Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with Standardized Extracts Enriched in Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial

Abstract

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

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OPEN ACCESS EC NEUROLOGYEC NEUROLOGY
Research Article
Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under
Treatment with Standardized Extracts Enriched in Cannabidiol and
Cannabigerol: Descriptive Observations in Preparation for
a Phase 2a Clinical Trial
Flávio Henrique de Rezende Costa1,2*, Simone Pellegrino1, Mariana Spitz3, Eduardo Rydz1, Gabriel de Castro
Micheli1, Elio Tanaka4, Brian Michael Ebner5, Jaron Gladstone5 and Andrew J Lees6
1Health Meds Laboratories, Rio de Janeiro, Brazil
2Multidisciplinary Clinic, Botagofo, Rio de Janeiro, Brazil
3Estate University of Rio de Janeiro, Brazil
4TNK, Curitiba- Brazil
5CBCeuticals, Coral Springs, Flórida, USA
6Queen Square Brain Bank for Neurological Disorders, University College London Queen Square Institute of Neurology, London, UK
*Corresponding Author: Flávio Henrique de Rezende Costa, Health Meds Laboratories, Rio de Janeiro and Multidisciplinary Clinic,
Botagofo, Rio de Janeiro, Brazil.
Received: December 29, 2021; Published: April 26, 2022
Background: Cannabis-based formulations are now widely used by patients with neurological and psychiatric problems but no stud-
ies 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: -
sociated anxiety, and pain. The potential anti-psychotic effects of CBD and CBD/CBG should also be further evaluated in a phase 2a
clinical trial.
Keywords: Cannabidiol; Cannabigerol; Parkinson’s Disease; Dementia With Lewy Bodies; Medical Cannabis
Abstract
Citation: Flávio Henrique de Rezende Costa., et al. “Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with
Standardized Extracts Enriched in Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial”.
EC Neurology 14.5 (2022): 01-15.
DOI: 10.31080/ecne.2022.14.01023

Citation: Flávio Henrique de Rezende Costa., et al. “Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with
Standardized Extracts Enriched in Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial”.
EC Neurology 14.5 (2022): 01-15.
Abbreviations
ANVISA: National Agency of Health Vigilance (Brazil); ASTM: Accelerated Aging of Sterile Barrier Systems for Medical Devices; CBD: Can-
nabidiol; CBG: Cannabigerol; CPGF: Cannabidiol Pharmaceutical Grade Formulations; DBS: Deep Brain Stimulation; DLB: Dementia with
Lewy Bodies;
GMP: Good Manufactured Practice; ICB: Impulsive, Compulsive Behaviors; MS-HPLC: Mass Spectroscopy – High-Performance Liquid Chro-
matography; MCT oil: Medium Chain Triglycerides Oil;

Introduction
In a A Manual of Diseases of the Nervous System published in 1888 the English neurologist William Gowers described the therapeutic
role of “Indian hemp” (Cannabis indica) sometimes combined with opium- as an effective treatment for tremor in Parkinson’s disease [1].
cannabis had been published [2]. During
the early 20th century, Merck Laboratories (Germany), Burroughs-Wellcome (England), Bristol-Meyers Squibb (USA), Parke-Davis (USA),
and Eli Lilly (USA) had in their portfolios of medications, extracts or tinctures of cannabis [3]. In 1937, the marijuana tax act – contrary
to the American Medical Association’s recommendation- led to the marked decline of medical use of cannabis and in 1941, cannabis was

cannabis resumed in the early ‘60s, with the discovery and synthesis of the principal psychoactive
constituent of Cannabis 
    

Cloning CB1 [6] and CB2 receptors [7] in the early 1990s opened the door to current knowledge about the endocannabinoid system
– or the endocannabinoidome as it is sometimes referred to - an intricate network of biochemically related receptors, enzymes, and me-
diators. The endocannabinoid system’s signaling involves regulating cells, tissues, and organs; organism homeostasis after insults; brain
development and release of neurotransmitters and cytokines related to synaptic plasticity [8].
So far medicinal research has concentrated on CBD, the second most abundant constituent of cannabis
   
inverse agonist [9]. It activates the TRPV1 channel [10] and 5-HT1A receptors [11]. It also is a GPR55 receptor antagonist [12] and inhibits
the enzymatic activity of fatty acid amide hydrolase (FAAH) and the endocannabinoid anandamide’s reuptake [13].
CBG has recently been evaluated in vitro and in vivo models [14]. It is a precursor of the most abundant cannabinoids and expresses an

