How cannabis compound could slow tumor growth

July 14, 2014

Science Daily/University of East Anglia

Scientists have shown how the main psychoactive ingredient in cannabis, THC, could reduce tumor growth in cancer patients. New research reveals the existence of previously unknown signaling platforms which are responsible for the drug's success in shrinking tumors.

Research published today reveals the existence of previously unknown signaling platforms which are responsible for the drug's success in shrinking tumours.

It is hoped that the findings could help develop a synthetic equivalent with anti-cancer properties.

The research was co-led with the Universidad Complutense de Madridin, Spain. The team used samples of human breast cancer cells to induce tumours in mice. They then targeted the tumours with doses of the cannabis compound THC (Tetrahydrocannabinol). They found that two cell receptors in particular were responsible for the drug's anti-tumour effects.

Dr Peter McCormick, from UEA's school of Pharmacy, said: "THC, the major active component of marijuana, has anti-cancer properties. This compound is known to act through a specific family of cell receptors called cannabinoid receptors. However, it was unclear which of these receptors were responsible for the anti-tumour effects of THC.

"We show that these effects are mediated via the joint interaction of CB2 and GPR55 -- two members of the cannabinoid receptor family. Our findings help explain some of the well-known but still poorly understood effects of THC at low and high doses on tumour growth.

"There has been a great deal of interest in understanding the molecular mechanisms behind how marijuana, and specifically THC, influence cancer pathology.

"There has also been a drive in the pharmaceutical industry to create synthetic equivalents that might have anti-cancer properties.

"By identifying the receptors involved we have provided an important step towards the future development of therapeutics that can take advantage of the interactions we have discovered to reduce tumour growth."

Dr McCormick added that cancer sufferers should not be tempted to self-medicate.

"Our research uses an isolated chemical compound and using the correct concentration is vital. Cancer patients should not use cannabis to self-medicate, but I hope that our research will lead to a safe synthetic equivalent being available in the future."

https://www.sciencedaily.com/releases/2014/07/140714100339.htm

Use of non-psychoactive cannabinoids in the treatment of neurodegenerative diseases

September 19, 2008

Science Daily/Complutense University of Madrid

Scientists at the Complutense University of Madrid (UCM) have studied the effects of a drug that reduces the progression of a disease similar to multiple sclerosis in animals. This discovery represents another step in the standing fight against the disease.

The research, published in the Journal of Biological Chemistry, aimed to study in depth the already known effects of lessening the symptoms and stopping the advance of multiple sclerosis that cannabinoids have, while developing a drug that would not have the psychoactive effects of the marijuana plant (Cannabis sativa). To achieve this, the scientists have focused their study on the role of the cannabinoids receptor CB2, present both in the immune system as well as in the defence-cells of the nervous system (microglial cells).

Multiple sclerosis is a neurodegenerative disease whose causes are not yet fully understood. It is known that the disease is produced by an autoimmune response where the defence-cells in the organism attack and destroy the nerve cells of the organism generating symptoms such as stiffness, twitching, progressive paralysis, etc.

The researchers managed by Professor Ismael Galve from the UCM, founded their conclusions on the role of the cannabinoids receptors in Experimental autoimmune encephalomyelitis, a disease that reproduces some of the processes and symptoms of multiple sclerosis. In the study it has been tested that administering a drug that activates receptor CB2 (but not CB1, responsible for the psychactive effects), the symptoms of the disease lessen and a reduction of 50% in nerve cell loss was perceived.

This research has introduced yet another novelty: The stimulation of the CB2 receptor not only reduces the excessive activation of brain cells in charge of the defence of the central nervous system, but it also reduces the supply of new defence-cells that travelling throughout the blood stream from bone marrow, would act as reinforcements for the defence-cells of the central nervous system.

