Evidence of Cannabis Synergism in Treating Cancer

“In a recent study, yet another standard treatment for cancer has been potentiated by cannabinoid agonists. Thisisthethirdchemotherapymedication I am aware of, where cannabinoid enhances the effects. Oncologists, who already know the benefit of cannabis for chemo side effects, need to continue to explore the potential to actually treat cancer.”

-          Dr. David Hepburn

Osteosarcoma is the most common primary malignant tumor of bone in children and adolescents. Bortezomib (BTZ) is an approved anticancer drug, classified as a selective reversible inhibitor of the ubiquitin-dependent proteasome system, that leads to cancer cell cycle arrest and apoptosis reducing the invasion ability of Osteosarcoma cells in vitro.

Recently BTZ has been evaluated in combination with Cannabinoids targeting CB1 receptor, demonstrating a promising synergic effect.

Read full article here:

https://www.ncbi.nlm.nih.gov/pubmed/30267762

Dr. Dave Hepburn website: https://doctordavidhepburn.com

THC Weakens Brain Connections Responsible for Pain

“In a fascinating study on humans, THC appears to disconnect areas of the brain responsible for feeling pain. It acts as a cognitive-emotional modulator.  Less pain and less unpleasantness associated with the pain. Very exciting research.”

-   Dr. David Hepburn

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 Analysis of local measures demonstrated a 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.

Read full article here:

https://cdn.doctorsonly.co.il/2018/10/Cannabis-analgesia-in-chronic-neuropathic-pain-Neurology-2018.pdf

Dr. Dave Hepburn website: https://doctordavidhepburn.com

Muscular Dystrophy and Cannabinoid Receptors

“As the dysfunction of the endocannabinoid system becomes implicated in more diseases including migraine, irritable bowel, fibromyalgia, epilepsy, and even menstrual cramps now add muscular dystrophy as a potential area of interest for endocannabinoids. Jerry Lewis should be smiling.”

-          Dr. David Hepburn

The endocannabinoid system refers to a widespread signaling system and its alterations implicated in a growing number of human diseases. However, the potential role of endocannabinoids in skeletal muscle is ordered the main sun is known.

In murine and human models, CB1 transcripts how the highest degree of expression at disease onset, and then decline over time. Similar changes are observed for PAX7, a key regulator of muscle stem cells. Bioinformatics and biochemical analysis revealed that PAX7 binds and upregulates the CB1 gene in dystrophic more than in healthy muscles.

Rimonabant, an antagonist of CB1, promotes human satellite cell differentiation in vitro, increases the number of regenerated myofibers, and prevents locomotor impairment in dystrophic mice. In conclusion, our study uncovers a PAX7–CB1 cross-talk potentially exacerbating DMD and highlights the role of CB1 receptors as target for potential therapies.

Read full article here:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160489/

Dr. David Hepburn website: https://doctordavidhepburn.com

US Government Funds Research on CBG, CBC, CBN and terpenes - Dr. David Hepburn

“Thepowerful NIH isfunding non clinicalresearchonminorcannabinoids and severalterpenesincludingmy personal favourite, beta caryophyllene. Thegoalis to mitigatetheepidemic of chronicpainthatwillaccompanythe grey tsunami and to decreasetheloss of productivity and increasedcost ($2000 per person per year) associatedwithchronicpain.” -   Dr. David Hepburn

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects, as well as to give potential applicants sufficient time to determine whether they need to obtain investigator registration and site licensure from the Drug Enforcement Agency (DEA) ,if appropriate. For applications that include human use of any of the compounds, this Notice provides time to determine whether an Investigational New Drug (IND) application is needed, or if the FDA will provide a written waiver indicating that an IND is not needed for the proposed research. No awards will be made to the investigators in the absence of appropriate FDA/IND documentations for proposed human subject studies.

The FOA is expected to be published in Winter 2019 with an expected application due date in March 2019.

Read full notice here:

https://grants.nih.gov/grants/guide/notice-files/NOT-AT-19-008.html

Dr. Dave Hepburn website: https://doctordavidhepburn.com

Cannabis Users Less Likely to Get Diabetes - Dr. David Hepburn

“A recentstudyfromCanadaindicatesthat cannabis usershave a significantlydecreasedrisk of having diabetes. Thisis no smalldiscoverygiventhat diabetes isone of thescourges of oursociety. Itwill be nothing short of fascinating to discoverhow cannabis can potentiallyprotectagainst diabetes. Staytuned.”-    Dr. David Hepburn 

A decreased likelihood of diabetes for cannabis users versus non-users was indicated after accounting for a range of potential con-founders, including mental health disorders. Before the protective effects of cannabis use for diabetes can be suggested, further epidemiological studies are needed that incorporate prospective designs, as well as feature innovative exposure measurements and statistical analyses.