    

PD [18], and Huntington’s disease [19].
A recently published general patient survey of CBG-predominant cannabis use reported improvement in anxiety, chronic pain, depres-

very few adverse side-effects [20].
Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with Standardized Extracts Enriched in
Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial
02

Citation: Flávio Henrique de Rezende Costa., et al. “Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with
Standardized Extracts Enriched in Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial”.
EC Neurology 14.5 (2022): 01-15.
 
(Epidiolex) [22] have been medically approved for the management of pain/spasticity in multiple sclerosis and for refractory epilepsy
in Dravet/Lennox Gastaut syndromes.
In 2019 the National Health Surveillance Agency (ANVISA) in Brazil created a protocol for the registration of CPGF [23]. Only formu-
  -
      
Cannabis
formulations can also be imported legally to Brazil, provided that they have received sanitary approval in the country of origin [25].
Clinical studies have demonstrated the potential of CBD in improving quality of life [26], reducing psychotic symptoms [27], and at-
tenuating REM sleep behavioral disorder [28]. The high density of CB1 cannabinoid receptors in the basal ganglia also led to its investiga-

levodopa-induced dyskinesias in one small clinical trial [30] but most of the few available studies have shown a limited role for phytocan-
nabinoids with regard to improvement of motor symptoms in PD [31].
Recent clinical and preclinical evidence has suggested that CBD may have antipsychotic properties [32]. In contrast to some of the
available anti-psychotic drugs CBD also appears to have no cardiac toxicity and does not increase the QT interval [33].
This paper describes pilot descriptive data collected in preparation for a controlled phase 2a study and describes the response of a
small number of patients with PD and DLB patients treated with four different CBD or CBD/CBG formulations.
-
SA. The extracts are produced in Florida-USA under GMP compliance (CBCeuticals Laboratories/Health Meds Laboratories) and imported
-
tion of analysis for each batch and passed the stability test protocol ASTM-F1980.
Methods
The medical records of 14 PD and 5 DLB patients were reviewed between April 2020 and June 2021. All patients were followed up in
a single medical facility (Multidisciplinary Clinic- Botafogo- Rio de Janeiro/Brazil).
A neurologist (FHRC), specialized in movement disorders, established a PD diagnosis based on the Queen Square Brain Bank Criteria
[34] and DBL using the Movement Disorders Society’s criteria [35]. At the baseline clinical interview the main complaints were divided
into motor or non-motor categories. The most frequent unmet needs for PD were disruptive RBD (N = 10), anxiety (n = 5), insomnia (n =

For DLB: disorientation with getting lost (n = 4), disruptive RBD (3), sleep fragmentation (n = 5), night agitation (n = 3), severe/complex
hallucinations (n = 4), and delirium (5).
           
(Health Meds Laboratories-Brazil) were available for prescription as enriched standardized extracts: 1) Cannabidiol (CBD) broad spec-
trum (100 mg/mL) 2) Cannabidiol/Cannabigerol (CBD/CBG) (2:1) broad spectrum (100mg/mL) (3) Cannabidiol/Cannabigerol (CBD/
CBG) (2:1) +THC 0.3% full spectrum (100mg/mL) 4) Cannabidiol (CBD)+THC 0.3% full spectrum (100mg/mL). All CBD or CBD/CBG for-

Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with Standardized Extracts Enriched in
Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial
03

Citation: Flávio Henrique de Rezende Costa., et al. “Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with
Standardized Extracts Enriched in Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial”.
EC Neurology 14.5 (2022): 01-15.
The formulations were presented in opaque bottles containing 60 ml. The excipient was Organic Medium Chain Triglycerides (MCT) oil
(USP - FDA GRAS). A graduated micropipette was available in each of the bottles, protected by a child-proof cap. Each drop of the solution
had 2.5 mg CBD or 2.5 mg CBD / CBG (2:1); therefore, 40 drops (1ml) contained 100mg of CBD or 100mg of CBD/CBG (2:1). In THC 0.3%
formulations each 1 mL delivered 3 mg of THC.
 
