Synthetic Compounds From Marijuana Appear to Fight HIV

“Synthetic anti-inflammatory compounds derived from the active ingredient of marijuana appear to show potential as anti-HIV agents, Wired.co.uk reports. Publishing their findings in the Journal of Leukocyte Biology, researchers from Temple University School of Medicine’s Department of Pathology and Laboratory Medicine and Center for Substance Abuse Research (CSAR) studied synthetic derivations of THC, or tetrahydrocannabinol, a key chemical compound in marijuana, in cultures of HIV-infected cells.

Cannabinoids, which are the primary active compounds in marijuana, bind to proteins called CB2 receptors on the surface of macrophage immune cells. The CB2 site may play a role in reducing inflammation in the central nervous system, which is a major concern for people living with HIV, even those whose virus is fully suppressed thanks to antiretrovirals (ARVs). It is the CB1 receptors, mostly found in neurons in the brain, however, that cause marijuana’s psychoactive effects. So synthetic THC that has been developed to bind only to CB2 receptors should not make people stoned.

It is believed that macrophage cells, which are found throughout the body, are a major component of the HIV reservoir and are probably the first cells infected after sexual transmission of the virus.

Using a non-clinical cell model, the investigators treated HIV-infected macrophages with one of three different synthetic compounds that bind to CB2. By periodically measuring the activity of the enzyme reverse transcriptase, which HIV needs to replicate itself, the investigators concluded after a seven-day period that all three compounds fought HIV replication.

The findings suggest that these “CB2 agonists” could be a potential addition to ARV therapy, and also that the human immune system could be prompted to fight the virus using similar mechanisms.”

http://www.aidsmeds.com/articles/pot_CB2_1667_23905.shtml

Compounds That Stimulate The Cannabinoid Type 2 Receptor In White Blood Cells Can Weaken HIV-1 Infection – MedicalNewsToday

“A new use for compounds related in composition to the active ingredient in marijuana may be on the horizon: a new research report published in the Journal of Leukocyte Biology shows that compounds that stimulate the cannabinoid type 2 (CB2) receptor in white blood cells, specifically macrophages, appear to weaken HIV-1 infection. The CB2 receptor is the molecular link through which the pharmaceutical properties of cannabis are manifested. Diminishing HIV-1 infection in this manner might make current anti-viral therapies more effective and provide some protection against certain HIV-1 complications.”

More:  http://www.medicalnewstoday.com/releases/259885.php

Synthetic derivatives of THC may weaken HIV-1 infection to enhance antiviral therapies – MedicalXpress

“A new use for compounds related in composition to the active ingredient in marijuana may be on the horizon: a new research report published in the Journal of Leukocyte Biology shows that compounds that stimulate the cannabinoid type 2 (CB2) receptor in white blood cells, specifically macrophages, appear to weaken HIV-1 infection. The CB2 receptor is the molecular link through which the pharmaceutical properties of cannabis are manifested. Diminishing HIV-1 infection in this manner might make current anti-viral therapies more effective and provide some protection against certain HIV-1 complications.

“The synthetic compounds we used in our study may show promise in helping the body fight HIV-1 infection,'” said Yuri Persidsky, M.D., Ph.D., a researcher involved in the work from the Department of Pathology and Laboratory Medicine at Temple University School of Medicine in Philadelphia, PA. “As compounds like these are improved further and made widely available, we will continue to explore their potential to fight other viral diseases that are notoriously difficult to treat.”

To make this discovery, scientists used a cell culture model to infect human macrophages with HIV-1 and added synthetic compounds similar to the active ingredient in marijuana to activate the CB2 receptor. At different times during the infection, samples from the culture were taken to see if the replication of the HIV virus was decreased. The researchers observed diminished HIV growth and a possible protective effect from some HIV-1 complications.