Although there was a considerable attenuation in the magnitude of the odds ratios after adjustment for confounders, there was still a decreased likelihood of diabetes for cannabis users versus non-users.

Read full article here:

https://www.ncbi.nlm.nih.gov/pubmed/30288813

Dr. David Hepburn website: https://doctordavidhepburn.com

Cannabis for Crohn’s? - Dr. David Hepburn

“Cannabis isgetting more attentionfortheawfulconditions of Crohn's and Ulcerative Colitis. Inflammatoryboweldisease, not to be confusedwith Irritable BowelDisease (though cannabis appears to havesomeeffect in both) isnotanuncommonconditionthat can lead to drasticmeasures.”

       -  Dr. David Hepburn

Research from the University of Bath said the findings could help explain why some patients with inflammatory bowel diseases (IBD) report medical marijuana can help their symptoms.

The researchers believe that, because cannabis use introduces cannabinoids into the body, these molecules could help relieve gut inflammation as the naturally produced endocannabinoids would.

Read full article here:

https://www.independent.co.uk/news/health/cannabis-marijuana-inflammatory-bowel-disease-crohns-colitis-ibd-ibs-digestion-symptoms-a8490246.html

Dr. Dave Hepburn website: https://doctordavidhepburn.com

Liverwort As A Legal High - Dr. David Hepburn

"Not only do the various cannabinoids in the cannabis plant act on many different receptors besides our cannabis receptors (CB1R and CB2R) throughout our body, but many other plants produce cannabinomimetics that act on our CB1R and CB2R, in the brain, bones, gut and elsewhere. It’s a busy, complicated network of receptors, ligands and exogenous compounds that are able to have a multitude of effects on our body, some for good and some for.... “good” if you want to be stoned."

-Dr. David Hepburn    

Recommended by Dr. David Hepburn:

Uncovering the psychoactivity of a cannabinoid from liverworts associated with a legal high.

Abstract

Phytochemical studies on the liverwort Radula genus have previously identified the bibenzyl (-)-cis-perrottetinene (cis-PET), which structurally resembles (-)-Δ9-trans-tetrahydrocannabinol (Δ9-trans-THC) from Cannabis sativa L. Radula preparations are sold as cannabinoid-like legal high on the internet, even though pharmacological data are lacking. 

Herein, we describe a versatile total synthesis of (-)-cis-PET and its (-)-trans diastereoisomer and demonstrate that both molecules readily penetrate the brain and induce hypothermia, catalepsy, hypolocomotion, and analgesia in a CB1 receptor-dependent manner in mice. The natural product (-)-cis-PET was profiled on major brain receptors, showing a selective cannabinoid pharmacology. This study also uncovers pharmacological differences between Δ9-THC and PET diastereoisomers. Most notably, (-)-cis-PET and (-)-trans-PET significantly reduced basal brain prostaglandin levels associated with Δ9-trans-THC side effects in a CB1 receptor-dependent manner, thus mimicking the action of the endocannabinoid 2-arachidonoyl glycerol. 

Therefore, the natural product (-)-cis-PET is a psychoactive cannabinoid from bryophytes, illustrating the existence of convergent evolution of bioactive cannabinoids in the plant kingdom. Our findings may have implications for bioprospecting and drug discovery and provide a molecular rationale for the reported effects upon consumption of certain Radula preparations as moderately active legal highs.

To read the full article please visit:

https://www.ncbi.nlm.nih.gov/pubmed/30397641

Dr. Dave Hepburn website:https://doctordavidhepburn.com

New Research Indicates Benefit of Cannabis in Autism - Dr. David Hepburn

"And furthermore, dosages and CBD:THC ratios are starting to emerge. “Mothers” in many countries, recognizing that cannabis is helping their autistic children, have risked breaking the law and organized en masse to change laws. And now, significant attention is being directed towards using cannabis in this difficult spectrum. 1:20 THC:CBD at about 4 mg/kg CBD and 0.3mg/kg THC per day."

- Dr. David Hepburn.

Recommended by Dr. David Hepburn:

Brief Report: Cannabidiol-Rich Cannabis in Children with Autism Spectrum Disorder and Severe Behavioral Problems-A Retrospective Feasibility Study.

