Qualifying Conditions Of Medical Cannabis License Holders In The United States.

Health Affairs

“The evidence for cannabis‘s treatment efficacy across different conditions varies widely, and comprehensive data on the conditions for which people use cannabis are lacking. We analyzed state registry data to provide nationwide estimates characterizing the qualifying conditions for which patients are licensed to use cannabis medically. We also compared the prevalence of medical cannabis qualifying conditions to recent evidence from the National Academies of Sciences, Engineering, and Medicine report on cannabis‘s efficacy in treating each condition. Twenty states and the District of Columbia had available registry data on patient numbers, and fifteen states had data on patient-reported qualifying conditions. Chronic pain is currently and historically the most common qualifying condition reported by medical cannabis patients (64.9 percent in 2016). Of all patient-reported qualifying conditions, 85.5 percent had either substantial or conclusive evidence of therapeutic efficacy. As medical cannabis use continues to increase, creating a nationwide patient registry would facilitate better understanding of trends in use and of its potential effectiveness.”

https://www.ncbi.nlm.nih.gov/pubmed/30715980

https://www.healthaffairs.org/doi/10.1377/hlthaff.2018.05266

[MEDICAL CANNABIS – A SOURCE FOR A NEW TREATMENT FOR AUTOIMMUNE DISEASE?].

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“Medical uses of Cannabis sativa have been known for over 6,000 years. Nowadays, cannabis is mostly known for its psychotropic effects and its ability to relieve pain, even though there is evidence of cannabis use for autoimmune diseases like rheumatoid arthritis centuries ago. The pharmacological therapy in autoimmune diseases is mainly based on immunosuppression of diffefent axes of the immune system while many of the drugs have major side effects. In this review we set out to examine the rule of Cannabis sativa as an immunomodulator and its potential as a new treatment option. In order to examine this subject we will focus on some major autoimmune diseases such as diabetes type I and rheumatoid arthritis.”

https://www.ncbi.nlm.nih.gov/pubmed/27215114

Synthetic Cannabinoids Influence the Invasion of Glioblastoma Cell Lines in a Cell- and Receptor-Dependent Manner.

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“The current treatment of glioblastoma is not sufficient, since they are heterogeneous and often resistant to chemotherapy.

Earlier studies demonstrated effects of specific cannabinoid receptor (CB) agonists on the invasiveness of glioblastoma cell lines, but the exact mechanism remained unclear.

Three human glioblastoma cell lines were treated with synthetic CB ligands. The effect of cannabinoids on microRNAs (miRs), Akt, and on the expression of proliferation and apoptosis markers were analyzed.

Furthermore, in a model of organotypic hippocampal slice cultures cannabinoid mediated changes in the invasiveness were assessed. MicroRNAs and the activation of Akt which are related to cell migration, apoptosis, and proliferation were evaluated and found not to be associated with changes in the invasiveness after treatment with CB ligands.

Also proliferation and/or apoptosis were not altered after treatment. The effects of cannabinoids on invasiveness could be blocked by the application of receptor antagonists and are likely mediated via CB₁/CB₂.

In conclusion, our results suggest that cannabinoids can influence glioblastoma cell invasion in a receptor and cell type specific manner that is independent of proliferation and apoptosis. Thus, cannabinoids can potentially be used in the future as an addition to current therapy.”

How effective and safe is medical cannabis as a treatment of mental disorders? A systematic review.

“We conducted a review of systematic reviews (SRs) and randomized-controlled trials (RCTs) to analyze efficacy and safety of cannabis-based medication in patients with mental disorders.

Five data bases were systematically searched (2006-August 2018); 4 SRs (of 11 RCTs) and 14 RCTs (1629 participants) were included. Diagnoses were: dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette`s disorder. Outcome variables were too heterogeneous to conduct a  meta-analysis. A narrative synthesis method was applied. The study quality was assessed using the risk-of-bias tool and SIGN-checklists.

THC- and CBD-based medicines, given as adjunct to pharmaco- and psychotherapy, were associated with improvements of several symptoms of mental disorders, but not with remission. Side effects occurred, but severe adverse effects were mentioned in single cases only. In order to provide reliable treatment recommendations, more and larger RCTs with follow-up assessments, consistent outcome measures and active comparisons are needed.”

https://www.ncbi.nlm.nih.gov/pubmed/30706168

https://link.springer.com/article/10.1007%2Fs00406-019-00984-4

Potential Use of Cannabinoids for the Treatment of Pancreatic Cancer.

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Cannabinoid extracts may have anticancer properties, which can improve cancer treatment outcomes.

The aim of this review is to determine the potentially utility of cannabinoids in the treatment of pancreatic cancer.

