Cannabidiol Normalizes Caspase 3, Synaptophysin, and Mitochondrial Fission Protein DNM1L Expression Levels in Rats with Brain Iron Overload: Implications for Neuroprotection.

“We have recently shown that chronic treatment with cannabidiol (CBD) was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats.

 Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson’s and Alzheimer’s, and has been related to cognitive deficits in animals and human subjects.

…we have analyzed the expression level of brain proteins involved with mitochondrial fusion and fission mechanisms (DNM1L and OPA1), the main integral transmembrane protein of synaptic vesicles (synaptophysin), and caspase 3, an apoptosis-related protein, to gain a better understanding of the potential of CBD in restoring the damage caused by iron loading in rats.

We found that CBD rescued iron-induced effects…

Our results suggest that iron affects mitochondrial dynamics, possibly trigging synaptic loss and apoptotic cell death and indicate that CBD should be considered as a potential molecule with memory-rescuing and neuroprotective properties to be used in the treatment of cognitive deficits observed in neurodegenerative disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/23893294

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Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders.

“Cannabidiol, the main nonpsychotropic constituent of Cannabis sativa, possesses a large number of pharmacological effects including anticonvulsive, sedative, hypnotic, anxiolytic, antipsychotic, anti-inflammatory, and neuroprotective, as demonstrated in clinical and preclinical studies.

 Many neurodegenerative disorders involve cognitive deficits, and this has led to interest in whether cannabidiol could be useful in the treatment of memory impairment associated to these diseases…

We used an animal model of cognitive impairment induced by iron overload in order to test the effects of cannabidiol in memory-impaired rats…

RESULTS:

A single acute injection of cannabidiol at the highest dose was able to recover memory in iron-treated rats. Chronic cannabidiol improved recognition memory in iron-treated rats. Acute or chronic cannabidiol does not affect memory in control rats.

CONCLUSIONS:

The present findings provide evidence suggesting the potential use of cannabidiol for the treatment of cognitive decline associated with neurodegenerative disorders.

 Further studies, including clinical trials, are warranted to determine the usefulness of cannabidiol in humans suffering from neurodegenerative disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/21870037

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Activation of spinal cannabinoid cb2 receptors inhibits neuropathic pain in streptozotocin-induced diabetic mice.

“The role of spinal cannabinoid systems in neuropathic pain of streptozotocin-induced diabetic mice was studied…

 … A low dose of WIN-55,212-2  significantly recovered the tail-flick latency in streptozotocin-induced diabetic mice… The selective cannabinoid CB2 receptor agonist L-759,656 also dose-dependently recovered the tail-flick latency in streptozotocin-induced diabetic mice…

 These results indicate that spinal cannabinoid systems are changed in diabetic mice and suggest that cannabinoid CB2 receptor agonists might have an ability to recover diabetic neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/23892011

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The Hypocretin/Orexin Receptor-1 as a Novel Target to Modulate Cannabinoid Reward.

“Although there is a high prevalence of users who seek treatment for cannabis dependence, no accepted pharmacologic treatment is available to facilitate and maintain abstinence.

 The hypocretin/orexin system plays a critical role in drug addiction, but the potential participation of this system in the addictive properties of cannabinoids is unknown.

 We investigated…  studies were performed to evaluate dopamine extracellular levels in the nucleus accumbens after acute Δ9-tetrahydrocannabinol administration..

… role of Hcrtr-1 in the reinforcing and motivational properties of WIN55,212-2 (THC) was confirmed…

CONCLUSIONS:

These findings demonstrate that Hcrtr-1 modulates the reinforcing properties of cannabinoids, which could have a clear therapeutic interest.”

http://www.ncbi.nlm.nih.gov/pubmed/23896204

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Hepatic Cannabinoid Receptor Type 1 Mediates Alcohol-Induced Regulation of Bile Acid Enzyme Genes Expression Via CREBH.

“In this study, we have investigated the effect of alcohol exposure on hepatic bile acid homeostasis and elucidated the mediatory roles of Cb1r and Crebh in this process.

We found that alcohol exposure or Cb1r-agonist 2-AG treatment increases hepatic bile acid synthesis and serum ALT, AST levels in vivo along with significant increase in Crebh gene expression and activation.

 Alcohol exposure activated Cb1r, Crebh, and perturbed bile acid homeostasis…

 Overall, our study demonstrates a novel regulatory mechanism of hepatic bile acid metabolism by alcohol via Cb1r-mediated activation of Crebh, and suggests that targeting Crebh can be of therapeutic potential in ameliorating alcohol-induced perturbation of bile acid homeostasis.”

http://www.ncbi.nlm.nih.gov/pubmed/23894352

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Palmitoylethanolamide: From endogenous cannabimimetic substance to innovative medicine for the treatment of cannabis dependence.

