Tag Archives: Delta-9-Tetrahydrocannabinol

Involvement of the opioid system in the anxiolytic-like effects induced by Delta(9)-tetrahydrocannabinol.

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Recent studies have shown that several pharmacological actions induced by cannabinoids, including antinociception and reward, involve the participation of the endogenous opioid system. The present study was designed to examine the possible involvement of the different opioid receptors in the anxiolytic-like responses induced by Delta(9)-tetrahydrocannabinol (THC)…

The administration of a low dose of THC produced clear anxiolytic-like responses…

CONCLUSIONS:

These results demonstrate that the endogenous opioid system is involved in the regulation of anxiety-like behaviour by cannabinoids and provide new findings to clarify further the interaction between these two neuronal systems.”

http://www.ncbi.nlm.nih.gov/pubmed/12185408

Anandamide hydrolysis: a new target for anti-anxiety drugs?

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“The major psychoactive constituent of cannabis, Delta(9)-tetrahydrocannabinol, affects emotional states in humans and laboratory animals by activating brain cannabinoid receptors. A primary endogenous ligand of these receptors is anandamide, the amide of arachidonic acid with ethanolamine. Anandamide is released in selected regions of the brain and is deactivated through a two-step process consisting of transport into cells followed by intracellular hydrolysis. Pharmacological blockade of the enzyme fatty acid amide hydrolase (FAAH), which is responsible for intracellular anandamide degradation, produces anxiolytic-like effects in rats without causing the wide spectrum of behavioral responses typical of direct-acting cannabinoid agonists. These findings suggest that anandamide contributes to the regulation of emotion and anxiety, and that FAAH might be the target for a novel class of anxiolytic drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/14604824

A role for cannabinoid CB1 receptors in mood and anxiety disorders.

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“Mood and anxiety disorders, the most prevalent of the psychiatric disorders, cause immeasurable suffering worldwide. Despite impressive advances in pharmacological therapies, improvements in efficacy and side-effect profiles are needed. The present literature review examines the role that the endocannabinoid system may play in these disorders and the potential value of targeting this system in the search for novel and improved medications.

Cannabis and its major psychoactive component (-)-trans-delta9-tetrahydrocannabinol, have profound effects on mood and can modulate anxiety and mood states. Cannabinoid receptors and other protein targets in the central nervous system (CNS) that modulate endocannabinoid function have been described. The discovery of selective modulators of some of these sites that increase or decrease endocannabinoid neurotransmission, primarily through the most prominent of the cannabinoid receptors in the CNS, the CB1 receptors, combined with transgenic mouse technology, has enabled detailed investigations into the role of these CNS sites in the regulation of mood and anxiety states. Although data point to the involvement of the endocannabinoid system in anxiety states, the pharmacological evidence seems contradictory: both anxiolytic- and anxiogenic-like effects have been reported with both endocannabinoid neurotransmission enhancers and blockers.

Due to advances in the development of selective compounds directed at the CB1 receptors, significant progress has been made on this target. Recent biochemical and behavioural findings have demonstrated that blockade of CB1 receptors engenders antidepressant-like neurochemical changes (increases in extracellular levels of monoamines in cortical but not subcortical brain regions) and behavioural effects consistent with antidepressant/antistress activity in rodents.”

http://www.ncbi.nlm.nih.gov/pubmed/16148437

Marijuana nutrients found to help prevent Alzheimer’s disease

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“A study conducted by scientists at Scripps Research Institute in California has found that, contrary to marijuana’s reputation, the ingredients of the drug can actually fight off the memory-impairing effects of Alzheimer’s disease.The researchers found that the active ingredient in marijuana — delta-9-tetrahydrocannabinol, or THC — is responsible for the positive effect, as it can prevent the breakdown of the neurotransmitter acetylcholine even better than commercially marketed prescription drugs.

The study also showed that THC could completely prevent the enzyme acetylcholinesterase (AchE) from forming amyloid plaques, whereas twice as much donepezil and tacrine — the two drugs approved for Alzheimer’s treatment — only reduced such clumping by 22 and 7 percent, respectively, the researchers reported in the journal Molecular Pharmaceutics. This led the scientists to conclude that a more effective Alzheimer’s drug could be developed in the future.”

