2017;Fanelli et al., 2017;Grella et al., 2014;Grotenhermen & Schnelle, 2003;Hazekamp & Heerdink, 2013; Reiman, 2009;Reiman et al., 2017;Shah et al., 2017;Webb & Webb, 2014;Zaller et al., 2015). ...
Article
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Background Chronic musculoskeletal pain (CMP) may lead to reduced physical function and is the most common cause of chronic non-cancer pain. Currently, the pharmacotherapeutic options against CMP are limited and frequently consist of pain management with non-steroidal anti-inflammatories, gabapentinoids, or opioids, which carry major adverse effects. Although the effectiveness of medical cannabis (MC) for CMP still lacks solid evidence, several patients suffering from it are exploring this therapeutic option with their physicians. Objectives Little is known about patients’ perceptions of their MC treatment for CMP. We aimed to increase this knowledge, useful for healthcare professionals and patients considering this treatment, by conducting a scoping literature review, following guidance by Arksey and O’Malley, to describe the views and perceptions of adult patients who had consumed MC to relieve chronic CMP. Methods Databases (PUBMED, EMBASE, Web of Science) and websites were searched using combinations of controlled and free vocabulary. All studies and study designs reporting on patients’ perceptions regarding MC against CMP were considered. Studies had to include adult patients reporting qualitatively or quantitatively, i.e., through questionnaires, on MC use to treat CMP or other non-cancer pain, since studies reporting exclusively on perceptions regarding CMP were very rare. Study characteristics were extracted and limitations of the study quality were assessed. The review includes patients’ demographic characteristics, patterns of MC use, perceived positive and negative effects, use of alcohol or other drugs, reported barriers to CM use, and funding sources of the studies. Results Participants of the 49 included studies reported that MC use helped them to reduce CMP and other chronic non-cancer pain, with only minor adverse effects, and some reported improved psychological well-being. In the included studies, men represent between 18 and 88% of the subjects. The mean age of participants in these studies (42/49) varied between 28.4 and 62.8 years old. The most common route of administration is inhalation. Conclusion MC users suffering from CMP or other chronic non-cancer pain perceived more benefits than harms. However, the information from these studies has several methodological limitations and results are exploratory. These user-reported experiences must thus be examined by well-designed and methodologically sound clinical or observational studies, particularly regarding CMP, where reports are very scarce.
... The latter drugs are placed in Schedule II and are, legislation-wise, considered to present more medical uses and less harm potential than Schedule I substances. Nevertheless, available evidence does not seem to support such a classification for cannabis, which is indeed indicative of a relatively low harm potential and several therapeutic applications [6][7][8][9]. Accordingly, many governs have made changes on legislations regarding cannabis so that it is becoming legal for medical purposes or even for recreational use in several countries [10][11][12]. It should be noted, however, that the apparent low-risk profile of cannabis does not imply it is exempt of risks. ...
Article
Full-text available
Cannabis is the third most used psychoactive drug worldwide. Despite being legally scheduled as a drug with high harm potential and no therapeutic utility in countries like the USA, evidence shows otherwise and legislative changes and reinterpretations of existing ambiguous laws make this drug increasingly available by legal means. Nevertheless, this substance is able to generate clear addiction syndromes in some individuals who use it, which are accompanied by brain alterations resembling those caused by other addictive drugs. Moreover, there is no available pharmacological treatment for this disorder. This fact motivates a deep study and comprehension of the neural basis of addiction-relevant cannabinoid effects. Interestingly, the cerebellum, a hindbrain structure which involvement in functions not related to motor control and planning is being increasingly recognized in the last decades, seems to be involved in the effects of addictive drugs and addiction-related processes and also presents a high density of cannabinoid receptors. Preclinical research on the involvement of the cerebellum in cannabis’ effects has focused in the drug’s motor incoordinating actions, potentially underestimating its participation in addiction. Therefore, this review addresses the studies reporting cerebellar involvement in cannabis effects both in experimental animals and human subjects and the possible relevance of these changes for addiction. Additionally, future experimental approaches will be proposed and hopefully this work will stimulate research on the cerebellum in cannabis addiction and help recognizing it as an important part of the neural circuitry affected in cannabis-related disorders.
... The latter drugs are placed in Schedule II and are, legislation-wise, considered to present more medical uses and less harm potential than Schedule I substances. Nevertheless, available evidence does not seem to support such a classification for cannabis, which is indeed indicative of a relatively low harm potential and several therapeutic applications [6][7][8][9]. Accordingly, many governs have made changes on legislations regarding cannabis so that it is becoming legal for medical purposes or even for recreational use in several countries [10][11][12]. It should be noted, however, that the apparent low-risk profile of cannabis does not imply it is exempt of risks. ...