“HIV/AIDS has posed one of the most significant health challenges in modern medicine,” said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. “Recent high profile vaccine failures mean that all options need to be on the table to prevent or treat this devastating infection. Research on the role of cannabinoid type 2 receptors and viral infection may one day allow targeting these receptors to be part of combination therapies that use exploit multiple weaknesses of the virus simultaneously.””

http://medicalxpress.com/news/2013-04-synthetic-derivatives-thc-weaken-hiv-.html

Scientists weaken HIV infection in immune cells using synthetic agents – MedicalXpress

“HIV, the virus that causes AIDS, is notorious for hiding within certain types of cells, where it reproduces at a slowed rate and eventually gives rise to chronic inflammation, despite drug therapy. But researchers at Temple University School of Medicine’s Department of Pathology and Laboratory Medicine and Center for Substance Abuse Research (CSAR) recently discovered that synthetic anti-inflammatory substances distantly related to the active ingredient of marijuana may be able to take the punch out of HIV while inside one of its major hideouts – immune cells known as macrophages.

The results suggest that selective CB2 agonists could potentially be used in tandem with existing antiretroviral drugs, opening the door to the generation of new drug therapies for HIV/AIDS. The data also support the idea that the human immune system could be leveraged to fight HIV infection.

“Our study suggests that the body’s own natural defenses can be made more powerful to fight some of the worst symptoms of HIV,” Persidsky explained. He also noted that stimulating CB2 receptors in white blood cells could produce similar benefits against other viral infections.

 The most promising compounds are those derived from THC (tetrahydrocannabinol), the main active substance in cannabis.”

More: http://medicalxpress.com/news/2013-05-scientists-weaken-hiv-infection-immune.html

Activation of Cortical Type 2 Cannabinoid Receptors Ameliorates Ischemic Brain Injury, Study Suggests

“A new study published in the March issue of The American Journal of Pathology suggests that cortical type 2 cannabinoid (CB2) receptors might serve as potential therapeutic targets for cerebral ischemia.

Researchers found that the cannabinoid trans-caryophyllene (TC) protected brain cells from the effects of ischemia in both in vivo and in vitro animal models. In rats, post-ischemic treatment with TC decreased cerebral infarct size and edema. In cell cultures composed of rat cortical neurons and glia exposed to oxygen-glucose deprivation and reoxygenation (OGD/R), TC decreased neuronal injury and mitochondrial depolarization, specifically through type 2 cannabinoid receptor (CB2R) pathways.

“To our knowledge, novel data presented in this study provide evidence for the first time supporting a previously unappreciated role of cortical CB2R, especially neuronal CB2Rs, in ischemia,” says lead investigator Won-Ki Kim, PhD, of the Department of Neuroscience, College of Medicine, Korea University in Seoul. “This study suggests that further investigation is warranted to establish the clinical usefulness of TC as a preventative and therapeutic agent for treatment of stroke.””

More: http://www.sciencedaily.com/releases/2013/02/130221141140.htm

Marijuana Derivative May Offer Hope in Cocaine Addiction – TIME

“A new study in mice has found that activating a receptor affected by marijuana can dramatically reduce cocaine consumption. The research suggests that new anti-addiction drugs might be developed using synthetic versions of cannabidiol (CBD), the marijuana component that activates the receptor—or even by using the purified natural compound itself.

Researchers formerly believed that the receptor, known as CB2, was not found in the brain and that therefore CBD had no psychoactive effects. But a growing body of research suggests otherwise. After THC, CBD is the second most prevalent active compound in marijuana.”

More: http://healthland.time.com/2011/07/26/marijuana-derivative-may-offer-hope-in-cocaine-addiction/

[From cannabis to selective CB2R agonists: molecules with numerous therapeutical virtues].

“Originally used in Asia for the treatment of pain, spasms, nausea and insomnia, marijuana is the most consumed psychotropic drug worldwide. The interest of medical cannabis has been reconsidered recently, leading to many scientific researches and commercialization of these drugs.

Natural and synthetic cannabinoids display beneficial antiemetic, anti-inflammatory and analgesic effects in numerous diseases, however accompanied with undesirable effects due to the CB1 receptor. Present researches focus on the design of therapeutical molecules targeting the CB2 receptors, and thus avoiding central side effects and therefore psychotropic effects caused by the CB1 receptor.”

http://www.ncbi.nlm.nih.gov/pubmed/23732102

Synthetic and Patented Cannabinoids

“Historically, laboratory synthesis of cannabinoids were often based on the structure of herbal cannabinoids, and a large number of analogs have been produced and tested, especially in a group led by Roger Adams as early as 1941 and later in a group led by Raphael Mechoulam.

