ArticlePDF Available

Abstract and Figures

Introduction: Parkinson's disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no neuroprotective treatments for PD have been found to date, the endocannabinoid system has emerged as a promising target. Methods: From a sample of 119 patients consecutively evaluated in a specialized movement disorders outpatient clinic, we selected 21 PD patients without dementia or comorbid psychiatric conditions. Participants were assigned to three groups of seven subjects each who were treated with placebo, cannabidiol (CBD) 75 mg/day or CBD 300 mg/day. One week before the trial and in the last week of treatment participants were assessed in respect to (i) motor and general symptoms score (UPDRS); (ii) well-being and quality of life (PDQ-39); and (iii) possible neuroprotective effects (BDNF and H(1)-MRS). Results: We found no statistically significant differences in UPDRS scores, plasma BDNF levels or H(1)-MRS measures. However, the groups treated with placebo and CBD 300 mg/day had significantly different mean total scores in the PDQ-39 (p = 0.05). Conclusions: Our findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities; however, studies with larger samples and specific objectives are required before definitive conclusions can be drawn.
Content may be subject to copyright.
http://jop.sagepub.com/
Journal of Psychopharmacology
http://jop.sagepub.com/content/early/2014/09/12/0269881114550355
The online version of this article can be found at:
DOI: 10.1177/0269881114550355
published online 18 September 2014J Psychopharmacol Crippa
Mateus M Bergamaschi, Antonio Carlos dos Santos, Antonio Lucio Teixeira, Jaime EC Hallak and José Alexandre S
Marcos Hortes N Chagas, Antonio W Zuardi, Vitor Tumas, Márcio Alexandre Pena-Pereira, Emmanuelle T Sobreira,
double-blind trial
Effects of cannabidiol in the treatment of patients with Parkinson's disease: An exploratory
Published by:
http://www.sagepublications.com
On behalf of:
British Association for Psychopharmacology
can be found at:Journal of PsychopharmacologyAdditional services and information for
http://jop.sagepub.com/cgi/alertsEmail Alerts:
http://jop.sagepub.com/subscriptionsSubscriptions:
http://www.sagepub.com/journalsReprints.navReprints:
http://www.sagepub.com/journalsPermissions.navPermissions:
What is This?
- Sep 18, 2014OnlineFirst Version of Record >>
by guest on September 21, 2014jop.sagepub.comDownloaded from by guest on September 21, 2014jop.sagepub.comDownloaded from
Journal of Psychopharmacology
1 –5
© The Author(s) 2014
Reprints and permissions:
sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/0269881114550355
jop.sagepub.com
Introduction
Cannabidiol (CBD) is one of the main components of Cannabis
sativa, but it is not involved in its psychomimetic effects.
Pharmacological studies on CBD have shown that the substance
has a wide spectrum of action with different effects on different
systems (Zuardi, 2008). The neuroprotective properties of CBD
have been under increasing scientific scrutiny in the context of
neurodegenerative diseases including Huntington’s disease,
Alzheimer’s disease and Parkinson’s disease (PD) (Iuvone et al.,
2009). Two investigations using animal models of PD have
been conducted to date to assess the neuroprotective effects of
CBD. In the first one, Lastres-Becker et al. (2005) showed that
the administration of CBD counteracted neurodegeneration
caused by the injection of 6-hydroxy-dopamine in the medial
prosencephalic bundle, an effect that could be related to the
modulation of glial cells and to antioxidant effects (Lastres-
Becker et al., 2005). In the next year, Garcia-Arencibia et al.
(2007) tested many cannabinoid compounds following the
lesion of dopaminergic neurons in the substantia nigra with
6-hydroxy-dopamine and found that the acute administration of
CBD seemed to have a neuroprotective action; nonetheless, the
administration of CBD one week after the lesion had no signifi-
cant effects (Garcia-Arencibia et al., 2007). This study also
pointed to a possible antioxidant effect with the upregulation of
mRNA of the enzyme Cu-Zn-superoxide dismutase following
the administration of CBD.
Despite the promising findings in animal models of PD, few
clinical trials have assessed the neuroprotective effects of CBD in
humans. An investigation with Cannabis users measured
N-acetylaspartate to creatine ratios (NAA/Cr) in the brain through
magnetic resonance spectroscopy (H1-MRS) to assess the neuro-
toxic and neuroprotective effects of cannabinoids present in the
drug and found a positive correlation between CBD and NAA/Cr
in the globus pallidus and putamen (r = 0.66; p = 0.004) (Hermann
et al., 2007). Furthermore, only one clinical trial has assessed the
Effects of cannabidiol in the treatment
of patients with Parkinson’s disease:
An exploratory double-blind trial
Marcos Hortes N Chagas1,2,3, Antonio W Zuardi1,2, Vitor Tumas1,
Márcio Alexandre Pena-Pereira1, Emmanuelle T Sobreira1, Mateus M
Bergamaschi1,2, Antonio Carlos dos Santos1,2, Antonio Lucio Teixeira4,
Jaime EC Hallak1,2 and José Alexandre S Crippa1,2
Abstract
Introduction: Parkinson’s disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no
neuroprotective treatments for PD have been found to date, the endocannabinoid system has emerged as a promising target.
Methods: From a sample of 119 patients consecutively evaluated in a specialized movement disorders outpatient clinic, we selected 21 PD patients
without dementia or comorbid psychiatric conditions. Participants were assigned to three groups of seven subjects each who were treated with placebo,
cannabidiol (CBD) 75 mg/day or CBD 300 mg/day. One week before the trial and in the last week of treatment participants were assessed in respect
to (i) motor and general symptoms score (UPDRS); (ii) well-being and quality of life (PDQ-39); and (iii) possible neuroprotective effects (BDNF and
H1-MRS).
Results: We found no statistically significant differences in UPDRS scores, plasma BDNF levels or H1-MRS measures. However, the groups treated with
placebo and CBD 300 mg/day had significantly different mean total scores in the PDQ-39 (p = 0.05).
Conclusions: Our findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities;
however, studies with larger samples and specific objectives are required before definitive conclusions can be drawn.
Keywords
Parkinson’s disease, cannabidiol, cannabis, treatment
1Department of Neuroscience and Behavior, Faculty of Medicine of
Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
2INCT Translational Medicine (CNPq), São Paulo, Brazil
3Barretos School of Health Sciences – Dr. Paulo Prata, Barretos, Brazil
4Laboratório Interdisciplinar de Investigação Médica, Universidade
Federal de Minas Gerais, Belo Horizonte, Brazil
Corresponding author:
Marcos Hortes N Chagas, Hospital das Clínicas da FMRP-USP- Terceiro
Andar; Av. Bandeirantes, 3900; 14048-900-Ribeirão Preto, SP, Brazil.
