Cannabinoid Receptor (CB1) Plays Crucial Role in Alzheimers Disease - Dr. Dave Hepburn

Tuesday, 9 October 2018


Article recommend by Dr. Dave Hepburn:

Genetic deletion of CB1 cannabinoid receptors exacerbates the Alzheimer-like symptoms in a transgenic animal model.

Abstract
Activating CB1 cannabinoid receptor has been demonstrated to produce certain therapeutic effects in animal models of Alzheimer's disease (AD). In this study, we evaluated the specific contribution of CB1 receptor to the progression of AD-like pathology in double transgenic APP/PS1 mice. A new mouse strain was generated by crossing APP/PS1 transgenic mice with CB1 knockout mice. Genetic deletion of CB1 drastically reduced the survival of APP/PS1 mice. In spite that CB1 mutant mice bearing the APP/PS1 transgene developed normally, they suddenly died within the first two months of life likely due to spontaneous seizures. This increased mortality could be related to an imbalance in the excitatory/inhibitory transmission in the hippocampus as suggested by the reduced density of inhibitory parvalbumin positive neurons observed in APP/PS1 mice lacking CB1 receptor at 7 weeks of age. We also evaluated the AD-like phenotype of APP/PS1 mice heterozygous for the CB1 deletion at 3 and 6 months of age. The memory impairment associated to APP/PS1 transgene was accelerated in these mice. Neither the soluble levels of Aβ or the density of Aβ plaques were modified in APP/PS1 mice heterozygous for CB1 deletion at any age. However, the reduction in CB1 receptor expression decreased the levels of PSD-95 protein in APP/PS1 mice, suggesting a synaptic dysfunction in these animals that could account for the acceleration of the memory impairment observed. In summary, our results suggest a crucial role for CB1 receptor in the progression of AD-related pathological events.

“Although several studies have shown that type-2 cannabinoid receptor (CB2R) is involved in Alzheimer's disease (AD) pathology, now a crucial role of CB1R has become evident. One of the more exciting areas of cannabis and endocannaboid research.”
Dr. Dave Hepburn

To read the full article please visit: 

Dr. David Hepburn website: 

US Study Shows Which Cannabis (and how) is Best for Insomnia.

Friday, 5 October 2018


Article recommend by Dr. David Hepburn:

Effectiveness of Raw, Natural Medical Cannabis Flower for Treating Insomnia under Naturalistic Conditions.

Abstract 

We use a mobile software application (app) to measure for the first time, which fundamental characteristics of raw, natural medical Cannabis flower are associated with changes in perceived insomnia under naturalistic conditions. Methods: Four hundred and nine people with a specified condition of insomnia completed 1056 medical cannabis administration sessions using the Releaf AppTM educational software during which they recorded real-time ratings of self-perceived insomnia severity levels prior to and following consumption, experienced side effects, and product characteristics, including combustion method, cannabis subtypes, and/or major cannabinoid contents of cannabis consumed. Within-user effects of different flower characteristics were modeled using a fixed effects panel regression approach with standard errors clustered at the user level. Results: Releaf AppTM users showed an average symptom severity reduction of -4.5 points on a 0⁻10 point visual analogue scale (SD = 2.7, d = 2.10, p < 0.001). Use of pipes and vaporizers was associated with greater symptom relief and more positive and context-specific side effects as compared to the use of joints, while vaporization was also associated with lower negative effects. Cannabidiol (CBD) was associated with greater statistically significant symptom relief than tetrahydrocannabinol (THC), but the cannabinoid levels generally were not associated with differential side effects. Flower from C. sativa plants was associated with more negative side effects than flower from C. indica or hybrid plant subtypes. Conclusions: Consumption of medical Cannabis flower is associated with significant improvements in perceived insomnia with differential effectiveness and side effect profiles, depending on the product characteristics. 