Abstract

Anecdotal evidence of successful cannabis treatment in autism spectrum disorder (ASD) are accumulating but clinical studies are lacking. This retrospective study assessed tolerability and efficacy of cannabidiol-rich cannabis, in 60 children with ASD and severe behavioral problems (age = 11.8 ± 3.5, range 5.0-17.5; 77% low functioning; 83% boys). Efficacy was assessed using the Caregiver Global Impression of Change scale. Adverse events included sleep disturbances (14%) irritability (9%) and loss of appetite (9%). One girl who used higher tetrahydrocannabinol had a transient serious psychotic event which required treatment with an antipsychotic. Following the cannabis treatment, behavioral outbreaks were much improved or very much improved in 61% of patients. This preliminary study supports feasibility of CBD-based cannabis trials in children with ASD.

To read the full article please visit:

https://www.ncbi.nlm.nih.gov/pubmed/30382443

Dr. Dave Hepburn website:https://doctordavidhepburn.com

Cannabis better than narcotics in treatment of back pain in Fibromyalgia - Dr. David Hepburn

Article Recommended by Dr. David Hepburn:

Effect of adding medical cannabis to analgesic treatment in patients with low back pain related to fibromyalgia: an observational cross-over single centre study.

Abstract

OBJECTIVES:

Low back pain (LBP) occurs in many patients with fibromyalgia (FM). The current study aimed to assess the possible pain and function amelioration associated with medical cannabis therapy (MCT) in this setting.

METHODS:

31 patients were involved in an observational cross-over study. The patients were screened, treated with 3 months of standardised analgesic therapy (SAT): 5 mg of oxycodone hydrochloride equivalent to 4.5 mg oxycodone and 2.5 mg naloxone hydrochloride twice a day and duloxetine 30 mg once a day. Following 3 months of this therapy, the patients could opt for MCT and were treated for a minimum of 6 months. Patient reported outcomes (PRO's) included: FIQR, VAS, ODI and SF-12 and lumbar range of motion (ROM) was recorded using the modified Schober test.

RESULTS:

While SAT led to minor improvement as compared with baseline status, the addition of MCT allowed a significantly higher improvement in all PRO's at 3 months after initiation of MCT and the improvement was maintained at 6 months. ROM improved after 3 months of MCT and continued to improve at 6 months.

CONCLUSIONS:

This observational cross-over study demonstrates an advantage of MCT in FM patients with LBP as compared with SAT. Further randomised clinical trial studies should assess whether these results can be generalised to the FM population at large.

"Cannabis more effective than narcotics? The opiate (narcotics) crisis is gruesome with roughly half of those who die being due to prescription opiates. Nobody does of cannabis; the safety profile is secure. But efficacy? Fibromyalgia patients with back pain actually do better on cannabis than on opiates. Remarkable."

-Dr. Dave Hepburn

To read the full article please visit:

https://www.ncbi.nlm.nih.gov/pubmed/30418116

Dr. Dave Hepburn website:https://doctordavidhepburn.com

Singing or Running Elevate Endocannabinoids and Boosts Mood - Dr. David Hepburn

Article Recommended by Dr. David Hepburn:

An Analysis of Endocannabinoid Concentrations and Mood Following Singing and Exercise in Healthy Volunteers

The euphoric feeling described after running is, at least in part, due to increased circulating endocannabinoids (eCBs). eCBs are lipid signaling molecules involved in reward, appetite, mood, memory and neuroprotection. 

The aim of this study was to investigate whether activities other than running can increase circulating eCBs. Nine healthy female volunteers (mean 61 years) were recruited from a local choir. Circulating eCBs, haemodynamics, mood and hunger ratings were measured before and immediately after 30 min of dance, reading, singing or cycling in a fasted state. 

Singing increased plasma levels of anandamide (AEA) by 42% (P < 0.05), palmitoylethanolamine (PEA) by 53% (P < 0.01) and oleoylethanolamine (OEA) by 34% (P < 0.05) and improved positive mood and emotions (P < 0.01), without affecting hunger scores. 

Dancing did not affect eCB levels or hunger ratings, but decreased negative mood and emotions (P < 0.01). 

Cycling increased OEA levels by 26% (P < 0.05) and tended to decrease how hungry volunteers felt, without affecting mood. 

"The “runners high” which was thought years ago to be courtesy of our endorphins is now known to be caused by our endogenous cannabinoid, anandamide (AEA). While dancing and cycling did not elevate AEA, singing actually did. No comments on if you sound like a hound being dragged through a keyhole. Anybody interested in starting a jogging choir to get high?  
Increases in AEA underlies the rewarding and pleasurable effects of singing and exercise and ultimately some of the long-term beneficial effects on mental health, cognition and memory."

