Tag Archives: plant

Anti-Aversive Effects of Cannabidiol on Innate Fear-Induced Behaviors Evoked by an Ethological Model of Panic Attacks Based on a Prey vs the Wild Snake Epicrates cenchria crassus Confrontation Paradigm

Posted on by

“Research on the interaction between different compounds extracted from the plant Cannabis sativa (Cannabis) and the endocannabinoid system has revealed a series of ligands that selectively bind to cannabinoid receptors. The activation of this system causes a wide spectrum of responses, some of which could be potentially therapeutic. Recently, much attention has been given to cannabidiol (CBD), a major constituent of Cannabis that is unable to mimic all of the effects of the plant but has a wide range of pharmacological effects. In the elevated plus-maze, this drug produces an anxiolytic-like effect…

… attention has been given to the potential anxiolytic properties of cannabidiol, because of its complex actions on the endocannabinoid system together with its effects on other neurotransmitter systems. The aim of this study was to investigate the effects of cannabidiol on innate fear-related behaviors evoked by a prey vs predator paradigm…

These results show that cannabidiol modulates defensive behaviors evoked by the presence of threatening stimuli…

In summary, the data presented in this study suggest that the complex action of CBD on the endocannabinoid-mediated system, together with its putative effect on the serotonin-mediated system, could have a pivotal role in the regulation of emotional states and thus constitute a novel pharmacological target for anti-panic therapy.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242302/

Scientists are high on idea that marijuana reduces memory impairment

Posted on by

“The more research they do, the more evidence Ohio State University scientists find that specific elements of marijuana can be good for the aging brain by reducing inflammation there and possibly even stimulating the formation of new brain cells.

The research suggests that the development of a legal drug that contains certain properties similar to those in marijuana might help prevent or delay the onset of Alzheimer’s disease. Though the exact cause of Alzheimer’s remains unknown, chronic inflammation in the brain is believed to contribute to memory impairment.

Any new drug’s properties would resemble those of tetrahydrocannabinol, or THC, the main psychoactive substance in the cannabis plant, but would not share its high-producing effects.

.”Could people smoke marijuana to prevent Alzheimer’s disease if the disease is in their family? We’re not saying that, but it might actually work. What we are saying is it appears that a safe, legal substance that mimics those important properties of marijuana can work on receptors in the brain to prevent memory impairments in aging. So that’s really hopeful,” Wenk said”

Read more: http://phys.org/news146320102.html

A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms.

Posted on by

“OBJECTIVES:

To determine whether plant-derived cannabis medicinal extracts (CME) can alleviate neurogenic symptoms unresponsive to standard treatment, and to quantify adverse effects.

SUBJECTS:

Twenty-four patients with multiple sclerosis (18), spinal cord injury (4), brachial plexus damage (1), and limb amputation due to neurofibromatosis (1).

INTERVENTION:

Whole-plant extracts of delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), 1:1 CBD:THC, or matched placebo were self-administered by sublingual spray at doses determined by titration against symptom relief or unwanted effects within the range of 2.5-120 mg/24 hours. Measures used: Patients recorded symptom, well-being and intoxication scores on a daily basis using visual analogue scales. At the end of each two-week period an observer rated severity and frequency of symptoms on numerical rating scales, administered standard measures of disability (Barthel Index), mood and cognition, and recorded adverse events.

RESULTS:

Pain relief associated with both THC and CBD was significantly superior to placebo. Impaired bladder control, muscle spasms and spasticity were improved by CME in some patients with these symptoms. Three patients had transient hypotension and intoxication with rapid initial dosing of THC-containing CME.

CONCLUSIONS:

Cannabis medicinal extracts can improve neurogenic symptoms unresponsive to standard treatments. Unwanted effects are predictable and generally well tolerated. Larger scale studies are warranted to confirm these findings.”

http://www.ncbi.nlm.nih.gov/pubmed/12617376

Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis.

Posted on by

“Central pain in multiple sclerosis (MS) is common and often refractory to treatment…

We conducted a single-center, 5-week (1-week run-in, 4-week treatment), randomized, double-blind, placebo-controlled, parallel-group trial in 66 patients with MS and central pain states (59 dysesthetic, seven painful spasms) of a whole-plant cannabis-based medicine (CBM), containing delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD) delivered via an oromucosal spray, as adjunctive analgesic treatment…

CONCLUSIONS:

Cannabis-based medicine is effective in reducing pain and sleep disturbance in patients with multiple sclerosis related central neuropathic pain and is mostly well tolerated.”

http://www.ncbi.nlm.nih.gov/pubmed/16186518

Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study.

Posted on by

“OBJECTIVE:

Cannabis may alleviate some symptoms associated with multiple sclerosis (MS). This study investigated the effect of an orally administered standardized Cannabis sativa plant extract in MS patients with poorly controlled spasticity.”

“CONCLUSION:

A standardized Cannabis sativa plant extract might lower spasm frequency and increase mobility with tolerable side effects in MS patients with persistent spasticity not responding to other drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/15327040

Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: relevance to Parkinson’s disease.