Email: mchagas@fmrp.usp.br; mchagas@facisb.edu.br
550355JOP0010.1177/0269881114550355Journal of PsychopharmacologyChagas et al.
research-article2014
Short report
by guest on September 21, 2014jop.sagepub.comDownloaded from
2 Journal of Psychopharmacology
therapeutic use and neuroprotective effect of CBD in PD patients
to date. Zuardi et al. (2009) conducted an open label study involv-
ing six patients with psychosis associated to PD and administered
CBD at doses ranging from 150 mg in the first week to 400 mg in
the fourth and last week of treatment according to the patients’
clinical response. There was a significant improvement in psycho-
sis and also in the total scores of a scale that measures general
symptoms of PD (Unified Parkinson’s disease rating scale –
UPDRS) (Zuardi et al., 2009). These results, together with the
findings from animal models of PD, point to the relevance of
additional clinical trials with CBD in PD patients.
Thus, we designed a clinical trial to assess the effects of CBD
in PD globally, including neurological assessments of motor and
functional symptoms, a psychiatric assessment and complemen-
tary tests (brain-derived neurotrophic factor plasma levels and
H1-MRS).
Method
Sample
Participants were selected from an initial sample of 119 patients
followed at the Movement Disorders Outpatient Clinic of the
Ribeirão Preto Medical School University Hospital who were
assessed by a neurologist, a psychiatrist and a neuropsychologist
over a period of 24 months. The inclusion criteria for the clinical
trial were: diagnosis of idiopathic PD, age above 45 years, use of
stable doses of anti-Parkinson medication for at least 30 days
before the trial and a score between 1 and 3 in the Hoehn and Yahr
scale. Exclusion criteria consisted of the presence of atypical
Parkinsonism, any previous or current psychiatric disorder, demen-
tia diagnosis according to the Diagnostic and Statistical Manual of
Mental Disorders (DSM-IV) criteria, relevant clinical comorbidity
and previous use of cannabis. According to these criteria, we
selected 23 patients to be included in the trial. Two patients refused
to participate while the remaining patients were divided into three
groups with seven participants each and matched according to age,
gender, PD duration and total score in the UPDRS (Figure 1).
The project was approved by the Local Ethics Committee
under process number HCRP 8990/2011 and the volunteers
signed an informed consent form to participate.
Study design
During a period of one week, the participants underwent psychiat-
ric and neurological assessments. After this baseline assessment,
the patients were randomly assigned to three groups in accordance
with the matching variables described above. Both the partici-
pants and investigators were blind in respect to the group each
subject belonged to for the whole period of the study. Patients
received placebo or doses of CBD (75 mg/day or 300 mg/day) for
6 weeks, in the last of which the baseline assessment was repeated.
Blood samples for plasma BDNF quantification and H1-MRS
scans were also performed in the last week of the trial.
CBD preparation
CBD was provided in powdered form with 99.9% purity by
THC-Pharma (Frankfurt, Germany). The drug was dissolved in
corn oil and placed in gelatin capsules containing 75 mg or 300
mg and stored in dark glass flasks at the Laboratory of Clinical
Psychopharmacology of the Ribeirão Preto Medical School.
Placebo consisted of capsules containing corn oil only. CBD and
placebo were supplied in identical capsules. The patients were
instructed to take the medication at night under the supervision of
relatives/caretakers.
Assessment instruments
The following scales were used: (i) UPDRS to assess PD symp-
toms; (ii) Parkinson’s Disease Questionnaire – 39 (PDQ-39) to
assess functioning and well-being; and (iii) Udvalg for kliniske
undersøgelser (UKU) side effect rating scale to evaluate possible
adverse effects of CBD.
The UPDRS (Fahn et al., 1987) consists of 42 items that
assess symptoms, signs and daily life activities of patients by
means of clinical observation and patient reports. The scale has
four parts: mentation, behavior and mood (Part I); activities of
daily living (Part II); motor exam (Part III); and complications of
therapy (Part IV).
The PDQ-39 (Jenkinson et al., 1995) is a questionnaire that
assesses functioning and well-being in PD patients, covering
characteristics that are specific to PD. Scores range between 0
and 100 and the questionnaire has good reliability and validity in
relation to other measures of quality of life (Fitzpatrick et al.,
1997; Jenkinson et al., 1997). The PDQ-39 can be divided into
eight factors: mobility, activities of daily living (ADL), emo-
tional well-being, stigma, social support, cognition, communica-
tion and bodily discomfort. The score in each factor is calculated
through the sum of the scores of each item corresponding to the
factor divided by the number of items and multiplied by 4. The
Patients without lifetime
psychiatric or dementia diagnoses
considered eligible for inclusion
N=23
Patients with PD consecutively
evaluated in the period between
February 2010 and November
2011
N=119
Patients who consented to
participate
N=21
Two patients refused to participate
Placebo
N=7
CBD 75mg
N=7
CBD 300mg
N=7
Figure 1. Flowchart describing the inclusion of patients from the
Movement Disorders Outpatient Clinic in the double-blind, placebo
controlled trial.
by guest on September 21, 2014jop.sagepub.comDownloaded from
Chagas et al. 3
result is then multiplied by 100 so that each factor has a score
ranging between 0 and 100.
Lastly, the UKU (Lingjaerde et al., 1987) is a detailed instru-
ment for the assessment of adverse medication effects including
psychic, neurologic, autonomic and other manifestations. Each
item is rated between 0 (absent) and 3 (severe). The rater has the
additional possibility of recording causal relations between medi-
cations and relevant clinical events and interference with the
patient’s daily life.
Complementary tests
BDNF. Approximately 10 ml of blood were collected in the base-
line week through venipuncture into tubes with sodium heparin.
The samples were then centrifuged twice for 10 minutes at 4oC
and plasma was stored at –74oC. Plasma BDNF levels were mea-
sured by ELISA according to the manufacturer’s instructions
(DuoSet, R&D Systems, Minneapolis, MN, USA) with concen-
trations described in pg/mL.
H1-MRS. Proton magnetic resonance scans were made at the
Center of Imaging Sciences and Medical Physics of the Ribeirão
Preto Medical School University Hospital by an experienced
technician. The scans were made using a Philips Achieva X-series
unit with a 3 T superconducting magnet (high field), 25 mT gra-
dient coils and a comercially-available circular-polarized head
coil. The different software used in the acquisition were provided
by the manufacturer together with the equipment.
Spectroscopy data were acquired using a single voxel (CSI
hybrid), point-resolved spectroscopy (PRESS) sequence and pre-
saturation for water supression with a MOIST sequence. The
bilateral basal ganglia (putamen) were defined as the volume of
interest (VDI). Echo time was short for the putamen (35 ms).