According to Ismael Galve, the results are important because the drug is capable of acting in an already sick animal, reducing the symptoms and the brain cell loss. The obtained results, along with other predecessors confirm the role of endogenous cannabinoids in the origin of experimental autoimmune encephalomyelitis and its possible application to multiple sclerosis. Therefore the role of the CB2 receptor in the regulation and neuro-immune response supports the research currently being carried out on the possible use of cannabinoid drugs in the treatment of neurodegenerative diseases.

The research has been carried out by the department of biochemistry and molecular biology of the Complutense University of Madrid, in collaboration with the Neuroscience research Institute of Lyon in France and the pharmaceutical company Pharmos.

https://www.sciencedaily.com/releases/2008/09/080916154721.htm

Opioids and Cannabinoids Influence Mobility of Spermatozoids

June 24, 2008

Science Daily/Basque Research

A PhD thesis from the University of the Basque Country has concluded that there are opioid and cannabinoid receptors in human sperm and that these influence the mobility of spermatozoid. The research by Mr Ekaitz Agirregoitia opens the door to more effective treatment of fertility problems.

Freshly released spermatozoids cannot achieve fertilisation, they must undergo some changes for this to occur. Amongst other, such changes take place due to receptors situated in the plasmatic membrane (the layer covering the cells) and opioid and cannabinoid receptors are two of these. On coming into contact with these, physiological reactions are generated in the body which are similar to, for example, sedation, analgesia and low blood pressure. Moreover, according to the research undertaken to date, both substances have an influence on the process of fertilisation.

It is known that the consumption of external opiates (heroin, methadone) reduces the mobility of spermatozoids and that external cannabinoids (hachis) causes changes in the reproductive process. Also, the body itself generates internal opioids and cannabinoids, secreted to enable us withstand pain or stress situations, and it is also known that this phenomenon affects the reproduction process.

Despite all this being previously known, there has been no thorough study of the opioid and cannabinoid receptors in the human sperm such as this one, carried out by Mr Ekaitz Agirregoitia Marcos for his PhD thesis, defended at the Faculty of Medicine and Odontology of the University of the Basque Country (UPV/EHU) and entitled in Basque, Opioide-hartzaileak eta kannabinoide-hartzaileak giza espermatozoideetan espresatzen dira eta haien mugikortasunean eragiten dute (Opioid receptors and cannabinoid receptors are expressed in human spermatozoids and influence their mobility).

The aim was to define this expression and the location of three opioid receptors and two cannabinoid receptors, as well as to analyse the influence of their activity in the mobility of spermatozoids. Mr Agirregoitia has a degree in Biology, specialising in Health Sciences. He is currently working as a substitute lecturer in the Department of Physiology, giving classes in Medical Biophysics and General Physiology. His PhD work was led by Dr. Jon Irazusta Astiazaran from the same Department and was undertaken in collaboration with Dr. Carmen Ochoa of the Euskalduna Clinic and Dr. Manolo Guzmán from the Complutense University in Madrid.

Pinpointing the receptors

This PhD has shown, for the first time, that all the types of opioid and cannabinoid receptors are found in human sperm. To date, only the MU opioid receptor has been found in equine sperm, and the presence in human sperm of the CB1 cannabinoid receptor was only discovered this year. Dr. Agirregoitia has used a number of techniques to find three opioid receptors (DELTA, KAPPA and MU) and two cannabinoid receptors (CB1 and CB2) in the human sperm. According to his research, all these are found at the head, the middle and the tail of the spermatozoids.

How is mobility influenced?

After defining the expression and location of the opioid and cannabinoid receptors, Dr. Agirregoitia initiated an analysis of their influence on the mobility of the spermatozoids. These receptors act like a kind of lock catch mechanism to which the opioids and cannabinoids attach themselves. Some of these substances (agonists) are capable of activating the cells, just like a key opening a lock. Others (antagonists), although fitting perfectly into the “locks”, are not capable of opening them and have the effect of blocking the receptor. Mr Agirregoitia studied both processes, incubating human sperm with agonist and antagonist synthetic substances to this end.