Posted on by

Abstract

“Cannabinoids have been reported to provide neuroprotection in acute and chronic neurodegeneration. In this study, we examined whether they are also effective against the toxicity caused by 6-hydroxydopamine, both in vivo and in vitro, which may be relevant to Parkinson’s disease (PD). First, we evaluated whether the administration of cannabinoids in vivo reduces the neurodegeneration produced by a unilateral injection of 6-hydroxydopamine into the medial forebrain bundle. As expected, 2 weeks after the application of this toxin, a significant depletion of dopamine contents and a reduction of tyrosine hydroxylase activity in the lesioned striatum were noted, and were accompanied by a reduction in tyrosine hydroxylase-mRNA levels in the substantia nigra. None of these events occurred in the contralateral structures. Daily administration of delta9-tetrahydrocannabinol (delta9-THC) during these 2 weeks produced a significant waning in the magnitude of these reductions, whereas it failed to affect dopaminergic parameters in the contralateral structures. This effect of delta9-THC appeared to be irreversible since interruption of the daily administration of this cannabinoid after the 2-week period did not lead to the re-initiation of the 6-hydroxydopamine-induced neurodegeneration. In addition, the fact that the same neuroprotective effect was also produced by cannabidiol (CBD), another plant-derived cannabinoid with negligible affinity for cannabinoid CB1 receptors, suggests that the antioxidant properties of both compounds, which are cannabinoid receptor-independent, might be involved in these in vivo effects, although an alternative might be that the neuroprotection exerted by both compounds might be due to their anti-inflammatory potential. As a second objective, we examined whether cannabinoids also provide neuroprotection against the in vitro toxicity of 6-hydroxydopamine. We found that the non-selective cannabinoid agonist HU-210 increased cell survival in cultures of mouse cerebellar granule cells exposed to this toxin. However, this effect was significantly lesser when the cannabinoid was directly added to neuronal cultures than when these cultures were exposed to conditioned medium obtained from mixed glial cell cultures treated with HU-210, suggesting that the cannabinoid exerted its major protective effect by regulating glial influence to neurons. In summary, our results support the view of a potential neuroprotective action of cannabinoids against the in vivo and in vitro toxicity of 6-hydroxydopamine, which might be relevant for PD. Our data indicated that these neuroprotective effects might be due, among others, to the antioxidant properties of certain plant-derived cannabinoids, or exerted through the capability of cannabinoid agonists to modulate glial function, or produced by a combination of both mechanisms.”

http://www.ncbi.nlm.nih.gov/pubmed/15837565

Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells

Posted on by

Journal of Neuro-Oncology

“Normal tissue toxicity limits the efficacy of current treatment modalities for glioblastoma multiforme (GBM).

We evaluated the influence of cannabinoids on cell proliferation, death, and morphology of human GBM cell lines and in primary human glial cultures, the normal cells from which GBM tumors arise. The influence of a plant derived cannabinoid agonist, Delta(9)-tetrahydrocannabinol Delta(9)-THC), and a potent synthetic cannabinoid agonist, WIN 55,212-2, were compared using time lapse microscopy.

We discovered that Delta(9)-THC decreases cell proliferation and increases cell death of human GBM cells more rapidly than WIN 55,212-2. Delta(9)-THC was also more potent at inhibiting the proliferation of GBM cells compared to WIN 55,212-2. The effects of Delta(9)-THC and WIN 55,212-2 on the GBM cells were partially the result of cannabinoid receptor activation.

The same concentration of Delta(9)-THC that significantly inhibits proliferation and increases death of human GBM cells has no significant impact on human primary glial cultures. Evidence of selective efficacy with WIN 55,212-2 was also observed but the selectivity was less profound, and the synthetic agonist produced a greater disruption of normal cell morphology compared to Delta(9)-THC.”

https://www.ncbi.nlm.nih.gov/pubmed/16078104

https://link.springer.com/article/10.1007%2Fs11060-004-5950-2

Antidepressant-like effects of Δ⁹-tetrahydrocannabinol and rimonabant in the olfactory bulbectomised rat model of depression.

Posted on by

Abstract

“The endocannabinoid signalling system is widely accepted to play a role in controlling the affective state. Plant cannabinoids are well known to have behavioural effects in animals and humans and the cannabinoid CB(1) receptor antagonist rimonabant has recently been shown to precipitate depression-like symptoms in clinical trial subjects. The aim of the present study was to investigate the behavioural and neurochemical effects of chronic administration of Δ⁹-tetrahydrocannabinol (THC) and rimonabant on intact and olfactory bulbectomised (OB) rats used as a model of depression. As expected, OB rats were hyperactive in the open field. Repeated THC (2 mg/kg, i.p. once every 48 h for 21 days) and rimonabant (5 mg/kg, i.p. once every 48 h for 21 days) reduced this hyperactivity, which is typical of clinically effective antidepressant drugs. In intact animals, chronic THC increased brain derived neurotrophic factor (BDNF) expression levels in the hippocampus and frontal cortex but rimonabant had no effect. Rimonabant increased the levels of phosphorylated extracellular signal regulated kinases (p-ERKs(1/2)) in the hippocampus and prefrontal cortex and THC also increased expression in frontal cortex. OB did not affect BDNF or p-ERK(1/2) expression in the hippocampus or frontal cortex and in, contrast to the intact animals, neither THC nor rimonabant altered expression in the OB rats. These findings indicate antidepressant-like behavioural properties of both THC and rimonabant in OB rats although additional studies are required to clarify the relationship between the chronic effects of cannabinoids in other pre-clinical models and in human depression.”

