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

Vapeorsmoke? - Dr. David Hepburn

“Whichisstronger, vapingorsmoking? Doctorsneveradvocatesmokingforanyreason and prefervapingovercombustion as thesafestinhalationdeliverymechanism. Surprisingly, a new studyfromthe US indicatesthatvapingis more powerful.”

-  Dr. David Hepburn

In a smallstudy of infrequent cannabis users, researchers have shown that, compared with smoking cannabis, vaping it increased the rate of short-term anxiety, paranoia, memory loss and distractionwhen doses werethesame.

Vaping devices heat cannabis to a temperature in which the mind-altering compounds in the plant are released as a vapor that is inhaled. Vaping is thought to be safer for cannabis and tobacco use because it doesn't produce many of the harmful components of burning material such as tar and other cancer-causing agents.

Read full articlehere:

https://www.sciencedaily.com/releases/2018/12/181204131115.htm

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

The CB2 receptor plays a significant role in heart function in people with pulmonary hypertension

"The role the endocannabinoid system (ECS) plays in cardiovascular pathology continues to point to a path for possible therapeutic targets. This study shows how the ECS works to prevent death of cardiac cells in pulmonary hypertension, which, if it sounds like a good thing....it is."  -Dr. Dave Hepburn

Article Recommended by Dr. David Hepburn:

CB2-deficiency is associated with a stronger hypertrophy and remodeling of the right ventricle in a murine model of left pulmonary artery occlusion.

Abstract

AIMS:

Pulmonary hypertension (PH) leads to right ventricular (RV) adaptation and remodeling and has deleterious long-term effects on RV function. The endocannabinoid receptor CB2 has been associated with protective effects in adaptation and remodeling of the left ventricle after ischemia. Therefore, we investigated the role of CB2 receptor in RV adaptation after occlusion of the left pulmonary artery (LPA) in a murine model.

MAIN METHODS:

C57/Bl6 (WT)- and CB2 receptor-deficient (Cnr2-/-)-mice underwent paramedian sternotomy and LPA was occluded using a metal clip. Right heart hemodynamic study (Millar®) preceded organ harvesting for immunohistochemistry and mRNA analysis 7 and 21 days (d) post-occlusion.

KEY FINDINGS:

LPA occlusion led to higher RV systolic pressure in Cnr2-/--hearts, while hemodynamics were comparable with WT-hearts after 21d. Cnr2-/--hearts showed higher macrophage infiltration and lower interleukin-10 expression after 7 d, but otherwise a comparable inflammatory mediator expression profile. 

Cardiomyocyte-hypertrophy was stronger in Cnr2-/--mice, presenting with higher tenascin-C expression than WT-hearts. Planimetry revealed higher collagen area in Cnr2-/--hearts and small areas of cardiomyocyte-loss. Surrounding cardiomyocytes were cleaved caspase-3- and TUNEL positive in Cnr2-/--hearts. This was associated by maladaptation of myosin heavy-chain isoforms and lower reactive oxygen scavenger enzymes induction in Cnr2-/--hearts. We found comparable morphological changes in both lungs between the two genotypes.

SIGNIFICANCE:

LPA occlusion led to increased systolic pressure and adaptation of RV in CB2-deficient mice. CB2 receptor seems to modulate RV adaptation through expression of contractile elements, reactive oxygen scavenger enzymes, and inflammatory response in order to prevent cardiomyocyte apoptosis.

To read the full article please visit:

https://www.ncbi.nlm.nih.gov/pubmed/30403990 

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

Exciting Promise of Role of CBD in Alzheimer’s Neuro-inflammation - Dr. David Hepburn

Article Recommended by Dr. David Hepburn:

"GPR55 is a receptor that is getting a lot of attention in medical research. 40% of drugs are meant to target this receptor due to it’s role in conditions ranging from colon cancer to dementia to MS. THC activates this receptor while CBD does the exact opposite, further underscoring the complicated relationship of the various cannabinoids and showing that “cannabis is not cannabis, it’s cannabis.” The CBD blockage of this receptor is showing promise in addressing certain disease states such as Alzheimers disease, as this recent rat research reveals."