“There are simply too many who are addicted to prescription sleeping pills even though there is a concern that those who take even a few may development cognitive impairment. The cannabis that appears to help best with insomnia is a CBD dominant, vaporized (not smoked) “indica.” Though “indica” doesn’t specifically say which terpenes are involved I always recommend high myrcene and linalool.”
Dr. David Hepburn

To read the full article please visit:
https://www.ncbi.nlm.nih.gov/pubmed/29997343

Dr. David Hepburn website:
doctordavidhepburn.com

Cannabis Extract Inhibits Superbug MRSA - Dr. David Hepburn

Wednesday, 3 October 2018


Article recommend by Dr. David Hepburn:

Antimicrobial activity of Cannabis sativa, Thuja orientalis and Psidium guajava leaf extracts against methicillin-resistant Staphylococcus aureus.

Abstract 
OBJECTIVE: 
This study examined the antimicrobial activity of Cannabis sativa, Thuja orientalis and Psidium guajava against methicillin-resistant Staphylococcus aureus (MRSA) and used a standardized purification protocol to determine the presence and abundance of bioactive compounds in the leaf extracts. 
METHODS: 
In vitro antimicrobial activities of the ethanolic extracts of C. sativa, T. orientalis and P. guajava were tested against MRSA. The presence of bioactive molecules in these three leaves was evaluated using biochemical assays and high-performance thin-layer chromatography (HPTLC). 
RESULTS:
Resistance to methicillin, penicillin, oxacillin and cefoxitin was observed in each of the clinical and nonclinical MRSA isolates. However, they were still vulnerable to vancomycin. Used individually, the 50% extract of each plant leaf inhibited MRSA growth. A profound synergism was observed when C. sativa was used in combination with T. orientalis (1:1) and when P. guajava was used in combination with T. orientalis (1:1). This was shown by larger zones of inhibition. This synergism was probably due to the combined inhibitory effect of phenolics present in the leaf extracts (i.e., quercetin and gallic acid) and catechin, as detected by HPTLC. 
CONCLUSION:
The leaf extracts of C. sativa, T. orientalis and P. guajava had potential for the control of both hospital- and community-acquired MRSA. Moreover, the inhibitory effect was enhanced when extracts were used in combination.

“MRSA is a terrible problem that every hospital and clinician fears. What an option this would prove to be. I have heard from several sources that certain cannabinoids and terpenes may do just as this study purports.”
Dr. David Hepburn


To read the full article please visit:
https://www.ncbi.nlm.nih.gov/pubmed/30120078

Dr. David Hepburn website:
doctordavidhepburn.com




Schizophrenia More Likely to Lead to Cannabis Use…. Not the Reverse - Dr Dave Hepburn

Tuesday, 2 October 2018


Article recommend by Dr. Dave Hepburn:

GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia.

Abstract 
Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested substance use and mental health-related traits, including smoking, alcohol use, schizophrenia and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study provides new insights into the etiology of cannabis use and its relation with mental health.

“It is well known that cannabis use is higher in those with schizophrenia. However, cannabis has never been shown to cause schizophrenia; in fact, the opposite appears to be true as more research is lining up showing that those with schizophrenia are more likely to turn to cannabis, possibly to help deal with the social isolation and/or a genetic predisposition as this study infers. Once again, any who claim that cannabis causes schizophrenia, are simply incorrect.” 
Dr. Dave Hepburn


To read the full article please visit:
https://www.ncbi.nlm.nih.gov/pubmed/30150663

Dr. David Hepburn website:
doctordavidhepburn.com
   


Cannabinoid Receptor Protects Against Hearing Loss Caused by Chemotherapy - Dr. David Hepburn

Monday, 1 October 2018


Article recommend by Dr. David Hepburn:

The Endocannabinoid/Cannabinoid Receptor 2 System Protects Against Cisplatin-Induced Hearing Loss