Post-processing included the application of a smooth Gaussian
filter and Fourier transformation.
Spectroscopy data were processed using software installed in
an auxiliary console of the acquisition equipment. The resonance
intensities of individual spectra were determined by the calcula-
tion of the integral of areas under the peaks of chemical disloca-
tion graphs.
Statistical analysis
We used one-factor ANOVA to compare the three groups when
variables had a normal distribution. When normality tests for the
whole sample or for specific groups did not indicate a normal
distribution, we used the Kruskal-Wallis test. Normality require-
ments for data distribution were confirmed using the Shapiro-
Wilk test. The groups were matched in respect to gender, age and
total UPDRS score. To analyze group differences in UPDRS and
PDQ-39 scores, we calculated the variations between baseline
and final (6 weeks) values and ran an ANOVA or Kruskal-Wallis
test according to the data distribuition. When the null hypothesis
was rejected, we used Bonferroni post-hoc tests to determine dif-
ferences across groups.
Results
Table 1 presents the clinical and demographic data of the three
groups, which were matched according to gender, age and total
UPDRS scores.
In respect to the UPDRS, we found no statistically significant
differences between mean score variations in the three groups.
However, in regard to the PDQ-39, we found significant differ-
ences between the total score of the placebo and CBD 300 mg/
day groups (p=0.05). The scores in factors “ADL” and “stigma”
also had statistically significant differences between groups tak-
ing placebo and CBD 300 mg/day (p=0.02) and CBD 75 mg/day
and 300 mg/day (p=0.04). Variations between baseline and final
mean scores in the UPDRS, PDQ-39, BDNF and NAA/Cr are
shown in Table 2.
There were no differences between the groups treated with
CBD and placebo in respect to BDNF levels at baseline and after
6 weeks, nor in the different measures using H1-MRS (NAA/
Cre). Also, no significant side effects were recorded in any of the
groups assessed with the UKU or through verbal reports.
Discussion
The endocannabinoid system has recently been implicated in the
neurobiology of PD, with possible neuroprotective effects. We
found significant improvements in measures of functioning and
well-being of PD patients treated with CBD 300 mg/day com-
pared to a group that received placebo. Despite this, we found no
differences across groups in what concerns the other measures,
including motor score as assessed with the UPDRS (Part III).
Quality of life is an important measure in clinical trials
because it refers to a number of areas related to personal well-
being. It is known that many therapies are able to improve the
core symptoms of a given disease without corresponding
Table 1. Clinical and demographic data of patients in each group at baseline.
Mean (SD) (min–max) CBD 75 mg/day CBD 300 mg/day Placebo ANOVA (F; p) or
Kruskal-Wallis test (p)
Gender (M/F) 5/2 5/2 5/2
Age (years) 65.86 (±10.59) (51–82) 63.43 (±6.48) (53–71) 67.29 (±7.23) (57–75) F2.18=0.387; p=0.685
Age at PD onset (years) 57.71 (±13.52) (37–79) 56.57 (±8.56) (46–68) 57.43 (±7.72) (50–69) F2.18=0.024; p=0.977
UPDRS total (on state) 30.39 (±11.91) (14–49) 38.86 (±13.99) (17–62) 40.17 (±11.20) (21–50) F2.18=1.245; p=0.313
PDQ-39 47.14 (±23.63) (11–69) 47.29 (±26.27) (10–86) 23.83 (±6.43) (18–33) F2.18=2.514; p=0.111
PD duration (years) 8.14 (±5.64) (2–15) 6.86 (±3.72) (3–12) 9.86 (±4.71) (5–17) F2.18=0.702; p=0.509
Education (years)a8.14 (±6.20) 10.71 (±7.18) 5.71 (±3.59) p=0.337
aNonparametric distribution.
by guest on September 21, 2014jop.sagepub.comDownloaded from
4 Journal of Psychopharmacology
improvements in quality of life. The PDQ-39 is a self-report
instrument that assesses several dimensions of PD providing a
detailed picture of the disease with little influence of symptom
oscillations throughout the day, especially in what refers to
treatment with levodopa. The score reduction in the PDQ-39
seen in the group of patients treated with CBD 300 mg com-
pared to the mean variation of the placebo group seems to be
mostly related with the ‘daily life activities’ factor (p<0.05) but
the relationship with ‘emotional well-being’ and ‘mobility’ fac-
tors also tended to be statistically significant.
Although we excluded patients with comorbid psychiatric
disorders, basal symptoms with no clinical significance or related
to the impairments of the disorder could be present and be some-
how connected with the observed improvement in emotional
well-being. A study on Cannabis and PD showed that the use of
the drug could be associated with subjective reports of emotional
well-being, even in the absence of significant improvement in
motor symptoms (Venderova et al., 2004). Recently, another
study revealed significant improvement in specific motor symp-
toms after treatment with Cannabis (Lotan et al., 2014). In addi-
tion, CBD’s possible anxiolytic (Bergamaschi et al., 2011; Crippa
et al., 2009), antidepressant (Saito et al., 2010; Zanelati et al.,
2010), antipsychotic (Zuardi et al., 1991; 1995) and sedative
(Chagas et al., 2013; 2014; Monti, 1977) properties could explain
the reports of improvements in emotional well-being, daily life
activities and, hence, quality of life, as a result of its action in the
non-motor symptoms of PD. It should be noted that the main
active component of Cannabis is Δ9-tetrahydrocannabinol
(THC), which was not investigated in this clinical trial.
Nonetheless, there is evidence of the effects of THC and Cannabis
in clinical trials (Lotan et al., 2014) and in animal models of PD
(van Vliet et al., 2008).
The mechanism of action of CBD, in general and particularly
in PD, remains unknown despite increasing efforts to explain it.
CBD acts in a number of sites and its action as a neuroprotective
agent is based on the following effects: local anti-inflammatory
properties, reduction of oxidative stress, attenuation of glial cell
activation and normalization of glutamate homeostasis
(Fernandez-Ruiz et al., 2013). It is noteworthy that the neuropro-
tective effect of CBD seems to be independent from its action on
the CB1 and CB2 receptors ( Garcia-Arencibia et al., 2007;
Lastres-Becker et al., 2005).
Despite the possible neuroprotective action of CBD, we
found no statistically significant differences across groups in
respect to UPDRS scores. Unfortunately the sample enrolled in
the study was too small, which restricts the reach of our analyses
and does not allow for definitive conclusions. Also, most partici-
pants were in the early stages of the disease, which hampers the
observation of broad variations, as these patients tend to have
low baseline scores. On the other hand, the inclusion of patients
with longer disease duration could also pose a problem to the
evaluation and the observation of positive effects due to
increased damage in the substantia nigra in the later phases of
the disease. Finally, although all UPDRS measures were made
during the on stage and in the morning, some items measured by
the scale may vary during the day and from day to day, which
does not necessarily mean improvement or worsening of the dis-
ease (Siderowf et al., 2002).