Preprint
Full-text available
Cannabis is the third most used psychoactive drug worldwide. Despite being legally scheduled as a drug with high harm potential and no therapeutic utility in countries like the United States, evidence shows otherwise and legislative changes and reinterpretations of existing ambiguous laws make this drug increasingly available by legal means. Nevertheless, this substance is able to generate clear addiction syndromes in some individuals who use it, which are accompanied by brain alterations resembling those caused by other addictive drugs. Moreover, there is no available pharmacological treatment for this disorder. This fact motivates a deep study and comprehension of the neural basis of addiction-relevant cannabinoid effects. Interestingly, the cerebellum, a hindbrain structure which involvement in functions not related to motor control and planning is being increasingly recognized in the last decades, seems to be involved in the effects of addictive drugs and addiction-related processes, and also presents a high density of cannabinoid receptors. Preclinical research on the involvement of the cerebellum in cannabis' effects has focused in the drug's motor incoordinating actions, potentially underestimating its participation in addiction. Therefore, this review addresses the studies reporting cerebellar involvement in cannabis effects both in experimental animals and human subjects and the possible relevance of these changes for addiction. Additionally, future experimental approaches will be proposed and hopefully this work will stimulate research on the cerebellum in cannabis addiction and help recognizing it as an important part of the neural circuitry affected in cannabis-related disorders.
Article
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Objective To establish the prevalence of long-term and serious harms of medical cannabis for chronic pain. Design Systematic review and meta-analysis. Data sources MEDLINE, EMBASE, PsycINFO and CENTRAL from inception to 1 April 2020. Study selection Non-randomised studies reporting on harms of medical cannabis or cannabinoids in adults or children living with chronic pain with ≥4 weeks of follow-up. Data extraction and synthesis A parallel guideline panel provided input on the design and interpretation of the systematic review, including selection of adverse events for consideration. Two reviewers, working independently and in duplicate, screened the search results, extracted data and assessed risk of bias. We used random-effects models for all meta-analyses and the Grades of Recommendations, Assessment, Development and Evaluation approach to evaluate the certainty of evidence. Results We identified 39 eligible studies that enrolled 12 143 adult patients with chronic pain. Very low certainty evidence suggests that adverse events are common (prevalence: 26.0%; 95% CI 13.2% to 41.2%) among users of medical cannabis for chronic pain, particularly any psychiatric adverse events (prevalence: 13.5%; 95% CI 2.6% to 30.6%). Very low certainty evidence, however, indicates serious adverse events, adverse events leading to discontinuation, cognitive adverse events, accidents and injuries, and dependence and withdrawal syndrome are less common and each typically occur in fewer than 1 in 20 patients. We compared studies with <24 weeks and ≥24 weeks of cannabis use and found more adverse events reported among studies with longer follow-up (test for interaction p<0.01). Palmitoylethanolamide was usually associated with few to no adverse events. We found insufficient evidence addressing the harms of medical cannabis compared with other pain management options, such as opioids. Conclusions There is very low certainty evidence that adverse events are common among people living with chronic pain who use medical cannabis or cannabinoids, but that few patients experience serious adverse events.
Article
The use of cannabis spans thousands of years and encompasses almost all dimensions of the human experience, including consumption for recreational, religious, social, and medicinal purposes. Its use in the management of pain has been anecdotally described for millennia. However, an evidence base has only developed over the last 100 years, with an explosion in research occurring in the last 20-30 years, as more states in the USA as well as countries worldwide have legalized and encouraged its use in pain management. Pain remains one of the most common reasons for individuals deciding to use cannabis medicinally. However, cannabis remains illegal at the federal level in the USA and in most countries of the world, making it difficult to advance quality research on its efficacy for pain treatment. Nonetheless, new products derived both from the cannabis plant and the chemistry laboratory are being developed for use as analgesics. This review examines the current landscape of cannabinoids research and future research directions in the management of pain.