Results: Cannabinol receptors have been identified in pancreatic cancer with several studies showing in vitroantiproliferative and proapoptotic effects. The main active substances found in cannabis plants are cannabidiol (CBD) and tetrahydrocannabinol (THC). There effects are predominately mediated through, but not limited to cannabinoid receptor-1, cannabinoid receptor-2, and G-protein-coupled receptor 55 pathways. In vitro studies consistently demonstrated tumor growth-inhibiting effects with CBD, THC, and synthetic derivatives. Synergistic treatment effects have been shown in two studies with the combination of CBD/synthetic cannabinoid receptor ligands and chemotherapy in xenograft and genetically modified spontaneous pancreatic cancer models. There are, however, no clinical studies to date showing treatment benefits in patients with pancreatic cancer.

Conclusions: Cannabinoids may be an effective adjunct for the treatment of pancreatic cancer. Data on the anticancer effectiveness of various cannabinoid formulations, treatment dosing, precise mode of action, and clinical studies are lacking.”

“Endogenous cannabinoids, synthetic or cannabis extracted from plants, can reduce tumor invasion and growth, induce tumor cell death, and inhibit tumor angiogenesis via cannabinoid receptor or receptor-independent pathways. Cannabinoid receptors appear to be highly expressed in pancreatic cancer compared with normal pancreatic tissue. CBD and THC appear to have antiproliferative and proapoptotic effects.”

Cannabinoids and Bone Regeneration.

 Publication Cover“Bone is a complex tissue of the with unique properties such as high strength and regeneration capabilities while carrying out multiple functions. Bone regeneration occurs both in physiological situations (bone turnover) and pathological situations (e.g. fractures), being performed by osteoblasts and osteoclasts. If this process is inadequate, fracture nonunion or aseptic loosening of implants occurs and requires a complex treatment.

Exogenous factors are currently used to increase bone regeneration process when needed, such as bisphosphonates and vitamin D, but limitations do exist. Cannabinoid system has been shown to have positive effects on bone metabolism. Cannabinoids at bone level mainly act on two receptors called CB-1 and CB-2, but GPR55, GPR119, TPRV1, TPRV4 receptors may also be involved. The CB-2 receptors are found in bone cells at higher levels compared to other receptors.

Endocannabinods represented by anandamide and 2-arachidonoylglycerol, can stimulate osteoblast formation, bone formation and osteoclast activity. CB-2 agonists including HU-308, HU-433, JWH133 and JWH015 can stimulate osteoblast proliferation and activity, while CB-2 antagonists such as AM630 and SR144528 can inhibit osteoclast differentiation and function. CB-1 antagonist AM251 has been shown to inhibit osteoclast differentiation and activity, while GPR55 antagonist cannabidiol increases osteoblast activity and decreases osteoclast function.

An optimal correlation of dose, duration, moment of action and affinity can lead to an increased bone regeneration capacity, with important benefits in many pathological situations which involve bone tissue. As adverse reactions of cannabinoids haven’t been described in patients under controlled medication, cannabinoids can represent future treatment for bone regeneration.”

https://www.ncbi.nlm.nih.gov/pubmed/30702341

https://www.tandfonline.com/doi/abs/10.1080/03602532.2019.1574303?journalCode=idmr20

A Cost-Effectiveness Model for Adjunctive Smoked Cannabis in the Treatment of Chronic Neuropathic Pain

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“A recent meta-analysis affirmed the benefit of medicinal cannabis for chronic neuropathic pain, a disabling and difficult-to-treat condition. As medicinal cannabis use is becoming increasingly prevalent among Americans, an exploration of its economic feasibility is warranted. We present this cost-effectiveness analysis of adjunctive cannabis pharmacotherapy for chronic peripheral neuropathy.

A growing body of scientific literature demonstrates reproducible efficacy of cannabis in the treatment of several medical conditions, including chronic neuropathic pain. Clinical trials of oral, smoked, and vaporized cannabis and cannabinoids have all demonstrated analgesic benefit of medicinal cannabis in the treatment of this costly and disabling condition. A recent meta-analysis of individual patient data from five randomized controlled trials of inhaled cannabis demonstrated pain relief comparable to gabapentin. Treatment guidelines for neuropathic pain recommend consideration of cannabinoids as third-line agents.

As recently proposed willingness-to-pay thresholds for the United States health marketplace range from $110,000 to $300,000 per QALY, cannabis appears cost-effective when augmenting second-line treatment for painful neuropathy. Further research is warranted to explore the long-term benefit of smoked cannabis and standardization of its dosing for chronic neuropathic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/30944870

https://www.liebertpub.com/doi/10.1089/can.2018.0027

“New study analyzes cost effectiveness of smoked cannabis to treat chronic neuropathic pain” https://www.eurekalert.org/pub_releases/2019-01/mali-nsa012919.php

Cannabinoid Ligands Targeting TRP Channels.