“Palmitoylethanolamide (PEA) is a fatty acid amide showing some pharmacodynamic similarities with Δ9-tetrahydrocannabinol, the principal psychoactive compound present in the cannabis plant.

Like Δ9-tetrahydrocannabinol, PEA can produce a direct or indirect activation of cannabinoid receptors.

 Furthermore, it acts as an agonist at TRPV1 receptor.

The hypothesis is that PEA has anti-craving effects in cannabis dependent patients, is efficacious in the treatment of withdrawal symptoms, produces a reduction of cannabis consumption and is effective in the prevention of cannabis induced neurotoxicity and neuro-psychiatric disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/23896215

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Anandamide deficiency and heightened neuropathic pain in aged mice.

“Damaging of peripheral nerves may result in chronic neuropathic pain for which the likelihood is increased in the elderly. We assessed in mice if age-dependent alterations of endocannabinoids contributed to the heightened vulnerability to neuropathic pain at old age.

We assessed nociception, endocannabinoids and the therapeutic efficacy of R-flurbiprofen in young and aged mice in the spared nerve injury model of neuropathic pain.

 R-flurbiprofen was used because it is able to reduce neuropathic pain in young mice in part by increasing anandamide.

Aged mice developed stronger nociceptive hypersensitivity after sciatic nerve injury than young mice.

This was associated with low anandamide levels in the dorsal root ganglia, spinal cord, thalamus and cortex, which further decreased after nerve injury…”

 More: http://www.ncbi.nlm.nih.gov/pubmed/23597506

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Analysis of THCA synthase gene expression in cannabis: A preliminary study by real-time quantitative PCR.

“In this paper we describe analyses performed by Real-Time Reverse-Transcriptase Polymerase Chain Reaction (real-time RT-PCR) on RNA of 12 samples, carried out for forensic purposes to investigate a correlation between tetrahydrocannabinol (THC) concentration in Cannabis and the tetrahydrocannabinol acid synthase (THCAS) gene expression. Samples were obtained from an experimental cultivation of declared potency Cannabis variety seeds and from seizures. The Rubisco gene and the 26S ribosomal RNA gene were used as internal control genes for their constant expression and stability. As results we found minor gene expression in samples from leaves of young plants. Further, grouping results for cannabis samples with similar characteristics, we have found an increased relative expression in samples with the highest percentage of THC coming from seized sample and adult plants.”

http://www.ncbi.nlm.nih.gov/pubmed/23890639

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[So called ((soft)) drugs: cannabis and the amotivational syndrome].

“… there is a minority of problematic cannabis users.

 There is a scientific consensus to claim that cannabis induces a state of dependence in a small proportion of users.

Severe abuse of cannabis can also lead to cognitive impairments, especially on memory, although these effects usually improve after the cessation of cannabis use.

The statistical link between cannabis use and the development of psychotic disorders is more worrying, although the causal nature of this relationship remains controversial.

 Finally, a chronic abuse of cannabis is reputed to induce an amotivational syndrome, mainly characterized by a state of apathy.

Although the symptoms of the amotivational syndrome are in keeping with some clinical observations, it remains difficult to ascertain whether this clinical picture is causally produced by cannabis abuse.”

http://www.ncbi.nlm.nih.gov/pubmed/23888577

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Police custody following driving under the influence of cannabis: A prospective study.

“We hypothesized that drug intoxication while driving could correspond to specific medical conditions of the detainees. Our objective was to evaluate medical features and addictive behaviours of suspected drug drivers and to collect data regarding assaults or injuries in these individuals.

We conducted a prospective study of suspected drug driving arrestees, who were compared to drink drivers or persons aged over 18 detained for other reasons. Data collected concerned persons’ characteristics, reported assaults, and observed injuries…

  Cannabis-only users accounted for 201 of 205 drug drivers (98%).

Suspected drug driving arrestees had good overall health rating.

Drug drivers were younger than controls and requested more rarely medical examination.

 They were rarely involved in addiction treatment and reported assaults or presented traumatic injuries less often than drink drivers and controls.

 Drug drivers were less often alcohol abusers than controls.

 Their opinion on custody was better than that of controls and they were considered unconditionally fit for detention more frequently.

 We conclude that arrested drug drivers were young, healthy, and infrequently reported assaults or presented traumatic injuries, which does not put them in a high risk medical condition…”

http://www.ncbi.nlm.nih.gov/pubmed/23890621

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