Newer compounds are no longer related to natural cannabinoids or are based on the structure of the endogenous cannabinoids.

Synthetic cannabinoids are particularly useful in experiments to determine the relationship between the structure and activity of cannabinoid compounds, by making systematic, incremental modifications of cannabinoid molecules.

Medications containing natural or synthetic cannabinoids or cannabinoid analogs:

  • Dronabinol (Marinol), is Δ9-tetrahydrocannabinol (THC), used as an appetite stimulant, anti-emetic, and analgesic
  • Nabilone (Cesamet), a synthetic cannabinoid and an analog of Marinol. It is Schedule II unlike Marinol, which is Schedule III
  • Sativex, a cannabinoid extract oral spray containing THC, CBD, and other cannabinoids used for neuropathic pain and spasticity in Canada and Spain. Sativex develops whole-plant cannabinoid medicines
  • Rimonabant (SR141716), a selective cannabinoid (CB1) receptor antagonist used as an anti-obesity drug under the proprietary name Acomplia. It is also used for smoking cessation

Other notable synthetic cannabinoids include:

  • CP-55940, produced in 1974, this synthetic cannabinoid receptor agonist is many times more potent than THC
  • Dimethylheptylpyran
  • HU-210, about 100 times as potent as THC
  • HU-331 a potential anti-cancer drug derived from cannabidiol that specifically inhibits topoisomerase II.
  • SR144528, a CB2 receptor antagonists
  • WIN 55, a potent cannabinoid receptor agonist
  • JWH-133, a potent selective CB2 receptor agonist
  • Levonantradol (Nantrodolum), an anti-emetic and analgesic but not currently in use in medicine”

http://www.news-medical.net/health/Synthetic-and-Patented-Cannabinoids.aspx

Cannabinoid Receptors

“Before the 1980s, it was often speculated that cannabinoids produced their physiological and behavioral effects via nonspecific interaction with cell membranes, instead of interacting with specific membrane-bound receptors.

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate.

These receptors are common in animals, and have been found in mammals, birds, fish, and reptiles.

At present, there are two known types of cannabinoid receptors, termed CB1 and CB2, with mounting evidence of more.

Cannabinoid receptor type 1

CB1 receptors are found primarily in the brain, to be specific in the basal ganglia and in the limbic system, including the hippocampus.

They are also found in the cerebellum and in both male and female reproductive systems. CB1 receptors are absent in the medulla oblongata, the part of the brain stem responsible for respiratory and cardiovascular functions. Thus, there is not a risk of respiratory or cardiovascular failure as there is with many other drugs. CB1 receptors appear to be responsible for the euphoric and anticonvulsive effects of cannabis.

Cannabinoid receptor type 2

CB2 receptors are almost exclusively found in the immune system, with the greatest density in the spleen.

While found only in the peripheral nervous system, a report does indicate that CB2 is expressed by a subpopulation of microglia in the human cerebellum.

CB2 receptors appear to be responsible for the anti-inflammatory and possibly other therapeutic effects of cannabis.”

http://www.news-medical.net/health/Cannabinoid-Receptors.aspx

Dysregulation of Cannabinoid CB1 Receptor and Associated Signaling Networks in Brains of Cocaine Addicts and Cocaine-Treated Rodents.

The endocannabinoid system is implicated in the neurobiology of cocaine addiction. This study evaluated the status of cannabinoid CB1 and CB2 receptors, the endocytic cycle of CB1 receptors, receptor regulatory kinases (GRK), and associated signaling (mTOR and p70S6K) in brain cortex of drug abusers and cocaine- and cannabinoid-treated rodents…

 In long-term cocaine addicts, mTOR and p70S6K activations were not altered when compared with controls, indicating that CB1 receptor signaling was dampened. The dysregulation of CB1 receptor, GRK2/3/5, and mTOR/p70S6K signaling by cocaine may contribute to alterations of neuroplasticity and/or neurotoxicity in brains of cocaine addicts.”

More: http://www.ncbi.nlm.nih.gov/pubmed/23727505