Microinjection of orexin-A into the rat locus coeruleus nucleus induces analgesia via cannabinoid type-1 receptors.

Posted on August 10, 2015 by David

“Locus coeruleus (LC) nucleus is involved in noradrenergic descending pain modulation.

LC receives dense orexinergic projections from the lateral hypothalamus. Orexin-A and -B are hypothalamic peptides which modulate a variety of brain functions via orexin type-1 (OX1) and orexin type-2 (OX2) receptors.

Previous studies have shown that activation of OX1 receptors induces endocannabinoid synthesis and alters synaptic neurotransmission by retrograde signaling via affecting cannabinoid type-1 (CB1) receptors.

In the present study the interaction of orexin-A and endocannabinoids was examined at the LC level in a rat model of inflammatory pain…

This data show that, activation of OX1 receptors in the LC can induce analgesia and also the blockade of OX1 or CB1 receptors is associated with hyperalgesia during formalin test.

Our findings also suggest that CB1 receptors may modulate the analgesic effect of orexin-A.

These results outline a new mechanism by which orexin-A modulates the nociceptive processing in the LC nucleus.”

http://www.ncbi.nlm.nih.gov/pubmed/26254729

Therapeutic potential of cannabis-related drugs.

Posted on July 29, 2015 by David

“In this review, I will consider the dual nature of Cannabis and cannabinoids.

The duality arises from the potential and actuality of cannabinoids in the laboratory and clinic and the ‘abuse’ of Cannabis outside the clinic.

The therapeutic areas currently best associated with exploitation of Cannabis-related medicines include pain, epilepsy, feeding disorders, multiple sclerosis and glaucoma.

As with every other medicinal drug of course, the ‘trick’ will be to maximise the benefit and minimise the cost.

After millennia of proximity and exploitation of the Cannabis plant, we are still playing catch up with an understanding of its potential influence for medicinal benefit.”

http://www.ncbi.nlm.nih.gov/pubmed/26216862

Cross-tolerance to cannabinoids in morphine-tolerant rhesus monkeys.

Posted on July 24, 2015 by David

“Opioids remain the drugs of choice for treating moderate to severe pain, although adverse effects limit their use. Therapeutic utility might be improved by combining opioids with other drugs to enhance analgesic effects, but only if adverse effects are not similarly changed.

Cannabinoids have been shown to enhance the antinociceptive potency of opioids without increasing other effects; this study examined whether the effectiveness of cannabinoids is altered in morphine-dependent monkeys.

Tolerance developed to the antinociceptive effects of morphine and cross-tolerance developed to cannabinoids under conditions that produced modest physical dependence.

Compared with the doses examined in this study, much smaller doses of opioids have antinociceptive effects when given with cannabinoids; it is possible that tolerance will not develop to chronic treatment with opioid/cannabinoid mixtures.”

http://www.ncbi.nlm.nih.gov/pubmed/26202613

Endocannabinoid 2-arachidonylglycerol protects primary cultured neurons against LPS-induced impairments in rat caudate nucleus.

Posted on July 17, 2015 by David

“Inflammation plays a pivotal role in the pathogenesis of many diseases in the central nervous system.

Caudate nucleus (CN), the largest nucleus in the brain, is also implicated in many neurological disorders.

2-Arachidonoylglycerol (2-AG), the most abundant endogenous cannabinoid and the true natural ligand for CB1 receptors, has been shown to exhibit neuroprotective effects through its anti-inflammatory action from proinflammatory stimuli in hippocampus.

In the present study, we discovered that 2-AG significantly protects CN neurons in culture against lipopolysaccharide (LPS)-induced inflammatory response.

Our study suggests the therapeutic potential of 2-AG for the treatment of some inflammation-induced neurological disorders and pain.”

http://www.ncbi.nlm.nih.gov/pubmed/24510751

Selective Reduction of THC’s Unwanted Effects through Serotonin Receptor Inhibition

Posted on July 15, 2015 by David

“While recreational marijuana users may seek the full range of its effects, broad medical use of THC—including for pain, nausea, and anxiety—is hindered by them.