-Dr. Dave Hepburn

To read the full article please visit:

https://www.frontiersin.org/articles/10.3389/fnbeh.2018.00269/full

Dr. Dave Hepburn website:https://doctordavidhepburn.com

Cannabis may be helpful in the treatment of children with autism in an open study

Article Recommended by Dr. David Hepburn:

Brief Report: Cannabidiol-Rich Cannabis in Children with Autism Spectrum Disorder and Severe Behavioral Problems-A Retrospective Feasibility Study.

Abstract

Anecdotal evidence of successful cannabis treatment in autism spectrum disorder (ASD) are accumulating but clinical studies are lacking. This retrospective study assessed tolerability and efficacy of cannabidiol-rich cannabis, in 60 children with ASD and severe behavioral problems (age = 11.8 ± 3.5, range 5.0-17.5; 77% low functioning; 83% boys). 

Efficacy was assessed using the Caregiver Global Impression of Change scale. Adverse events included sleep disturbances (14%) irritability (9%) and loss of appetite (9%). One girl who used higher tetrahydrocannabinol had a transient serious psychotic event which required treatment with an antipsychotic.

Following the cannabis treatment, behavioral outbreaks were much improved or very much improved in 61% of patients. This preliminary study supports feasibility of CBD-based cannabis trials in children with ASD.

"Data continues to support the use of CBD as a area to focus in on for treatment of ASD. Studies currently underway (including one being funded by the US Department of Defence) should shed further light on why it helps for some patients and for some symptoms of this complicated disease."

-Dr. Dave Hepburn

To read the full article please visit:

https://www.ncbi.nlm.nih.gov/pubmed/30382443

Dr. Dave Hepburn website:https://doctordavidhepburn.com

Cannabis use is associated with a greater likelihood for suicide attempts in adolescents

Article Recommended by Dr. David Hepburn:

Cannabis use and suicide attempts among 86,254 adolescents aged 12-15 years from 21 low- and middle-income countries.

Abstract

BACKGROUND:

Evidence suggests that cannabis use may be associated with suicidality in adolescence. Nevertheless, very few studies have assessed this association in low- and middle-income countries (LMICs). In this cross-sectional survey, we investigated the association of cannabis use and suicidal attempts in adolescents from 21 LMICs, adjusting for potential confounders.

METHOD:

Data from the Global school-based Student Health Survey was analyzed in 86,254 adolescents from 21 countries [mean (SD) age = 13.7 (0.9) years; 49.0% girls]. Suicide attempts during past year and cannabis during past month and lifetime were assessed. Multivariable logistic regression analyses were conducted.

RESULTS:

The overall prevalence of past 30-day cannabis use was 2.8% and the age-sex adjusted prevalence varied from 0.5% (Laos) to 37.6% (Samoa), while the overall prevalence of lifetime cannabis use was 3.9% (range 0.5%-44.9%). The overall prevalence of suicide attempts during the past year was 10.5%. Following multivariable adjustment to potential confounding variables, past 30-day cannabis use was significantly associated with suicide attempts (OR = 2.03; 95% CI: 1.42-2.91). Lifetime cannabis use was also independently associated with suicide attempts (OR = 2.30; 95% CI: 1.74-3.04).

CONCLUSION:

Our data indicate that cannabis use is associated with a greater likelihood for suicide attempts in adolescents living in LMICs. The causality of this association should be confirmed/refuted in prospective studies to further inform public health policies for suicide prevention in LMICs.

“Although causality cannot be established, there is some indication for concern. The adolescent brain is a minefield and neuromaturation, particularly when concerning areas of the brain responsible for controlling impulsive behavior and decision making (executive thought), is not complete until about age 25.”

- Dr. David Hepburn 

To read the full article please visit:

https://www.ncbi.nlm.nih.gov/pubmed/30447436

Dr. Dave Hepburn website:

https://doctordavidhepburn.com

Use of THC in Adolescence May Reduce Ability to Cope with Stress in Adulthood

Article Recommended by Dr. David Hepburn:

Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood.

Abstract

Δ9-tetrahydrocannabinol (THC) consumption during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. The interaction between genetic or environmental events and cannabinoid exposure in the adolescent period can also contribute to exacerbate behavioural deficits in adulthood. 

Here we investigate the effects of THC treatment as well as the consequences of concomitant THC and stress exposure during adolescence in the extinction of fear memory in adult mice. 

Adolescent mice treated with THC and exposed to stress exhibit impaired cued fear extinction in adulthood. However, no effect was observed in animals exposed to these two factors separately. 

