Cannabinoid Receptor 2-Mediated Attenuation of CXCR4-Tropic HIV Infection in Primary CD4+ T Cells

Posted on by

“Agents that activate cannabinoid receptor pathways have been tested as treatments for cachexia, nausea or neuropathic pain in HIV-1/AIDS patients… Cannabinoid agonists activate the CB1R and CB2R cannabinoid receptors…

Cannabinoid agonists are currently under investigation for the treatment of AIDS-associated cachexia, nausea, and neuropathic pain. One such drug, dronabinol (Δ9-THC; Marinol®), has won Food and Drug Administration (FDA) approval for treatment of HIV-associated anorexia. Additionally, the prescription of smoked or ingested cannabis (marijuana) for treatment of AIDS-related symptoms has been approved…. Despite the use of cannabinoids by HIV/AIDS patients, few studies have investigated the impact of such drugs in regard to viral pathogenesis or immune regulation…

….Indeed, both smoked marijuana and dronabinol were reported to increase total CD4+ T cell number and naïve T cell number over a 21-day period. A decrease in viral load was also observed in these patients. Similarly, in SIV infected rhesus macaques, Δ9-THC exposure reduced viral load and CD4+ T cell depletion, significantly increasing animal survival over an 11 month period.

. Our findings suggest that CB2R activation in CD4+ T cells can inhibit actin reorganization and impair productive infection following cell-free or cell-associated viral acquisition of CXCR4-tropic HIV-1 in resting cells.

Therefore, the clinical use of CB2R agonists in the treatment of AIDS symptoms may also exert beneficial adjunctive antiviral effects against CXCR4-tropic viruses in late stages of HIV-1 infection.

Further study of cannabinoids and other neuroendocrine regulators that selectively modulate immune function may result in the discovery of new anti-viral drugs that can also mitigate AIDS-associated symptoms.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309010/

Cannabinoid Inhibition of Macrophage Migration to the Trans-Activating (Tat) Protein of HIV-1 Is Linked to the CB2 Cannabinoid Receptor

Posted on by

“Macrophage-like cells are primary targets for infection by HIV-1…  In the present study, the exogenous cannabinoids δ-9-tetrahydrocannabinol (THC) and (−)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol (CP55940) were shown to significantly inhibit migration of human U937 macrophage-like cells to the Tat protein in a concentration-related manner….

Collectively, the pharmacological and biochemical knockdown data indicate that cannabinoid-mediated modulation of macrophage migration to the HIV-1 Tat protein is linked to the CB2 cannabinoid receptor. Furthermore, these results suggest that the CB2 cannabinoid receptor has potential to serve as a therapeutic target for ablation of HIV-1-associated untoward inflammatory response…

,,, the CB2 receptor has the potential to serve as a molecular target for ablating hyperinflammatory responses of macrophage-like cells while avoiding untoward psychotropic effects caused by activation of the CB1 receptor.

 In conclusion, the immunosuppressive and anti-inflammatory properties of select cannabinoids may have profound therapeutic potential in moderating HIV-associated immunopathology, including microglial activation, chemokine/cytokine dysregulation, and monocyte infiltration in the CNS.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846023/

Attenuation of HIV-1 replication in macrophages by cannabinoid receptor 2 agonists.

Posted on by

“Previous studies showed that activation of the CB2 can attenuate inflammatory responses and affect HIV-1 infectivity in T cells and microglia. Here, we report that CB2 agonists can also act as immunomodulators on HIV-1-infected macrophages.

   We speculate that these findings indicate that prevention of viral entry is not a central mechanism for CB2-mediated suppression in viral replication.

However, CB2 may affect the HIV-1 replication machinery.

Results from a single-round infection with the pseudotyped virus revealed a marked decrease in HIV-1 LTR activation by the CB2 ligands.

Together, these results indicate that CB2 may offer a means to limit HIV-1 infection in macrophages.”

http://www.ncbi.nlm.nih.gov/pubmed/23463725

Cannabinoids may be therapeutic in breast cancer.

Posted on by

“Cannabinoids are a group of compounds synthesized exclusively by the Cannabis sativa plant, commonly known as marijuana. In 1990, the first cannabinoid-specific membrane (CB1) was characterized and cloned (Matsuda, Lolait, Brownstein, Young, & Bonner, 1990), which catapulted biomedical research on these unique compounds.

