Use of medical cannabis to reduce pain and improve quality of life in cancer patients.

Journal of Clinical Oncology

“Early attention to pain and symptoms in those with cancer improves both quality of life and survival. Opioid medications are the mainstay treatment of cancer-related pain.

Cannabinoids are increasingly used as adjunctive treatments for cancer pain, but clinical evidence supporting their use as an “opioid sparing agent” or to improve quality of life is as yet unknown.

Our study sought to determine if the addition of cannabinoids (medical cannabis) resulted in the reduction of the average opioid dose required for pain control, and improve self-reported quality of life indices.

Patients with cancer pain benefited from the addition of cannabinoids.

The average opioid dose decreased following access to medical cannabis.

Self-reported ratings of several quality of life indicators showed statistically significant improvement.

Our study shows a signal that cannabinoids may reduce cancer patients’ reliance on opioids to control pain.

Further prospective controlled studies are needed to further elucidate the role of cannabinoids in the treatment of cancer pain.”

https://www.ncbi.nlm.nih.gov/pubmed/28148191

Cannabis Roots: A Traditional Therapy with Future Potential for Treating Inflammation and Pain

Image result for cannabis and cannabinoid research

“The cannabis plant is known for its multiple uses: the leaves, flowers, seeds, stalks, and resin glands have all been exploited for food, fuel, fiber, medicine, and other uses.

The roots of the cannabis plant have a long history of medical use stretching back millennia. However, the therapeutic potential of cannabis roots has been largely ignored in modern times.

In the first century, Pliny the Elder described in Natural Histories that a decoction of the root in water could be used to relieve stiffness in the joints, gout, and related conditions. By the 17th century, various herbalists were recommending cannabis root to treat inflammation, joint pain, gout, and other conditions.

Active compounds identified and measured in cannabis roots include triterpenoids, friedelin (12.8 mg/kg) and epifriedelanol (21.3 mg/kg); alkaloids, cannabisativine (2.5 mg/kg) and anhydrocannabisativine (0.3 mg/kg); carvone and dihydrocarvone; N-( p-hydroxy-b-phenylethyl)-p-hydroxy-trans-cinnamamide (1.6 mg/kg); various sterols such as sitosterol (1.5%), campesterol (0.78%), and stigmasterol (0.56%); and other minor compounds, including choline. Of note, cannabis roots are not a significant source of D9 – tetrahydrocannabinol (THC), cannabidiol, or other known phytocannabinoids.

Conclusion: The current available data on the pharmacology of cannabis root components provide significant support to the historical and ethnobotanical claims of clinical efficacy. Certainly, this suggests the need for reexamination of whole root preparations on inflammatory and malignant conditions employing modern scientific techniques.”

http://online.liebertpub.com/doi/full/10.1089/can.2017.0028

Perioperative Patient Beliefs Regarding Potential Effectiveness of Marijuana (Cannabinoids) for Treatment of Pain: A Prospective Population Survey.

logo

“Cannabinoids have an expanding presence in medicine.

Perioperative patients’ perceptions of the effectiveness of these compounds, and acceptance if prescribed for pain, have not been previously described. Our primary objective was to describe patients’ beliefs regarding the potential effectiveness of cannabinoids for the treatment of acute and chronic pain, as well as gauge patient acceptance of these compounds if prescribed by a physician.

More than 80% of this cohort of preoperative patients believed that marijuana could be at least somewhat effective for the treatment of pain after surgery and would be willing to use cannabinoid compounds if prescribed by their physician.

Patients generally believe that marijuana could be at least somewhat effective for the management of pain and are willing to use cannabinoid compounds for this indication, if prescribed by a physician.”

Cannabinoid system of dorsomedial telencephalon modulates behavioral responses to noxious stimulation in the fish Leporinus macrocephalus.