Article
Résumé Le système endocannabinoïde participe à la régulation de l’homéostasie générale de l’organisme et plus particulièrement du système nerveux. Les endocannabinoïdes sont des neurotransmetteurs synthétisés principalement par les neurones du système nerveux central. Il y a deux récepteurs, CB1, principalement exprimé dans le système nerveux central et CB2 principalement exprimé à la périphérie dans le système nerveux immunitaire, mais aussi plus faiblement dans les neurones et les cellules gliales du système nerveux. CB1 et CB2 sont des récepteurs de la grande famille des récepteurs couplés à une protéine G (RCPG) dont l’activité est modulée par la protéine inhibitrice Gi/o, mais aussi par la β-arrestine, et ils présentent une régulation adaptable des cascades de signalisation intracellulaires. De ce fait, CB1 et CB2 présentent une « signalisation biaisée ». Du fait que CB1 présente deux cascades de signalisation intracellulaires (Gi/o et la β-arrestine), il a été possible de définir un nouveau concept de pharmacologie moléculaire, la « sélectivité fonctionnelle », permettant la synthèse de ligands spécifiques activant un récepteur cannabinoïde, mais par l’intermédiaire d’une seule voie de signalisation (Gi/o ou β-arrestine) : ces ligands sont appelés « ligands biaisés ». CB1 est le récepteur du Δ9-tétrahydrocannabinol (Δ9-THC), le principal composant psychotrope du cannabis, mais aussi des deux principaux endocannabinoïdes (cannabinoïdes endogènes), l’anandamide (AEA) et le 2-arachidonoyl-glycérol (2-AG). D’autres constituant du cannabis, les phytocannabinoïdes, tels que le cannabidiol et le cannabinol, sont aussi actifs sur les systèmes cannabinoïdes. La mise en évidence de sites de liaison allostériques sur CB1 a permis de synthétiser des ligands allostériques présentant une affinité de liaison avec une modulation soit activatrice, soit inhibitrice, susceptibles de cibler des conformations sélectives du récepteur déclenchant des réponses pharmacologiques spécifiques. La pharmacologie des récepteurs endocannabinoïdes dans un but thérapeutique est principalement ciblée sur la douleur, mais aussi sur la sclérose en plaques et le glaucome. Mais du fait des effets secondaires psychotropes non désirés des phytocannabinoïdes, en particulier du Δ9-THC, leur utilisation dans le traitement des pathologies neurologiques ou inflammatoires, est quelque peu controversée. Cependant, du fait de leur large expression dans le système nerveux et de leur mise en jeu dans les processus physiologiques et pathologiques du système nerveux, l’étude des système endocannabinoïdes est très développée pour le développement de nouvelles molécules thérapeutiques.
Article
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Background: In the context of the shifting legal landscape of medical cannabis, different methods of cannabis administration have important public health implications. How medical marijuana laws (MML) may influence patterns of use of alternative methods of cannabis administration (vaping and edibles) compared to traditional methods (smoking) is unclear. The purpose of this study was to determine if the prevalence of use of alternative methods of cannabis administration varied in relation to the presence of and variation in MMLs among states in the United States. Method: Using Qualtrics and Facebook, we collected survey data from a convenience sample of n=2838 individuals who had used cannabis at least once in their lifetime. Using multiple sources, U.S. states were coded by MML status, duration of MML status, and cannabis dispensary density. Adjusted logistic and linear regression analyses were used to analyze outcomes of ever use, preference for, and age of initiation of smoking, vaping, and edibles in relation to MML status, duration of MML status, and cannabis dispensary density. Results: Individuals in MML states had a significantly higher likelihood of ever use of vaping (OR: 2.04, 99% CI: 1.62-2.58) and edibles (OR: 1.78, 99% CI: 1.39-2.26) than those in states without MMLs. Longer duration of MML status and higher dispensary density were also significantly associated with ever use of vaping and edibles. Conclusions: MMLs are related to state-level patterns of utilization of alternative methods of cannabis administration. Whether discrepancies in MML legislation are causally related to these findings will require further study. If MMLs do impact methods of use, regulatory bodies considering medical or recreational legalization should be aware of the potential impact this may have on cannabis users.
Article
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Objective To determine if medical marijuana provides pain relief for patients with chronic noncancer pain (CNCP) and to determine the therapeutic dose, adverse effects, and specific indications. Data sources In April 2014, MEDLINE and EMBASE searches were conducted using the terms chronic noncancer pain, smoked marijuana or cannabinoids, placebo and pain relief, or side effects or adverse events. Study selection An article was selected for inclusion if it evaluated the effect of smoked or vaporized cannabinoids (nonsynthetic) for CNCP; it was designed as a controlled study involving a comparison group, either concurrently or historically; and it was published in English in a peer-review journal. Outcome data on pain, function, dose, and adverse effects were collected, if available. All articles that were only available in abstract form were excluded. Synthesis A total of 6 randomized controlled trials (N = 226 patients) were included in this review; 5 of them assessed the use of medical marijuana in neuropathic pain as an adjunct to other concomitant analgesics including opioids and anticonvulsants. The 5 trials were considered to be of high quality; however, all of them had challenges with masking. Data could not be pooled owing to heterogeneity in delta-9-tetrahydrocannabinol potency by dried weight, differing frequency and duration of treatment, and variability in assessing outcomes. All experimental sessions in the studies were of short duration (maximum of 5 days) and reported statistically significant pain relief with nonserious side effects. Conclusion There is evidence for the use of low-dose medical marijuana in refractory neuropathic pain in conjunction with traditional analgesics. However, trials were limited by short duration, variability in dosing and strength of delta-9- Tetrahydrocannabinol, and lack of functional outcomes. Although well tolerated in the short term, the long-term effects of psychoactive and neurocognitive effects of medical marijuana remain unknown. Generalizing the use of medical marijuana to all CNCP conditions does not appear to be supported by existing evidence. Clinicians should exercise caution when prescribing medical marijuana for patients, especially in those with nonneuropathic CNCP.