From this PhD thesis, presented at the UPV/EHU, it was concluded that, for the movement of the spermatozoids to be maintained, a minimum number of DELTA receptors must remain active. On the other hand, it is pointed out that the activation of the MU opioid receptor inhibits the mobility of the spermatozoids, i.e. it causes them to slow down. Finally, the PhD concludes that the KAPPA opioid receptor participates in another process which has nothing to do with mobility.

As regards the cannabinoid system, the activation of the CB1 y CB2 receptors causes the percentage of spermatozoids with rapid and progressive mobility to be reduced. Even so, as a consequence of the activation of the CB1 receptor, the number of slow spermatozoids rises, while the activation of CB2 increases the number of spermatozoids with progressive but slow movement.

The most effective diagnoses and treatments

It is known that opiods and cannabinoids regulate the function of reproduction through the central nervous system and, according to this PhD thesis, they are also able to control the process through the receptors located in the spermatozoids themselves. Thus, the type and concentration of internal opioids and cannabinoids found in the spermatozoid on its way to the egg will condition its mobility.

This work opens the door – in the medium to long term – to the diagnosis and treatment of numerous pathologies. For example, an analysis of the components of the system of opioid and cannabinoid receptors would enable us to better understand fertility problems due to currently unknown causes, exhibited by both spermatozoids as well as the female reproductive organ. Also, when designing treatment aimed at fomenting the mobility of spermatozoids, it will enable the prescribing of treatment that activates or inhibits the appropriate receptor in order to benefit the process of fertilisation.

https://www.sciencedaily.com/releases/2008/06/080620115953.htm

Marijuana-like Compounds Suppress the Immune Response

April 26, 2006

Science Daily/American Society for Biochemistry and Molecular Biology

A group of Japanese scientists has discovered that cannabinoids can cause some white blood cells to lose their ability to migrate to the sites of infection and inflammation. These findings, which appear in the May 5 issue of the Journal of Biological Chemistry, could have potential use in the development of novel anti-inflammatory drugs.

The cannabinoids are a group of chemicals that include marijuana. These compounds bind to and activate the body's cannabinoid receptors. There are two types of cannabinoid receptor: the peripheral cannabinoid receptor (CB2) which is predominantly found in immune cells, and the central cannabinoid receptor (CB1) which occurs in the central nervous system.

Recent studies have suggested that CB2 may be involved in a wide range of physiologic phenomena related to immunity, although research on this function is still at an early stage. Among the possible immunological roles for CB2 is an involvement in the initiation of white blood cell migration to sites of infection and inflammation.

In the Journal of Biological Chemistry study, which was featured as a "Paper of the Week", Yumi Tohyama and colleagues used an in vitro model of blood cell migration to study the involvement of CB2 in the recruitment white blood cells. They found that treating the blood cells with compounds that bind to CB2 suppresses the migration of the cells. When they examined the cells, they discovered that they had lost their ability to develop a front/rear polarity, which is something they need to effectively migrate to sites of infection and inflammation.

Because cannabinoids seem to suppress activated white blood cells, Tohyama believes they could have a potential use in the treatment of inflammatory diseases.

The Journal of Biological Chemistry's Papers of the Week is an online feature which highlights the top one percent of papers received by the journal. Brief summaries of the papers and explanations of why they were selected for this honor can be accessed directly from the home page of the Journal of Biological Chemistry online at www.jbc.org.

The American Society for Biochemistry and Molecular Biology (ASBMB) is a nonprofit scientific and educational organization with over 11,000 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions, and industry.

Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's primary purpose is to advance the sciences of biochemistry and molecular biology through its publications, the Journal of Biological Chemistry, the Journal of Lipid Research, Molecular and Cellular Proteomics, and Biochemistry and Molecular Biology Education, and the holding of scientific meetings.

https://www.sciencedaily.com/releases/2006/04/060426174508.htm  

Cannabinoids' Role in Retinal Function Described

December 8, 1999

Science Daily/University of California, San Diego

A team led by scientists from the University of California, San Diego (UCSD) has demonstrated the prevalence of cannabinoid receptors in the retina, indicating an important role for cannabinoids—a family of compounds which includes the psychoactive components of marijuana and hashish—in retinal function and perhaps vision in general.

