Cannabinoid Delivery Systems for Pain and Inflammation Treatment.

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“There is a growing body of evidence to suggest that cannabinoids are beneficial for a range of clinical conditions, including pain, inflammation, epilepsy, sleep disorders, the symptoms of multiple sclerosis, anorexia, schizophrenia and other conditions.

The transformation of cannabinoids from herbal preparations into highly regulated prescription drugs is therefore progressing rapidly. The development of such drugs requires well-controlled clinical trials to be carried out in order to objectively establish therapeutic efficacy, dose ranges and safety.

The low oral bioavailability of cannabinoids has led to feasible methods of administration, such as the transdermal route, intranasal administration and transmucosal adsorption, being proposed. The highly lipophilic nature of cannabinoids means that they are seen as suitable candidates for advanced nanosized drug delivery systems, which can be applied via a range of routes.

Nanotechnology-based drug delivery strategies have flourished in several therapeutic fields in recent years and numerous drugs have reached the market. This review explores the most recent developments, from preclinical to advanced clinical trials, in the cannabinoid delivery field, and focuses particularly on pain and inflammation treatment. Likely future directions are also considered and reported.”

https://www.ncbi.nlm.nih.gov/pubmed/30262735

https://www.mdpi.com/1420-3049/23/10/2478

Association of Cannabinoid Administration With Experimental Pain in Healthy Adults A Systematic Review and Meta-analysis

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“Patients have reliably endorsed the belief that cannabis is helpful in alleviating pain.

Cannabinoids (the collective term for all of the drugs examined in this study, including plant-based cannabis, which can contain multiple compounds) have long been considered effective for reducing pain and are frequently proposed as treatment options in pain management.

Cannabinoid drugs may prevent the onset of pain by producing small increases in pain thresholds but may not reduce the intensity of experimental pain already being experienced; instead, cannabinoids may make experimental pain feel less unpleasant and more tolerable, suggesting an influence on affective processes.

Cannabis-induced improvements in pain-related negative affect may underlie the widely held belief that cannabis relieves pain.”

“Cannabinoid drugs make pain feel ‘less unpleasant, more tolerable'”  https://www.sciencedaily.com/releases/2018/09/180919111454.htm

“Medical marijuana increases pain threshold for patients”  https://www.upi.com/Health_News/2018/09/19/Medical-marijuana-increases-pain-threshold-for-patients/1771537292969/?rc_fifo=1

“Study reveals cannabinoid drugs make pain feel ‘less unpleasant, more tolerable'”  https://medicalxpress.com/news/2018-09-reveals-cannabinoid-drugs-pain-unpleasant.html

“Cannabinoid drugs reduce perceived unpleasantness of painful stimuli and increase tolerance” https://www.news-medical.net/news/20180919/Cannabinoid-drugs-reduce-perceived-unpleasantness-of-painful-stimuli-and-increase-tolerance.aspx

“Cannabinoids appear to increase pain tolerability”  https://www.healio.com/psychiatry/practice-management/news/online/%7B7626bb3f-ce35-4968-99bc-50ecdaac79b7%7D/cannabinoids-appear-to-increase-pain-tolerability

Care After Chemotherapy: Peripheral Neuropathy, Cannabis for Symptom Control, and Mindfulness.

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“As cancer therapies improve, patients are living longer. With these improvements in therapy comes a responsibility to optimize patients’ quality of life during cancer therapy and beyond. This report reviews three timely and important topics.

The first section reviews the mechanism underlying chemotherapy-induced peripheral neuropathy and evaluates the evidence for interventions to prevent and treat peripheral neuropathy. It also provides a framework for approaching the diagnosis and management of this common and bothersome side effect.

The second section addresses the controversial but effective use of cannabinoids for cancer and chemotherapy symptoms. Although clinical trials are difficult to conduct because of the political and social stigma of this class of drugs, this review provides evidence of the efficacy of cannabinoids for treatment of pain and nausea.

The last section addresses the mind-body connection, with a focus on the negative emotions patients with cancer often experience. This section assesses the literature regarding mindfulness-based programs to improve cancer-related stress. These three topics may appear unrelated, but all address one common goal: treating the body and the mind to optimize quality of life during and after cancer therapy.”

“Although commercially available dronabinol is not superior to other antiemetics and oromucosal nabiximols is not very effective for treating cancer pain, cannabis has been shown to be effective for treating pain and may help patients reduce opioid intake.”

Cannabinoids and spinal cord stimulation for the treatment of failed back surgery syndrome refractory pain

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“This study aimed to evaluate pain and its symptoms in patients with failed back surgery syndrome (FBSS) refractory to other therapies, treated with a combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in association with spinal cord stimulation (SCS).

Results: Effective pain management as compared to baseline result was achieved in all the cases studied. The positive effect of cannabinoid agonists on refractory pain was maintained during the entire duration of treatment with minimal dosage titration. Pain perception, evaluated through numeric rating scale, decreased from a baseline mean value of 8.18±1.07–4.72±0.9 by the end of the study duration (12 months) (P<0.001).

Conclusion: The results indicate that cannabinoid agonists (THC/CBD) can have remarkable analgesic capabilities, as adjuvant of SCS, for the treatment of chronic refractory pain of FBSS patients.”

https://www.ncbi.nlm.nih.gov/pubmed/30233233

https://www.dovepress.com/cannabinoids-and-spinal-cord-stimulation-for-the-treatment-of-failed-b-peer-reviewed-article-JPR

“Outcomes indicate remarkable analgesic capabilities of cannabinoid agonists (THC/CBD) as an adjuvant to SCS for treating chronic refractory pain in FBSS patients, since all the cases studied achieved effective pain management compared to baseline.”

https://www.mdlinx.com/journal-summaries/cannabinoids-delta-9-tetrahydrocannabinol-thc-cannabidiol/2018/09/13/7544234/

Emerging Evidence for Cannabis’ Role in Opioid Use Disorder.

