Tag Archives: Cannabinoids

The cannabinoid system and pain.

Posted on by
Reply

Cover image

“Chronic pain states are highly prevalent and yet poorly controlled by currently available analgesics, representing an enormous clinical, societal, and economic burden. Existing pain medications have significant limitations and adverse effects including tolerance, dependence, gastrointestinal dysfunction, cognitive impairment, and a narrow therapeutic window, making the search for novel analgesics ever more important. In this article, we review the role of an important endogenous pain control system, the endocannabinoid (EC) system, in the sensory, emotional, and cognitive aspects of pain. Herein, we briefly cover the discovery of the EC system and its role in pain processing pathways, before concentrating on three areas of current major interest in EC pain research; 1. Pharmacological enhancement of endocannabinoid activity (via blockade of EC metabolism or allosteric modulation of CB1receptors); 2. The EC System and stress-induced modulation of pain; and 3. The EC system & medial prefrontal cortex (mPFC) dysfunction in pain states. Whilst we focus predominantly on the preclinical data, we also include extensive discussion of recent clinical failures of endocannabinoid-related therapies, the future potential of these approaches, and important directions for future research on the EC system and pain.”

https://www.ncbi.nlm.nih.gov/pubmed/28625720

http://www.sciencedirect.com/science/article/pii/S002839081730285X

Synaptic functions of endocannabinoid signaling in health and disease.

Posted on by
Reply

Cover image

“Endocannabinoids (eCBs) are a family of lipid molecules that act as key regulators of synaptic transmission and plasticity. They are synthetized “on demand” following physiological and/or pathological stimuli. Once released from postsynaptic neurons, eCBs typically act as retrograde messengers to activate presynaptic type 1 cannabinoid receptors (CB1) and induce short- or long-term depression of neurotransmitter release. Besides this canonical mechanism of action, recent findings have revealed a number of less conventional mechanisms by which eCBs regulate neural activity and synaptic function, suggesting that eCB-mediated plasticity is mechanistically more diverse than anticipated. These mechanisms include non-retrograde signaling, signaling via astrocytes, participation in long-term potentiation, and the involvement of mitochondrial CB1. Focusing on paradigmatic brain areas, such as hippocampus, striatum, and neocortex, we review typical and novel signaling mechanisms, and discuss the functional implications in normal brain function and brain diseases. In summary, eCB signaling may lead to different forms of synaptic plasticity through activation of a plethora of mechanisms, which provide further complexity to the functional consequences of eCB signaling.”

https://www.ncbi.nlm.nih.gov/pubmed/28625718

http://www.sciencedirect.com/science/article/pii/S0028390817302861

Assessing the role of serotonergic receptors in cannabidiol’s anticonvulsant efficacy.

Posted on by
Reply

“Cannabidiol (CBD) is a phytocannabinoid that has demonstrated anticonvulsant efficacy in several animal models of seizure. The current experiment validated CBD’s anticonvulsant effect using the acute pentylenetetrazol (PTZ) model.

While this work further confirms the anticonvulsant efficacy of CBD and supports its application in the treatment of human seizure disorders, additional research on CBD’s mechanism of action must be conducted.”

https://www.ncbi.nlm.nih.gov/pubmed/28624721

http://www.epilepsybehavior.com/article/S1525-5050(17)30122-1/fulltext

Metabolism of the Endocannabinoid Anandamide: Open Questions after 25 Years.

Posted on by
Reply

Image result for frontiers in molecular neuroscience

“Cannabis extracts have been used for centuries, but its main active principle ∆9-tetrahydrocannabinol (THC) was identified about 50 years ago. Yet, it is only 25 years ago that the first endogenous ligand of the same receptors engaged by the cannabis agents was discovered. This “endocannabinoid (eCB)” was identified as N-arachidonoylethanolamine (or anandamide (AEA)), and was shown to have several receptors, metabolic enzymes and transporters that altogether drive its biological activity. Here I report on the latest advances about AEA metabolism, with the aim of focusing open questions still awaiting an answer for a deeper understanding of AEA activity, and for translating AEA-based drugs into novel therapeutics for human diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/28611591

http://journal.frontiersin.org/article/10.3389/fnmol.2017.00166/full

Endocannabinoid System in Neurodegenerative Disorders.

