Cannabis for Chronic Pain: Challenges and Considerations.

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy banner

“The National Academies of Sciences, Engineering, and Medicine has found substantial evidence that cannabis (plant) is effective for the treatment of chronic pain in adults, and moderate evidence that oromucosal cannabinoids (extracts, especially nabiximols) improve short-term sleep disturbances in chronic pain. ”

https://www.ncbi.nlm.nih.gov/pubmed/29637590

https://onlinelibrary.wiley.com/doi/abs/10.1002/phar.2115

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Cannabis and joints: scientific evidence for the alleviation of osteoarthritis pain by cannabinoids.

 

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“Cannabis has been used for millennia to treat a multitude of medical conditions including chronic pain.

Osteoarthritis (OA) pain is one of the most common types of pain and patients often turn to medical cannabis to manage their symptoms.

While the majority of these reports are anecdotal, there is a growing body of scientific evidence which supports the analgesic potential of cannabinoids to treat OA pain.

OA pain manifests as a combination of inflammatory, nociceptive, and neuropathic pain, each requiring modality-specific analgesics. The body’s innate endocannabinoid system (ECS) has been shown to ameliorate all of these pain subtypes.

This review summarizes the components of the ECS and details the latest research pertaining to plant-based and man-made cannabinoids for the treatment of OA pain. Recent pre-clinical evidence supporting a role for the ECS to control OA pain is described as well as current clinical evidence of the efficacy of cannabinoids for treating OA pain in mixed patient populations.

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The Role of Cannabis Legalization in the Opioid Crisis

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“The United States remains gripped by the opioid crisis. Each day, 90 Americans die from opioid overdoses. Owing to the incredible reach of the opioid crisis—it has affected people of every race, sex, and age across our country—many stakeholders are trying to combat the crisis using multipronged approaches emphasizing prevention, treatment, and law enforcement.

In this issue of JAMA Internal Medicine, Bradford et al and Wen and Hockenberry report results suggesting that cannabis legalization may play a beneficial role in the opioid crisis.”

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2676997

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Association of Medical and Adult-Use Marijuana Laws With Opioid Prescribing for Medicaid Enrollees

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“In this population-based, cross-sectional study using the all-capture Medicaid prescription data for 2011 to 2016, medical marijuana laws and adult-use marijuana laws were associated with lower opioid prescribing rates (5.88% and 6.38% lower, respectively).

Medical and adult-use marijuana laws have the potential to lower opioid prescribing for Medicaid enrollees, a high-risk population for chronic pain, opioid use disorder, and opioid overdose, and marijuana liberalization may serve as a component of a comprehensive package to tackle the opioid epidemic.

These findings suggest that medical and adult-use marijuana laws have the potential to reduce opioid prescribing for Medicaid enrollees, a segment of population with disproportionately high risk for chronic pain, opioid use disorder, and opioid overdose.

Marijuana is one of the potential nonopioid alternatives that can relieve pain at a relatively lower risk of addiction and virtually no risk of overdose.”

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2677000

“Medicare, Medicaid Opioid Scripts Decline in Medical Marijuana States”  https://www.medpagetoday.com/neurology/opioids/72105

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Association Between US State Medical Cannabis Laws and Opioid Prescribing in the Medicare Part D Population

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“In this study, we investigated whether medical cannabis access was associated with prescription opioid prescribing in Medicare Part D. We found that overall opioid prescribing in Part D was lower when states permit access to medical cannabis. When examining data by individual drug classes, we found that prescriptions for hydrocodone and morphine had statistically significant negative associations with medical cannabis access via dispensaries; while not statistically significant, there were also negative associations between dispensary MCLs and fentanyl and “other opioid” use. Combined with previously published studies suggesting cannabis laws are associated with lower opioid mortality, these findings further strengthen arguments in favor of considering medical applications of cannabis as one tool in the policy arsenal that can be used to diminish the harm of prescription opioids.”

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2676999

“Rise of medical marijuana eases abuse of opioids, study says”   https://www.ajc.com/news/rise-medical-marijuana-eases-abuse-opioids-study-says/uyXDks4G81MMIsrmq2mkeL/

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Chronic Pain Treatment With Cannabidiol in Kidney Transplant Patients in Uruguay.

Transplantation Proceedings Home

“Chronic pain is a major therapeutic problem in kidney transplant patients owing to nephrotoxicity associated with nonsteroidal antiiflammatory drugs.

Benefits in chronic pain treatment with cannabidiol (CBD) have been reported.

This study assesses the effect, safety, and possible drug interactions in kidney transplant patients treated with CBD for chronic pain.

RESULTS:

We assessed 7 patients with a mean age of 64.5 years (range, 58-75 years). CBD initial dose was 100 mg/d, CBD dose reduction to 50 mg/d has been done on day 4 to patient 1 for persistent nausea. Tacrolimus dose reduction in patient 3 was undertaken on days 4, 7, and 21 owing to persisting elevated levels (even before CBD) and itching, and on day 21 in patient 5. Tacrolimus levels decreased in patient 2 but were normal in the control 1 week later. Patients on cyclosporine were stable. Adverse effects were nausea, dry mouth, dizziness, drowsiness, and intermittent episodes of heat. CBD dose decrease was required in 2 patients. Two patients had total pain improvement, 4 had a partial response in the first 15 days, and in 1 there was no change.

