Cannabis Use Does Shrink parts of the Brain…in Some People

“The brain is obviously affected by cannabis, detrimentally for some. The hippocampus in particular may be especially sensitive to the impact of heavy cannabis use, given its high concentration of cannabinoid receptors type1. But does regular use change the size of the hippocampus? Apparently in those with a genetic predisposition.”

- Dr. David Hepburn

Abstract:

Cannabis use and dopaminergic gene polymorphism had both distinct and interactive effects on the hippocampus.

Emergingalterations of hippocampal total and specific subregional volumes were found in cannabis users relative to controls (i.e., CA1, CA2/3, and CA4), and associations between cannabis use levels and total and specific subregional volumes.

Furthermore, total hippocampal volume and the fissure subregion were affected by cannabis×DAT1 polymorphism (i.e., 9/9R and in 10/10R alleles), reflecting high and low levels of dopamine availability.

Read full article here:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797324/

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

Does Cannabis Use Affect Genes or Vice Versa?

“The exciting world of epigenetic reaches into cannabis use and notes external changes to genes involved in dopamine and ECS pathways. Interesting aside as to the effects of education and sex on cannabis use.”

- Dr. David Hepburn

Abstract:

Genetic and sociodemographic risk factors potentially associated with cannabis use (CU) were investigated in 40 cannabis users and 96 control subjects. DNA methylation analyses were also performed to explore the possibility of epigenetic changes related to CU.

Read full article here:

https://www.ncbi.nlm.nih.gov/pubmed/29353877

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

Cannabis Use in Adolescents Lowest in 15 Years

“While a growing number of youth believe that cannabis is safe, it's used in adolescence makes many (myself included) very twitchy. So it comes as a pleasant surprise that cannabis use in those age 12-17 in the US, despite its increased availability, is 6.5%, the lowest in 15 years.”

- Dr. David Hepburn

Abstract:

This national report summarizes key findings from the 2016 National Survey on Drug Use and Health (NSDUH) for indicators of substance use and mental health among people aged 12 years old or older in the civilian, noninstitutionalized population of the United States. Results are provided for the overall category of individuals aged 12 or older as well as by age subgroups.

The NSDUH questionnaire underwent a partial redesign in 2015 to improve the quality of the NSDUH data and to address the changing needs of policymakers and researchers. For measures that started a new baseline in 2015, estimates are discussed only for 2016.

Read the full article here:

https://www.samhsa.gov/data/sites/default/files/NSDUH-FFR1-2016/NSDUH-FFR1-2016.htm#summary

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

Cannabis Use Reduces Premature Death

“This headline is a feather in any product/drug’s cap. Cannabis use is associated with decreased rates of obesity, diabetes mellitus, mortality from traumatic brain injury, use of alcohol and prescription drugs, driving fatalities, and opioid overdose deaths. These data suggest that Cannabis use may decrease premature deaths.”

- Dr. David Hepburn 

Abstract:

Adverse effects of moderate Cannabis use on physical health are subtle and rarely fatal, while Cannabis use is associated with decreased rates of obesity, diabetes mellitus, mortality from traumatic brain injury, use of alcohol and prescription drugs, driving fatalities, and opioid overdose deaths.

These data suggest that Cannabis use may decrease premature deaths. To date, no studies have attempted to estimate the impacts of Cannabis use on premature death that include both adverse and beneficial effects on physical health. Marijuana use is estimated to reduce premature deaths from diabetes mellitus, cancer, and traumatic brain injury by 989 to 2,511 deaths for each 1% of the population using Cannabis. 

Read the full article here:

https://scholarworks.iu.edu/dspace/handle/2022/21632

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Dr. David 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

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

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

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