In a new study, Xavier Viñals, Estefania Moreno, Peter McCormick, Rafael Maldonado, Patricia Robledo, and colleagues demonstrate that the cognitive effects of THC are triggered by a pathway separate from some of its other effects.

That pathway involves both a cannabinoid receptor and a serotonin receptor, and when this pathway is blocked, THC can still exert several beneficial effects, including analgesia, while avoiding impairment of memory.

The results of this study are potentially highly important, in that they identify a way to reduce some of what are usually thought of as THC’s unwanted side effects when used for medicinal purposes while maintaining several important benefits, including pain relief.

The widening acceptance of a role for THC in medicine may be accelerated by the option to reduce those side effects by selective pharmacological disruption or blocking of the heteromer.”

http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002193

Signaling Mechanism of Cannabinoid Receptor-2 Activation-Induced β-Endorphin Release.

Posted on June 26, 2015 by David

“Activation of cannabinoid receptor-2 (CB2) results in β-endorphin release from keratinocytes, which then acts on primary afferent neurons to inhibit nociception.

Our data also suggest that stimulation of MAPK contributes to the peripheral analgesic effect of CB2 receptor agonists.”

http://www.ncbi.nlm.nih.gov/pubmed/26108183

Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems: A Clinical Review.

Posted on June 24, 2015 by David

“Use of marijuana for chronic pain, neuropathic pain, and spasticity due to multiple sclerosis is supported by high-quality evidence.

Several of these trials had positive results, suggesting that marijuana or cannabinoids may be efficacious for these indications.

CONCLUSIONS AND RELEVANCE:

Medical marijuana is used to treat a host of indications, a few of which have evidence to support treatment with marijuana and many that do not. Physicians should educate patients about medical marijuana to ensure that it is used appropriately and that patients will benefit from its use.”

http://www.ncbi.nlm.nih.gov/pubmed/26103031

Cannabinoids for Medical Use: A Systematic Review and Meta-analysis.

Posted on June 24, 2015 by David

“Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear.

To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids.

There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome.

Cannabinoids were associated with an increased risk of short-term AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination.”

http://www.ncbi.nlm.nih.gov/pubmed/26103030

http://jama.jamanetwork.com/article.aspx?articleid=2338251

Emerging targets in treating pain.

Posted on June 19, 2015 by David

“Chronic pain poses an enormous socioeconomic burden for the more than 30% of people who suffer from it, costing over $600 billion per year in the USA. In recent years, there has been a surge in preclinical and clinical research endeavors to try to stem this epidemic. Preclinical studies have identified a wide array of potential targets, with some of the most promising translational research being performed on novel opioid receptors, cannabinoid receptors, selective ion channel blockers, cytokine inhibitors, nerve growth factor inhibitors, N-methyl-D-aspartate receptor antagonists, glial cell inhibitors, and bisphosphonates.

SUMMARY:

There are many obstacles for the development of effective medications to treat chronic pain, including the inherent challenges in identifying pathophysiological mechanisms, the overlap and multiplicity of pain pathways, and off-target adverse effects stemming from the ubiquity of drug target receptor sites and the lack of highly selective receptor ligands. Despite these barriers, the number and diversity of potential therapies have continued to grow, to include disease-modifying and individualized drug treatments.”

http://www.ncbi.nlm.nih.gov/pubmed/26087270

http://www.thctotalhealthcare.com/category/pain-2/

Is cannabis use associated with less opioid use among people who inject drugs?

Posted on June 9, 2015 by David

“Clinical, experimental, and ethnographic research suggests that cannabis may be used to help manage pain.

Ethnographic research has revealed that some people are using cannabis to temper their illicit opioid use. We seek to learn if there is an association between cannabis use and the frequency of nonmedical opioid use among people who inject drugs (PWID).

…people who used cannabis used opioids less often than those who did not use cannabis…

There is a statistical association between recent cannabis use and lower frequency of nonmedical opioid use among PWID.

This may suggest that PWID use cannabis to reduce their pain and/or nonmedical use of opioids.”

http://www.ncbi.nlm.nih.gov/pubmed/26051162