Conclusion: The experimental evidence
indicates that cannabinoids protect normal neurons from toxic insults.
Cannabinoids and cell fate.Conclusion:
Regarding the central nervous
system, most of the experimental evidence indicates that cannabinoids may
protect neurons from toxic
insults such as glutamaergic overstimulation, ischemia and oxidative
Conclusion: The psychotropic cannabinoid
receptor agonist Δ9tetrahydrocannabinol (THC) and cannabidiol,
(a non-psychoactive constituent of marijuana), both reduced NMDA, AMPA and
kainate receptor mediated neurotoxicities.
Conclusion: Excitotoxic neuronal death
underlies many neurodegenerative
disorders. This study demonstrates the importance of agonist efficacy and
the duration of treatment on the neuroprotective effects of cannabinoids.
Conclusion: In glaucoma, the increased
release of glutamate is the major cause
of retinal ganglion cell death. In conclusion, our results indicate that
lipid peroxidation and ONOO- formation play an important role in NMDA-induced
retinal neurotoxicity and cell loss in the retina, and that THC and CBD, by
reducing the formation of these compounds, are effective neuroprotectants.
Memantine and Δ9
-tetrahydrocannabinol alone were without effect, however, co-administration of
the drugs significantly decreased number of haloperidol-induced jaw movements.
The antitremor activity of the combination was antagonized (i) by injections of
L-glutamate into the dorsal striatum, entopeduncular nucleus, substantia nigra
pars reticulata, globus pallidus, supratrigeminal and trigeminal motor nuclei
but not into the subthalamic and cuneiform nuclei; (ii) by injections of CGS
21680 into the ventrolateral striatum; (iii) by injections of bicuculline into
the rostral part of the parvicellular reticular nucleus. The presented results
identify brain areas
influencing parkinsonian-like tremor in rats; these data can help advance
the development of novel treatments for repetitive involuntary
Conclusion: Marijuana users were high
functioning, demonstrating comparable IQs to controls and relatively better
processing speed. Marijuana users demonstrated relative cognitive
impairments in verbal memory, spatial working memory,
spatial planning, and motivated decision making but comorbid use of alcohol,
which was heavier in marijuana users, was unexpectedly found to be associated
with better performance in some of these areas.
Conclusion: At the population level, it
does not appear that current illicit drug use is associated with impaired
cognitive functioning in early middle age.
Smoking marijuana resulted in
intoxication, as assessed by a behavioral rating scale, but did not
significantly alter mean behavioral performance on the
attention task. There was no significant rCBF change in the nucleus
accumbens or other reward-related brain regions, nor in basal ganglia or
have a high density of cannabinoid receptors.
Conclusion: The observers conclude that
heavy marijuana use produces no irreversible mental deficits.
Conclusion: We conclude that marijuana does
not have a long-term negative impact on global intelligence.
Conclusion: Compared with controls,
marijuana users had significantly less bilateral orbitofrontal gyri volume,
higher functional connectivity in the orbitofrontal cortex (OFC) network, and
higher structural connectivity in tracts that innervate the OFC (forceps minor)
as measured by fractional anisotropy (FA)
Conclusion: The team found that rats treated
with HU-210 on a regular basis showed neurogenesis the growth of new
brain cells in the hippocampus. This region of
the brain is associated with learning and memory, as well as anxiety and
depression. The effect is the opposite of most legal and illicit drugs such as
alcohol, nicotine, Heroin, and cocaine.
Conclusion: Our findings demonstrate that
CBD exerts robust neuroprotective effects in vivo in HI piglets, modulating
excitotoxicity, oxidative stress and
inflammation, and that both CB2 and 5HT1A receptors are implicated
in these effects.
Conclusion: Cannabidiol (CBD), the main
non-psychotomimetic component of the plant Cannabis sativa, exerts
therapeutically promising effects on human
mental health such as inhibition of psychosis,
anxiety and depression. However, the mechanistic bases of CBD action are
unclear. Here we investigate the potential involvement of
neurogenesis in the anxiolytic effect of CBD
Cannabinoids exert a neuroprotective
influence on some neurological diseases, including
Huntington', multiple sclerosis and
epilepsy. Cannabinoids may
exert effects via a number of mechanisms and interactions with
factors and neuropeptides.
