Cannabis: Non-addictive pathway to pain relief?

Medicinal properties of cannabis examined

January 12, 2017

Science Daily/Oregon Health & Science University

OHSU research suggests an avenue for developing treatments for chronic pain that harness the medicinal properties of cannabis while minimizing the threat of addiction.

The study, conducted in a rodent model, provides additional rationale for the development of therapeutics using cannabinoid receptors to treat chronic pain, which afflicts about 30 percent of the U.S. population. OHSU investigators studied the function of two forms of cell membrane receptors that bind cannabinoids that occur naturally within the body, called endocannabinoids.

"It may be an avenue where we can get better pain medications that are not addictive," said senior author Susan Ingram, Ph.D., an associate professor of neurosurgery in the OHSU School of Medicine.

Ingram and colleagues report the treatment of chronic pain has challenged the medical system, with medications that are ineffective or create serious side effects: "However, emerging data indicate that drugs that target the endocannabinoid system might produce analgesia with fewer side effects compared with opioids."

The body's endocannabinoid system comprises receptors, endocannabinoid molecules and enzymes that make and degrade the endocannabinoids located in the brain and throughout the central and peripheral nervous system. The research team focused on two cannabinoid receptors, known as CB1 and CB2, in the rostral ventromedial medulla -- a group of neurons located in the brainstem known to modulate pain. The study is the first to examine CB1 and CB2 receptor function at the membrane level in late adolescent and adult neurons.

The researchers observed that chronic inflammatory pain increased activity of CB2 receptors and decreased CB1 activity. Cannabis activates both CB1 and CB2 receptors equally. The study suggests that selective activation of CB2 receptors contributes to the medicinal benefit of cannabis while minimizing the propensity of the other cannabinoid receptor, CB1, to induce tolerance and withdrawal. Ingram said the next phase of the research will further explore this area of brain circuitry, which ultimately could lead to the development of a new class of pain medications.

Co-authors include lead author Ming-Hua Li, Ph.D., and Katherine L. Suchland, both with the Department of Neurological Surgery, OHSU School of Medicine.

The study was funded by grants from the National Institutes of Health (DA035316 and R56NS093894) and American Heart Association (13SDG14590005, MH.L.).

https://www.sciencedaily.com/releases/2017/01/170112130145.htm

Pain relief without the high

January 4, 2017

Science Daily/Leiden, Universiteit

Researchers at Leiden University led by Mario van der Stelt (Leiden Institute for Chemistry) have set ‘gold standards’ for developing new painkillers based on the medicinal effects of cannabis.

Medicinal marijuana

Medicinal marijuana is in frequent use as a painkiller, but its psycho-active side-effects are a major disadvantage. The pharmaceutical industry is desperately seeking a synthetic form of cannabis that inhibits inflammation and pain, but without the high. Leiden researchers have now brought the development of such drugs a step closer. In an article in Nature Communications they set out 'gold standards' for the use of reference substances, to improve trials with synthetic cannabis.

Many of the clinical trials carried out to date with with synthetic cannabis have failed, with no measurable effect being recorded in patients. One of the causes of these failures can be found in the pre-clinical lab, during testing with animals. Substances are often used in these tests whose biochemical and molecular-pharmaceutical effects have never been properly characterised. As a result, there have been a lot of contradictory publications on research findings, the results of which cannot be reproduced. This is having a major effect on the allocation of research funding, the use of animal testing and the exposure of patients to non-active substances.

International and public-private collaboration

Marjolein Soethoudt, a PhD candidate in Van der Stelt's research group, studied together with 12 international academic groups, the National Institute of Health (US) and pharmaceuticals concern Hoffman-LaRoche (Switzerland), the 18 most commonly used reference substances, including the psychoactive ingredient in marijuana, Δ9-THC. They carried out their studies under standardised conditions in 36 different tests, to analyse the molecular pharmacological characteristics of the substances. They hoped to be able to identify the most suitable reference sustances for the research on synthetic cannabis. The research led to three 'gold standards' that should make it possible to give an impetus to the development of new painkillers and anti-inflammatories.

Cannabinoid CB2 receptor

Δ9-THC binds to two types of proteins in the human body: the cannabinoid CB1 receptor in the brain and the cannabinoid CB2 receptor in the immune system. Activating the CB1 receptor in the brain makes you high, while activating the CB2 receptor has an anti-inflammatory effect. The three 'gold standards' are molecules that are highly selective in activating only the CB2 receptor and ignoring the CB1 receptor. These three gold standards also appeared to cause the fewest side-effects, nor did they give the mice a high. Earlier studies have shown that these substances do have an analgesic and anti-inflammatory effect. The researchers advise that these three gold standards should be used in future in research on new medicines that rely on the activation of the cannabinoid CB2 receptor for their effectiveness.

Neuroscientists discover previously unknown function of cannabinoid receptor

Study could improve our insights into brain diseases

May 2, 2016

Science Daily/DZNE - German Center for Neurodegenerative Diseases

In the brain, there is a delicate interplay of signaling substances and cellular activity. Scientists have now identified another key player within this ensemble. In a laboratory study they found that the 'cannabinoid type 2 receptor' influences information processing inside the hippocampus. The research results might help advance our understanding of schizophrenia and Alzheimer's, say the authors.

The cannabinoid type 2 receptor -- also called "CB2 receptor" -- is a special membrane protein. Its function is to receive chemical signals that control cellular activity. "Until now, this receptor was considered part of the immune system without function in nerve cells. However, our study shows that it also plays an important role in the signal processing of the brain," explains Professor Dietmar Schmitz, Speaker for the DZNE-Site Berlin and Director of the Neuroscience Research Center of the Charité (NWFZ/NeuroCure). Schmitz coordinated the current study, which involved Berlin colleagues and also scientists from the University of Bonn and from the "National Institute on Drug Abuse" of the US.

As the researchers demonstrated in an animal model, the CB2 receptor raises the excitation threshold of nerve cells in the hippocampus. "Operation of the brain critically depends on the fact that nerve impulses sometimes have an exciting impact on downstream cells and in other cases they have a suppressing effect," says Dr Vanessa Stempel, lead author of the current publication, who is now doing research in Cambridge, UK. "The CB2 receptor works like a set screw by which such communication processes can be adjusted."

Component of the "endocannabinoid system"

The CB2 receptor is part of the endocannabinoid system (ECS). This family of receptors and signaling substances exists in many organisms including humans. It is a biochemical control system which is involved in the regulation of numerous physiological processes. Its name refers to the fact that chemicals derived from the cannabis plant bind to receptors of the ECS. So far, there are two known types of these receptors: The CB2 receptor has no psychoactive effect. Hence, the mind-altering effects triggered by the consumption of cannabis are ascribed to the "cannabinoid type 1 receptor."

Potential therapeutic applications

The results of the current study could contribute to a better understanding of disease mechanisms and provide a starting point for novel medications. "Brain activity is disturbed in schizophrenia, depression, Alzheimer's disease and other neuropsychiatric disorders. Pharmaceuticals that bind to the CB2 receptor could possibly influence the activity of brain cells and thus become part of a therapy," Professor Schmitz concludes.

https://www.sciencedaily.com/releases/2016/05/160502111228.htm