CONCLUSIONS:

During this follow-up, CBD was well-tolerated, and there were no severe adverse effects. Plasma levels of tacrolimus were variable. Therefore, longer follow-up is required.”

https://www.ncbi.nlm.nih.gov/pubmed/29579828

http://www.transplantation-proceedings.org/article/S0041-1345(17)30962-4/fulltext

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Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability.

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“Cannabinoids combined with opioids produce synergistic antinociceptive effects, decreasing the lowest effective antinociceptive opioid dose (i.e., opioid-sparing effects) in laboratory animals.

Although pain patients report greater analgesia when cannabis is used with opioids, no placebo-controlled studies have assessed the direct effects of opioids combined with cannabis in humans or the impact of the combination on abuse liability.

This double-blind, placebo-controlled, within-subject study determined if cannabis enhances the analgesic effects of low dose oxycodone using a validated experimental model of pain and its effects on abuse liability.

Cannabis enhances the analgesic effects of sub-threshold oxycodone, suggesting synergy, without increases in cannabis’s abuse liability. These findings support future research into the therapeutic use of opioid-cannabinoid combinations for pain.”

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Sex differences in antinociceptive response to Δ-9-tetrahydrocannabinol and CP 55,940 in the mouse formalin test.

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“Cannabinoids have shown promise for the treatment of intractable pain states and may represent an alternative pharmacotherapy for pain management.

A growing body of clinical evidence suggests a role for sex in pain perception and in cannabinoid response.

We examined cannabinoid sensitivity and tolerance in male and female mice expressing a desensitization-resistant form (S426A/S430A) of the cannabinoid type 1 receptor (CB1R).

Mice were assessed for acute and inflammatory nociceptive behaviors in the formalin test following pretreatment with either vehicle or mixed CB1R/CB2R agonists, Δ-9-tetrahydrocannabinol ([INCREMENT]-THC) (1-6 mg/kg) or CP 55,940 (0.06-0.2 mg/kg). Tolerance to the effects of 6 mg/kg [INCREMENT]-THC or 0.1 mg/kg CP 55,940 was examined by the formalin test following chronic daily dosing.

Female mice showed decreased sensitivity to the effects of [INCREMENT]-THC and CP 55,940 compared with male mice. The S426A/S430A mutation increased the attenuation of nociceptive behaviors for both agonists in both sexes. Female mice displayed delayed tolerance to [INCREMENT]-THC compared with male mice, whereas the S426A/S430A mutation conferred a delay in tolerance to [INCREMENT]-THC in both sexes. Male S426A/S430A mutant mice also display resistance to tolerance to CP 55,940 compared with wild-type controls.

This study demonstrates sex and genotype differences in response for two different cannabinoid agonists. The results underscore the importance of including both male and female mice in preclinical studies of pain and cannabinoid pharmacology.”

https://www.ncbi.nlm.nih.gov/pubmed/29461336

https://insights.ovid.com/crossref?an=00001756-900000000-98413

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The Cannabinoids Δ8THC, CBD, and HU-308 Act via Distinct Receptors to Reduce Corneal Pain and Inflammation

Mary Ann Liebert, Inc. publishers

“Corneal injury can result in dysfunction of corneal nociceptive signaling and corneal sensitization.

Activation of the endocannabinoid system has been reported to be analgesic and anti-inflammatory.

The purpose of this research was to investigate the antinociceptive and anti-inflammatory effects of cannabinoids with reported actions at cannabinoid 1 (CB1R) and cannabinoid 2 (CB2R) receptors and/or noncannabinoid receptors in an experimental model of corneal hyperalgesia.

Topical cannabinoids reduce corneal hyperalgesia and inflammation.

The antinociceptive and anti-inflammatory effects of Δ8THC are mediated primarily via CB1R, whereas that of the cannabinoids CBD and HU-308, involve activation of 5-HT1A receptors and CB2Rs, respectively.

Cannabinoids could be a novel clinical therapy for corneal pain and inflammation resulting from ocular surface injury.”

https://www.ncbi.nlm.nih.gov/pubmed/29450258

http://online.liebertpub.com/doi/abs/10.1089/can.2017.0041

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Contribution of spinal 5-HT5A receptors to the antinociceptive effects of systemically administered cannabinoid agonist WIN 55,212-2 and morphine.

Canadian Journal of Physiology and Pharmacology

“The antinociceptive effects of cannabinoids and opioids have been known for centuries.

Serotonin and its receptors are also known to play important roles in nociception. However, the contribution of spinal 5-HT5A receptors in antinociceptive effects of cannabinoids and opioids has not been studied.

We conducted this study to clarify spinal mechanisms of the actions of the antinociceptive effects of cannabinoids and opioids.

Our findings show that spinal 5-HT5A receptors are involved in the antinociceptive effects of WIN 55,212-2 and morphine.”

https://www.ncbi.nlm.nih.gov/pubmed/29406831

http://www.nrcresearchpress.com/doi/10.1139/cjpp-2017-0567#.Wnr8P2inHrc

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