Physiology & Behavior

“Fish dorsomedial telencephalon has been considered a pallial region homologous to mammals amygdala, being considered a possible substrate for nociception modulation in this animal group. The present study aimed to evaluate the participation of the cannabinoid system of Dm telencephalon on nociception modulation in the fish Leporinus macrocephalus. We demonstrated that cannabidiol microinjection in Dm telecephalon inhibits the behavioral nociceptive response to the subcutaneous injection of 3% formaldehyde, and this antinociception is blocked by previous treatment with AM251 microinjection. Furthermore, AM251 microinjection in Dm prior to restraint stress also blockades the stress-induced antinociception. These results reinforce the hypothesis that this pallial telencephalic structure has a pivotal role in nociception modulation in fish.”

https://www.ncbi.nlm.nih.gov/pubmed/28754268

http://www.sciencedirect.com/science/article/pii/S0031938417302299?via%3Dihub

Effects of Centrally Administered Endocannabinoids and Opioids on Orofacial Pain Perception in Rats.

British Journal of Pharmacology

“Endocannabinoids and opioids play a vital role in mediating pain-induced analgesia.

The specific effects of these compounds within orofacial region are largely unknown. In this study we tried to determine whether the increase of cannabinoid and opioid concentration in cerebrospinal fluid affects impulse transmission between the motor centers localized in the vicinity of the third and fourth cerebral ventricles.

We demonstrated that in the orofacial area analgesic activity is modulated by AEA and that EM-2-induced antinociception was mediated by MOR and CB1 receptors. The action of AEA and EM-2 is tightly regulated by FAAH and FAAH/MAGL, by preventing the breakdown of endogenous cannabinoids in regions where they are produced on demand.

Therefore, the current findings support the therapeutic potential of FAAH and FAAH/MAGL inhibitors as novel pharmacotherapeutic agents for orofacial pain.”

https://www.ncbi.nlm.nih.gov/pubmed/28771697

http://onlinelibrary.wiley.com/doi/10.1111/bph.13970/abstract

Single oral dose of cannabinoid derivate loaded PLGA nanocarriers relieves neuropathic pain for eleven days.

Nanomedicine Home

“Neuropathic pain, resistant to opiates and other drugs, is a chronic/persistent state with a complex treatment and often poor efficacy. In this scenario, cannabinoids are increasingly regarded as a genuine alternative. In this paper, and in an experimental animal model of neuropathic pain, we studied the efficacy of three kinds of PLGA nanoparticles containing synthetic cannabinoid CB13: (i) plain nanoparticles (PLGA); (ii) particles coated with PEG chains (PLGA+PEG) and (iii) particles possessing hydrophilic surfaces obtained by covalently binding PEG chains (PLGA-PEG). The optimized formulation, CB13-PLGA-PEG, showed high drug loading (13%) and small size (<300nm) with a narrow distribution and controlled surface properties (near-neutral zeta potential and stable PEG corona). Animal nociceptive behavioral studies were conducted by paw pressure and acetone tests. Versus the free CB13, CB13-PLGA-PEG nanoparticles showed a very noticeable analgesic efficacy with the longest sustained pain-relieving effect, lasting up to eleven days after one oral dose.”

https://www.ncbi.nlm.nih.gov/pubmed/28756090

http://www.nanomedjournal.com/article/S1549-9634(17)30140-5/fulltext

Endocannabinoid Transport Proteins: Discovery of Tools to Study Sterol Carrier Protein-2.

Elsevier

“The endocannabinoid (eCB) neurotransmitter system regulates diverse neurological functions including stress and anxiety, pain, mood, and reward. Understanding the mechanisms underlying eCB regulation is critical for developing targeted pharmacotherapies to treat these and other neurologic disorders.

Cellular studies suggest that the arachidonate eCBs, N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), are substrates for intracellular binding and transport proteins, and several candidate proteins have been identified. Initial evidence from our laboratory indicates that the lipid transport protein, sterol carrier protein 2 (SCP-2), binds to the eCBs and can regulate their cellular concentrations.