the concept of “start low and go slow” (2.5 mg - 12.5 mg CBD at bedtime) with a focus on determining the lowest dose for symptomatic
control. The dose titration was variable, depending on the target symptoms.
A pharmacist oversaw pharmacovigilance by phone or by email contact.
Follow-up medical consultations took place every 2-3 months when target symptoms were reassessed, and a physician made dosage
adjustments.
Ethical considerations
The study received ethics committee approval and institutional board review (CEP/UNESA: 45936121.2.0000.5284 / Plataforma Bra-
sil). All patients received the prescriptions based on ANVISA resolution number 335 - which regulates the importing process of cannabis
derivatives to Brazil (25). Patients signed an informed consent form and completed an electronic form made available on the regulator’s

the prescribing physician’s name, the formulation, and the patient’s name associated with a code generated by the regulatory agency. The
laboratory staff could assist the patients or their guardians during the entire ANVISA clearance process. All personal data followed the
guidelines of the Federal Government’s data protection law.
Measurements and calculations
Data were extracted from the records of each patient (ComAmigo® version 9.16.61 www.cebim.com.br). The variables age, gender,
disease duration, follow-up duration, H/Y stage, levodopa, and cannabinoids doses were tabulated in the SPSS (version 18 for MAC) for
calculating the means and standard deviations (SD). The concomitant use of psychotropic medications was noted in each case.

LIMITED, or INEFFECTIVE. Symptoms graded as GOOD/MODERATE were deemed satisfactory, and LIMITED/INEFFECTIVE were con-
sidered unsatisfactory. Changes in drug prescription regimes were noted, focusing on recording reduction or withdrawal of sedatives or
neuroleptics.
Data was sent to a medical auditor (ELT) and another neurologist specializing in movement disorders (MS) to check and discuss any
inconsistencies.
Results
The mean age of the PD patients was 72.6 years (42 - 94) and for DLB , 82.2 years. (8 3- 92). Most of the patients were male (PD =
10 and DLB = 3). The disease duration was 6.57 years. (± 2.70) for PD and 4.2 years. (± 1.30) for DLB. The follow-up duration was 3.78
months (± 5.63) for PD and 4.2 months (± 1.30) for DLB. The average levodopa dose was 490 mg (± 212), with a mean H / Y of 3 (± 0.84)
in the PD group (Table 1 to 6).
Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with Standardized Extracts Enriched in
Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial
04

Citation: Flávio Henrique de Rezende Costa., et al. “Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with
Standardized Extracts Enriched in Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial”.
EC Neurology 14.5 (2022): 01-15.
Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with Standardized Extracts Enriched in
Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial
05
PD DLB
Patients (n) 14 5
Age (years) 72.6 (42-94) 82.2 (83-92)
Gender n (%) (male) 10 (72) 3 (60)
Disease Duration (yrs) (SD) 6.57 (± 2.70) 4.2 (± 1.30)
Follow up duration (months) (SD) 3.78 (± 5.63) 4.2 (± 1.30)
Hoehn and Yahr (SD) 3 (± 0.84)
Mean Levodopa dose mg (SD) 490 (± 212)
Daily CBD mean dose mg (SD) 67.50 (± 38.6) 52 (± 44.8)
Daily CBG mean dose mg (SD) 22.50 (± 16.82) 8.75 (± 8.33)
Daily THC mean dose mg (SD)* 2.32 (± 1.46) 0.02 mg (± 0.01)
Daily THC mean dose mg (SD)** 0.83 (± 2.24) 0.02 mg (± 0.01)
Table 1: Patients’ characteristics.
  