 Cannabinoids refer to both marijuana-derived compounds with the active ingredient of 9-tetrahydrocannabinol (THC) and also the synthetic molecules that activate the same primary targets as THC.

Therapeutic properties of marijuana have been well established; however, the clinical use of either plant-sourced or pure cannabinoids remains limited.

The anticachexia properties of cannabinoids are found in tetrahydrocannabinol (oral capsules of synthetically generated THC) and are used to manage weight loss, wasting syndrome, and nausea and vomiting associated with cancer treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/23448745

Medical Marijuana: Sleeping Medicine

Posted on by

“The most frequent comment by those ignorant of the medical properties of cannabis or those believing the U.S. Government’s propaganda, is that marijuana patients use it only to get “high” which incidentally can be somewhat like a Starbucks espresso jolt or maybe two or three martinis.

Anybody who knows anything at all about marijuana knows that it causes euphoria or a feeling of well being. After all, isn’t that why we take medicine when we are sick—to feel better?

At any rate, marijuana users, as medical patients of which there are at least 400,000 with legal permits, or as many as ten million “illegal” users who use it instead of alcohol, tobacco, prescription tranquilizers or antidepressants, have found it beneficial for a wide variety of illnesses and diseases.

It is certain that the euphoria or feeling of comfort is very important for all these conditions. If some ignorant people consider that to be getting high, no users will disagree.

Many medical patients use it only in the evening to enable them to sleep. This is true especially with those in chronic pain, which represents about 70 percent of patients. Pain frequently or even most usually prevents sleep and some patients tell me, “if I can get a decent night’s sleep, I can fight alligators all day”.

Sleeping pills are prescribed mostly for those in pain who cannot sleep without those pills. The crazy thing about this is that many or maybe most sleeping pills are as addicting as heroin. Valium, the most prescribed sleeping pill for many years, produced millions of addicts, and there are many valium-like drugs with similar problems.

In my experience with 4,000 plus patients, I was told by hundreds that by using marijuana they were able to cut down or eliminate completely most prescription sleeping pills.

The U.S. Government purports that marijuana is addicting. This is not so. If a person uses it frequently to relieve or control pain, the patient wants relief. Does that mean he is addicted to relief? If one takes aspirin everyday, is he addicted to aspirin? To me, the comparison is valid.

One of the critical signs of addiction is uncomfortable withdrawal symptoms. Most marijuana users will run out of their medicine once in a while. Do they get withdrawal symptoms? If so, they are very minor, like running out of aspirin.

It is known that very heavy marijuana use (which is uncommon because it costs more than gold) can cause mild withdrawal symptoms, such as disrupted sleep and nervousness (from Merck Manual).

I think the final coup de grace is also given by the Merck Manual “any drug which causes euphoria and diminishes anxiety can cause dependence” (not addiction—my comment).”-

Dr. Phillip Leveque

http://www.salem-news.com/articles/june272007/marijuana_sleep_62707.php

Cannabis for better sleep

Posted on by

“The use of both natural cannabinoids and cannabis extracts are associated with improved sleep in patients with various debilitating illnesses, according to a review of clinical trial data published in the journal Chemistry & Biodiversity.

“Cannabis … has been utilized for [the] treatment of pain and sleep disorders since ancient times,” authors wrote. “Modern clinical trials indicate that patients administered cannabis extracts report experiencing “more restful sleep, [an] increase [in] their daytime level of function, and [a] markedly improve[d] … quality of life.”

According to available data, of the 2,000 subjects that have been administered cannabis extracts in clinical trials, most “demonstrate marked improvement in subjective sleep parameters.”

Trial volunteers have not reported developing tolerance to the drug, even after using it for several years.

Full text of the study, “Cannabis, pain, and sleep: Lessons from therapeutic clinical trials of Sativex, a cannabis-based medicine,” appears in the journal Chemistry & Biodiversity.”

http://azarius.net/news/193/Cannabis_for_better_sleep/

Cannabis ‘helped woman to sleep’

Posted on by

“A YOUNG mother using cannabis to help her sleep has been given the benefit of the probation act at Wexford District Court.