Abstract
Previous studies have demonstrated the presence of cannabinoid 2 receptor (CB2R) in the rat cochlea which was induced by cisplatin. In an organ of Corti-derived cell culture model, it was also shown that an agonist of the CB2R protected these cells against cisplatin-induced apoptosis. In the current study, we determined the distribution of CB2R in the mouse and rat cochleae and examined whether these receptors provide protection against cisplatin-induced hearing loss. In a knock-in mouse model expressing the CB2R tagged with green fluorescent protein, we show distribution of CB2R in the organ of Corti, stria vascularis, spiral ligament and spiral ganglion cells. A similar distribution of CB2R was observed in the rat cochlea using a polyclonal antibody against CB2R. Trans-tympanic administration of (2-methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone (JWH015), a selective agonist of the CB2R, protected against cisplatin-induced hearing loss which was reversed by blockade of this receptor with 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone (AM630), an antagonist of CB2R. JWH015 also reduced the loss of outer hair cells (OHCs) in the organ of Corti, loss of inner hair cell (IHC) ribbon synapses and loss of Na+/K+-ATPase immunoreactivity in the stria vascularis. Administration of AM630 alone produced significant hearing loss (measured by auditory brainstem responses) which was not associated with loss of OHCs, but led to reductions in the levels of IHC ribbon synapses and strial Na+/K+-ATPase immunoreactivity. Furthermore, knock-down of CB2R by trans-tympanic administration of siRNA sensitized the cochlea to cisplatin-induced hearing loss at the low and middle frequencies. Hearing loss induced by cisplatin and AM630 in the rat was associated with increased expression of genes for oxidative stress and inflammatory proteins in the rat cochlea. In vitro studies indicate that JWH015 did not alter cisplatin-induced killing of cancer cells suggesting this agent could be safely used during cisplatin chemotherapy. These data unmask a protective role of the cochlear endocannabinoid/CB2R system which appears tonically active under normal conditions to preserve normal hearing. However, an exogenous agonist is needed to boost the activity of endocannabinoid/CB2R system for protection against a more traumatic cochlear insult, as observed with cisplatin administration.

“One of the several possible nasty side effects of a common anticancer medication, is hearing loss. Activation of CB2R appears to prevent this, indicating an important role of the ECS (endocannabinoid system) in neuroprotection."
Dr. David Hepburn

To read the full article please visit:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110918/

Dr. David Hepburn website:
doctordavidhepburn.com


Majority of Pain Specialists Prescribe Cannabis - Dr. David Hepburn

Friday, 28 September 2018


Article recommend by Dr. David Hepburn:

Personal experience and attitudes of pain medicine specialists in Israel regarding the medical use of cannabis for chronic pain.

Abstract:
INTRODUCTION:
The scientific study of the role of cannabis in pain medicine still lags far behind the growing use driven by public approval. Accumulated clinical experience is therefore an important source of knowledge. However, no study to date has targeted physicians who actually use cannabis in their daily practice. 
METHODS: 
Registered, active, board-certified pain specialists in Israel (n=79) were asked to complete a Web-based survey. The survey was developed using the Qualtrics Online Survey Software. Questions were formulated as multiple-choice questions, and these addressed three areas of interest: 1) doctors' personal experience; 2) the role of cannabis in pain medicine; and 3) cannabis medicalization and legalization. 
RESULTS: 
Sixty-four percent of all practicing pain specialists in Israel responded. Almost all prescribe cannabis. Among them, 63% find cannabis moderately to highly effective, 56% have encountered mild or no side effects, and only 5% perceive it as significantly harmful. Common indications are neuropathic pain (65%), oncological pain (50%), arthralgias (25%), and any intractable pain (29%). Leading contraindications are schizophrenia (76%), pregnancy/breastfeeding (65%), and age <18 years (59%). Only 12% rated cannabis as more hazardous than opiates. On a personal note, 45% prefer cannabis for themselves or a family member. Lastly, 54% would like to see cannabis legalized in Israel. 
CONCLUSION:
In this survey, pain clinicians experienced in prescribing cannabis over prolonged periods view it as an effective and relatively safe treatment for chronic pain, based on their own experience. Their responses suggest a possible change of paradigm from using cannabis as the last resort.

“For virtually all types of pain, specialists in Israel, a country with a long experience with medical cannabis, use it not only for patients but 45% actually prefer cannabis for themselves or a family member.”
Dr. David Hepburn

To read the full article please visit:
https://www.ncbi.nlm.nih.gov/pubmed/30104896

Dr. David Hepburn website:
doctordavidhepburn.com

CBD Shows More Potential in Treatment of Brain Tumour - Dr. David Hepburn

Wednesday, 26 September 2018


Article recommend by Dr. Dave Hepburn:

Targeting Glioma Initiating Cells With A Combined Therapy Of Cannabinoids And Temozolomide.