Leptin is a peptide hormone involved in the
regulation of food intake and energy balance via its actions on specific
hypothalamic nuclei. Leptin receptors are widely expressed throughout the
brain, especially in the hippocampus, basal
ganglia, cortex and cerebellum. Leptin has also shown neuroprotective
properties in a number of neurological disorders, such as
Conclusion: The endocannabinoid system is
expressed in the intact spinal cord, and it is dramatically upregulated after
Conclusion: Considering that cannabidiol
presents an extremely safe profile and is currently being used clinically,
these results suggest that this compound could be useful in the treatment of
intervertebral disc degeneration.
Conclusion: The THC(+) group was compared
with the THC(-) group with respect to injury mechanism, severity, disposition,
and mortality. A positive THC screen is associated with decreased mortality in
adult patients sustaining TBI.
Conclusion: We found that the brain-injured
animals treated with the agonist showed a marked recovery.
Conclusion: When 2-AG was administered
together with additional inactive 2-acyl-glycerols that are normally present in
the brain, functional recovery was significantly enhanced.
Conclusion: An ultralow dose of THC that
lacks any psychotrophic activity protects the brain from neuroinflammation
induced cognitive damage and might be used as an effective drug for the
treatment of neuroinflammatory conditions, including neurodegenerative
Conclusion: Our results suggest that CBC
raises the viability of NSPCs while inhibiting their
astroglia, possibly through up-regulation of ATP and adenosine signalling.
A recent meta-analysis of 144 animal studies
including 1,473 subjects (rats, mice, and primates), published in the Journal
of Cerebral Blood Flow & Metabolism in December 2014, found that in those
who had suffered an ischemic stroke (temporary or permanent), the amount of the
brain injured as a result was reduced in those subjects that had used
cannabinoid therapies as opposed to those that had not.
Conclusion: Cannabinoids effectively limit
cell damage and provide patients with neuroprotective effects following a
Conclusion: Neuroprotective effects of
cannabinoids could provide the basis for potential therapeutic uses of
cannabinoids and/or endocannabinoids in stroke.
in vivo administration of CBD or BD1063
enhanced morphine-evoked supraspinal antinociception, alleviated NMDA-induced
convulsive syndrome, and reduced the infarct size caused by permanent
unilateral middle cerebral artery occlusion.
Conclusions: CB2R agonist alleviated
neuroinflammation and protected blood-brain barrier permeability in a rat ICH
model. Further molecular mechanisms revealed which is probably mediated by
enhancing the expression of MKP-1, then inhibited MAPKs signal transduction.
Various pathobiological processes contribute
to secondary brain injury closely interact with the
Hence, we summarize the
response to ICH and recent progress in treatments targeting the
immune system in this
review. The emerging therapeutic strategies that target the
immune system after
ICH are a particular focus and have been summarized.
Cannabis has been used for centuries to
treat seizures. Characterized by recurrent seizures,
multiple disorders caused by varied etiologies, including congenital syndromes,
stroke, infection, and
traumatic brain injury. Many
patients with epilepsy also
have sensorimotor, cognitive, psychological, psychiatric, and social
impairments, as well as impaired quality of life and an increased risk of
premature death. Epilepsy
most commonly affects children, the elderly, and individuals with low
Produced in an activity-dependent manner,
endocannabinoids travel to the presynaptic cell and bind to cannabinoid
receptor 1 (CB1Rs). CB1Rs are guanine nucleotide-binding protein-coupled
receptors linked to pertussis-sensitive Gi/o a subunits. Activation of the
α subunit triggers dissociation of the ßγ complex, which
reduces adenylate cyclase production of cyclic adenosine monophosphate,
inhibits N- and P/Q-type voltage-gated calcium channels, stimulates A-type
potassium channels, activates guanine nucleotide-binding protein-coupled
inwardly-rectifying potassium channels, and inhibits the vesicular release
CB1Rs can also regulate the presynaptic release of multiple
neuromodulators such as acetylcholine, dopamine, and
CB1Rs are distributed primarily in axon terminals in the
neocortex (especially cingulate, frontal, and parietal regions),
hippocampus, amygdala, basal ganglia,
thalamus, hypothalamus, nucleus accumbens, substantia nigra, ventral tegmental
area, cerebellum, and brainstem.
For over a millennium, pre-clinical and
clinical evidence have shown that cannabinoids such as CBD can be used to
reduce seizures effectively, particularly in patients with treatment-resistant
Conclusion: Phytocannabinoids produce
anticonvulsant reactions through the endocannabinoid system, with few adverse
Conclusion: The endocannabinoid system plays
an active role in seizure termination but does not regulate
Conclusion: Our own results confirm the
overall impression from the literature review of better cognitive performance
in the cannabis user group. A majority of the studies report better cognitive
functioning in the cannabis-related schizophrenia and psychosis groups compared
to non-drug groups.