with Lewy bodies. * n=5 PD and n=1 DLB patients on THC containing formulations. ** All patients included.
# Diagnosis Gender Age Disease
Duration
(years)
Disease Stage H/Y Comorbidities Initial
Concurrent
Drugs
#1 PD M 63 6 6 2 Essential hyperten-
sion, Chronic pain
(coxofemural osteo-
arthritis)
Levodopa 600mg/day;
Rasagiline 1mg/day,
domperidone 10mg t.i.d,
Amantadine 100mg t.i.d,
Rotigotine 8mg/day,
#2 PD M 69 5 1 3 Obesity Levodopa 900mg/day,
Rasagiline 1mg/day, entaca-
pone 1 gr/dia, clonazepam
2mg, duloxetin 60mg, dom-
peridone 10mg t.i.d
#3 PD F 88 7 5 3 Essential hyperten-
sion, osteoarthritis
(low back pain)
Levodopa 400mg/day,
sertraline 100mg//day,
zolpidem 10mg bedtime
#4 PD M 46 6 5 2 Levodopa 600mg/day;
Rasagiline 1mg/day,
domperidone 10mg t.i.d,
pramipexol 4.5 mg/day
#5 PD M 53 6 1 3 Levodopa 500mg/day;
Rasagiline 1mg/day,
domperidone 10mg t.i.d,
clozapine 12.5mg/day

Citation: Flávio Henrique de Rezende Costa., et al. “Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with
Standardized Extracts Enriched in Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial”.
EC Neurology 14.5 (2022): 01-15.
Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with Standardized Extracts Enriched in
Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial
06
#6 PD M 80 12 6 4 PD Dementia (PIGD) Levodopa 400mg/day,
Rasagiline 1mg/day, Riv-
astigmine Patch 9,5mg/day,
melatonin 5mg
#7 PD M 94 8 3 4 Osteoarthritis Levodopa 400mg/day,
Rasagiline 1mg/day
#8 PD M 77 6 4 2.5 Essential hyperten-
sion
Levodopa 300mg/day, Riv-
astigmine Patch 9,5mg/day
#9 PD M 90 12 1 5 Advanced pharyn-
geal neoplasm (pal-
liative care)
Levodopa 400mg/day,
Rasagiline 1mg/day, Riv-
astigmine Patch 9,5mg/day,
melatonin 5mg, escitalo-
pram 5mg/day, clonazepam
0.25mg
#10 PD M 85 6 2 3 Colostomy (past
bowel diverticulum
perforation)
Levodopa 900mg/day,
amantadine 100mg/day,
venlafaxine 75mg/day,
Lithium (prescribed by
another physician)
#11 PD F 88 4 5 3 Levodopa 500mg/day;
Rasagiline 1mg/day,
amantadine 100mg/day,
Lorazepan 2mg bedtime
#12 PD F 79 2 5 2 Hypothyroidism=
levothyroxine
125mcg/day
Levodopa 150mg/day, rasa-
giline 1mg/day, domperi-
-
tisone 0.2 mg bedtime
#13 PD M 80 5 5 3 Levodopa 300mg/dia,
Rotigotine 4mg/day, galan-
tamine 16mg/day, zolpidem
6.25mg, quetiapine 75mg
bedtime,
#14 PD F 75 7 4 3 Thrombophilia Levodopa 500mg/day;
Rasagiline 1mg/day, Rotigo-
tine 8mg/day, amantadine
100mg/day, venalafaxine
75mg/day, domperidone
30mg/day, dabigatran
Table 2: PD: demographics, comorbidities, and initial concurrent treatment.
PIGD=Postural instability with gait disability. PD= Parkinson’s disease.

