The New Weed on the Block

“This cannabinomimetic of medical interest in that it might harness the same cannabis receptors without causing some of the unwanted side effects of THC. If it works well, the US government might have to make it illegal.”

- Dr. David Hepburn

Abstract:

The recent discovery of another source of a cannabinoid comes from a plant that is a relative of the mosses called liverwort. One genus of the plant, Radula, boasts a handful of species that produce a chemical that is a lot like tetrahydrocannabinol (THC) from Cannabis sativa, or marijuana.

Why a liverwort, which lives and reproduces quite differently from a plant like Cannabis, would make this molecule remains a mystery. What we now know, however, is the cannabinoid from liverwort and the one in Cannabis are almost exactly the same and have quite similar effects in the mammalian brain.

Read the full article here:

https://www.scientificamerican.com/article/lowly-moss-like-plant-seems-to-copy-cannabis/

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

Less Morphine Required When Cannabinoid Receptor Activated

“Many pain patients, with time, require increases of dose and/or frequency of the potentially deadly opiate morphine in order to obtain pain control. However, by activation of the CB2 receptor, tolerance and dependance of morphine was diminished.”

- Dr. David Hepburn

Abstract:

Morphine is widely used as an analgesic to treat moderate to severe pain, but chronic morphine use is associated with development of tolerance and dependence, which limits its analgesic efficacy.

A previous research has showed that non analgetic dose of a cannabinoid type 2 (CB2) receptor agonist reduced morphine tolerance in cancer pain. A previous study also showed the colocalization of CB2 and transient receptor potential vanilloid 1 (TRPV1) in human and rat dorsal root ganglia (DRG) sensory neurons.

Read the full article here:

https://www.ncbi.nlm.nih.gov/pubmed/28901432

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

Why Women Don’t Forget

“Men appear to have 41% more CB1 receptors in the brain. Unfortunately for men of the male species, this is inversely related to working memory. (No memory of working). The sex difference in the ECS is becoming more interesting in explaining reactions and abilities in both.”

-    Dr. David Hepburn 

Abstract:

The endocannabinoid system (ECS) has a widespread neuron modulatory function in the central nervous system and is involved in important aspects of brain function including brain development, cortical rhythms, plasticity, reward, and stress sensitivity. 

Many of these effects are mediated via the cannabinoid CB1 receptor (CB1R) subtype. 

Animal studies convincingly have shown the interaction between the ECS and sex hormones, as well as a sex difference of higher brain CB1R in males. Human in vivo studies of sex difference has yielded discrete pant findings.

Read the full article here:

https://www.ncbi.nlm.nih.gov/pubmed/30296558

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

No Change in Hippocampus Volume With Youth Cannabis Users

“A number of studies have found evidence of structural brain changes in teens and young adults who smoke marijuana, however is research indicates that there are no changes into adulthood in the hippocampus (memory).”

-    Dr. David Hepburn 

Abstract:

Cannabis exposure, particularly heavy cannabis use, has been associated with neuroanatomical alterations in regions rich with cannabinoid receptors such as the hippocampus in some but not in other (mainly cross-sectional) studies. However, it remains unclear whether continued heavy cannabis use alters hippocampal volume, and whether an earlier age of onset and/or a higher dosage exacerbate these changes.

Read full article here:

https://www.ncbi.nlm.nih.gov/pubmed/28741422

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

Endocannabinoids Worsen Heart Function After Heart Attack

“The ECS reacts to try to balance our inner milieu when that milieu is disturbed. Sometimes, as our body tries to help itself, it can end up doing some damage. Endocannabinoids do not cause heart attacks, of course, but they are releases in response to this major stressor.”

-   Dr. David Hepburn.

Intravenous administration of endocannabinoid 2-arachidonoylglycerol into wildtype C57BL6 mice induced a rapid increase of blood neutrophil and monocyte counts as measured by flow cytometry.

This effect was blunted when using cannabinoid receptor 2 knockout mice. In response to myocardial infarction induced in wildtype mice, the lipidomic analysis revealed significantly elevated plasma and cardiac levels of the endocannabinoid 2-arachidonoylglycerol 24 h after infarction, but no changes in anandamide, palmitoylethanolamide and oleoylethanolamide.

Read full article here:

https://www.ncbi.nlm.nih.gov/pubmed/30295758

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

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

Those Using Cannabis Are Much More Successful Getting Off Opioids - Dr. David Hepburn

Article recommend by Dr. David Hepburn:

High-intensity cannabis use is associated with retention in opioid agonist treatment: a longitudinal analysis.

Abstract 

BACKGROUND AND AIMS:

Cannabis use is common among people on opioid agonist treatment (OAT), causing concern for some care providers. However, there is limited and conflicting evidence on the impact of cannabis use on OAT outcomes. Given the critical role of retention in OAT in reducing opioid-related morbidity and mortality, we aimed to estimate the association of at least daily cannabis use on the likelihood of retention in treatment among people initiating OAT. As a secondary aim we tested the impacts of less frequent cannabis use. 

DESIGN:

Data were drawn from two community-recruited prospective cohorts of people who use illicit drugs (PWUD). Participants were followed for a median of 81 months (interquartile range = 37-130). 

SETTING:

Vancouver, Canada. 

PARTICIPANTS:

This study comprised a total of 820 PWUD (57.8% men, 59.4% of Caucasian ethnicity, 32.2% HIV-positive) initiating OAT between December 1996 and May 2016. The proportion of women was higher among HIV-negative participants, with no other significant differences. 

MEASUREMENTS:

The primary outcome was retention in OAT, defined as remaining in OAT (methadone or buprenorphine/naloxone-based) for two consecutive 6-month follow-up periods. The primary explanatory variable was cannabis use (at least daily versus less than daily) during the same 6-month period. Confounders assessed included: socio-demographic characteristics, substance use patterns and social-structural exposures. 

FINDINGS:

In adjusted analysis, at least daily cannabis use was positively associated with retention in OAT [adjusted odds ratio (aOR) = 1.21, 95% confidence interval (CI) = 1.04-1.41]. Our secondary analysis showed that compared with non-cannabis users, at least daily users had increased odds of retention in OAT (aOR = 1.20, 95% CI = 1.02-1.43), but not less than daily users (aOR = 1.00, 95% CI = 0.87-1.14). 

CONCLUSIONS:

Among people who use illicit drugs initiating opioid agonist treatment in Vancouver, at least daily cannabis use was associated with approximately 21% greater odds of retention in treatment compared with less than daily consumption.

"The role of cannabis (both CBD and THC) has already been shown to be useful as a substitute for higher dose opioids for pain control (typically post op), but now, it ALSO can help those who are addicted to successfully get off and stay off opioids.”

Dr. David Hepburn

To read the full article please visit: 

https://www.ncbi.nlm.nih.gov/pubmed/30238568

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

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

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

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”

Dr. David Hepburn

To read the full article please visit:

https://www.ncbi.nlm.nih.gov/pubmed/30121138

Dr. Dave Hepburn website:

https://doctordavidhepburn.com