Recreational Cannabis — Minimizing the Health Risks from Legalization

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“Most adults who occasionally use cannabis find it pleasurable and don’t experience substantial problems.
There is a growing body of research on the medical benefits of consuming cannabis flowers or extracts, and legalization should make it easier to study the therapeutic potential and allow access for patients who could benefit.”
 
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Leveraging allostery to improve G protein-coupled receptor (GPCR)-directed therapeutics: cannabinoid receptor 1 as a discovery target.

 

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“Allosteric modulators of G-protein coupled receptors (GPCRs) hold the promise of improved pharmacology and safety over typical orthosteric GPCR ligands.

These features are particularly relevant to the cannabinoid receptor 1 (CB1R) GPCR, since typical orthosteric CB1R ligands are associated with adverse events that limit their translational potential.

Areas covered: The contextual basis for applying allostery to CB1R is considered from pharmacological, drug-discovery, and medicinal standpoints.

Rational design of small-molecule CB1R allosteric modulators as potential pharmacotherapeutics would be greatly facilitated by direct experimental characterization of structure-function correlates underlying the biological activity of chemically-diverse CB1R allosteric modulators, CB1R allosteric ligand-binding binding pockets, and amino acid contact residues critical to allosteric ligand engagement and activity.

In these regards, designer covalent probes exhibiting well-characterized molecular pharmacology as CB1R allosteric modulators are emerging as valuable molecular reporters enabling experimental interrogation of CB1R allosteric site(s) and informing the design of new CB1R agents as drugs.

Expert opinion: Synthesis and pharmacological profiling of CB1R allosteric ligands will continue to provide valuable insights into CB1R structure-function correlates. The resulting data should expand the repertoire of novel agents capable of exerting therapeutic benefit by modulating CB1R-dependent signaling.”

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Vaccenic acid suppresses intestinal inflammation by increasing the endocannabinoid anandamide and non-cannabinoid signaling molecules in a rat model of the metabolic syndrome.

“Vaccenic acid (VA), the predominant ruminant-derived trans fat in the food chain, ameliorates hyperlipidemia yet mechanisms remain elusive. We investigated whether VA could influence tissue endocannabinoids (EC) by altering the availability of their biosynthetic precursor, arachidonic acid (AA) in membrane phospholipids (PL).

Interestingly, VA increased jejunal concentrations of anandamide and those of the non-cannabinoid signaling molecules, oleoylethanolamide and palmitoylethanolamide, relative to CD (P<0.05). This was consistent with a lower jejunal protein abundance (but not activity) of their degrading enzyme, fatty acid amide hydrolase and mRNA expression TNFα and IL-1β (P<0.05).

The ability of VA to reduce 2-AG in the liver and VAT provides a potential mechanistic explanation to alleviate ectopic lipid accumulation. The opposing regulation of EC and other non-cannabinoid lipid signaling molecules by VA suggests an activation of benefit via the EC system in the intestine.”

http://www.ncbi.nlm.nih.gov/pubmed/26891736

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Cannabis use improves retention and virological outcomes in patients treated for hepatitis C

“Despite the widespread use of polypharmacy, the management of hepatitis C virus (HCV) treatment-related side-effects is often incomplete, and many patients turn to cannabis for symptom relief.

Our results suggest that modest cannabis use may offer symptomatic and virological benefit to some patients undergoing HCV treatment by helping them maintain adherence to the challenging medication regimen.”

http://journals.lww.com/eurojgh/Abstract/2006/10000/Cannabis_use_improves_retention_and_virological.5.aspx

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Sativex® and clinical-neurophysiological measures of spasticity in progressive multiple sclerosis.

“Despite the proven efficacy of Sativex® (9-delta-tetrahydrocannabinol plus cannabidiol) oromucosal spray in reducing spasticity symptoms in multiple sclerosis (MS), little is known about the neurophysiological correlates of such effects.

The aim of the study was to investigate the effects of Sativex on neurophysiological measures of spasticity (H/M ratio) and corticospinal excitability in patients with progressive MS.

This was a randomized, double-blind, placebo-controlled, crossover study…

Our findings confirm the clinical benefit of Sativex on MS spasticity.”

http://www.ncbi.nlm.nih.gov/pubmed/26289497

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New horizons for newborn brain protection: enhancing endogenous neuroprotection.

“Intrapartum-related events are the third leading cause of childhood mortality worldwide and result in one million neurodisabled survivors each year. Infants exposed to a perinatal insult typically present with neonatal encephalopathy (NE).

The contribution of pure hypoxia-ischaemia (HI) to NE has been debated; over the last decade, the sensitising effect of inflammation in the aetiology of NE and neurodisability is recognised.

