Author Archives: David Worrell

The Effect of Medical Marijuana Laws on Body Weight.

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“This study is the first to examine the effects of medical marijuana laws (MMLs) on body weight, physical wellness, and exercise.

Using data from the 1990 to 2012 Behavioral Risk Factor Surveillance System and a difference-in-difference approach, we find that the enforcement of MMLs is associated with a 2% to 6% decline in the probability of obesity.

We find some evidence of age-specific heterogeneity in mechanisms. For older individuals, MML-induced increases in physical mobility may be a relatively important channel, while for younger individuals, a reduction in consumption of alcohol, a substitute for marijuana, appears more important.

These findings are consistent with the hypothesis that MMLs may be more likely to induce marijuana use for health-related reasons among older individuals, and cause substitution toward lower-calorie recreational ‘highs’ among younger individuals.

Our estimates suggest that MMLs induce a $58 to $115 per-person annual reduction in obesity-related medical costs.”

http://www.ncbi.nlm.nih.gov/pubmed/26602324

Involvement of opioid system in antidepressant-like effect of the cannabinoid CB1 receptor inverse agonist AM-251 after physical stress in mice.

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“Cannabinoid inverse agonists possess antidepressant-like properties…

Numerous studies reported the interaction between opioid and cannabinoid pathways.

In this study, we used acute foot-shock stress in mice to investigate the involvement of opioid pathway in the antidepressant-like effect of the cannabinoid CB1 receptor inverse agonist AM-251.

In conclusion, the present study for the first time revealed the possible role of opioid signaling in the antidepressant-like properties of AM-251 in foot-shock stress model. “

http://www.ncbi.nlm.nih.gov/pubmed/26609670

Daily Marijuana Use Is Not Associated with Brain Morphometric Measures in Adolescents or Adults

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“No statistically significant differences were found between daily users and nonusers on volume or shape in the regions of interest.

Effect sizes suggest that the failure to find differences was not due to a lack of statistical power, but rather was due to the lack of even a modest effect.

In sum, the results indicate that, when carefully controlling for alcohol use, gender, age, and other variables, there is no association between marijuana use and standard volumetric or shape measurements of subcortical structures.

The press may not cite studies that do not find sensational effects, but these studies are still extremely important. While the literature clearly supports a deleterious short-term effect of marijuana on learning and memory, it seems unlikely that marijuana use has the same level of long-term deleterious effects on brain morphology as other drugs like alcohol.”

http://www.jneurosci.org/content/35/4/1505.full

Long-Term Data of Efficacy, Safety and Tolerability in a Real Life Setting of THC/CBD Oromucosal Spray-Treated Multiple Sclerosis Patients.

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“Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray was approved as add-on therapy for spasticity in patients with Multiple Sclerosis (MS).

We showed our forty-weeks post-marketing experience regarding efficacy and safety of THC/CBD spray in an Italian cohort of 102 MS patients…

In conclusion, treatment with THC/CBD spray appears to be a valid answer to some of the unmet needs in MS patients, such as spasticity and other refractory-to-treatment symptoms. “

http://www.ncbi.nlm.nih.gov/pubmed/26608223

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques.

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“Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques.

Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques.

Our results indicate that Δ9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques.

This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group.”

A Sativex(®) -like combination of phytocannabinoids as a disease-modifying therapy in a viral model of multiple sclerosis.

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“Sativex(®) is an oromucosal spray, containing equivalent amounts of Δ(9) -tetrahydrocannabinol (Δ(9) -THC) and cannabidiol (CBD)-botanical drug substance (BDS), which has been approved for the treatment of spasticity and pain associated to multiple sclerosis (MS).

In this study, we investigated whether Sativex may also serve as a disease-modifying agent in the Theiler’s murine encephalomyelitis virus-induced demyelinating disease model of MS.

The data support the therapeutic potential of Sativex to slow MS progression and its relevance in CNS repair.”

http://www.ncbi.nlm.nih.gov/pubmed/25857324

The disease-modifying effects of a Sativex-like combination of phytocannabinoids in mice with experimental autoimmune encephalomyelitis are preferentially due to Δ9-tetrahydrocannabinol acting through CB1 receptors.