Conclusion: The first small-scale clinical
studies with CBD treatment of patients with psychotic symptoms further confirm
the potential of CBD as an effective, safe and well-tolerated
Conclusion: Experimental studies show that
cannabidiol reduces psychosis-like effects of
Δ9-tetrahydrocannabinol and synthetic analogs.
Conclusion: our data support the view that
inhibition of microglial activation may improve schizophrenia symptoms.
Conclusion: Although data available are
sufficient to suggest a
possible involvement of the endogenous cannabinoid system in the
neurobiology of depression, additional studies should be performed in order to
better elucidate the role of this system in the physiopathology of
Conclusion: These findings indicate
antidepressant-like behavioural properties of both THC and rimonabant in OB
rats although additional studies are required to clarify the relationship
between the chronic effects of cannabinoids in other pre-clinical models and in
Conclusion: CBD induces antidepressant-like
effects comparable to those of imipramine. These effects of CBD were probably
mediated by activation of 5-HT(1A) receptors.
Conclusion: Endocannabinoids (ECBs) such as
anandamide (AEA) act by activating cannabinoid type 1 (CB1) or 2
(CB2) receptors. The anxiolytic effect of drugs that facilitate ECB
effects is associated with increase in AEA levels in several encephalic areas,
including the prefrontal
cortex (PFC). We observed that drugs which interfere with ECB
reuptake/metabolism in both the PL and in the dentate gyrus of the dHIP induced
anxiolytic-like effect, in both the EPM and in the VCT via CB1
receptors, suggesting that CB1 signaling in these brain regions
modulates defensive responses to both innate and learned threatening stimuli.
This data further strengthens previous results indicating modulation of
hippocampal and MPFC activity via CB1 by ECBs, which could be
therapeutically targeted to treat anxiety disorders. Modulation of hippocampal
and MPFC activity via CB1 by ECBs, which could be therapeutically
targeted to treat anxiety disorders.
The cannabinoid receptor type 1
(CB1) antagonist SR141716 (3 mg/kg) caused an increase in
conditioned freezing upon repeated tone presentation on three consecutive days.
2-AG fear-promoting effects depended on CB1 signaling in GABAergic
neurons, while an involvement of glutamatergic neurons remained
inconclusive due to the high freezing shown by vehicle-treated
amyotrophic lateral sclerosis
Conclusion: Based on the currently available
scientific data, it is reasonable to think that cannabis might significantly
slow the progression of ALS,
potentially extending life expectancy and substantially reducing the overall
burden of the disease.
Conclusion: Although the small number of
people with ALS that reported
using cannabis limits the interpretation of the survey findings, the results
indicate that cannabis may be moderately effective at reducing symptoms of
appetite loss, depression, pain, spasticity, and drooling.
Multiple sclerosis (MS) is a chronic central
nervous system inflammatory disease of autoimmune etiology, mediated by
activated T-cells with evolving evidence of a significant contribution from B
cells and cells of the innate immune system.
Multiple sclerosis is a
chronic, predominantly immune-mediated disease of the central nervous system,
and one of the most common causes of
in young adults globally. Multiple sclerosis is increasing in incidence and
prevalence globally, even in traditionally low-prevalence regions of the world.
Classifying multiple sclerosis into distinct disease phenotypes can be
challenging, and recent refinements have been proposed to clarify existing
definitions. The prognosis of multiple sclerosis varies substantially across
The epidemiology of multiple sclerosis (MS)
includes a consideration of genetic and environmental factors. Comparative
studies of different populations have revealed prevalence and incidence rates
that vary with geography and ethnicity. With a prevalence ranging from 2 per
100,000 in Japan to greater than 100 per 100,000 in Northern Europe and North
America, the burden of MS is similarly unevenly influenced by longevity and
Conclusion: There is evidence that
nabiximols oromucosal spray may reduce subjective symptoms of spasticity and
that dronabinol is effective against neuropathic pain in patients with MS.
Conclusion: Smoked cannabis was superior to
placebo in symptom and pain reduction in
participants with treatment-resistant spasticity.
Conclusion: Cannabinoids inhibit
neurodegeneration in models of multiple sclerosis. In addition
to symptom management, cannabis may also slow the neurodegenerative processes
that ultimately lead to chronic disability in multiple sclerosis
Conclusion: Our results suggest that JWH-133
acts at CB2 receptors, most likely within the dorsal horn of the
spinal cord, to suppress the hypersensitivity associated with
The psychotic symptoms evaluated by the
Brief Psychiatric Rating Scale and the Parkinson Psychosis Questionnaire showed
a significant decrease under CBD treatment. CBD did not worsen the motor
function and decreased the total scores of the Unified Parkinson' Disease
Rating Scale. No
adverse reaction was observed during the treatment. These preliminary data
suggest that CBD may be effective, safe and well tolerated for the treatment of
the psychosis in PD.