Citation: Flávio Henrique de Rezende Costa., et al. “Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with
Standardized Extracts Enriched in Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial”.
EC Neurology 14.5 (2022): 01-15.
Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with Standardized Extracts Enriched in
Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial
07
Number Diagnosis Formulation Daily CBD Dose
(mg)
Daily CBG
Dose(mg)
Daily THC
Dose(mg)
#1 PD Cannabidiol + Cannabigerol 2:1 (100mg/mL) + THC 0.3% 100 50 4,5
#2 PD Cannabidiol (100mg/mL) 100
#3 PD Cannabidiol + Cannabigerol 2:1 (100mg/mL) 41.66 20.83
#4 PD Cannabidiol (100mg/mL) + THC 0.3 % 25 0,75
#5 PD Cannabidiol + Cannabigerol 2:1 (100mg/mL) 12.5
#6 PD Cannabidiol (100mg/mL) 50
#7 PD Cannabidiol + Cannabigerol 2:1 (100mg/mL) 8.33 4.16
#8 PD Cannabidiol (100mg/mL) 125 0
#9 PD Cannabidiol + Cannabigerol 2:1 (100mg/mL) + THC 0.3% 33.33 16.66 1,5
#10 PD Cannabidiol (100mg/mL) 75 0
#11 PD Cannabidiol + Cannabigerol 2:1 (100mg/mL) + THC 0.3% 41.66 20.83 1,87
#12 PD Cannabidiol (100mg/mL) + THC 0.3 % 100 3
#13 PD Cannabidiol (100mg/mL) 100
#14 PD Cannabidiol (100mg/mL) 100
#1 DLB Cannabidiol (100mg/mL) 100
#2 DLB Cannabidiol (100mg/mL) 100
#3 DLB Cannabidiol + Cannabigerol 2:1 (100mg/mL) 30 15
#4 DLB Cannabidiol + Cannabigerol 2:1 (100mg/mL) + THC 0.3% 25 2.5 0.025
#5 DLB Cannabidiol (100mg/mL) 5
Table 3: Formulations and daily doses of each patient.
# Diagnosis Unmet Need Before Treatment Effect On Un-
met Needs
Overall Ef-
fect
Comments
#1 PD 1)Pain**** and compulsion 2)
insomnia 3) RBD* 4) Anxiety***
GOOD GOOD Rigidity reduction only on 4.5 mg of THC
#2 PD 
gait) 2) Low back pain 3) RBD
INEFFECTIVE LIMITED The patient discontinued treatment after
one month. Improvement in sleep duration.
#3 PD 1) insomnia 2) RDB* 3) pain 4)
Mild hallucinations (benign)**
GOOD GOOD Zolpidem withdrawn. Fewer episodes of
somnambulism.
#4 PD 1) Problematic wearing off phe-
nomenon 2) impulsivity (compul-
sive internet stock market “day
trade” behavior 3) severe anxiety
4) RBD*/insomnia
MODERATE LIMITED No impact on motor symptoms / no impact
on wearing off/ Drowsiness in doses
>50mg CBD/THC 0.3%. Patient on prepara-
tion for DBS.

Citation: Flávio Henrique de Rezende Costa., et al. “Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with
Standardized Extracts Enriched in Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial”.
EC Neurology 14.5 (2022): 01-15.
Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with Standardized Extracts Enriched in
Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial
08
#5 PD 1) Problematic motor and “non-
motor wearing-off phenomenon.
Severe tremor 2) Transient
psychosis/hallucinations (induced
by dopaminergic overstimulation:
suicide attempt
LIMITED LIMITED Clozapine withdrawal. No effect on the

preparation for DBS.
#6 PD 1) Hallucinations** 2) cognitive
decline 3) RDB*/ wandering 4)
severe gait disability
GOOD GOOD Remains without the use of neuroleptics.
No impact on motor symptoms. Add on ef-
fect on hallucinations
#7 PD 1) Insomnia 2) Nocturnal pain ****
-
tions (anxiety***) 4) RBD*
GOOD GOOD Market attenuation of non-motor nocturnal

#8 PD 1) Anxiety*** 2) Complex halluci-
nations** 3) Insomnia 4) RBD*
GOOD GOOD Stable without neuroleptics. No impact on
motor symptoms
#9 PD 1) Hallucinations** 2) Cogni-
tive decline 3) Severe rigidity 4)
Insomnia
GOOD MODERATE Palliative care in end of life. No effect on
rigidity. Morphine sparing effect. No end-
of-life delirium. Patient died comfortably
#10 PD 1)Gait balance problems 2) Apathy
3) Mild depressive symptoms
GOOD GOOD Better on the balance after lithium with-
dr aw.
#11 PD 1) Severe pain****: Dopamine
agonist-induced cervical dystonia
2) anxiety*** 3) RBInsomniania
GOOD GOOD Other actions for pain management: imme-
diate pramipexol withdrawal and US-guid-
ed botulinum toxin cervical injection.
#12 PD 1) Severe levodopa/rasagiline
induced nausea and hypotension
2) Anxiety
GOOD GOOD Nausea improvement. Orthostatic hypoten-