Abstract 

Glioblastoma multiforme (GBM) is the most frequent and aggressive type of brain tumor due, at least in part, to its poor response to current anticancer treatments. These features could be explained, at least partially, by the presence within the tumor mass of a small population of cells termed Glioma Initiating Cells (GICs) that has been proposed to be responsible for the relapses occurring in this disease. Thus, the development of novel therapeutic approaches (and specifically those targeting the population of GICs) is urgently needed to improve the survival of the patients suffering this devastating disease. Previous observations by our group and others have shown that Δ9-Tetrahydrocannabinol (THC, the main active ingredient of marijuana) and other cannabinoids including cannabidiol (CBD) exert antitumoral actions in several animal models of cancer, including gliomas. We also found that the administration of THC (or of THC + CBD at a 1:1 ratio) in combination with temozolomide, the benchmark agent for the treatment of GBM, synergistically reduces the growth of glioma xenografts. In this work we investigated the effect of the combination of TMZ and THC:CBD mixtures containing different ratios of the two cannabinoids in preclinical glioma models, including those derived from GICs. Our findings show that TMZ + THC:CBD combinations containing a higher proportion of CDB (but not TMZ + CBD alone) produce a similar antitumoral effect as the administration of TMZ together with THC and CBD at a 1:1 ratio in xenografts generated with glioma cell lines. In addition, we also found that the administration of TMZ + THC:CBD at a 1:1 ratio reduced the growth of orthotopic xenografts generated with GICs derived from GBM patients and enhanced the survival of the animals bearing these intracranial xenografts. Remarkably, the antitumoral effect observed in GICs-derived xenografts was stronger when TMZ was administered together with cannabinoid combinations containing a higher proportion of CBD. These findings support the notion that the administration of TMZ together with THC:CBD combinations - and specifically those containing a higher proportion of CBD - may be therapeutically explored to target the population of GICs in GBM.

“Another study pointing to the exciting potential of cannabis for dealing with one of the most refractory of brain tumours, GBM. Interesting that CBD rather than THC might be more effective. “
Dr. David Hepburn

To read the full article please visit: 

Dr. Dave Hepburn website:

New Study: THC Reduces Neuropathic Pain - Dr. David Hepburn

Monday, 24 September 2018


Article recommend by Dr. Dave Hepburn:

Cannabis analgesia in chronic neuropathic pain is associated with altered brain connectivity.

Abstract

OBJECTIVE: 
To characterize the functional brain changes involved in δ-9-tetrahydrocannabinol (THC) modulation of chronic neuropathic pain. 

METHODS: 
Fifteen patients with chronic radicular neuropathic pain participated in a randomized, double-blind, placebo-controlled trial employing a counterbalanced, within-subjects design. Pain assessments and functional resting state brain scans were performed at baseline and after sublingual THC administration. We examined functional connectivity of the anterior cingulate cortex (ACC) and pain-related network dynamics using graph theory measures. 

RESULTS: 
THC significantly reduced patients' pain compared to placebo. THC-induced analgesia was correlated with a reduction in functional connectivity between the anterior cingulate cortex (ACC) and the sensorimotor cortex. Moreover, the degree of reduction was predictive of the response to THC. Graph theory analyses of local measures demonstrated reduction in network connectivity in areas involved in pain processing, and specifically in the dorsolateral prefrontal cortex (DLPFC), which were correlated with individual pain reduction. 

CONCLUSION: 
These results suggest that the ACC and DLPFC, 2 major cognitive-emotional modulation areas, and their connections to somatosensory areas, are functionally involved in the analgesic effect of THC in chronic pain. This effect may therefore be mediated through induction of functional disconnection between regulatory high-order affective regions and the sensorimotor cortex. Moreover, baseline functional connectivity between these brain areas may serve as a predictor for the extent of pain relief induced by THC.