Parkinson' disease is a
progressive neurodegenerative disease characterized by
tremor and bradykinesia and is a
common neurologic ailment. Male sex and advancing age are independent risk
factors and, as the population ages, is taking an increasing toll on
productivity and medical resources. There are a number of other extrapyramidal
conditions that can make the diagnosis challenging.
Conclusion: Parkinson' 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. Our findings point to a possible
effect of CBD in improving quality of life measures in PD patients with
no psychiatric comorbidities
Conclusion: Significant improvement of sleep
and pain scores. No significant adverse
reaction of the drug were observed. The study suggests that cannabis might
have a place in the therapeutic armamentarium of PD.
Conclusion: Given its antioxidant properties
and its ability to activate CB2 but to block CB1
receptors, Δ9-THCV has a promising pharmacological profile for
delaying disease progression in PD and also for ameliorating parkinsonian
Conclusion: Our results support the view of
a potential neuroprotective action of cannabinoids against the in vivo and in
vitro toxicity of 6-hydroxydopamine, which might be relevant for PD. Our data
indicated that these neuroprotective effects might be due, among others, to the
antioxidant properties of certain plant-derived cannabinoids, or exerted
through the capability of cannabinoid agonists to modulate glial function, or
produced by a combination of both mechanisms.
Conclusion: We have demonstrated
up-regulation of the CB1 receptor in direct response to
injury in a human PD cell culture model, and a direct neuronal protective
effect of Δ9-THC that may be mediated through PPAR?
Parkinson' disease (PD) is a slow insidious
neurological disorder characterized by a loss of dopaminergic neurons in the
midbrain. The elements of the endocannabinoid system are highly expressed in
the neural circuit of basal ganglia wherein they bidirectionally interact with
dopaminergic, glutamatergic, and GABAergic signaling systems. Additional
benefits provided by cannabinoid related compounds including CE-178253,
oleoylethanolamide, nabilone and HU-210 have been reported to possess efficacy
against bradykinesia and levodopa-induced dyskinesia in PD. The molecular
identification of the CB1 and CB2 receptors, the ion
channel TRPV1, with their respective endogenous ligand systems has opened a
whole arena of pharmacological effects elicited by each one of these specific
receptor targets. CB1 and CB2 receptors belong to the
superfamily of guanine nucleotide-binding protein-coupled receptors, which are
coupled to inhibitory G proteins.
CB1 receptors are most
highly expressed on axons and nerve terminals, but substantial functional
evidence also confirms their expression on somata. Autoradiography
investigations have convincingly reported that the basal ganglia encompass the
highest levels of both mRNA expression and binding sites for the CB1
receptor. Including striatum, other three regions that receive striatal
efferent outputs, such as the globus pallidus, entopeduncular nucleus, and
substantia nigra pars reticulata (SNpr), contain high levels of CB1
receptor binding sites. CB1 receptors are positioned in
striatonigral (direct striatal efferent pathway) and striatopallidal (indirect
striatal efferent pathway) projection neurons, which use gamma-aminobutyric
acid (GABA) as a neurotransmitter. Glutamic acid decarboxylase, prodynorphin,
substance P, as well as D1 or D2 dopaminergic receptors are other markers
co-expressed in these pathways. Immunohistochemical, immunoblot and
autoradiographical studies have suggested the presence of CB1
receptor in substantia nigra, striatum and globus pallidus. CB1
receptor immunolabeling is also abundant in SNpr.
A second cannabinoid
receptor was discovered in a human promyelocytic cDNA library within a few
years following discovery of the CB1 receptor. Based on its homology
to the CB1 receptor and similar ligand binding profile, this
receptor was named the CB2 receptor. CB2 receptors are
primarily expressed on immune cells.
Prolific expression of CB2
receptors is found in β lymphocytes, large granular lymphocytes,
lymphocytes, and Th lymphocytes.