Therapeutic hypothermia is standard care for NE in high-income countries; however, its benefit in encephalopathic babies with sepsis or in those born following chorioamnionitis is unclear.

It is now recognised that the phases of brain injury extend into a tertiary phase, which lasts for weeks to years after the initial insult and opens up new possibilities for therapy.

There has been a recent focus on understanding endogenous neuroprotection and how to boost it or to supplement its effectors therapeutically once damage to the brain has occurred as in NE.

In this review, we focus on strategies that can augment the body’s own endogenous neuroprotection.

We discuss in particular remote ischaemic postconditioning whereby endogenous brain tolerance can be activated through hypoxia/reperfusion stimuli started immediately after the index hypoxic-ischaemic insult.

Therapeutic hypothermia, melatonin, erythropoietin and cannabinoids are examples of ways we can supplement the endogenous response to HI to obtain its full neuroprotective potential.

Achieving the correct balance of interventions at the correct time in relation to the nature and stage of injury will be a significant challenge in the next decade.”

http://www.ncbi.nlm.nih.gov/pubmed/26063194

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Modulation of HIVGP120 Antigen-Specific Immune Responses In Vivo by Δ9-Tetrahydrocannabinol.

“Approximately 25 % of HIV patients use marijuana for its putative therapeutic benefit…

Previously, a surrogate in vitro mouse model was established, which induced CD8+ T cell proliferation and gp120-specific IFNγ production. ∆9-Tetrahydrocannabinol (THC), the predominant psychoactive compound in marijuana, suppressed or enhanced the responses depending on the magnitude of cellular activation.

The purpose of the current study was to investigate whether THC produced similar effects in vivo and therefore a mouse model to induce HIVgp120-specific immune responses was established…

Collectively, our findings demonstrate that under certain conditions, THC enhances HIV antigen-specific immune responses, which occurs through CB1/CB2-dependent and -independent mechanisms.”

http://www.ncbi.nlm.nih.gov/pubmed/25900076

http://www.thctotalhealthcare.com/category/hivaids/

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Efficacy and safety of medical cannabinoids in older subjects: a systematic review.

“This systematic review aims to integrate the evidence on indications, efficacy, safety and pharmacokinetics of medical cannabinoids in older subjects…

Although trials studying medical cannabinoids included older subjects, there is a lack of evidence of its use specifically in older patients. Adequately powered trials are needed to assess the efficacy and safety of cannabinoids in older subjects, as the potential symptomatic benefit is especially attractive in this age group.”

http://www.ncbi.nlm.nih.gov/pubmed/24509411

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Foot Pain Associated With HIV Reduced By Smoked Cannabis In Placebo Trial

“In a randomized placebo-controlled trial, patients smoking cannabis experienced a 34 percent reduction in intense foot pain associated with HIV- twice the rate experienced by patients who smoked placebo.

“This placebo-controlled clinical trial showed that people with HIV who smoked cannabis had substantially greater pain reduction than those who did not smoke the cannabis,” said study lead author Donald I. Abrams, MD, UCSF professor of clinical medicine.

 “These results provide evidence that there is a measurable medical benefit to smoking cannabis for these patients.”

The results of this first study indicate that cannabis may indeed be useful in the amelioration of a very distressing, disabling, and difficult to treat complication of HIV…”

More: http://www.medicalnewstoday.com/releases/62917.php

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Medical Marijuana Encouraged For Pets Battling Cancer

“A veterinarian in Southern California is pushing the idea to help pets with cancer fight pain or regain their appetite by giving them pot.

Medical marijuana supporters argue that pot helps reduce chronic pain and nausea. Veterinarian Dr. Douglas Kramer of VetGuru.com said over the years, he’s talked to hundreds of people who’ve given pot to their pets.

“Medical marijuana might have a therapeutic benefit to help animals, especially those with terminal conditions,” Kramer said. “It’s quite clear that people are using it and it has both good an bad effects and they need to discuss it openly with their vet.”

Kramer is pushing for more research and discussion. And, his idea is starting to get traction. Time Magazine and Mother Jones recently explored the controversial issue.

“If people are thinking to take their own medical marijuana and give it to their dogs in a non-controlled dose, the risk of intoxication is too risky to advocate for that,” UC Davis Veterinary Medical Hospital Dr. Karl Jandrey said.

The American Veterinary Medical Association said more research into the effects of marijuana on animals needs to be done before proceeding with treatment since not all drugs affect humans and animals in the same way.”

http://www.digtriad.com/news/watercooler/article/284229/176/Medical-Marijuana-Isnt-Just-For-Humans

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