Shelly Donnelly, Moortown Great, Ballmitty, had pleaded guilty to the possession of cannabis at her home on June 11, 2010.

Judge Donnchadh O Buachalla heard that the property at Moortown Great was searched and a small quantity of cannabis herb was found. It was for Donnelly’s own use.

Eva Lalor, for Donnelly, said her client is 24years-old and has a fiveyear-old daughter with her long-term partner.

Ms Lalor said Donnelly was suffering from insomnia following a family bereavement and was using cannabis to help her sleep. Donnelly, who has no previous convictions, is now on medication to help her sleep.

Judge O Buachalla gave her the benefit of the probation act, saying that he hopes she has learnt her lesson from the experience.”

http://www.independent.ie/regionals/wexfordpeople/news/cannabis-helped-woman-to-sleep-27726026.html

Stab victim started taking cannabis to sleep

Posted on by

A YOUNG man started smoking cannabis herb to help him sleep after he was stabbed through the heart and lungs, a court heard. Francis Kelly (23) spent two weeks in intensive care, and started taking the drug after he came out of hospital….

He was in intensive care for two weeks and was on tablets while he was in hospital.

Mr O’Doherty said that Kelly couldn’t sleep when he left hospital and he started taking it to help him relax.”

More: http://www.herald.ie/news/stab-victim-started-taking-cannabis-to-sleep-27997127.html

Cannabis helped night worker sleep

Posted on by
Mark Jackson has escaped without having a conviction recorded for his latest drug offences. 
“
Mark Jackson has escaped without having a conviction recorded for his latest drug offences.

HOSPITALITY manager Mark Jackson has been fined for possessing marijuana, which he smoked after night work to help him get some sleep.

Jackson has a history of drug use dating back to 2000, when the Supreme Court gave him a suspended jail sentence for supplying drugs.

However, his last drug-related offence was in 2005.

Jackson, a 48-year-old who supports four dependents, pleaded guilty in Mackay Magistrate’s Court yesterday to the unlawful possession of a small amount of marijuana and a pipe last October 20.

Police executed a search warrant at his Andergrove home at 12.45am and Jackson was the sole occupant, prosecutor Constable Janelle Young said.

Asked if he had anything to declare, he said he had a bong beside his bed.

A homemade pipe and a small amount of marijuana were found.

He told police he had smoked some marijuana that morning, after night work, because it helped him to sleep.

The items were seized and he was issued with a property receipt.

Duty lawyer John Aberdeen said Jackson “holds a managerial position in hospitality” and did mostly night work.

His previous convictions in 2000 and 2005 were acknowledged but the new offences involved only a small amount of drugs for personal use, Mr Aberdeen said.

Mr Aberdeen asked for no conviction to be recorded because of the length of time that had elapsed since the last offence.

Magistrate Damien Dwyer imposed a fine of $600 and ordered that no conviction be recorded.”

http://www.dailymercury.com.au/news/marijuana-helped-night-worker-get-some-sleep/1228013/

Smoking Cannabis Reduces Pain, Helps Sleep And Improves Mood For Those With Chronic Symptoms

Posted on by

“For patients with chronic (long-term) neuropathic pain, smoking cannabis was found to reduce symptoms of pain, improve mood and help sleep, a report published in CMAJ (Canadian Medical Journal Association) revealed. When damage or dysfunction of the nervous system results in chronic neuropathic pain, patients have few treatment options, such as antidepressants, local anesthetics, anticonvulsants or opioids. However, these medications often have undesirable side effects and do not work for everybody.

The authors inform that oral cannabinoids have been effective in reducing the symptoms of some types of pain. However, they many have different effects and risks compared to smoked cannabis.

Investigators from McGill University Health Centre (MUHC) and McGill University carried out a randomized, controlled trial to determine the analgesic effect of smoked cannabis in 21 patients, aged 18 years or more, all of them with chronic neuropathic pain. THC levels (drug potencies) were divided into 2.5%, 6% and 9.4%. Some participants also received a placebo (0%).

The researchers inform that there was a correlation between increased THC content and better sleep quality. Symptoms of depression and/or anxiety were also reduced at 9.5% THC level.”

More: http://www.medicalnewstoday.com/articles/199376.php