The neuroprotective effects of CBD are not easily measured
in humans and, although they have been reported in animal mod-
els, we failed to find such effects with the measures used here.
We hypothesized that the administration of CBD could increase
BDNF levels and the ratios of metabolites NAA and Cr as meas-
ured with H1-MRS, which are related to neuronal viability. Some
Table 2. Variations in the scores of UPDRS, PDQ-39, BDNF levels and NAA/Cr between baseline and final assessment.
Placebo CBD 75 mg/day CBD 300 mg/day ANOVA (F; p) or Kruskal-
Wallis test (p)
Variation/Baseline-
Final (DP)
Variation/Baseline-
Final (DP)
Variation/Baseline-Final
(DP)
UPDRS total on 3.83 (±6.85) 3.00 (±5.97) 6.57 (±5.83) F=0.631; p=0.544
UPDRS part I 0.17 (±0.75) 0.86 (±1.07) 0.29 (±1.38) F=0.737; p=0.493
UPDRS part IIa2.50 (±4.18) –1.29 (±3.45) 2.85 (±4.14) p=0.146
UPDRS part IIIa2.17 (±8.23) 3.85 (±5.37) 3.00 (±5.16) p=0.675
UPDRS part IV –1.00 (±2.19) –0.43 (±1.99) 0.43 (±2.64) F=0.644; p=0.538
PDQ-39 total 6.50 (±8.48)b10.00 (±12.15) 25.57 (±16.30)bF=4.142; p=0.034
Mobility 4.17 (±9.70) 5.71 (±12.89) 19.64 (±17.22) F=2.574; p=0.106
ADL –0.69 (±6.68)b16.07 (±16.21) 21.43 (±13.91)bF=4.847; p=0.022
Emotional well-being 2.78 (±13.09) 5.36 (±10.12) 17.85 (±11.21) F=3.339; p=0.060
Stigmaa3.13 (±5.23) –4.46 (±16.42)b15.18 (±14.37)bp=0.038
Social supporta0.00 (±10.54) 2.38 (±12.47) 5.95 (±12.47) p=0.694
Cognitiona13.57 (±30.72) 14.29 (±21.56) 7.14 (±4.31) p=0.332
Communication 0.00 (±11.79) 0.00 (±23.57) 9.52 (±14.77) F=0.657; p=0.531
Physical discomfort 13.89 (±15.52) 5.95 (±25.78) 23.81 (±18.28) F=1.323; p=0.292
BDNF levels –1,385.25 (±6,814.65) 822,67 (±7,884.29) –3,522.97 (±18,993.18) F=0.158; p=0.855
H1-MRS
NAA/Cre righta0.11 (0.18) 0.11 (0.18) 0.10 (0.18) p=0.875
NAA/Cre left 0.19 (0.18) –0.01 (0.07) 0.07 (0.22) F=1.890; p=0.183
aNonparametric distribution; bp<0.05, Bonferroni’s post hoc test.
by guest on September 21, 2014jop.sagepub.comDownloaded from
Chagas et al. 5
limitations should also be noted including those related to H1-
MRS and BDNF measures: the 6-week period might have been
insufficient for the occurrence of detectable changes in spectros-
copy measures linked to neuronal viability, added to the fact that
this measure has not been explored in depth in PD. Probably, a
longer treatment period should be tested before definitive conclu-
sions are drawn. Also, BDNF levels have large inter-individual
variations, which increases standard deviations and may hinder
the occurrence of differences in small samples.
Nowadays, most drugs used in the treatment of PD act in
the dopaminergic system and little is known about the role of
other neurotransmitter systems in the disease. The endocan-
nabinoid system seems to be an important target of investiga-
tion, mostly because of its action in those considered as the
non-motor symptoms of PD and of reports of its possible neu-
roprotective effects.
Conclusions
This study points to a possible effect of CBD in improving meas-
ures related to the quality of life of PD patients without psychiat-
ric comorbidities. We found no statistically significant differences
concerning the motor symptoms of PD; however, studies involv-
ing larger samples and with systematic assessment of specific
symptoms of PD are necessary in order to provide stronger con-
clusions regarding the action of CBD in PD.
Acknowledgements
A.W.Z., J.A.C and J.E.H. have the US patent of Cannabidiol derivatives.
A.W.Z., J.E.H., A.L.T., A.C.S and J.A.C. are recipients of a Conselho
Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil)
fellowships award. M.M.B. is a post-doctoral fellow of Fundação de
Amparo à Pesquisa de São Paulo.
Conflict of interest
The authors declare that there is no conflict of interest.
Funding
This research received no specific grant from any funding agency in the
public, commercial, or not-for-profit sectors.
References
Bergamaschi MM, Queiroz RH, Chagas MH, et al. (2011) Cannabidiol
reduces the anxiety induced by simulated public speaking in treat-
ment-naive social phobia patients. Neuropsychopharmacology 36:
1219–1226.
Chagas MH, Crippa JA, Zuardi AW, et al. (2013) Effects of acute sys-
temic administration of cannabidiol on sleep-wake cycle in rats. J
Psychopharmacol 27: 312–316.
Chagas MH, Eckeli AL, Zuardi AW, et al. (2014) Cannabidiol can
improve complex sleep-related behaviours associated with rapid eye
movement sleep behaviour disorder in Parkinson’s disease patients:
A case series. J Clin Pharm Ther 39: 564–566.
Crippa JA, Zuardi AW, Martin-Santos R, et al. (2009) Cannabis and
anxiety: A critical review of the evidence. Hum Psychopharmacol
24: 515–523.
Fahn S and Elton RL and members of the UPDRS Development
Committee (1987) Unified Parkinson’s Disease Rating Scale
(UPDRS). In: Fahn S, Marsden CD, Calne DB, et al (eds) Recent
Developments in Parkinson’s Disease. Florahm Park, N.J., Mac-
millan Health Care.
Fernandez-Ruiz J, Sagredo O, Pazos MR, et al. (2013) Cannabidiol for
neurodegenerative disorders: Important new clinical applications for
this phytocannabinoid? Br J Clin Pharmacol 75: 323–333.
Fitzpatrick R, Jenkinson C, Peto V, et al. (1997) Desirable properties
for instruments assessing quality of life: Evidence from the PDQ-39.
J Neurol Neurosurg Psychiatry 62: 104.