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Study registration: The study was registered with www.controlled-trials.com (ISRCTN19449752). Perspective: This study evaluated the safety of cannabis use by patients with chronic pain over one year. The study found that there was a higher rate of adverse events among cannabis users compared to controls but not for serious adverse events at an average dose of 2.5g herbal cannabis per day.
Article
With the current nationwide epidemic of opioid abuse, dependence, and fatalities, clinicians are being asked by federal agencies and professional societies to control their prescribing of narcotic medications for pain. Federal guidelines emphasize tapering, discontinuing, and limiting initiation of these drugs except in provision of end-of-life care.¹ Reducing reliance on opioids, however, is a massive task. According to one estimate, more than 650 000 opioid prescriptions are dispensed each day in the United States.² Unless the nation develops an increased tolerance to chronic pain, reduction in opioid prescribing leaves a vacuum that will be filled with other therapies.
Article
Unlabelled: Cannabinoids show promise as therapeutic agents, particularly as analgesics, but their development and clinical use has been complicated by recognition of their botanical source, cannabis, as a substance of misuse. Although research into endogenous cannabinoid systems and potential cannabinoid pharmaceuticals is slowly increasing, there has been intense societal interest in making herbal (plant) cannabis available for medicinal use; 23 U.S. States and all Canadian provinces currently permit use in some clinical contexts. Whether or not individual professionals support the clinical use of herbal cannabis, all clinicians will encounter patients who elect to use it and therefore need to be prepared to advise them on cannabis-related clinical issues despite limited evidence to guide care. Expanded research on cannabis is needed to better determine the individual and public health effects of increasing use of herbal cannabis and to advance understanding of the pharmaceutical potential of cannabinoids as medications. This article reviews clinical, research, and policy issues related to herbal cannabis to support clinicians in thoughtfully advising and caring for patients who use cannabis, and it examines obstacles and opportunities to expand research on the health effects of herbal cannabis and cannabinoids. Perspective: Herbal cannabis is increasingly available for clinical use in the United States despite continuing controversies over its efficacy and safety. This article explores important considerations in the use of plant Cannabis to better prepare clinicians to care for patients who use it, and identifies needed directions for research.
Article
In this work, the author explains the remarkable advances that have been made in scientific research on cannabis with the discovery of specific receptors and the existence of naturally occurring cannabis-like substances in the brain. He provides an objective and up-to-date assessment of the scientific basis for the medical use of cannabis and what risks this may entail. The recreational use of the drug and how it affects users is described along with some predictions about how attitudes to cannabis may change in the future.
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Cannabinoid compounds include phytocannabinoids, endocannabinoids, and synthetics. The two primary phytocannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), with CB1 receptors in the brain and peripheral tissue and CB2 receptors in the immune and hematopoietic systems. The route of delivery of cannabis is important as the bioavailability and metabolism are very different for smoking versus oral/sublingual routes. Gold standard clinical trials are limited; however, some studies have thus far shown evidence to support the use of cannabinoids for some cancer, neuropathic, spasticity, acute pain, and chronic pain conditions.
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As of March 2015, 23 states and the District of Columbia had medical marijuana laws in place. Physicians should know both the scientific rationale and the practical implications for medical marijuana laws. To review the pharmacology, indications, and laws related to medical marijuana use. The medical literature on medical marijuana was reviewed from 1948 to March 2015 via MEDLINE with an emphasis on 28 randomized clinical trials of cannabinoids as pharmacotherapy for indications other than those for which there are 2 US Food and Drug Administration-approved cannabinoids (dronabinol and nabilone), which include nausea and vomiting associated with chemotherapy and appetite stimulation in wasting illnesses. Use of marijuana for chronic pain, neuropathic pain, and spasticity due to multiple sclerosis is supported by high-quality evidence. Six trials that included 325 patients examined chronic pain, 6 trials that included 396 patients investigated neuropathic pain, and 12 trials that included 1600 patients focused on multiple sclerosis. Several of these trials had positive results, suggesting that marijuana or cannabinoids may be efficacious for these indications. Medical marijuana is used to treat a host of indications, a few of which have evidence to support treatment with marijuana and many that do not. Physicians should educate patients about medical marijuana to ensure that it is used appropriately and that patients will benefit from its use.