Notably, resistance to fear extinction was associated with decreased neuronal activity in the basolateral amygdala (BLA) and the infralimbic prefrontal cortex, suggesting a long-term dysregulation of the fear circuit. 

"Yet another study underscoring why THC use in youth is of concern. Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood. As the youth brain is one that is “under construction”, THC should be used in this demographic under medical guidance…only."

Dr. Dave Hepburn

To read the full article please visit:

https://www.ncbi.nlm.nih.gov/pubmed/30439419

Dr. David Hepburn website: 
doctordavidhepburn.com 

Sexually Activity in Rats Increased by Cannabinoid 1 Receptor Activation

Article recommend by Dr. Dave Hepburn:

"Men and rats have been closely compared (primarily by women); hence this study is pertinent. The activation of CB1 receptors (the same receptors acted on by plant THC) by the endogenous cannabinoid, anandamide, transforms boring non copulating rats into sexually active animals." 

Dr. Dave Hepburn

Sexual interaction is essential for the transformation of non-copulating rats into sexually active animals by the endocannabinoid anandamide.

Abstract

The endocannabinoid anandamide (AEA) transforms half of the population of previously non-copulating (NC) rats into sexually active animals in a long-lasting manner. The aim of this work was to explore the nature of this transformation.

We identified the dose range in which AEA induces mating behavior in previously NC rats, which evidenced a dose-based, biphasic profile for AEA to induce the transformation of NC rats. We demonstrate that the sexual interaction with a receptive female, involving at least an intromission, is essential for AEA to induce the transformation of NC rats.

This AEA-induced conversion is centrally mediated and involves the activation of CB1 receptors. Results indicate that the sexual impairment of this population of NC rats relies on their incapacity to initiate sexual activity and that an unidentified brain inhibitory influence on sexual behavior expression is removed by AEA treatment, allowing previously NC rats to show copulatory behavior in a long-lasting manner.

To read the full article please visit:

https://www.ncbi.nlm.nih.gov/pubmed/30439451

Dr. David Hepburn website:
doctordavidhepburn.com

Move Over Epidiolex...Already! - Dr. Dave Hepburn

Article recommend by Dr. Dave Hepburn:

A prospective open-label trial of a CBD/THC cannabis oil in dravet syndrome.

Abstract

INTRODUCTION: 

Both Tetrahydrocannabidiol (THC) and cannabidiol (CBD) components of cannabis, have been shown to have anticonvulsant effects. Cannabis oils are used to treat seizures in drug-resistant epilepsy (DRE). Recent trials provide data on dosing, side effects, and efficacy of CBD, yet there is a paucity of information on THC in epilepsy. Primary objective was to establish dosing and tolerability of TIL-TC150 - a cannabis plant extract produced by Tilray®, containing 100 mg/mL CBD and 2 mg/mL THC- in children with Dravet syndrome. Secondary objectives were to assess impact of therapy on seizures, electroencephalogram (EEG) and quality of life. 

METHODS: 

Twenty children received add-on therapy with TIL-TC150. The dose ranged from 2 to 16 mg/kg/day of CBD and 0.04 to 0.32 mg/kg/day of THC. Patients were monitored for tolerability and adverse events, and secondary objectives. 

RESULTS: 

Nineteen participants completed the 20-week intervention. Mean dose achieved was 13.3 mg/kg/day of CBD (range 7-16 mg/kg/day) and 0.27 mg/kg/day of THC (range 0.14-0.32 mg/kg/day). Adverse events, common during titration included somnolence, anorexia, and diarrhea. Abnormalities of liver transaminases and platelets were observed with concomitant valproic acid therapy. There was a statistically significant improvement in quality of life, reduction in EEG spike activity, and median motor seizure reduction of 70.6%, with 50% responder rate of 63%. 

CONCLUSIONS: 

TIL-TC150 was safe and well tolerated in our subjects. TIL-TC150 treatment resulted in a reduction in seizure counts, spike index on EEG, and improved quality of life measures. This study provides safety and dosing information for THC-containing cannabinoid preparations.

“A new and improved treatment that includes a touch of THC (which children handle much better than adults). The uptight FDA/DEA/US government would rather not allow any THC due to adherence to tired, old, uneducated biases. It’s a shame for American children that their government remains so willfully ignorant.”

Dr. Dave Hepburn

To read the full article please visit:
https://www.ncbi.nlm.nih.gov/pubmed/30250864

Dr. David Hepburn website:
doctordavidhepburn.com

Cannabis Extract Inhibits Superbug MRSA - Dr. David Hepburn

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

US Study Shows Which Cannabis (and how) is Best for Insomnia - Dr. David Hepburn

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

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

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

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

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