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“Many diseases involve Transient receptor potential (TRP) channel dysfunction, including neuropathic pain, inflammation, and respiratory disorders. In the pursuit of new treatments for these disorders, it was discovered that cannabinoids can modulate a certain subset of TRP channels. The TRP vanilloid (TRPV), TRP ankyrin (TRPA), and TRP melastatin (TRPM) subfamilies were all found to contain channels that can be modulated by several endogenous, phytogenic, and synthetic cannabinoids. To date, six TRP channels from the three subfamilies mentioned above have been reported to mediate cannabinoid activity: TRPV1, TRPV2, TRPV3, TRPV4, TRPA1, and TRPM8. The increasing data regarding cannabinoid interactions with these receptors has prompted some researchers to consider these TRP channels to be “ionotropic cannabinoid receptors.””

https://www.ncbi.nlm.nih.gov/pubmed/30697147

https://www.frontiersin.org/articles/10.3389/fnmol.2018.00487/full

Pills to pot: observational analyses of cannabis substitution among medical cannabis users with chronic pain.

“Chronic pain is common, costly and challenging to treat. Many individuals with chronic pain have turned to cannabis as an alternative form of pain management.

We report results from an ongoing, online survey of medical cannabis users with chronic pain nationwide about how cannabis affects pain management, health, and pain medication use. We also examined whether and how these parameters were affected by concomitant recreational use, and duration of use (novice: <1 year vs. experienced: ≥1 year). 1,321 participants (59% female, 54% ≥50 years old) completed the survey.

Consistent with other observational studies, ∼80% reported substituting cannabis for traditional pain medications (53% for opioids, 22% for benzodiazepines), citing fewer side effects and better symptom management as their rationale for doing so. Medical only users were older (52 vs. 47, p<0.0001), less likely to drink alcohol (66% vs. 79%, p<0.0001), and more likely to be currently taking opioids (21% vs. 11%, p<0.0001) than users with a combined recreational + medical history. Compared to novice users, experienced users were more likely to be male (64% vs. 58%, p<0.0001), take no concomitant pain medications (43% vs. 30%), and report improved health (74% vs. 67%, p=0.004) with use.

Given that chronic pain is the most common reason for obtaining a medical cannabis license, these results highlight clinically important differences among the changing population of medical cannabis users. More research is needed to better understand effective pain management regimens for medical cannabis users.

PERSPECTIVE: This article presents results that confirm previous clinical studies suggesting that cannabis may be an effective analgesic and potential opioid substitute. Participants reported improved pain, health, and fewer side effects as rationale for substituting. This article highlights how use duration and intentions for use affect reported treatment and substitution effects.”

https://www.ncbi.nlm.nih.gov/pubmed/30690169

https://www.jpain.org/article/S1526-5900(18)30735-1/fulltext

Dark Classics in Chemical Neuroscience: Δ9-Tetrahydrocannabinol.

 ACS Chemical Neuroscience

“Cannabis (Cannabis sativa) is the most widely used illicit drug in the world, with an estimated 192 million users globally.

The main psychoactive component of cannabis is (-)-trans-Δ9-tetrahydrocannabinol (Δ9-THC), a molecule with a diverse range of pharmacological actions. The unique and distinctive intoxication caused by Δ9-THC primarily reflects partial agonist action at central cannabinoid type 1 (CB1) receptors.

Δ9-THC is an approved therapeutic treatment for a range of conditions, including chronic pain, chemotherapy-induced nausea and vomiting, and is being investigated in indications such as anorexia nervosa, agitation in dementia, and Tourette’s syndrome.

It is available as a regulated pharmaceutical in products such as Marinol®, Sativex®, and Namisol®, as well as in an ever-increasing range of unregistered medicinal and recreational cannabis products.

While cannabis is an ancient medicament, contemporary use is embroiled in legal, scientific, and social controversy, much of which relates to the potential hazards and benefits of Δ9-THC itself.

Robust contemporary debate surrounds the therapeutic value of Δ9-THC in different diseases, its capacity to produce psychosis and cognitive impairment, and the addictive and “gateway” potential of the drug.

This review will provide a profile of the chemistry, pharmacology, toxicology, and recreational and therapeutic uses of Δ9-THC, as well as the historical and societal importance of this unique, distinctive, and ubiquitous psychoactive substance.”

https://www.ncbi.nlm.nih.gov/pubmed/30689342

https://pubs.acs.org/doi/10.1021/acschemneuro.8b00651