“Neuropathic pain, so difficult to control, is extremely common. This study is yet another feather in the THC cap. By interrupting one of the pain pathways contributing to neuropathic pain, sublingual THC joins CBD as potentially a useful pain treatment."
Dr. David Hepburn

To read the full article please visit:
https://www.ncbi.nlm.nih.gov/pubmed/30185448

Dr. Dave Hepburn website:
doctordavidhepburn.com

CBD could reverse brain aging - Dr. Dave Hepburn

Friday, 21 September 2018


Article recommend by Dr. Dave Hepburn:

Antiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron overload

Abstract: 

Iron accumulation in the brain has been recognized as a common feature of both normal aging and neurodegenerative diseases. Cognitive dysfunction has been associated to iron excess in brain regions in humans. We have previously described that iron overload leads to severe memory deficits, including spatial, recognition, and emotional memory impairments in adult rats. In the present study we investigated the effects of neonatal iron overload on proteins involved in apoptotic pathways, such as Caspase 8, Caspase 9, Caspase 3, Cytochrome c, APAF1, and PARP in the hippocampus of adult rats, in an attempt to establish a causative role of iron excess on cell death in the nervous system, leading to memory dysfunction. Cannabidiol (CBD), the main non-psychotropic component of Cannabis sativa, was examined as a potential drug to reverse iron-induced effects on the parameters analyzed. Male rats received vehicle or iron carbonyl (30 mg/kg) from the 12th to the 14th postnatal days and were treated with vehicle or CBD (10 mg/kg) for 14 days in adulthood. Iron increased Caspase 9, Cytochrome c, APAF1, Caspase 3 and cleaved PARP, without affecting cleaved Caspase 8 levels. CBD reversed iron-induced effects, recovering apoptotic proteins Caspase 9, APAF1, Caspase 3 and cleaved PARP to the levels found in controls. These results suggest that iron can trigger cell death pathways by inducing intrinsic apoptotic proteins. The reversal of iron-induced effects by CBD indicates that it has neuroprotective potential through its anti-apoptotic action.


“Studies like these are why we, at Plena, are inching closer to serious consideration of using CBD as a supplement for neuro-protection in the aging population. I continue to be excited by the volume of research that points to the safe, simple yet significant benefits of CBD in many different areas to help us age optimally. Everyone should have the chance to die young….at an old age." 
Dr. Dave Hepburn.

To read the full article please visit:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120904/

https://www.plena-global.com/

Dr. Dave Hepburn website:
doctordavidhepburn.com

CBD to prevent schizophrenia? - Dr. David Hepburn

Wednesday, 19 September 2018


Article recommend by Dr. David Hepburn:

Cannabidiol Administered During Peri-Adolescence Prevents Behavioral Abnormalities in an Animal Model of Schizophrenia

Abstract: 
Schizophrenia is considered a debilitating neurodevelopmental psychiatric disorder and its pharmacotherapy remains problematic without recent major advances. The development of interventions able to prevent the emergence of schizophrenia would therefore represent an enormous progress. Here, we investigated whether treatment with cannabidiol (CBD – a compound of Cannabis sativa that presents an antipsychotic profile in animals and humans) during peri-adolescence would prevent schizophrenia-like behavioral abnormalities in an animal model of schizophrenia: the spontaneously hypertensive rat (SHR) strain. Wistar rats and SHRs were treated with vehicle or CBD from 30 to 60 post-natal days. In experiment 1, schizophrenia-like behaviors (locomotor activity, social interaction, prepulse inhibition of startle and contextual fear conditioning) were assessed on post-natal day 90. Side effects commonly associated with antipsychotic treatment were also evaluated: body weight gain and catalepsy throughout the treatment, and oral dyskinesia 48 h after treatment interruption and on post-natal day 90. In experiment 2, serum levels of triglycerides and glycemia were assessed on post-natal day 61. In experiment 3, levels of BDNF, monoamines, and their metabolites were evaluated on post-natal days 61 and 90 in the prefrontal cortex and striatum. Treatment with CBD prevented the emergence of SHRs’ hyperlocomotor activity (a model for the positive symptoms of schizophrenia) and deficits in prepulse inhibition of startle and contextual fear conditioning (cognitive impairments). CBD did not induce any of the potential motor or metabolic side effects evaluated. Treatment with CBD increased the prefrontal cortex 5-HIAA/serotonin ratio and the levels of 5-HIAA on post-natal days 61 and 90, respectively. Our data provide pre-clinical evidence for a safe and beneficial effect of peripubertal and treatment with CBD on preventing positive and cognitive symptoms of schizophrenia, and suggest the involvement of the serotoninergic system on this effect.