-Dr. Dave Hepburn

Anti-neuroinflammatory effects of GPR55 antagonists in LPS-activated primary microglial cells

Abstract

Background

Neuroinflammation plays a vital role in Alzheimer’s disease and other neurodegenerative conditions. Microglia are the resident mononuclear immune cells of the central nervous system, and they play essential roles in the maintenance of homeostasis and responses to neuroinflammation. The orphan G-protein-coupled receptor 55 (GPR55) has been reported to modulate inflammation and is expressed in immune cells such as monocytes and microglia. However, its effects on neuroinflammation, mainly on the production of members of the arachidonic acid pathway in activated microglia, have not been elucidated in detail.

Methods

In this present study, a series of coumarin derivatives, that exhibit GPR55 antagonism properties, were designed. The effects of these compounds on members of the arachidonic acid cascade were studied in lipopolysaccharide (LPS)-treated primary rat microglia using Western blot, qPCR, and ELISA.

Results

We demonstrate here that the various compounds with GPR55 antagonistic activities significantly inhibited the release of PGE2 in primary microglia. The inhibition of LPS-induced PGE2 release by the most potent candidate KIT 17 was partially dependent on reduced protein synthesis of mPGES-1 and COX-2. KIT 17 did not affect any key enzyme involved on the endocannabinoid system. We furthermore show that microglia expressed GPR55 and that a synthetic antagonist of the GPR receptor (ML193) demonstrated the same effect of the KIT 17 on the inhibition of PGE2.

Conclusions

Our results suggest that KIT 17 is acting as an inverse agonist on GPR55 independent of the endocannabinoid system. Targeting GPR55 might be a new therapeutic option to treat neurodegenerative diseases with a neuroinflammatory background such as Alzheimer’s disease, Parkinson, and multiple sclerosis (MS).

To read the full article please visit:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240959/ 

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

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

Impressive New Ways that CBD Works - Dr. Dave Hepburn

Article recommend by Dr. David Hepburn:

Cannabidiol enhances morphine antinociception, diminishes NMDA-mediated seizures and reduces stroke damage via the sigma 1 receptor.

Abstract

Cannabidiol (CBD), the major non-psychotomimetic compound present in the Cannabis sativa plant, exhibits therapeutic potential for various human diseases, including chronic neurodegenerative diseases, such as Alzheimer's and Parkinson's, ischemic stroke, epilepsy and other convulsive syndromes, neuropsychiatric disorders, neuropathic allodynia and certain types of cancer. CBD does not bind directly to endocannabinoid receptors 1 and 2, and despite research efforts, its specific targets remain to be fully identified. Notably, sigma 1 receptor (σ1R) antagonists inhibit glutamate N-methyl-D-aspartate acid receptor (NMDAR) activity and display positive effects on most of the aforesaid diseases. Thus, we investigated the effects of CBD on three animal models in which NMDAR overactivity plays a critical role: opioid analgesia attenuation, NMDA-induced convulsive syndrome and ischemic stroke. In an in vitro assay, CBD disrupted the regulatory association of σ1R with the NR1 subunit of NMDAR, an effect shared by σ1R antagonists, such as BD1063 and progesterone, and prevented by σ1R agonists, such as 4-IBP, PPCC and PRE084. The 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. These positive effects of CBD were reduced by the σ1R agonists PRE084 and PPCC, and absent in σ1R-/- mice. Thus, CBD displays antagonist-like activity toward σ1R to reduce the negative effects of NMDAR overactivity in the abovementioned experimental situations.

"As the mystery of how CBD actually works is unveiled, many receptors OTHER than cannabinoid receptors are involved. This mechanism/receptors help explain why CBD works for seizures and make morphine more effective (thus requiring a smaller dose)"

Dr. Dave Hepburn

To read the full article please visit:

https://www.ncbi.nlm.nih.gov/pubmed/30223868

Dr. David Hepburn website:
doctordavidhepburn.com

Yet Another Cannabinoid Shows Remarkable Promise - Dr. David Hepburn

Article recommend by Dr. David Hepburn:

Effect of cannabidiolic acid and -tetrahydrocannabinol on carrageenan-induced hyperalgesia and edema in a rodent model of inflammatory pain.

Abstract

RATIONALE:

Cannabidiol (CBD), a non-intoxicating component of cannabis, or the psychoactive Δ9-tetrahydrocannabiol (THC), shows anti-hyperalgesia and anti-inflammatory properties.