Some reports have also
stated the importance of vanilloid TRPV1 receptors in the basal ganglia and
their ability to interact with ECBs. TRPV1 receptors have been studied for
their role as molecular integrators of nociceptive stimuli present abundantly
on sensory neurons. Apart from sensory neurons, TRPV1 receptors are also found
in the basal ganglia circuitry co-localized with tyrosine hydroxylase,
indicating that they are located in dopaminergic neurons of the nigrostriatal
The orphan guanine nucleotide-binding protein-coupled receptor
55 (GPR55) has been discovered as another possible cannabinoid receptor.
In comparison to CB receptors, GPR55 is coupled to Gq, Gα12, and
Two sets of neuronal circuits exist for striatal
MSNs that connect to the output nuclei of the basal ganglia. One is a direct
circuit (direct pathway) or via a sequence of connections that include the STN
and the external segment of the globus pallidus (GPe) (indirect pathway). The
output nuclei [SNpr and the internal segment of the globus pallidus (GPi)]
connect to the thalamus, which further has efferent extensions that form the
cortico-basal ganglia-thalamo-cortical loop. The physiological effect of
dopamine originating from the SNpc on MSNs is intricate and not fully revealed.
In fact, the intensity of membrane depolarization on the dopamine receptor
dictates the type of effect produced. D1 dopamine receptors are positively
coupled to adenylyl cyclase; hence, their activation increases the cytosolic
cAMP level and subsequently elicits numerous downstream effects including an
increase in NMDA receptor-mediated currents. In contrast, D2 dopamine receptors
are negatively coupled to adenylyl cyclase and their activation decreases
neuronal excitability and neuronal feedback to glutamatergic
Activation of D1/D2 heteromers are demonstrated to mediate
mechanisms like, increased intracellular Ca2+ levels, activation of
calcium/calmodulin-dependent protein kinase II (CaMKII) and release of
brain-derived neurotrophic factor (BDNF).
Several attempts have been made to treat
Alzheimer' disease (AD) using anti-amyloid strategies with disappointing
results. It is clear that the "amyloid cascade hypothesis" alone cannot fully
explain the neuronal damage in AD, as evidenced both by autopsy and imaging
plays a significant role in neurodegenerative diseases, whereas the debate is
ongoing about its precise role, whether it is protective or harmful. In this
review, we focus on the potential mechanism of glial activation and how local
and systemic factors influence disease progression. We focus on
neuroinflammation in AD, especially in the earliest stages, a vicious cycle of
glial priming, release of pro-inflammatory factors, and neuronal damage. We
review the evidence from imaging studies, regarding the temporal relationship
between amyloid deposition and neuroinflammation, the influence of systemic
inflammation on glial activation, both in acute and chronic stimulation and the
relevance of inflammation as a diagnostic and therapeutic target.
Conclusion: These sets of data strongly
suggest that THC could be a potential therapeutic treatment option for
through multiple functions and pathways.
Conclusion: Alzheimer' disease (AD) is
characterized by enhanced ß-amyloid peptide (ßA) deposition along
with glial activation in senile plaques, selective neuronal loss, and cognitive
deficits. Cannabinoids are neuroprotective agents against excitotoxicity in
vitro and acute brain damage in vivo. Recent studies on therapeutic strategies
for neurodegenerative diseases such as Parkinson' disease and AD have focused
on the neuroprotective properties (e.g., slowing the ongoing neurodegeneration)
rather than just on palliating symptoms of the diseases (Dawson and Dawson,
2002). Because cannabinoids combine both
neuroprotective actions, our findings may set the basis for the use of these
compounds as a therapeutic approach for AD.
is the leading cause of
dementia among the elderly, and with the ever-increasing size of this
population, cases of Alzheimer' disease
are expected to triple over the next 50 years. AChE inhibitors such as THC and
its analogues may provide an improved therapeutic for
augmenting acetylcholine levels by preventing neurotransmitter degradation and reducing
Aß amalgamation, thereby simultaneously treating both the symptoms and
progression of Alzheimer'
Conclusion: Alzheimer' disease (AD) brain
shows an ongoing inflammatory condition and
anti-inflammatories diminish the risk of
neurologic disease. Cannabinoids are neuroprotective and
anti-inflammatory agents with
therapeutic potential. We have shown that chronically administered
cannabinoid showed marked beneficial effects concomitant with inflammation
reduction and increased Aß clearance.
Conclusion: Currently, the treatment of
Tourette's syndrome (TS) is unsatisfactory. A single-dose, cross-over study in
12 patients, as well as a 6-week, randomised trial in 24 patients, demonstrated
that Δ9-tetrahydrocannabinol (THC), the most psychoactive
ingredient of cannabis, reduces tics in TS patients.
No serious adverse reaction occurred and no
impairment on neuropsychological performance was observed.