#13 PD 1) Moderate hallucinations**2)
RBD* and insomnia 3) Cognitive
decline (PDD)
GOOD GOOD Quetiapine dose unchanged. Add on effect
on hallucinations.
#14 PD 1) wearing off (freezing of gait) 2)
Cognitive decline 3) RBD*/ benign
hallucinations** 5) Anxiety***
(despite venlafaxine use) 6) pain
(knee arthrosis)
GOOD MODERATE No impact on wearing off phenomenon
RDB symptom abolished/marked improve-
ment of hallucinations
Table 4: RBD= Rem sleep behavior disorder. *RBD symptoms abolished and substantial increment in sleep duration. ** Marked improve-
ment in hallucinations. *** Marked response in anxiety symptoms. **** Pain responders. PD= Parkinson’s disease.

Citation: Flávio Henrique de Rezende Costa., et al. “Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with
Standardized Extracts Enriched in Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial”.
EC Neurology 14.5 (2022): 01-15.
Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with Standardized Extracts Enriched in
Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial
09
# Diag-
nosis
Gender Age Disease
Duration
(yrs)
Disease Stage H/Y Comorbidi-
ties
Initial Concurrent
Drugs
#1 DLB M 83 3 2 N/A Coronary disease (past
coronary angioplasty with
stents implants)
Levodopa 400mg/day,
melatonin 10mg bedtime,
rivastigmine Patch 4,5 mg/day,
eszopiclone 2mg bedtime
#2 DLB F 71 3 5 N/A Rivastigmine Patch 9,5 mg/
day, melatonin 5mg day,
memantine 10 mg bedtime,
mirtazapine 15mg bedtime,
alprazolam 0.5mg bedtime
#3 DLB M 87 4 4 N/A 
vein thrombosis / parox-

anticoagulant: dabigatran
Donepezil 10mg/day, meman-
tine 20mg/day, escitalopram
10mg/day, alprazolam 2mg/
day, levodopa 400mg/day
#4 DLB F 78 6 5 N/A Severe weight loss Rivastigmine Patch 4,5 mg/
day, trazodone 25mg/day,
olanzapine 2,5mg, eszopiclone
2mg/day
#5 DLB M 92 5 5 N/A Arterial peripheral vas-
cular disease, Pulmonary

tract infections with de-
lirium (prolonged double J
catheter)
Rivastigmine Patch 13.3 mg/
day, clozapine 12.5mg bedtime,
venlafaxine 75mg/day
Table 5: DLB: demographics, comorbidities, and initial concurrent treatment. DLB= Dementia with Lewy bodies.
# Diagnosis Unmet need before treatment Effect on unmet needs Overall Effect comments
#1 DLB -
ing, agitation, and RBD 3) Severe complex
hallucinations, 4) Drug hypersensitivity.
INEFFECTIVE INEFFECTIVE 
#2 DLB 1) Severe complex hallucinations*** 2) wan-
dering** 3) anxiety
MODERATE LIMITED Limited effect on the
speed of cognitive
decline. The patient still
deteriorating on multiple
other aspects: Language
visuospatial skills

Citation: Flávio Henrique de Rezende Costa., et al. “Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with
Standardized Extracts Enriched in Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial”.
EC Neurology 14.5 (2022): 01-15.
#3 DLB 1) Severe hallucinations*** 2) wander-
ing** 3) RBD* 4) fast cognitive decline and
sundowning
GOOD MODERATE Mild mental confusion
/ somnolence in doses
above 45mg of CBD/CBG
2:1. Stable on the actual
dose.
#4 DLB 1) Severe hallucinations*** 2) wandering**
3) RBD*, fast cognitive decline and sun-
downing 4) severe parkinsonism 5) severe
weight loss
GOOD GOOD Olanzapine and eszopi-
clone was withdrawn
#5 DLB 1) Insomnia and nocturnal agitation 2)
Marked parkinsonism with gait balance