The UCSD researchers, in collaboration with colleagues from The Neurosciences Institute in San Diego and the University of Washington in Seattle, have described for the first time the specific distribution and effects on retinal function of the cellular receptor proteins activated by cannabinoids.

These findings, published in the December 7 issue of the Proceedings of the National Academy of Sciences (PNAS), may provide a missing link in efforts to unravel the complicated and fascinating machinery by which the retina turns light into meaningful information in the brain. The work also provides greater understanding of the effects of marijuana and hashish, drugs which have been used by man for millennia.

“The retina is incredibly complex, highly sensitive to shifts in light levels, and responsive to contrasts, colors and lines,” said Alex Straiker, principal author of the PNAS paper and a graduate student in UCSD's neuroscience program. “We understand very little about how the retina works. By demonstrating that this receptor system is present, we add another piece to the puzzle, opening one more window into how the eye works. It also suggests that marijuana affects vision because it plugs into an existing signaling system that is abundant in the retina.”

Cannabinoids are naturally occurring compounds in vertebrates, and are known to play an important role in intercellular signaling. The chemical THC found in marijuana is a cannabinoid, though different from the ones produced by the body. Two cannabinoid receptors, CB1 and CB2, were discovered only the last ten years. CB1 exists primarily in the central nervous system, while CB2 is found primarily in the peripheral nervous system.

The PNAS paper reports that the retinal cells of rhesus monkeys, chicks, salamanders, goldfish, mice and rats, all similar in many respects to the human eye, contain high levels of CB1. The researchers also found CB1 receptors localized in both rod and cone photoreceptors, the retinal structures that respond to light, processing colors and black and white images. The extensive and consistent localization of these receptors in the retinas of a variety of species suggests that they play a fundamental role in modulating the transmission of signals critical for visual perception.

“The fact that this system is so highly conserved in species separated by hundreds of millions of years of evolution suggests that it's important,” said Straiker. “Nature likes to tinker, so any time you see something this consistent, it raises eyebrows.” The paper also points to a functional role of cannabinoids in the inhibition of calcium channels involved in visual signaling.

“Two key players in the processing of light information in the retina are photoreceptors, which catch light and turn it into a signal that can be interpreted by other cells, and bipolar cells, which are next in line in the flow of information,” said Straiker. “Communication between the cells requires the release of a neurotransmitter called glutamate, triggered by calcium currents passing through a specific calcium channel. Cannabinoids are known to inhibit calcium channels. If you shut down the channel, you shut down the release of glutamate, and profoundly alter the cell's ability to signal.”

Some of the reported effects of the use of marijuana and hashish include the perception of a snowy visual field, increased light intensity and altered vision. In fact, Straiker said his interest in seeking CB1 receptors in the retina was sparked in part by accounts of dramatic alterations in visual perception following marijuana use.

These findings suggest that at least some of the visual effects of marijuana and hashish use occur at the earliest stage of visual processing, as the calcium channels critical for the normal processing of visual information are inhibited.

Co-authors of the paper are Harvey Karten, professor of neurosciences, and Greg Maguire, formerly assistant adjunct professor of ophthalmology, both of the UCSD School of Medicine; Nephi Stella and Daniele Piomelli, formerly at The Neurosciences Institute, and Ken Mackie of the University of Washington.

The research was supported by the National Institutes of Health, The Glaucoma Foundation, and the Neurosciences Institute, which receives major support from Novartis.

Straiker is a graduate student in the UCSD Graduate Program in Neurosciences, ranked as the premier neuroscience graduate program in the country by a National Research Council survey of the National Academy of Sciences. Straiker is presently continuing his work as a graduate student and researcher in the Molecular Neurobiology Laboratory at The Salk Institute, a participating institution.

https://www.sciencedaily.com/releases/1999/12/991208061213.htm