Garcia-Arencibia M, Gonzalez S, De Lago E, et al. (2007) Evaluation of
the neuroprotective effect of cannabinoids in a rat model of Parkin-
son’s disease: Importance of antioxidant and cannabinoid receptor-
independent properties. Brain Res 1134: 162–170.
Hermann D, Sartorius A, Welzel H, et al. (2007) Dorsolateral prefrontal
cortex N-acetylaspartate/total creatine (NAA/tCr) loss in male recre-
ational cannabis users. Biol Psychiatry 61: 1281–1289.
Iuvone T, Esposito G, De Filippis D, et al. (2009) Cannabidiol: A prom-
ising drug for neurodegenerative disorders? CNS Neurosci Ther 15:
65–75.
Jenkinson C, Fitzpatrick R, Peto V, et al. (1997) The Parkinson’s Disease
Questionnaire (PDQ-39): Development and validation of a Parkin-
son’s disease summary index score. Age Ageing 26: 353–357.
Jenkinson C, Peto V, Fitzpatrick R, et al. (1995) Self-reported function-
ing and well-being in patients with Parkinson’s disease: Comparison
of the short-form health survey (SF-36) and the Parkinson’s Disease
Questionnaire (PDQ-39). Age Ageing 24: 505–509.
Lastres-Becker I, Molina-Holgado F, Ramos JA, et al. (2005) Cannabi-
noids provide neuroprotection against 6-hydroxydopamine toxicity
in vivo and in vitro: Relevance to Parkinson’s disease. Neurobiol
Dis 19: 96–107.
Lingjaerde O, Ahlfors UG, Bech P, et al. (1987) The UKU side effect rat-
ing scale. A new comprehensive rating scale for psychotropic drugs
and a cross-sectional study of side effects in neuroleptic-treated
patients. Acta Psychiatr Scand Suppl 334: 1–100.
Lotan I, Treves TA, Roditi Y, et al. (2014) Cannabis (medical marijuana)
treatment for motor and non-motor symptoms of Parkinson disease:
An open-label observational study. Clin Neuropharmacol 37: 41–44.
Monti JM (1977) Hypnoticlike effects of cannabidiol in the rat. Psycho-
pharmacology (Berl) 55: 263–265.
Saito VM, Wotjak CT, and Moreira FA (2010) [Pharmacological exploi-
tation of the endocannabinoid system: New perspectives for the
treatment of depression and anxiety disorders?]. Rev Bras Psiquiatr
32 (Suppl 1): S7–14.
Siderowf A, Mcdermott M, Kieburtz K, et al. (2002) Test-retest reliabil-
ity of the unified Parkinson’s disease rating scale in patients with
early Parkinson’s disease: Results from a multicenter clinical trial.
Mov Disord 17: 758–763.
Van Vliet SA, Vanwersch RA, Jongsma MJ, et al. (2008) Therapeu-
tic effects of Delta9-THC and modafinil in a marmoset Parkinson
model. Eur Neuropsychopharmacol 18: 383–389.
Venderova K, Ruzicka E, Vorisek V, et al. (2004) Survey on cannabis use
in Parkinson’s disease: Subjective improvement of motor symptoms.
Mov Disord 19: 1102–1106.
Zanelati TV, Biojone C, Moreira FA, et al. (2010) Antidepressant-like
effects of cannabidiol in mice: Possible involvement of 5-HT1A
receptors. Br J Pharmacol 159: 122–128.
Zuardi AW (2008) Cannabidiol: From an inactive cannabinoid to a drug
with wide spectrum of action. Rev Bras Psiquiatr 30: 271–280.
Zuardi AW, Crippa JA, Hallak JE, et al. (2009) Cannabidiol for the treat-
ment of psychosis in Parkinson’s disease. J Psychopharmacol 23:
979–983.
Zuardi AW, Morais SL, Guimaraes FS, et al. (1995) Antipsychotic effect
of cannabidiol. J Clin Psychiatry 56: 485–486.
Zuardi AW, Rodrigues JA and Cunha JM (1991) Effects of cannabidiol
in animal models predictive of antipsychotic activity. Psychophar-
macology (Berl) 104: 260–264.
by guest on September 21, 2014jop.sagepub.comDownloaded from
... A levodopa é considerada um medicamento padrão ouro no tratamento da doença de Parkinson pois estudos mostram que ele é o medicamento disponível no mercado que tem melhor resultado nos diversos estágios em que o paciente pode se encontrar. Contudo, essa opção de tratamento torna-se cada vez mais questionada, pois causa aumento de discinesia, náuseas e contrações musculares, que piora a qualidade de vida (CHAGAS et al., 2014). ...
... Tais fatos mostram certa limitação dos fármacos atuais no tratamento do mal de Parkinson, o que constata a importância da busca de alternativas para a melhora do prognóstico atual para as pessoas acometidas (CHAGAS et al., 2014). ...
... Quando se fala sobre os pacientes com o agravo, a qualidade de vida deve ser levada em consideração nos estudos, devido a importância de analisar medidas que visem bem-estar pessoal do ser em questão. É nesse sentido que o uso de algumas drogas, como a Cannabis pode contribuir para a qualidade de vida daquelas pessoas, já que ela causa, em relação a outros medicamentos, menos discinesias, tremor de repouso, menos hipotensão postural, menos interação medicamentosa e proporciona um maior leque de opções (CHAGAS et al., 2014). ...
Book
Full-text available
Este opúsculo intitulado “Qualidade de vida relacionada à saúde: aspectos gerais e impactos de intervenções” foi proposto para trazer, de forma simples e didática, uma reflexão sobre a qualidade de vida, em uma abordagem interdisciplinar e contemporânea. Afi- nal, tem sido cada vez mais latente a busca humana por melhores padrões de vida. Ademais, é fundamental compreender que a qualidade de vida não necessariamente está presente exclusivamente em in- divíduos considerados saudáveis. É possível gozar de um bom padrão de vida ainda que sejamos doentes crônicos. É preciso reconhecer os caminhos para uma vida com mais qualidade e descobrir como vencer as dificuldades inerentes aos processos de adoecimento. Propomos, portando, falar sobre a temática em 11 capítulos, os quais foram distribuídos em três partes: Parte I – aspectos gerais sobre a qualidade de vida de indivíduos com agravos; Parte II – impactos de intervenções na qualidade de vida; e Parte III – qualidade de vida relacionada ao trabalho. Desejamos uma boa leitura!
... One available trial examined CBD in Parkinson's disease. 55,56 Twenty-one patients with Parkinson's disease without dementia or comorbid psychiatric conditions were assigned placebo, CBD 75 mg/day, or CBD 300 mg/day for six weeks. 55 The researchers found no differences in or between any group for the Unified Parkinson Disease Rating Scale, concentrations of Brain-Derived Neurotrophic Factor, or in Proton Magnetic Resonance Spectroscopy indices. ...
