7. The Neuro-MedicalAgenda:
I. Cannabidiol (CBD) and Cannabidivarin (CBDV) have
potential in treatment of Neuronal Hyperexcitablity
[Epilepsies]
II. Delta-9-tetrahydracannabinol (THC) and Cannabidiol
(CBD), combination of phytocannabinoids, are
neuroprotective and have potential in therapeutic
treatment of neurodegenerative diseases such as
Huntington’s Disease
III. Cannabidiol (CBD) encourages neuritogenesis and has
potential in therapeutic treatment of Parkinsons Disease 7
8. Cannabidiol (CBD), Activate and Desensitize
Transient Receptor
Potential Vanilloid 1 (TRPV1) Channels in
Vitro: Potential for the
Treatment of Neuronal Hyperexcitability
Patch Clamp Analysis – records currents of single
or multiple ion channels
TRPV 1 activation
TRPV 2 activation
Microelectrode Array – neural interfaces that
obtain neural signals and convert to deliver to
electronic circuitry
Amplitude, Duration, and Frequency
8
16. Effective:
• Cannabinoids targetTRP molecules as one of
their mechanisms of action in controlling
Neuronal excitability.
• Increase activation ofTRPV 1 andTRPV 2
channels
• CBDV is the only compound known to shorten
burst duration 16
17. The Neuro-MedicalAgenda:
I. Cannabidiol (CBD) and Cannabidivarin (CBDV) have
potential in treatment of Neuronal Hyperexcitablity
[Epilepsies]
II. Delta-9-tetrahydracannabinol (THC) and Cannabidiol
(CBD), combination of phytocannabinoids, are
neuroprotective and have potential in therapeutic
treatment of neurodegenerative diseases such as
Huntington’s Disease
III. Cannabidiol (CBD) encourages neuritogenesis and has
potential in therapeutic treatment of Parkinsons Disease
and other neurodegenerative diseases such as Alzheimer’s
Disease and Huntington’s Disease 17
18. Sativex-like Combination of
Phytocannabinoids is Neuroprotective in
Malonate-Lesioned Rats, an Inflammatory
Model of Huntington’s
Disease: Role of CB1 and CB2 Receptors
• Volume of Edema
• Number of Surviving Neurons
• Number of Degenerating
Neurons
• Presence of microgliosis
• Presence of astrogliosis
• Expression of biomarkers:
INOS, IGF-1, and CB1 18
19. ..in Vivo NMR
• Malonate – 2M malonate – injection in left striatum
• + Sativex – THC and CBD administered (1:1), prior to
and post- malonate
19
24. • The combination of phytocannabinoids display
neuroprotective properties against growing edema.
• This neuroprotectivity allows higher cell survival while
also decreasing the number suffering degeneration.
• CombinationTHC:CBD reduces astrogliosis and
microgliosis caused by and contributing to neuronal
death
Effective:
24
25. The Neuro-MedicalAgenda:
I. Cannabidiol (CBD) and Cannabidivarin (CBDV) have
potential in treatment of Neuronal Hyperexcitablity
[Epilepsies]
II. Delta-9-tetrahydracannabinol (THC) and Cannabidiol
(CBD), combination of phytocannabinoids, are
neuroprotective and have potential in therapeutic
treatment of neurodegenerative diseases such as
Huntington’s Disease
III. Cannabidiol (CBD) encourages neuritogenesis and has
potential in therapeutic treatment of Parkinsons
Disease and other neurodegenerative diseases such as
Alzheimer’s Disease and Huntington’s Disease 25
26. NeurogenesisSites in the Brain
• Hippocampus
• LateralVentricles
• Dentate Gyrus
• Striatum
• Septum
• Thalamus
• Hypothalamus
• Olfactory bulb
Neurite – any projection protruding
from a neuron 26
27. The neuroprotection of cannabidiol against
MPP+-induced toxicity in
PC12 cells involves trkA receptors,
upregulation of axonal and synaptic
proteins, neuritogenesis, and might be
relevant to Parkinson’s disease
…you go and save the
best for last
• MPP+ is neurotoxic
• CBD is neuroprotective and encourages
differentiation
• CBD increases [neurogenesis] proteins
27
33. Effective:
• MPP+ is a common neurotoxin in producing
similar neurotoxic effects to Parkinson’s
Disease
• CBD is protective against the cell death and
neurite loss induced by MPP+
• CBD encourages neuritogenesis.
33
34. The Neuro-MedicalAgenda:
I. Cannabidiol (CBD) and Cannabidivarin (CBDV) have potential
in treatment of Neuronal Hyperexcitablity [Epilepsies]
II. Delta-9-tetrahydracannabinol (THC) and Cannabidiol (CBD),
combination of phytocannabinoids, are neuroprotective and
have potential in therapeutic treatment of
neurodegenerative diseases such as Huntington’s Disease
III. Cannabidiol (CBD) encourages neuritogenesis and has
potential in therapeutic treatment of Parkinsons Disease
and other neurodegenerative diseases such as Alzheimer’s
Disease and Huntington’s Disease
34
37. Sources:
• minor Images from chemspider.com and google.com – cannabinoids
and target molecules
• Addiction Potential image; Jack E. Henningfield, PhD for National
Institute of Drug Abuse
• Lethal Dose image; DRCNet Online Library of Drug Policy
• ACS Chemical Neuroscience, Sativex-like Combination of
Phytocannabinoids is Neuroprotective in Malonate-Lesioned Rats, an
Inflammatory Model of Huntington’s Disease: Role of CB1 and CB2
Receptors; 2012.
• ACS Chemical Neuroscience, Nonpsychotropic Plant Cannabinoids,
Cannabidivarin (CBDV) and Cannabidiol (CBD), Activate and
Desensitize Transient Receptor Potential Vanilloid 1 (TRPV1)
Channels in Vitro: Potential for the Treatment of Neuronal
Hyperexcitability; 2014.
• Toxicology in Vitro, The neuroprotection of cannabidiol against
MPP+-induced toxicity in PC12 cells involves trkA receptors,
upregulation of axonal and synaptic proteins, neuritogenesis, and
might be relevant to Parkinson's disease;, 2015.
• Molecular Neurodegeneration, Promising cannabinoid-based
therapies for Parkinson’s disease: motor symptoms to
neuroprotection; 2015.
• Neurotherapeutics, Cannabinoids in Neurodegenerative Disorders
and Stroke/Brain Trauma: From Preclinical Models to Clinical
Applications; 2015.
• British Journal of Pharmacology, The role of cannabinoids in adult
neurogenesis; 2015. 37