Here, we present methods for evaluating SCP-2 binding of eCBs and their application to the discovery of the first inhibitor lead molecules. Using a fluorescent probe displacement assay, we found SCP-2 binds the eCBs, AEA (Ki=0.68±0.05μM) and 2-AG (Ki=0.37±0.02μM), with moderate affinity. A series of structurally diverse arachidonate analogues also bind SCP-2 with Ki values between 0.82 and 2.95μM, suggesting a high degree of tolerance for arachidonic acid head group modifications in this region of the protein. We also report initial structure-activity relationships surrounding previously reported inhibitors of Aedis aegypti SCP-2, and the results of an in silico high-throughput screen that identified structurally novel SCP-2 inhibitor leads.

The methods and results reported here provide the basis for a robust probe discovery effort to fully elucidate the role of facilitated transport mediated by SCP-2 in eCB regulation and function.”

https://www.ncbi.nlm.nih.gov/pubmed/28750817

http://www.sciencedirect.com/science/article/pii/S007668791730174X?via%3Dihub

 

Endocannabinoids Have Opposing Effects On Behavioral Responses To Nociceptive And Non-nociceptive Stimuli.

“The endocannabinoid system is thought to modulate nociceptive signaling making it a potential therapeutic target for treating pain.

However, there is evidence that endocannabinoids have both pro- and anti-nociceptive effects. In previous studies using Hirudo verbana (the medicinal leech), endocannabinoids were found to depress nociceptive synapses, but enhance non-nociceptive synapses. Here we examined whether endocannabinoids have similar bidirectional effects on behavioral responses to nociceptive vs. non-nociceptive stimuli in vivo.

These results provide evidence that endocannabinoids can have opposing effects on nociceptive vs. non-nociceptive pathways and suggest that cannabinoid-based therapies may be more appropriate for treating pain disorders in which hyperalgesia and not allodynia is the primary symptom.”

Delta-9-tetrahydrocannabinol decreases masticatory muscle sensitization in female rats through peripheral cannabinoid receptor activation.

European Journal of Pain

“This study investigated whether intramuscular injection of delta-9-tetrahydrocannabinol (THC), by acting on peripheral cannabinoid (CB) receptors, could decrease nerve growth factor (NGF)-induced sensitization in female rat masseter muscle; a model which mimics the symptoms of myofascial temporomandibular disorders.

It was found that CB1 and CB2 receptors are expressed by trigeminal ganglion neurons that innervate the masseter muscle and also on their peripheral endings.

These results suggest that reduced inhibitory input from the peripheral cannabinoid system may contribute to NGF-induced local myofascial sensitization of mechanoreceptors. Peripheral application of THC may counter this effect by activating the CB1 receptors on masseter muscle mechanoreceptors to provide analgesic relief without central side effects.

SIGNIFICANCE:

Our results suggest THC could reduce masticatory muscle pain through activating peripheral CB1 receptors. Peripheral application of cannabinoids could be a novel approach to provide analgesic relief without central side effects.”

https://www.ncbi.nlm.nih.gov/pubmed/28722246

http://onlinelibrary.wiley.com/doi/10.1002/ejp.1085/abstract

Antinociceptive effects of HUF-101, a fluorinated cannabidiol derivative.

Cover image

“Cannabidiol (CBD) is a phytocannabinoid with multiple pharmacological effects and several potential therapeutic properties. Its low oral bioavailability, however, can limit its clinical use.

Preliminary results indicate that fluorination of the CBD molecule increases its pharmacological potency. Here, we investigated whether HUF-101 (3, 10, and 30mg/kg), a fluorinated CBD analogue, would induce antinociceptive effects.

These findings show that HUF-101 produced antinociceptive effects at lower doses than CBD, indicating that the addition of fluoride improved its pharmacological profile. Furthermore, some of the antinociceptive effects of CBD and HUF-101 effects seem to involve the activation of CB1 and CB2 receptors.”

https://www.ncbi.nlm.nih.gov/pubmed/28720466

http://www.sciencedirect.com/science/article/pii/S0278584617302233