... 55,56 Twenty-one patients with Parkinson's disease without dementia or comorbid psychiatric conditions were assigned placebo, CBD 75 mg/day, or CBD 300 mg/day for six weeks. 55 The researchers found no differences in or between any group for the Unified Parkinson Disease Rating Scale, concentrations of Brain-Derived Neurotrophic Factor, or in Proton Magnetic Resonance Spectroscopy indices. The group receiving CBD 300 mg/day had signifi-cant improvements compared with placebo in the Parkinson's Disease Questionnaire-39 (p = 0.05). ...
... The group receiving CBD 300 mg/day had signifi-cant improvements compared with placebo in the Parkinson's Disease Questionnaire-39 (p = 0.05). 55 Four of the subjects had Parkinson's disease-associated rapid eye movement (REM) sleep behavior disorder, which is characterized by nightmares and loss of muscle tone or strength during REM sleep. 56 All REM sleep behavior disorder-affected patients received CBD (75 mg/day in one patient and 300 mg/day in three patients). ...
Article
Full-text available
After completing the activity, learners will be able to ● Discuss cannabidiol's known pharmacologic profile ● Identify FDA-approved indications for prescription cannabidiol and other indications in which research is promising ● Distinguish the FDA-approved cannabidiol from various nonprescription products in terms of quality and risk/benefit profile ● Maximize the pharmacist's role in helping patients who are good candidates for prescription cannabidiol or use nonprescription cannabidiol products either with or without other prescription drug therapies After completing the continuing education activity, pharmacy technicians will be able to ● Discuss the basic facts about cannabidiol products ● Acquire reputable sources for patients who have an interest in cannabidiol to find information ● Distinguish between nonprescription and prescription cannabidiols ● Infer when to refer patients to the pharmacist for recommendations or referral
... Additionally, pharmacological inhibition of 2-AG degradation increased SN 2-AG levels, promoted DAN activity and dopamine release, and rescued the motor deficits. Therefore, we reveal a DAN-specific pathophysiological mechanism of DAGLB dysfunction in the pathogenesis of Parkinsonism and provide the rationale and preclinical evidence for the potential beneficial effects of 2-AG augmentation in alleviating Parkinsonism 45 . ...
Article
Full-text available
Endocannabinoid (eCB), 2-arachidonoyl-glycerol (2-AG), the most abundant eCB in the brain, regulates diverse neural functions. Here we linked multiple homozygous loss-of-function mutations in 2-AG synthase diacylglycerol lipase β (DAGLB) to an early onset autosomal recessive Parkinsonism. DAGLB is the main 2-AG synthase in human and mouse substantia nigra (SN) dopaminergic neurons (DANs). In mice, the SN 2-AG levels were markedly correlated with motor performance during locomotor skill acquisition. Genetic knockdown of Daglb in nigral DANs substantially reduced SN 2-AG levels and impaired locomotor skill learning, particularly the across-session learning. Conversely, pharmacological inhibition of 2-AG degradation increased nigral 2-AG levels, DAN activity and dopamine release and rescued the locomotor skill learning deficits. Together, we demonstrate that DAGLB-deficiency contributes to the pathogenesis of Parkinsonism, reveal the importance of DAGLB-mediated 2-AG biosynthesis in nigral DANs in regulating neuronal activity and dopamine release, and suggest potential benefits of 2-AG augmentation in alleviating Parkinsonism. 2- arachidonoylglycerol (2-AG), an abundant endocannabinoid in the brain, regulates diverse neural functions. Here, the authors identified four loss-of-function mutations in dicylglycerol lipase β (DAGLB) from six patients with early onset Parkinsonism. In mice, loss of DAGLB in dopamine neurons reduced neuronal activity and impaired locomotor function and augmentation of 2-AG levels boosted neuronal activity and rescued locomotor deficits.
... Clinical studies have demonstrated the potential of CBD in improving quality of life [26], reducing psychotic symptoms [27], and attenuating REM sleep behavioral disorder [28]. The high density of CB1 cannabinoid receptors in the basal ganglia also led to its investigation as a possible therapy in Parkinson's disease [29]. ...
Article
Full-text available
Background: Cannabis-based formulations are now widely used by patients with neurological and psychiatric problems but no studies have been published on the clinical utility of CBD/CBG enriched extracts for parkinsonism's symptoms. Objectives: To describe preliminary clinical data collection of PD and DLB patients under CBD/CBG medical prescription. Methods: Review of electronic records of 14 PD and 5 DLB patients. Four extracts were available 1) CBD broad spectrum (100 mg/ mL) 2) CBD/CBG broad spectrum (100 mg/mL 2:1) (3) CBD/CBG (2:1) + THC0.3% full spectrum (100mg/mL) 4) CBD+THC0.3% full spectrum (100 mg/mL). All the patients received authorization from ANVISA (Brazil) to import the formulations for medical use. Outcomes of each unmet need (UMN) were tabulated and graded. Results: Demographics: PD N = 14 (10 male). DLB: N = 5 (3 male). Mean age: PD: 76.2 yrs. (46-94). DLB: 82.2 yrs. (83-92). Disease duration: PD (6.57 yrs.), DLB (4.2 yrs.); PD H/Y stage (3); PD levodopa dose: 490 mg (150-900). Mean daily doses: PD CBD: 65.17 mg (8.33-125 mg), CBG: 22,50 mg (4.16-50 mg), THC: 2,32 mg (0,75-4,5 mg). DLB CBD: 52 mg (5-100 mg). CBG: 8,75 mg (2,5-15 mg), THC: 0,225 mg. Positive results were seen for RBD, insomnia, anxiety, and pain. All pain responders were on CBG and/or THC formulations. Hallucinations were also attenuated in both patient groups. Safety and tolerability were favorable in this small sample. Conclusions: Future clinical trials in Parkinson's disease and DLB with cannabinoids should focus on their potential benefit for associated anxiety, and pain. The potential anti-psychotic effects of CBD and CBD/CBG should also be further evaluated in a phase 2a clinical trial. Abstract Citation: Flávio Henrique de Rezende Costa., et al. "Parkinson's Disease and Dementia with Lewy Bodies, Patients Under Treatment with Standardized
... Similarly, the same group showed, in a doubleblind exploratory study, that the treatment with isolated CBD in capsules (300 mg/day) during 6 weeks induced improvement in daily activities and emotional wellness of patients when compared to those treated with placebo. However, changes related to motor behavior were not reported (Chagas et al., 2014). ...