Posted on by
Reply

Journal of Neurochemistry

“Most neurodegenerative disorders (NDDs) are characterized by cognitive impairment and other neurological defects. The definite cause of and pathways underlying the progression of these NDDs are not well defined. Several mechanisms have been proposed to contribute to the development of NDDs. These mechanisms may proceed concurrently or successively, and they differ among cell types at different developmental stages in distinct brain regions. The endocannabinoid system, which involves cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), endogenous cannabinoids and the enzymes that catabolize these compounds, has been shown to contribute to the development of NDDs in several animal models and human studies. In this review, we discuss the functions of the endocannabinoid (EC) system in NDDs and converse the therapeutic efficacy of targeting the endocannabinoid system to rescue NDDs.”

https://www.ncbi.nlm.nih.gov/pubmed/28608560

http://onlinelibrary.wiley.com/doi/10.1111/jnc.14098/abstract

Medicinal Uses of Marijuana and Cannabinoids

Posted on by
Reply

Publication Cover

“In the past two decades, there has been increasing interest in the therapeutic potential of cannabis and single cannabinoids, mainly cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC). THC and cannabis products rich in THC exert their effects mainly through the activation of cannabinoid receptors (CB1 and CB2). Since 1975, 140 controlled clinical trials using different cannabinoids or whole-plant preparations for the treatment of a large number of disorders and symptoms have been conducted. Results have led to the approval of cannabis-based medicines [dronabinol, nabilone, and the cannabis extract nabiximols (Sativex®, THC:CBD = 1:1)] as well as cannabis flowers in several countries. Controlled clinical studies provide substantial evidence for the use of cannabinoid receptor agonists in cancer chemotherapy induced nausea and vomiting, appetite loss and cachexia in cancer and HIV patients, neuropathic and chronic pain, and in spasticity in multiple sclerosis. In addition, there is also some evidence suggesting a therapeutic potential of cannabis-based medicines in other indications including Tourette syndrome, spinal cord injury, Crohn’s disease, irritable bowel syndrome, and glaucoma. In several other indications, small uncontrolled and single-case studies reporting beneficial effects are available, for example in posttraumatic stress disorder, attention deficit hyperactivity disorder, and migraine. The most common side effects of THC and cannabis-based medicines rich in THC are sedation and dizziness (in more than 10% of patients), psychological effects, and dry mouth. Tolerance to these side effects nearly always develops within a short time. Withdrawal symptoms are hardly ever a problem in the therapeutic setting. In recent years there is an increasing interest in the medical use of CBD, which exerts no intoxicating side effects and is usually well-tolerated. Preliminary data suggest promising effects in the treatment of anxiety disorders, schizophrenia, dystonia, and some forms of epilepsy. This review gives an overview on clinical studies which have been published over the past 40 years.”

http://www.tandfonline.com/doi/abs/10.1080/07352689.2016.1265360?needAccess=true&journalCode=bpts20

“Review Identifies 140 Controlled Clinical Trials Related to Cannabis”  http://blog.norml.org/2017/06/04/review-identifies-140-controlled-clinical-trials-related-to-cannabis/

Analysis of Natural Product Regulation of Cannabinoid Receptors in the treatment of Human Disease.

Posted on by
Reply

Cover image

“The organized tightly regulated signaling relays engaged by the cannabinoid receptors (CBs) and their ligands, G proteins and other effectors, together constitute the endocannabinoid system (ECS). This system governs many biological functions including cell proliferation, regulation of ion transport and neuronal messaging. This review will firstly examine the physiology of the ECS, briefly discussing some anomalies in the relay of the ECS signaling as these are consequently linked to maladies of global concern including neurological disorders, cardiovascular disease and cancer.

While endogenous ligands are crucial for dispatching messages through the ECS, there are also commonalities in binding affinities with copious exogenous ligands, both natural and synthetic. Therefore, this review provides a comparative analysis of both types of exogenous ligands with emphasis on natural products given their putative safer efficacy and the role of Δ9-tetrahydrocannabinol (Δ9-THC) in uncovering the ECS.

Efficacy is congruent to both types of compounds but noteworthy is the effect of a combination therapy to achieve efficacy without the unideal side-effects. An example is Sativex that displayed promise in treating Huntington’s disease (HD) in preclinical models allowing for its transition to current clinical investigation. Despite the in vitro and preclinical efficacy of Δ9-THC to treat neurodegenerative ailments, its psychotropic effects limit its clinical applicability to treating feeding disorders.