Read more: http://www.naturalnews.com/020667_Marijuana_Alzheimers_drugs.htm

Marijuana and Alzheimer’s – How Marijuana Outperforms Drugs for Alzheimer’s Disease

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“Marijuana and Alzheimer’s – Alzheimer’s Help without Nasty Drug-Induced Side Effects.”

marijuanaplants 235x147 Marijuana and Alzheimers How Marijuana Outperforms Drugs for Alzheimer’s Disease

“The war on drugs has most people believing there is no legitimate argument for marijuana, causing it to be highly looked down upon and illegal under federal law throughout the United States. But there is an exceptionally large body of research pointing to the positive impact marijuana can have on various health ailments, with recent research revealing a link between marijuana and Alzheimer’s – showing that THC, the psychoactive component of marijuana, may be beneficial for Alzheimer’s patients.

As published in the journal Molecular Pharmacology, a Skaggs Institute for Chemical Biology study shows that Δ9-tetrahydrocannabinol (THC) both “competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid β-peptide (Aβ) aggregation.” In other words, cannabinoid molecules found in cannabis could halt the progression of Alzheimer’s disease.”

Read more by  : http://naturalsociety.com/marijuana-and-alzheimers-outperforms-harmful-drugs/

“A Molecular Link Between the Active Component of Marijuana and Alzheimer’s Disease Pathology” – Free full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562334/

Cannabidiol affects the expression of genes involved in zinc homeostasis in BV-2 microglial cells.

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“Cannabidiol (CBD) has been shown to exhibit anti-inflammatory, antioxidant and neuroprotective properties. Unlike Δ(9)-tetrahydrocannabinol (THC), CBD is devoid of psychotropic effects and has very low affinity for both cannabinoid receptors, CB(1) and CB(2). We have previously reported that CBD and THC have different effects on anti-inflammatory pathways in lipopolysaccharide-stimulated BV-2 microglial cells, in a CB(1)/CB(2) independent manner. Moreover, CBD treatment of BV-2 cells, was found to induce a robust change in the expression of genes related to oxidative stress, glutathione deprivation and inflammation. Many of these genes were shown to be controlled by Nrf2 and ATF4 transcription factors. Using the Illumina MouseRef-8 BeadChip platform, DAVID Bioinformatics and Ingenuity Pathway Analysis, we identified functional sets of genes and networks affected by CBD. A subset of genes was found to be regulated by the metal responsive element (MRE)-binding transcription factor-1 (MTF-1) and is shown to be related to zinc homeostasis. We found that CBD upregulates the expression of the mRNAs for metallothionein 2 (Mt2), N-myc-downstream regulated gene 1 and matrix metalloproteinase 23 as well as of the zinc transporters ZnT1/Slc30a1 and Zip4/Slc39a4 but downregulates the expression of the mRNA for the zinc transporter Zip10/Slc39a10 as well as for the zinc finger protein 472. Among these genes, ZnT1, Mt2 and the zinc transporters ZIPs are known to function together to control the intracellular zinc concentration. These results show that CBD, but much less so THC, affects the expression of genes involved in zinc homeostasis and suggest that the regulation of zinc levels could have an important role through which CBD may exert its antioxidant and anti-inflammatory effects.”

http://www.ncbi.nlm.nih.gov/pubmed/22178458

The Cannabinoid CB2 Receptor as a Target for Inflammation-Dependent Neurodegeneration

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“THE CANNABINOID CB2 RECEPTOR AS A BIORATIONAL TARGET FOR THE TREATMENT OF NEURODEGENERATION. The presence of CB2 receptors in microglia in the human Alzheimer’s diseased brain suggests that CB2 may provide a novel target for a range of neuropathologies.