Article
Full-text available
Historically, Cannabis is one of the first plants to be domesticated and used in medicine, though only in the last years the amount of Cannabis-based products or medicines has increased worldwide. Previous preclinical studies and few published clinical trials have demonstrated the efficacy and safety of Cannabis-based medicines in humans. Indeed, Cannabis-related medicines are used to treat multiple pathological conditions, including neurodegenerative disorders. In clinical practice, Cannabis products have already been introduced to treatment regimens of Alzheimer’s disease, Parkinson’s disease and Multiple Sclerosis’s patients, and the mechanisms of action behind the reported improvement in the clinical outcome and disease progression are associated with their anti-inflammatory, immunosuppressive, antioxidant, and neuroprotective properties, due to the modulation of the endocannabinoid system. In this review, we describe the role played by the endocannabinoid system in the physiopathology of Alzheimer, Parkinson, and Multiple Sclerosis, mainly at the neuroimmunological level. We also discuss the evidence for the correlation between phytocannabinoids and their therapeutic effects in these disorders, thus describing the main clinical studies carried out so far on the therapeutic performance of Cannabis-based medicines.
... This may also explain why both the CB1 agonist and antagonist may have been involved with LID. Indeed, the authors also referred that in the interaction between CB1 and D1, D2 receptors can modulate the LID (Wang et al., 2022), but the exact mechanism is still not understood, which is reflected in the fact that experimental and clinical trials reveal contradicting results (Sieradzan et al., 2001;Carroll et al., 2004;Chagas et al., 2014). Additionally, the relevance of the TRPV1 receptor as a new therapeutic target against LID is still not clearly understood and the experimental results, including the interaction with CB1, also remain controversial. ...
Article
Background: The endocannabinoid system is a widespread neuromodulatory system affecting several biological functions and processes. High densities of type 1 cannabinoid (CB1) receptors and endocannabinoids are found in basal ganglia, which makes them an interesting target group for drug development in basal ganglia disorders such as Parkinson's disease (PD). Objective: The aim of this study was to investigate CB1 receptors in PD with [18 F]FMPEP-d2 positron emission tomography (PET) and the effect of dopaminergic medication on the [18 F]FMPEP-d2 binding. Methods: The data consisted of 16 subjects with PD and 10 healthy control subjects (HCs). All participants underwent a [18 F]FMPEP-d2 high-resolution research tomograph PET examination for the quantitative assessment of cerebral binding to CB1 receptors. To investigate the effect of dopaminergic medication on the [18 F]FMPEP-d2 binding, 15 subjects with PD underwent [18 F]FMPEP-d2 PET twice, both on and off antiparkinsonian medication. Results: [18 F]FMPEP-d2 distribution volume was significantly lower in the off scan compared with the on scan in basal ganglia, thalamus, hippocampus, and amygdala (P < 0.05). Distribution volume was lower in subjects with PD off than in HCs globally (P < 0.05), but not higher than in HCs in any brain region. Conclusions: Subjects with PD have lower CB1 receptor availability compared with HCs. PD medication increases CB1 receptor toward normal levels. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Article
Full-text available
Background Cannabidiol (CBD), a major cannabinoid of Cannabis sativa, is widely consumed in prescription and non-prescription products. While CBD is generally considered ‘non-intoxicating’, its effects on safety-sensitive tasks are still under scrutiny. Aim We investigated the effects of CBD on driving performance. Methods Healthy adults ( n = 17) completed four treatment sessions involving the oral administration of a placebo, or 15, 300 or 1500 mg CBD in a randomised, double-blind, crossover design. Simulated driving performance was assessed between ~45–75 and ~210–240 min post-treatment (Drives 1 and 2) using a two-part scenario with ‘standard’ and ‘car following’ (CF) components. The primary outcome was standard deviation of lateral position (SDLP), a well-established measure of vehicular control. Cognitive function, subjective experiences and plasma CBD concentrations were also measured. Non-inferiority analyses tested the hypothesis that CBD would not increase SDLP by more than a margin equivalent to a 0.05% blood alcohol concentration (Cohen’s d z = 0.50). Results Non-inferiority was established during the standard component of Drive 1 and CF component of Drive 2 on all CBD treatments and during the standard component of Drive 2 on the 15 and 1500 mg treatments (95% CIs < 0.5). The remaining comparisons to placebo were inconclusive (the 95% CIs included 0 and 0.50). No dose of CBD impaired cognition or induced feelings of intoxication ( ps > 0.05). CBD was unexpectedly found to persist in plasma for prolonged periods of time (e.g. >4 weeks at 1500 mg). Conclusion Acute, oral CBD treatment does not appear to induce feelings of intoxication and is unlikely to impair cognitive function or driving performance (Registration: ACTRN12619001552178).
Article
Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by the decrease in dopaminergic neurons in the brain leading to motor and nonmotor symptoms. With the increased availability of cannabidiol in the United States and interest in the PD community for PD-related symptom management in complementary to pharmacologic treatment, this review provides nurse practitioners with useful information on existing studies and regulatory considerations on the implication of cannabidiol in PD.
Article
Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. The symptoms of PD are characterized not only by motor alterations but also by a spectrum of nonmotor symptoms. Some of these are psychiatric manifestations such as sleep disorders; depression; cognitive difficulties that can evolve into dementia; and symptoms of psychosis, which include hallucinations, illusions, and delusions. Parkinson’s disease psychosis (PDP) occurs in 18%–50% of patients with PD. Treating PDP is challenging because antipsychotic drugs tend to be inefficient or may even worsen the motor symptoms of the disease. Methods: This is a narrative review in which an extensive literature search was performed on the Scopus, EMBASE, PubMed, ISI Web of Science, and Google Scholar databases, from inception to August 2021. The terms “Parkinson’s disease psychosis,” “Parkinson psychosis,” “neurodegenerative psychosis,” and “dopamine psychosis” were among the keywords used in the search. Objective: This review aims to summarize the current understanding of the molecular mechanisms involved in PDP, as well as recent innovative alternatives for its treatment. Results: Recently, views on the etiology of hallucinations and illusions have evolved remarkably. PDP has been cemented as a multifactorial entity that is dependent not only on extrinsic mechanisms but also novel intrinsic mechanisms including genetic factors, neurostructural alterations, functional disruptions, visual processing disturbances, and sleep disorders. Consequently, innovative pharmacological and biological treatments have been proposed. Pimavanserin, a selective 5-HT2A inverse agonist, stands out after its approval for the treatment of PDP-associated hallucinations and illusions. Conclusion: Future results from upcoming clinical trials should further characterize the role of this drug in the management of PDP as well as other treatment options with novel mechanisms of action, such as saracatinib, SEP-363856, cannabidiol, electroconvulsive therapy, and transcranial magnetic stimulation.