We therefore propose further investigation of other compounds and their combinations such as the triterpene, α,β-amyrin that exhibited greater binding affinity to CB1 than CB2 and was more potent than Δ9-THC and the N-alkylamides that exhibited CB2 selective affinity, the latter can be explored towards peripherally exclusive ECS modulation. The synthetic CB1 antagonist, Rimonabant was pulled from market for the treatment of diabetes, however its analogue SR144528 maybe an ideal lead molecule towards this end and HU-210 and Org27569 are also promising synthetic small molecules.”

https://www.ncbi.nlm.nih.gov/pubmed/28583800

http://www.sciencedirect.com/science/article/pii/S0163725817301511

Problematic Use of Prescription Opioids and Medicinal Cannabis Among Patients Suffering from Chronic Pain

Posted on by
Reply

 

409715“To assess prevalence rates and correlates of problematic use of prescription opioids and medicinal cannabis (MC) among patients receiving treatment for chronic pain.

Problematic use of opioids is common among chronic pain patients treated with prescription opioids and is more prevalent than problematic use of cannabis among those receiving MC.”

https://academic.oup.com/painmedicine/article-abstract/18/2/294/2924709/Problematic-Use-of-Prescription-Opioids-and?redirectedFrom=fulltext

The Analgesic Potential of Cannabinoids

Posted on by
Reply

 

Image result for Journal of Opioid Management

“Cannabinoids are derivatives of Cannabis sativa, the hemp plant, which evolved in the temperate regions of Central Asia. Cannabis was used as a medicine in ancient China (2700 BC) and India (1000 BC). Historically and anecdotally cannabinoids have been used as analgesic agents.

In recent years, there has been an escalating interest in developing cannabis-derived medications to treat severe pain. This review provides an overview of the history of cannabis use in medicine, cannabinoid signaling pathways, and current data from preclinical as well as clinical studies on using cannabinoids as potential analgesic agents. Clinical and experimental studies show that cannabis-derived compounds act as anti-emetic, appetite modulating and analgesic agents.

Since opioids are the only therapy for severe pain, analgesic ability of cannabinoids may provide a much-needed alternative to opioids. Moreover, cannabinoids act synergistically with opioids and act as opioid sparing agents, allowing lower doses and fewer side effects from chronic opioid therapy. Thus, rational use of cannabis based medications deserves serious consideration to alleviate the suffering of patients due to severe pain.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728280/

Study shows non-hallucinogenic cannabinoids are effective anti-cancer drugs

Posted on by
Reply

Related image

“New research has shown that the non-hallucinogenic components of cannabis could act as effective anti-cancer agents. The anti-cancer properties of tetrahydrocannabinol (THC), the primary hallucinogenic component of cannabis, has been recognised for many years, but research into similar cannabis-derived compounds, known as cannabinoids, has been limited.

The study was carried out by a team at St George’s, University of London. It has been published in the journal Anticancer Research. The team, led by Dr Wai Liu and colleagues carried out laboratory investigations using a number of cannabinoids, either alone or in combination with each other, to measure their anti-cancer actions in relation to leukaemia.

Of six cannabinoids studied, each demonstrated anti-cancer properties as effective as those seen in THC. Importantly, they had an increased effect on cancer cells when combined with each other.

Dr Liu said: “This study is a critical step in unpicking the mysteries of cannabis as a source of medicine. The cannabinoids examined have minimal, if any, hallucinogenic side effects, and their properties as anti-cancer agents are promising.

“These agents are able to interfere with the development of cancerous cells, stopping them in their tracks and preventing them from growing. In some cases, by using specific dosage patterns, they can destroy cancer cells on their own.

“Used in combination with existing treatment, we could discover some highly effective strategies for tackling cancer. Significantly, these compounds are inexpensive to produce and making better use of their unique properties could result in much more cost effective anti-cancer drugs in future.”

The study examined two forms of cannabidiol (CBD), two forms of cannabigerol (CBG) and two forms of cannabigevarin (CBGV). These represent the most common cannabinoids found in the cannabis plant apart from THC.” https://www.sgul.ac.uk/alumni/magazine/study-shows-non-hallucinogenic-cannabinoids-are-effective-anti-cancer-drugs

“Enhancing the Activity of Cannabidiol and Other Cannabinoids In Vitro Through Modifications to Drug Combinations and Treatment Schedules”  http://ar.iiarjournals.org/content/33/10/4373.abstract

“Non-hallucinogenic cannabinoids are effective anti-cancer drugs” https://www.sciencedaily.com/releases/2013/10/131014094105.htm

“Cannabinoids used in sequence with chemotherapy are a more effective treatment for cancer. New research has confirmed that cannabinoids – the active chemicals in cannabis – are effective in killing leukaemia cells, particularly when used in combination with chemotherapy treatments.” https://www.sgul.ac.uk/news/news-archive/cannabinoids-used-in-sequence-with-chemotherapy-are-a-more-effective-treatment-for-cancer
 
“Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration.” https://www.ncbi.nlm.nih.gov/pubmed/28560402