“Schizophrenia is undoubtedly one of the scourges of our time, robbing so many of so much. While studies have indicated that CBD mitigates some of the symptoms of psychosis without the side effects of others neuroleptic, could it also actually prevent schizophrenia?” Dr. David Hepburn

To read the full article please visit:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113576/

Dr. David Hepburn website:
doctordavidhepburn.com

New study: Autism and Cannabis - Dr. David Hepburn

Monday, 17 September 2018



Article recommend by Dr. David Hepburn:

Military Funds Research of Cannabis-based Autism Treatment for Kids

Study: The trial aims to study the effectiveness of cannabidivarin (CBDV) on irritability and repetitive behaviors in children with ASD. 

Raising a child with autism spectrum disorder (ASD) can be an overwhelming experience for parents and have far-reaching effects on the entire family. According to CDC estimates, one in every 68 children has ASD and many exhibit aggressive, self-injurious and repetitive behaviors.

The hope is that CBDV can be an effective treatment for these behaviors without the significant side effects present in current treatments, according to Hollander.


“The remarkable thing to me about this study is, not that it only involves CBDV, but that it is being sponsored by the US Department of Defence. Clearly, we have progressed.”
Dr. David Hepburn



To read the full article please visit:
https://www.childrenshospitals.org/newsroom/childrens-hospitals-today/articles/2018/03/military-funds-research-of-cannabis-based-autism-treatment-for-kids

Dr. Dave Hepburn website:

doctordavidhepburn.com

Cannabis leads to fewer bladder infections - Dr. David Hepburn

Thursday, 13 September 2018


Article recommend by Dr. David Hepburn:


The Association Between Tetrahydrocannabinol and Lower Urinary Tract Symptoms Utilizing the National Health and Nutrition Examination Survey.

Abstract:

OBJECTIVE: 
To further define the relationship between tetrahydrocannabinol (THC) and lower urinary tract symptoms (LUTS), specifically how THC use associates with the frequency of LUTS in young community-dwelling men in the United States. 

MATERIALS AND METHODS: 
The National Health and Nutrition Examination Survey (NHANES) database was queried (2005-2008). Men ages 20-59 who completed the urinary and substance abuse questionnaires were included. The presence of LUTS was defined as having ≥2 of the following: nocturia (≥2), hesitancy, incomplete emptying, or incontinence. THC use was self-reported, and participants were considered regular smokers if they endorsed smoking at least once per month. Multivariable logistic regression was performed to analyze the relationship between THC and LUTS. 

RESULTS: 
Among 3,037 men who met inclusion criteria, 14.4% (n=477) of subjects reported THC use. In multivariable analyses, adjusting for clinical variables, regular THC users remained significantly less likely to report LUTS (odds ratio of 0.55; CI 95% 0.408-0.751, p<0.01) compared to non-users. 

CONCLUSION: 
Obesity, diabetes, and multiple co-morbidities are well-established risk factors for LUTS within the NHANES. Regular THC use, however, appears to be protective from LUTS in young community-dwelling men.

“Bladder infections are an extremely common concern. Should this extrapolate to all demographics, this would be very significant."

To read the full article please visit:
https://www.ncbi.nlm.nih.gov/pubmed/30142408

Dr. Dave Hepburn website:

Tobacco smokers have reduced brain receptors for cannabis - Dr. David Hepburn

Tuesday, 11 September 2018


Article Recommended by Dr. David Hepburn:


Decreased Cannabinoid CB1 Receptors in Male Tobacco Smokers Examined With Positron Emission Tomography.

Abstract 

Background:
Previous studies showed reduction of brain cannabinoid CB1 receptors in adults with cannabis and alcohol use disorders. Preclinical data suggest that these receptors also contribute to nicotine reward and dependence. Tobacco smoking may confound clinical studies of psychiatric disorders because many patients with such disorders smoke tobacco. Whether human subjects who smoke tobacco but are otherwise healthy have altered CB1 receptor binding in brain is unknown. 