 The first approved cannabinoid drugs were analogues of Δ9-tetrahydrocannabinol (Δ9-THC). Dronabinol is a natural isomer of THC that is found in the cannabis plant, and Marinol™ contains synthetic dronabinol. Marinol, and another analogue nabilone (Cesamet™ ) are used to prevent nausea and vomiting after treatment with anti-cancer medicines. More recently, GW-100 (Sativex™) which combines nearly equal amounts of Δ9-THC and cannabidiol in a whole plant extract from cultivated cannabis, has been approved in Canada…

We conclude that the administration of CB2 agonists and antagonists may differentially alter microglia-dependent neuroinflammation. CB2 specific compounds have considerable therapeutic appeal over CB1 compounds, as the exclusive expression of CB2 on immune cells within the brain provides a highly specialised target, without the psychoactivity that plagues CB1 directed therapies.

In addition, CB2 activation appears to prevent or decrease microglial activation.

In a rodent model of Alzheimer’s disease microglial activation was completely prevented by administration of a selective CB2 agonist.”

http://www.ncbi.nlm.nih.gov/pubmed/18615177

Marijuana linked to preventing and treating Alzheimer’s disease

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“Alzheimer’s disease is the leading cause of dementia among the elderly, and with the ever-increasing size of this population, cases of Alzheimer’s disease are expected to triple over the next 50 years. Consequently, the development of treatments that slow or halt the disease progression have become imperative to both improve the quality of life for patients as well as reduce the health care costs attributable to Alzheimer’s disease.

Here, we demonstrate that the active component of marijuana, Δ9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid β-peptide (Aβ) aggregation, the key pathological marker of Alzheimer’s disease. Computational modeling of the THC-AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the critical region involved in amyloidgenesis.

Compared to currently approved drugs prescribed for the treatment of Alzheimer’s disease, THC is a considerably superior inhibitor of Aβaggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.”

http://www.agoracosmopolitan.com/news/health/2011/11/26/1936.html

A molecular link between the active component of marijuana and Alzheimer’s disease pathology.

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“A link between the endocannabinoid system and Alzheimer’s disease has been discovered which has provided a new therapeutic target for the treatment of patients suffering from Alzheimer’s disease. These studies have demonstrated the ability of cannabinoids to provide neuroprotection against β-amyloid peptide (Aβ) toxicity.

Here, we demonstrate that the active component of marijuana, Δ9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid β-peptide (Aβ) aggregation, the key pathological marker of Alzheimer’s disease. 

 Compared to currently approved drugs prescribed for the treatment of Alzheimer’s disease, THC is a considerably superior inhibitor of Aβ aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.

Since the characterization of the Cannabis sativa-produced cannabinoid, Δ9-tetrahydrocannabinol (THC), in the 1960’s,1 this natural product has been widely explored as an anti-emetic, anti-convulsive, anti-inflammatory, and analgesic.”

Read more: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562334/

 

Endocannabinoid system: emerging role from neurodevelopment to neurodegeneration.

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“The endocannabinoid system, including endogenous ligands (‘endocannabinoids’ ECs), their receptors, synthesizing and degrading enzymes, as well as transporter molecules, has been detected from the earliest stages of embryonic development and throughout pre- and postnatal development. ECs are bioactive lipids, which comprise amides, esters and ethers of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) are the best studied ECs, and act as agonists of cannabinoid receptors.

Thus, AEA and 2-AG mimic several pharmacological effects of the exogenous cannabinoid delta9-tetrahydrocannabinol (Delta(9)-THC), the psychoactive principle of cannabis sativa preparations like hashish and marijuana. Recently, however, several lines of evidence have suggested that the EC system may play an important role in early neuronal development as well as a widespread role in neurodegeneration disorders. Many of the effects of cannabinoids and ECs are mediated by two G protein-coupled receptors (GPCRs), CB1 and CB2, although additional receptors may be implicated. Both CB1 and CB2 couple primarily to inhibitory G proteins and are subject to the same pharmacological influences as other GPCRs. This new system is briefly presented in this review, in order to put in a better perspective the role of the EC pathway from neurodevelopment to neurodegenerative disorders, like Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis.

In addition, the potential exploitation of antagonists of CB1 receptors, or of inhibitors of EC metabolism, as next-generation therapeutics is discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/19356123