GOOD MODERATE Clozapine was with-
drawn
Table 6: *RBD responders. ** Marked improvement in wandering. *** Marked response in hallucinations.
DLB= Dementia with Lewy bodies.
Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with Standardized Extracts Enriched in
Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial
10
Regarding prescribed formulations, PD patients were on CBD enriched n = 6, CBD/CBG 2:1 enriched n = 3, CBD/CBG 2:1 enriched +
THC 0.3% n = 3, CBD/THC 0.3% n = 2 full spectrum. DBL patients were on CBD enriched n = 3, CBD/CBG 2: 1 enriched n = 1, CBD/CBG 2:
1 enriched +THC 0.3% n = 1.
The average CBD dose was 67.5 mg for PD (± 38.6) and 52mg (± 44.8) for DLB. The CBG dose was 22.5 mg for PD (± 16.82) and 8.7mg
(± 8.33) for DLB. The average THC dose was 2.32 mg for PD (± 1.46) and 0.02 mg for DLB (± 0.01); this variable was calculated only in
patients using THC-containing formulations. Considering all patients in the PD and DLB groups, the average THC dose was 0.83 mg (±
2.24) for PD, and 0.025 mg (± 0.01) for DLB.
Marked improvements were observed on RBD (9/10), insomnia (9/9), anxiety (5/5) in the PD patients. There was also improvement
in reported pain (3/5), impulsive-compulsive behaviors (ICB’s) (2/2), and visual hallucinations (6/7). All pain responders were on for-
mulations with CBG and THC.
RBD symptoms were markedly reduced in 9 patients (PD#1, PD#3, PD#4, PD#6, PD#7, PD#8, PD#11, PD#13, PD#14). For instance,
PD # 14 had a long history of sleep disturbance having kicked her husband several times during vivid dreams episodes. All her symptoms
vanished after 50mg CBD nocte. The dose was titrated to 50mg twice a day, and this patient also experienced a marked attenuation of late
afternoon visual hallucinations.

(PD#1, PD#7, PD#8, PD#11, PD#14). PD#11 had experienced several months of pain and antecollis dystonic posture. The patient was in
great distress, markedly anxious, and experiencing severe insomnia. Dopamine agonist-induced cervical dystonia was initially considered
as a cause of pain and abnormal cervical posture. Pramipexole was suspended and rasagiline and low dose amantadine were slowly intro-
duced but with no improvement. After four weeks, CBD/CBG 2:1 + THC 0.3% formulation was started and titrated to 62.5 mg (25 drops)
at night. A marked improvement in anxiety symptoms and sleep disturbance was promptly observed.

Citation: Flávio Henrique de Rezende Costa., et al. “Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with
Standardized Extracts Enriched in Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial”.
EC Neurology 14.5 (2022): 01-15.
Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with Standardized Extracts Enriched in
Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial
11
A modest response in musculoskeletal pain was observed only in those patients with formulations that contained CBD or CBG with or
without THC (PD#1, PD #7, and PD#11). CBD isolated formulations did not produce analgesic effects in PD#2 and PD#14.
An antipsychotic effect occurred in six patients (PD#3, PD#6, PD#8, PD#9, PD#13, PD#14)- usually associated with improved sleep
quality and decreased anxiety symptoms.
In DLB patients, improvements in wandering (3/4), disruptive RBD (2/3), sleep fragmentation (4/5), night agitation (2/3), and hallu-
cinations (4/5) were reported and in two patients (DLB#4 and DLB#5) with delirium and agitation it was possible to discontinue sedative
and anti-psychotic medication. DLB#3 showed a marked reduction in visual hallucinations, despite having drowsiness with CBD/CBG 2:

and no visual hallucinations at the current dose.
Concerning DLB#1, intervention with CBD enriched (THC Free) was considered ineffective. The patient was looked after by his elderly
-