Methods:
We measured CB1 receptors in brains of 18 healthy men who smoke tobacco (frequent chronic cigarette smokers), and 28 healthy men who do not smoke tobacco, using positron emission tomography and [18F]FMPEP-d2, a radioligand for CB1 receptors. We collected arterial blood samples during scanning to calculate the distribution volume (VT), which is nearly proportional to CB1 receptor density. Repeated-measures analysis of variance compared VT between groups in various brain regions. 

Results: 
Brain CB1 receptor VT was about 20% lower in subjects who smoke tobacco than in subjects who do not. Decreased VT was found in all brain regions, but reduction did not correlate with years of smoking, number of cigarettes smoked per day, or measures of nicotine dependence. 

Conclusions: 
Tobacco-smoking healthy men have a widespread reduction of CB1 receptor density in brain. Reduction of CB1 receptors appears to be a common feature of substance use disorders. Future clinical studies on the CB1 receptor should control for tobacco smoking.


"Reduction of CB1 receptors appears to be a common feature of substance use disorders. This may have important therapeutic ramifications”

To read the full article please visit:
https://www.ncbi.nlm.nih.gov/pubmed/30121138

Dr. Dave Hepburn website:





Cannabis lozenges reduce pain efficiently - Dr. David Hepburn

Friday, 7 September 2018

Article recommended by Dr. Dave Hepburn

Self-Reported Effectiveness and Safety of Trokie® Lozenges: A Standardized Formulation for the Buccal Delivery of Cannabis Extracts.


Abstract:
Therapeutic use of cannabinoids, the main active ingredients of Cannabissativa L., is often hindered by their limited bioavailability and undesirable psychoactivity. We conducted an observational study in December 2016 and another one in February 2018 to investigate respectively: (i) the effectiveness of Trokie® lozenges, a standardized formulation containing cannabis extracts, to deliver cannabinoids via buccal absorption and (ii) its long-term safety. Participants were members of the Palliative Care Corporation health clinic, registered California cannabis patients, and had a diagnosis of chronic non-cancer pain. For the effectiveness study, 49 participants were asked to self-report pain perception before and after 1-12 weeks of taking Trokie® lozenges, using an 11-point pain intensity numeric rating scale (PI-NRS). A mean reduction in PI-NRS score of 4.9 ± 2.0 points was observed. Onset of analgesia typically varied between 5 and 40 min, which seems consistent with, at least partial, buccal absorption. In the safety study, 35 participants were asked to complete a questionnaire about adverse events (AEs) associated with Trokie® lozenges. AEs were reported by 16 subjects (46%), the most common being dizziness/unsteadiness (N = 7), bad taste (N = 5), and throat irritation/dry mouth (N = 4). None of the self-reported AEs resulted in a serious medical situation and most of them had limited impact on daily functions. Despite the AEs, 90% of participants reported being "satisfied" or "very satisfied" with the product. These observations suggest that buccal administration of standardized extracts via Trokie® lozenges may represent an efficacious and safe approach to cannabis administration.


“Yet another study pointing the promising analgesic properties of cannabis, this using a quicker different delivery mechanism than ingestion.”
Dr. Dave Hepburn 


To read the full article please visit:


David Hepburn website:






THC inhibits endometrial cancer

Wednesday, 5 September 2018


Article recommended by Dr. David Hepburn


Tetrahydrocannabinol inhibits epithelial-mesenchymal transition and metastasis by targeting matrix metalloproteinase-9 in endometrial cancer.