http://www.ncbi.nlm.nih.gov/pubmed/22634064

Cannabis-like chemical combats chief genetic cause of autism

Posted on by

“Natural cannabis-like chemicals in the brain may help combat the leading genetic cause of autism, research has shown.

Scientists linked blockages in a signalling pathway dependent on the compounds, called 2-AG endocannabinoid transmitters, with symptoms of Fragile X syndrome.

Correcting the fault with drugs led to dramatic behavioural improvements in mice with a version of the condition.

Fragile X syndrome is the most common known genetic cause of autism.

It results from a mutation in the FMR1 gene on the female X chromosome. Men possess one copy of the chromosome, paired with a male Y chromosome, and women two.

Boys are much more likely to be born with Fragile X than girls. This is thought to be because with two X chromosomes, a defect in one may be compensated for by the other.

People with the syndrome suffer mental impairment, learning difficulties, and may be hyperactive or impulsive. They also possess notable physical characteristics such as an elongated face, flat feet and large ears.

“What we hope is to one day increase the ability of people with Fragile X syndrome to socialise and engage in normal cognitive functions,” said lead researcher Professor Daniele Piomelli, from the University of California at Irvine in the United States.

The study was the first to identify the role of endocannabinoids in the neurobiology of Fragile X, she said.

About endocannabinoids

Endocannabinoid compounds are created naturally in the body and share a similar chemical structure with THC, the primary psychoactive component of the marijuana plant, Cannabis.

Endocannabinoids are distinctive because they link with protein molecule receptors — called cannabinoid receptors — on the surface of cells. For instance, when a person smokes marijuana, the cannabinoid THC activates these receptors. And because the body’s natural cannabinoids control a variety of factors — such as pain, mood and appetite — they’re attractive targets for drug discovery and development.”

Read more: http://www.belfasttelegraph.co.uk/news/health/cannabis-chemical-combats-chief-genetic-cause-of-autism-16216090.html#ixzz2DRLsbjJO

The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin

Posted on by

  “Cannabis sativa is the source of a unique set of compounds known collectively as plant cannabinoids or phytocannabinoids. This review focuses on the manner with which three of these compounds, (−)-trans-Δ9-tetrahydrocannabinol (Δ9-THC), (−)-cannabidiol (CBD) and (−)-trans-Δ9-tetrahydrocannabivarin (Δ9-THCV), interact with cannabinoid CB1 and CB2 receptors. Δ9-THC, the main psychotropic constituent of cannabis, is a CB1 and CB2 receptor partial agonist and in line with classical pharmacology, the responses it elicits appear to be strongly influenced both by the expression level and signalling efficiency of cannabinoid receptors and by ongoing endogenous cannabinoid release. CBD displays unexpectedly high potency as an antagonist of CB1/CB2 receptor agonists in CB1– and CB2-expressing cells or tissues, the manner with which it interacts with CB2 receptors providing a possible explanation for its ability to inhibit evoked immune cell migration. Δ9-THCV behaves as a potent CB2 receptor partial agonist in vitro. In contrast, it antagonizes cannabinoid receptor agonists in CB1-expressing tissues. This it does with relatively high potency and in a manner that is both tissue and ligand dependent. Δ9-THCV also interacts with CB1 receptors when administered in vivo, behaving either as a CB1 antagonist or, at higher doses, as a CB1 receptor agonist. Brief mention is also made in this review, first of the production by Δ9-THC of pharmacodynamic tolerance, second of current knowledge about the extent to which Δ9-THC, CBD and Δ9-THCV interact with pharmacological targets other than CB1 or CB2 receptors, and third of actual and potential therapeutic applications for each of these cannabinoids.”

“…cannabis is a source not only of Δ9-THC, CBD and Δ9-THCV but also of at least 67 other phytocannabinoids and as such can be regarded as a natural library of unique compounds. The therapeutic potential of many of these ligands still remains largely unexplored prompting a need for further preclinical and clinical research directed at establishing whether phytocannabinoids are indeed ‘a neglected pharmacological treasure trove’. As well as leading to a more complete exploitation of Δ9-THC and CBD as therapeutic agents and establishing the clinical potential of Δ9-THCV more clearly, such research should help to identify any other phytocannabinoids that have therapeutic applications per se or that constitute either prodrugs from which semisynthetic medicines might be manufactured or lead compounds from which wholly synthetic medicines might be developed.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219532/