No improvement in motor symptoms was observed, except in patient #1 (CBD/CBG 2:1 + THC 0.3%) who reported reduced stiffness
with 4.5mg THC daily. PD #5 had severe off tremor that failed to respond This patient is currently undergoing a evaluation for a DBS
surgical implant.
Discussion
This study provides tentative support for earlier studies demonstrating phytocannabinoids’ potential in managing some PD non-

The high average age in both groups, multiple comorbidities, concurrent use of multiple drugs, and relatively long disease duration in

The response rate was high in sleep disorders, especially in the disruptive forms of RBD and PD/DLB sleep fragmentation. In PD, 9 of
-
derline RBD and sleep disruption both in PD and DLB [36]. Preclinical studies have shown that CBD enhances in vivo acetylcholine levels
from the basal forebrain and increments sleep duration [37].
Current RBD drug treatment options are melatonin and clonazepam [38] - the latter although highly effective can interfere with cogni-
tion and normal sleep architecture, and put patients at greater risk of falls [39].
-
ety attacks) and improved sleep quality. Mild drowsiness occurred, however, in CBD/CBD (2:1) dose above 12.5 mg (5 drops)- indicating
that dose titration should be individualized and symptom-focused.

-

Citation: Flávio Henrique de Rezende Costa., et al. “Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with
Standardized Extracts Enriched in Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial”.
EC Neurology 14.5 (2022): 01-15.
Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with Standardized Extracts Enriched in
Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial
12
sive painting), and reduced muscle stiffness (need a reference here). Previous studies have also shown that doses of isolated CBD between

Our study emphasizes the need for lower doses in all formulations, compared with previous reports in the elderly, and provides some
support for cannabinoids exerting an entourage effect [40].
   
dementia and increased mortality in PD patients [41]. Current treatment options are restricted to cholinomimetics and atypical antipsy-
chotics such as clozapine In DBL, the use of neuroleptics is even more challenging due to neuroleptics hypersensitivity and neuroleptics
have been associated with increased mortality in dementias [39].
A moderate response to pain was observed only in those on CBG or THC formulations (PD#1, PD#7, PD#11), supporting the view that
combinations of cannabinoids may be best for this indication [40]. .
  
promptly reversed with dose reduction.
Even though the data were structured for each patient, no previously validated scale was applied in this study and there was no ran-
domization. The outcomes were assessed exclusively based on the patients’ or caregivers’ reports in a semi-structured clinical interview
conducted by a neurologist with training in movement disorders. On the other hand, checking the data by an independent neurologist and
a medical auditor helped with data transparency.
Finally, the present work was possible due to Brazilian legislation changes. The recent ANVISA regulations provided access to stan-
dardized extracts via import process, although not yet available in the Brazilian National Health System under universal coverage [25].
  -
cacy in various medical indications [23].
Perspectives for Future Studies
            
encourage the need for well-conducted randomized clinical trials with CBD or CBD/CBG to examine its antipsychotic potential. Further
trials with phytocannabinoids for tremor and l-dopa induced dyskinesias in PD should also be conducted.
Conclusions
This report describes the potential of CBD/CBG formulations for non-motor symptoms treatment in PD and DLB- such as anxiety, sleep
disorders, visual hallucinations, impulsivity, and pain and will be helpful in designing a phase 2a randomized placebo-controlled clinical
trial.

Prof. Flávio Rezende works part-time in Research and Development (R&D) for Health Meds Laboratories (Brazil) and advisor physician
for Cbeuticals Laboratories (USA).
Simone Pellegrino de Oliveira works full-time as a Pharmacist for Health Meds-Brazil.

Citation: Flávio Henrique de Rezende Costa., et al. “Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with
Standardized Extracts Enriched in Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial”.
EC Neurology 14.5 (2022): 01-15.
13
Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with Standardized Extracts Enriched in
Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial
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Citation: Flávio Henrique de Rezende Costa., et al. “Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with
Standardized Extracts Enriched in Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial”.
EC Neurology 14.5 (2022): 01-15.
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Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial
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Citation: Flávio Henrique de Rezende Costa., et al. “Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with
Standardized Extracts Enriched in Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial”.
EC Neurology 14.5 (2022): 01-15.
15
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Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial
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Volume 14 Issue 5 May 2022
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