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“Sativex®, an equimolecular combination of Δ9-tetrahydrocannabinol-botanical drug substance (Δ9-THC-BDS) and cannabidiol-botanical drug substance (CBD-BDS), is a licensed medicine that may be prescribed for alleviating specific symptoms of multiple sclerosis (MS) such as spasticity and pain.

However, further evidence suggest that it could be also active as disease-modifying therapy given the immunomodulatory, anti-inflammatory and cytoprotective properties of their two major components.

In this study, we investigated this potential in the experimental autoimmune encephalitis (EAE) model of MS in mice.

We compared the effect of a Sativex-like combination of Δ9-THC-BDS (10mg/kg) and CBD-BDS (10mg/kg) with Δ9-THC-BDS (20mg/kg) or CBD-BDS (20mg/kg) administered separately by intraperitoneal administration to EAE mice.

Treatments were initiated at the time that symptoms appear and continued up to the first relapse of the disease.

The results show that the treatment with a Sativex-like combination significantly improved the neurological deficits typical of EAE mice, in parallel with a reduction in the number and extent of cell aggregates present in the spinal cord which derived from cell infiltration to the CNS.

These effects were completely reproduced by the treatment with Δ9-THC-BDS alone, but not by CBD-BDS alone which only delayed the onset of the disease without improving disease progression and reducing the cell infiltrates in the spinal cord.

Next, we investigated the potential targets involved in the effects of Δ9-THC-BDS by selectively blocking CB1 or PPAR-γ receptors, and we found a complete reversion of neurological benefits and the reduction in cell aggregates only with rimonabant, a selective CB1 receptor antagonist.

Collectively, our data support the therapeutic potential of Sativex as a phytocannabinoid formulation capable of attenuating EAE progression, and that the active compound was Δ9-THC-BDS acting through CB1 receptors.”

The endocannabinoid system in guarding against fear, anxiety and stress.

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“The endocannabinoid (eCB) system has emerged as a central integrator linking the perception of external and internal stimuli to distinct neurophysiological and behavioural outcomes (such as fear reaction, anxiety and stress-coping), thus allowing an organism to adapt to its changing environment.

eCB signalling seems to determine the value of fear-evoking stimuli and to tune appropriate behavioural responses, which are essential for the organism’s long-term viability, homeostasis and stress resilience; and dysregulation of eCB signalling can lead to psychiatric disorders.

An understanding of the underlying neural cell populations and cellular processes enables the development of therapeutic strategies to mitigate behavioural maladaptation.”

http://www.ncbi.nlm.nih.gov/pubmed/26585799

Characterization of Lignanamides from Hemp (Cannabis sativa L. ) Seed and their Antioxidant and Acetylcholinesterase Inhibitory Activities.

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Image result for J Agric Food Chem.

“Hempseed is known for its content in fatty acids, proteins and fiber, which contribute to its nutritional value.

Here we studied the secondary metabolites of hempseed aiming at identifying bioactive compounds that could contribute to its health benefits.

This investigation led to the isolation of four new lignanamides cannabisin M, 2, cannabisin N, 5, cannabisin O, 8 and 3,3′-demethyl-heliotropamide, 10, together with ten known lignanamides, among which 4 was identified for the first time from hempseed.

Structures were established on the basis of NMR, HR-MS, UV, IR as well as by comparison with the literature data.

Lignanamides 2, 7, 9-14 showed good antioxidant activity among which 7, 10 and 13 also inhibited acetylcholinesterase in vitro.

The new identified compounds in this study added to the diversity of hempseed composition and the bioassays implied that hempseed, with lignanamides as nutrients, may be a good source of bioactive and protective compounds.”  http://www.ncbi.nlm.nih.gov/pubmed/26585089

“Alzheimer’s Disease (AD) is the most common single cause of dementia in our ageing society. On full assessment and diagnosis of AD, initiation of an AChe inhibitor is recommended as early as possible, it is important that AChe inhibitor therapy is considered for patients with mild to moderate AD.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014378/

 “The Effects of Hempseed Meal Intake and Linoleic Acid on Drosophila Models of Neurodegenerative Diseases and Hypercholesterolemia. Our results indicate that hempseed meal (HSM) and linoleic acid are potential candidates for the treatment of Alzheimer’s disease (AD) and cardiovascular disease. These results show that HSM may prove of great utility as a health food, with potential for the prevention of AD and cardiovascular disease.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933972/