Abstract:

Currently available antidepressants have a substantial time lag to induce therapeutic response and a relatively low efficacy. The development of drugs that addresses these limitations is critical to improving public health. Cannabidiol (CBD), a non-psychotomimetic component of Cannabis sativa, is a promising compound since it shows large-spectrum therapeutic potential in preclinical models and humans. However, its antidepressant properties have not been completely investigated. Therefore, the aims of this study were to investigate in male rodents (i) whether CBD could induce rapid and sustained antidepressant-like effects after a single administration and (ii) whether such effects could be related to changes in synaptic proteins/function. Results showed that a single dose of CBD dose-dependently induced antidepressant-like effect (7-30 mg/kg) in Swiss mice submitted to the forced swim test (FST), 30 min (acute) or 7 days (sustained) following treatment. Similar effects were observed in the Flinders Sensitive and Flinders Resistant Line (FSL/FRL) rats and the learned helplessness (LH) paradigm using Wistar rats. The acute antidepressant effects (30 min) were associated with increased expression of synaptophysin and PSD95 in the medial prefrontal cortex (mPFC) and elevated BDNF levels in both mPFC and hippocampus (HPC). CBD also increased spine density in the mPFC after 30 min, but not 7 days later. Intracerebroventricular injection of the TrkB antagonist, K252a (0.05 nmol/μL), or the mTOR inhibitor, rapamycin (1 nmol/μL), abolished the behavioral effects of CBD. These results indicate that CBD induces fast and sustained antidepressant-like effect in distinct animal models relevant for depression. These effects may be related to rapid changes in synaptic plasticity in the mPFC through activation of the BDNF-TrkB signaling pathway. The data support a promising therapeutic profile for CBD as a new fast-acting antidepressant drug.

“The amount of literature continues to grow supporting cannabinoids’ positive role on cancers. In addition to inducing cancer cells to try to commit suicide (apoptosis), decreasing their blood supply (angiogenesis) and inhibiting it’s growth, cannabinoids also play a role in discouraging the spread (metastasis) in certain cancers including endometrial cancer, a frightening cancer for many women." 
Dr. David Hepburn

To read the full article please visit:

https://www.ncbi.nlm.nih.gov/pubmed/29805589

David Hepburn website:

doctordavidhepburn.com






CBD Induces Rapid and Sustained Antidepressant Like Effects

Friday, 31 August 2018


Article recommended by Dr. David Hepburn:


Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex.

Abstract:

Currently available antidepressants have a substantial time lag to induce therapeutic response and a relatively low efficacy. The development of drugs that addresses these limitations is critical to improving public health. Cannabidiol (CBD), a non-psychotomimetic component of Cannabis sativa, is a promising compound since it shows large-spectrum therapeutic potential in preclinical models and humans. However, its antidepressant properties have not been completely investigated. Therefore, the aims of this study were to investigate in male rodents (i) whether CBD could induce rapid and sustained antidepressant-like effects after a single administration and (ii) whether such effects could be related to changes in synaptic proteins/function. Results showed that a single dose of CBD dose-dependently induced antidepressant-like effect (7-30 mg/kg) in Swiss mice submitted to the forced swim test (FST), 30 min (acute) or 7 days (sustained) following treatment. Similar effects were observed in the Flinders Sensitive and Flinders Resistant Line (FSL/FRL) rats and the learned helplessness (LH) paradigm using Wistar rats. The acute antidepressant effects (30 min) were associated with increased expression of synaptophysin and PSD95 in the medial prefrontal cortex (mPFC) and elevated BDNF levels in both mPFC and hippocampus (HPC). CBD also increased spine density in the mPFC after 30 min, but not 7 days later. Intracerebroventricular injection of the TrkB antagonist, K252a (0.05 nmol/μL), or the mTOR inhibitor, rapamycin (1 nmol/μL), abolished the behavioral effects of CBD. These results indicate that CBD induces fast and sustained antidepressant-like effect in distinct animal models relevant for depression. These effects may be related to rapid changes in synaptic plasticity in the mPFC through activation of the BDNF-TrkB signaling pathway. The data support a promising therapeutic profile for CBD as a new fast-acting antidepressant drug.

“This is not insignificant. Clearly, CBD is psychoactive but in ways that harness the brain’s natural neuroplasticity to create synapses in areas that create and control emotions. The fact that CBD induces fast and sustained antidepressant-like effects is very encouraging. Clinical studies should follow, as a fast acting antidepressant is a much sought after commodity."
Dr. David Hepburn 

To read the full article please visit:

https://www.ncbi.nlm.nih.gov/pubmed/29869197

Dr. David Hepburn website:

doctordavidhepburn.com