Article
Full-text available
OBJETIVO: Este artigo revisa o sistema endocanabinoide e as respectivas estratégias de intervenções farmacológicas. MÉTODO: Realizou-se uma revisão da literatura sobre o sistema endocanabinoide e a sua farmacologia, considerando-se artigos originais ou de revisão escritos em inglês. DISCUSSÃO: Canabinoides são um grupo de compostos presentes na Cannabis Sativa (maconha), a exemplo do Δ9-tetraidrocanabinol e seus análogos sintéticos. Estudos sobre o seu perfil farmacológico levaram à descoberta do sistema endocanabinoide do cérebro de mamíferos. Este sistema é composto por pelo menos dois receptores acoplados a uma proteína G, CB1 e CB2, pelos seus ligantes endógenos (endocanabinoides; a exemplo da anandamida e do 2-araquidonoil glicerol) e pelas enzimas responsáveis por sintetizá-los e metabolizá-los. Os endocanabinoides representam uma classe de mensageiros neurais que são sintetizados sob demanda e liberados de neurônios pós-sinápticos para restringir a liberação de neurotransmissores clássicos de terminais pré-sinápticos. Esta sinalização retrógrada modula uma diversidade de funções cerebrais, incluindo ansiedade, medo e humor, em que a ativação de receptores CB1 pode exercer efeitos dos tipos ansiolítico e antidepressivo em estudos préclínicos. CONCLUSÃO: Experimentos com modelos animais sugerem que drogas que facilitam a ação dos endocanabinoides podem representar uma nova estratégia para o tratamento de transtornos de ansiedade e depressão.
Article
Full-text available
The use of cannabis as a therapeutic agent for various medical conditions has been well documented. However, clinical trials in patients with Parkinson disease (PD) have yielded conflicting results. The aim of the present open-label observational study was to assess the clinical effect of cannabis on motor and non-motor symptoms of PD. Twenty-two patients with PD attending the motor disorder clinic of a tertiary medical center in 2011 to 2012 were evaluated at baseline and 30 minutes after smoking cannabis using the following battery: Unified Parkinson Disease Rating Scale, visual analog scale, present pain intensity scale, Short-Form McGill Pain Questionnaire, as well as Medical Cannabis Survey National Drug and Alcohol Research Center Questionnaire. Mean (SD) total score on the motor Unified Parkinson Disease Rating Scale score improved significantly from 33.1 (13.8) at baseline to 23.2 (10.5) after cannabis consumption (t = 5.9; P < 0.001). Analysis of specific motor symptoms revealed significant improvement after treatment in tremor (P < 0.001), rigidity (P = 0.004), and bradykinesia (P < 0.001). There was also significant improvement of sleep and pain scores. No significant adverse effects of the drug were observed. The study suggests that cannabis might have a place in the therapeutic armamentarium of PD. Larger, controlled studies are needed to verify the results.
Article
Full-text available
Unlabelled: Cannabidiol (CBD) is one of the main components of Cannabis sativa and has a wide spectrum of action, including effects in the sleep-wake cycle. Objective: The objective of this paper is to assess the effects on sleep of acute systemic administration of CBD. Method: Adult male Wistar rats were randomly distributed into four groups that received intraperitoneal injections of CBD 2.5 mg/kg, CBD 10 mg/kg, CBD 40 mg/kg or vehicle (n=seven animals/group). Sleep recordings were made during light and dark periods for four days: two days of baseline recording, one day of drug administration (test), and one day after drug (post-test). Results: During the light period of the test day, the total percentage of sleep significantly increased in the groups treated with 10 and 40 mg/kg of CBD compared to placebo. REM sleep latency increased in the group injected with CBD 40 mg/kg and was significantly decreased with the dose of 10 mg/kg on the post-test day. There was an increase in the time of SWS in the group treated with CBD 40 mg/kg, although this result did not reach statistical significance. Conclusion: The systemic acute administration of CBD appears to increase total sleep time, in addition to increasing sleep latency in the light period of the day of administration.
Article
What is known and objective: Cannabidiol (CBD) is the main non-psychotropic component of the Cannabis sativa plant. REM sleep behaviour disorder (RBD) is a parasomnia characterized by the loss of muscle atonia during REM sleep associated with nightmares and active behaviour during dreaming. We have described the effects of CBD in RBD symptoms in patients with Parkinson's disease. Cases summary: Four patients treated with CBD had prompt and substantial reduction in the frequency of RBD-related events without side effects. What is new and conclusion: This case series indicates that CBD is able to control the symptoms of RBD.
Article
Objectives: to briefly outline the development and validation of the Parkinson's Disease Questionnaire (PDQ-39) and then to provide evidence for the use of the measure as either a profile of health status scores or a single index figure. Design: the PDQ-39 was administered in two surveys: a postal survey of patients registered with local branches of the Parkinson's Disease Society of Great Britain (n = 405) and a survey of patients attending neurology clinics for treatment for Parkinson's disease (n = 146). Data from the eight dimensions of the PDQ-39 were factor-analysed. This produced a single factor on the data from both surveys. Outcome measures: the eight dimensions of the PDQ-39 and the new single index score—the Parkins's disease summary index (PDSI), together with clinical assessments (the Columbia rating scale and the Hoehn and Yahr staging score). Results: in the postal survey 227 patients returned questionnaires (58.2%). All 146 patients approached in the clinic sample agreed to take part. Higher-order principal-components factor analysis was undertaken on the eight dimensions of the PDQ-39 and produced one factor on both datasets. Consequently it was decided that the scores of the eight domains could be summed to produce a single index figure. The psychometric properties of this index were explored using reliability tests and tests of construct validity. The newly derived single index was found to be both internally reliable and valid. Discussion: data from the PDQ-39 can be presented either in profile form or as a single index figure. The profile should be of value in studies aimed at determining the impact of treatment regimes upon particular aspects of functioning and well-being in patients with Parkinson's disease, while the PDSI will provide a summary score of the impact of the illness on functioning and well-being and will be of use in the evaluation of the overall effect of different treatments. Furthermore, the PDSI reduces the number of statistical comparisons and hence the role of chance when exploring data from the PDQ-39.
Article
An anonymous questionnaire sent to all patients attending the Prague Movement Disorder Centre revealed that 25% of 339 respondents had taken cannabis and 45.9% of these described some form of benefit. © 2004 Movement Disorder Society
Article
Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, antioxidant, antiemetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti-inflammatory and antioxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with Δ(9) -tetrahydrocannabinol is already under clinical evaluation in patients with Huntington's disease to determine its potential as a disease-modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant-derived cannabinoids like Δ(9) -tetrahydrocannabinol, i.e. CB(1) and CB(2) receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB(2) receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.