Wednesday, 28 November 2018

Liverwort as a legal high


"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:

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

Friday, 23 November 2018

New research indicates benefit of cannabis in autism


"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:


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

Wednesday, 21 November 2018

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:

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


Monday, 19 November 2018

Exciting Promise of Role of CBD in Alzheimer’s Neuro-inflammation 

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:


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

Friday, 16 November 2018

Cannabis better than narcotics in treatment of back pain in Fibromyalgia


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:

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