 Cannabis and Cannabinoid Research cover image “The opioid epidemic has become an immense problem in North America, and despite decades of research on the most effective means to treat opioid use disorder (OUD), overdose deaths are at an all-time high, and relapse remains pervasive.

Although there are a number of FDA-approved opioid replacement therapies and maintenance medications to help ease the severity of opioid withdrawal symptoms and aid in relapse prevention, these medications are not risk free nor are they successful for all patients. Furthermore, there are legal and logistical bottlenecks to obtaining traditional opioid replacement therapies such as methadone or buprenorphine, and the demand for these services far outweighs the supply and access.

To fill the gap between efficacious OUD treatments and the widespread prevalence of misuse, relapse, and overdose, the development of novel, alternative, or adjunct OUD treatment therapies is highly warranted. In this article, we review emerging evidence that suggests that cannabis may play a role in ameliorating the impact of OUD. Herein, we highlight knowledge gaps and discuss cannabis’ potential to prevent opioid misuse (as an analgesic alternative), alleviate opioid withdrawal symptoms, and decrease the likelihood of relapse.

Conclusion: The compelling nature of these data and the relative safety profile of cannabis warrant further exploration of cannabis as an adjunct or alternative treatment for OUD.”

https://www.ncbi.nlm.nih.gov/pubmed/30221197

https://www.liebertpub.com/doi/10.1089/can.2018.0022

Restored Self: A Phenomenological Study of Pain Relief by Cannabis.

Pain Medicine

“OBJECTIVE:

To explore the subjective experience of pain relief by cannabis.

RESULTS:

Three key themes that emerged from the analysis were explored: 1) the Sigh of Relief, describing the corporal sensation of using cannabis, including a sense of relaxation and reduction in pain; 2) the Return to Normality, describing the comprehensive effect of using cannabis, including an increased ability to sleep, focus, and function; and 3) the Side Effects of using cannabis.

CONCLUSIONS:

We propose the term Restored Self to conceptualize the effect of medical cannabis. Restored Self is the experience of regaining one’s sense of self, sense of normality, and sense of control over one’s life.”

Understanding the endocannabinoid system as a modulator of the trigeminal pain response to concussion.

“Post-traumatic headache is the most common symptom of postconcussion syndrome and becomes a chronic neurological disorder in a substantial proportion of patients.

This review provides a brief overview of the epidemiology of postconcussion headache, research models used to study this disorder, as well as the proposed mechanisms.

An objective of this review is to enhance the understanding of how the endogenous cannabinoid system is essential for maintaining the balance of the CNS and regulating inflammation after injury, and in turn making the endocannabinoid system a potential modulator of the trigeminal response to concussion.

The review describes the role of endocannabinoid modulation of pain and the potential for use of phytocannabinoids to treat pain, migraine and concussion.”

https://www.ncbi.nlm.nih.gov/pubmed/30202590

ANTINOCICEPTIVE TOLERANCE TO NSAIDS PARTIALLY MEDIATED VIA ENDOCANNABINOIDS IN ANTERIOR CINGULATE CORTEX OF RATS.

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“Pain is characterized as a complex experience, dependent not only on the regulation of nociceptive sensory systems but also on the activation of mechanisms that control emotional processes in limbic brain areas.

Non-opioid, non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used analgesics in the treatment of not-severe pain. We have recently shown that repeated doses result in tolerance to these drugs like opioids.

Here we investigated the central brain mechanisms of non-opioid induced antinociception in the non-acute pain models of rats, such as the ‘formalin test’ and a relation between administration of NSAIDs in the limbic brain area, – the anterior cingulated cortex (ACC), – and the endocannabinoid system.

The present data support the notion that endocannabinoids’ CB1 receptor contributes in part to antinociceptive effects of NSAIDs and probably involved in activation of the descending opioid modulatory system of pain.”

Role of Endocannabinoid System in the Peripheral Antinociceptive Action of Aripiprazole.

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“Recently, we demonstrated that the antipsychotic dopaminergic and serotoninergic agonist aripiprazole induced peripheral antinociception. However, the mechanism underlying this effect has not been fully established.

Here, our aim was to identify possible relationships between this action of aripiprazole and the endocannabinoid system.

CONCLUSIONS:

These results provide evidence for the involvement of the endocannabinoid system in peripheral antinociception induced by aripiprazole treatment.”

Cannabis analgesia in chronic neuropathic pain is associated with altered brain connectivity.

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“To characterize the functional brain changes involved in δ-9-tetrahydrocannabinol (THC) modulation of chronic neuropathic pain.

RESULTS:

THC significantly reduced patients’ pain compared to placebo. THC-induced analgesia was correlated with a reduction in functional connectivity between the anterior cingulate cortex (ACC) and the sensorimotor cortex. Moreover, the degree of reduction was predictive of the response to THC. Graph theory analyses of local measures demonstrated reduction in network connectivity in areas involved in pain processing, and specifically in the dorsolateral prefrontal cortex (DLPFC), which were correlated with individual pain reduction.

CONCLUSION:

These results suggest that the ACC and DLPFC, 2 major cognitive-emotional modulation areas, and their connections to somatosensory areas, are functionally involved in the analgesic effect of THC in chronic pain. This effect may therefore be mediated through induction of functional disconnection between regulatory high-order affective regions and the sensorimotor cortex. Moreover, baseline functional connectivity between these brain areas may serve as a predictor for the extent of pain relief induced by THC.”

https://www.ncbi.nlm.nih.gov/pubmed/30185448

http://n.neurology.org/content/early/2018/09/05/WNL.0000000000006293