OBJECTIVES:

The present study evaluates the anti-inflammatory and anti-hyperalgesia effects of CBD's potent acidic precursor, cannabidiolic acid (CBDA), in a rodent model of carrageenan-induced acute inflammation in the rat hind paw, when administered systemically (intraperitoneal, i.p.) or orally before and/or after carrageenan. In addition, we assess the effects of oral administration of THC or CBDA, their mechanism of action, and the efficacy of combined ineffective doses of THC and CBDA in this model. Finally, we compare the efficacy of CBD and CBDA.

RESULTS:

CBDA given i.p. 60 min prior to carrageenan (but not 60 min after carrageenan) produced dose-dependent anti-hyperalgesia and anti-inflammatory effects. In addition, THC or CBDA given by oral gavage 60 min prior to carrageenan produced anti-hyperalgesia effects, and THC reduced inflammation. The anti-hyperalgesia effects of THC were blocked by SR141716 (a cannabinoid 1 receptor antagonist), while CBDA's effects were blocked by AMG9810 (a transient receptor potential cation channel subfamily V member 1 antagonist). In comparison to CBDA, an equivalent low dose of CBD did not reduce hyperalgesia, suggesting that CBDA is more potent than CBD for this indication. Interestingly, when ineffective doses of CBDA or THC alone were combined, this combination produced an anti-hyperalgesia effect and reduced inflammation.

CONCLUSION:

CBDA or THC alone, as well as very low doses of combined CBDA and THC, has anti-inflammatory and anti-hyperalgesia effects in this animal model of acute inflammation.

“CBDA is the precursor of CBD and is the raw form of cannabis. Already considered 100x more powerful than CBD as an anti-nauseant (anti emetic) and may have a role in the reduction of breast cancer metastasis PLUS anxiety. Stay tuned to see how interesting a molecule this non psychoactive little gem might be.”

Dr. David Hepburn

To read the full article please visit: 

https://www.ncbi.nlm.nih.gov/pubmed/30225659

Dr. David Hepburn website: 

doctordavidhepburn.com

New Study of Cannabinoids in Prostate Cancer - Dr. David Hepburn

Article recommend by Dr. David Hepburn:

Cannabinoid WIN 55,212-2 induces cell cycle arrest and apoptosis, and inhibits proliferation, migration, invasion, and tumor growth in prostate cancer in a cannabinoid-receptor 2 dependent manner.

Abstract

BACKGROUND: 

Cannabinoids have demonstrated anticarcinogenic properties in a variety of malignancies, including in prostate cancer. In the present study, we explored the anti-cancer effects of the synthetic cannabinoid WIN 55,212-2 (WIN) in prostate cancer. 

METHODS: 

Established prostate cancer cells (PC3, DU145, LNCaP) were treated with varying concentrations of WIN. Cell proliferation was determined by the MTS assay. The anti-migration and anti-invasive potential of WIN was examined by the wound healing assay and the matrigel invasion assay. Cell cycle analysis was performed by flow cytometry, and mechanistic studies were performed by Western blot. Athymic mice (n = 10) were inoculated with human PC3 cells. Once tumors reached 100 mm3 , animals were randomized into two groups: saline control and WIN (5 mg/kg), delivered by intraperitoneal injection three times per week for 3 weeks. 

RESULTS: 

WIN significantly reduced prostate cancer cell proliferation, migration, invasion, induced apoptosis, and arrested cells in Go/G1 phase in a dose-dependent manner. Mechanistic studies revealed these effects were mediated through a pathway involving cell cycle regulators p27, Cdk4, and pRb. Pre-treatment with a CB2 antagonist, AM630, followed by treatment with WIN resulted in a reversal of the anti-proliferation and cell cycle arrest previously seen with WIN alone. In vivo, administration of WIN resulted in a reduction in the tumor growth rate compared to control (P < 0.05). 

CONCLUSIONS: 

The following study provides evidence supporting the use of WIN as a novel therapeutic for prostate cancer.

“Important news for men with prostates and the women who love them (the men...not the prostates). Potential novel therapeutics for this very common cancer that is the second leading cause of cancer death in American men, behind lung cancer.”

Dr. David Hepburn

To read the full article please visit: 

https://www.ncbi.nlm.nih.gov/pubmed/30242861

Dr. David Hepburn website: 

doctordavidhepburn.com