GPR12 is a constitutively active, Gs protein-coupled receptor that currently has no confirmed endogenous ligands. GPR12 may be involved in physiological processes such as maintenance of oocyte meiotic arrest and brain development, as well as pathological conditions such as metastatic cancer. In this study, the potential effects of various classes of cannabinoids on GPR12 were tested using a cAMP accumulation assay. Our data demonstrate that cannabidiol (CBD), a major non-psychoactive phytocannabinoid, acted as an inverse agonist to inhibit cAMP accumulation stimulated by the constitutively active GPR12. Thus, GPR12 is a novel molecular target for CBD. The structure-activity relationship studies of CBD indicate that both the free hydroxyl and the pentyl side chain are crucial for the effects of CBD on GPR12. Furthermore, studies using cholera toxin, which blocks Gs protein and pertussis toxin, which blocks Gi protein, revealed that Gs, but not Gi is involved in the inverse agonism of CBD on GPR12. CBD is a promising novel therapeutic agent for cancer, and GPR12 has been shown to alter viscoelasticity of metastatic cancer cells. Since we have demonstrated that CBD is an inverse agonist for GPR12, this provides novel mechanism of action for CBD, and an initial chemical scaffold upon which highly potent and efficacious agents acting on GPR12 may be developed with the ultimate goal of blocking cancer metastasis.
PMID: 28888984 [PubMed – as supplied by publisher]
Cannabis constituent synergy in a mouse neuropathic pain model.
Pain. 2017 Sep 01;:
Authors: Casey SL, Atwal N, Vaughan CW
Cannabis and its psychoactive constituent Δ9-tetrahydrocannabinol (THC) have efficacy against neuropathic pain however, this is hampered by their side-effects. It has been suggested that co-administration with another major constituent cannabidiol (CBD) might enhance the analgesic actions of THC and minimise its deleterious side-effects. We examined the basis for this phytocannabinoid interaction in a mouse chronic constriction injury (CCI) model of neuropathic pain. Acute systemic administration of THC dose-dependently reduced CCI-induced mechanical and cold allodynia, but also produced motor incoordination, catalepsy and sedation. CBD produced a lesser dose-dependent reduction in allodynia, but did not produce the cannabinoid side-effects. When co-administered in a fixed ratio, THC and CBD produced a biphasic dose-dependent reduction in allodynia. At low doses, the THC:CBD combination displayed a 200-fold increase in anti-allodynic potency, but had lower efficacy compared to that predicted for an additive drug interaction. By contrast, high THC:CBD doses had lower potency, but greater anti-allodynic efficacy compared to that predicted for an additive interaction. Only the high dose THC:CBD anti-allodynia was associated with cannabinoid side-effects and these were similar to those of THC alone. Unlike THC, the low dose THC:CBD anti-allodynia was not cannabinoid receptor mediated. These findings demonstrate that CBD synergistically enhances the pain relieving actions of THC in an animal neuropathic pain model, but has little impact on the THC-induced side-effects. This suggests that low dose THC:CBD combination treatment has potential in the treatment of neuropathic pain.
PMID: 28885457 [PubMed – as supplied by publisher]
Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis.
Pain. 2017 Sep 01;:
Authors: Philpott HT, O’Brien M, McDougall JJ
Osteoarthritis (OA) is a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy. Cannabidiol (CBD) is a non-euphoria producing constituent of cannabis that has the potential to relieve pain. The aim of this study was to determine if CBD is anti-nociceptive in OA, and whether inhibition of inflammation by CBD could prevent the development of OA pain and joint neuropathy. OA was induced in male Wistar rats (150-175g) by intra-articular injection of sodium monoiodoacetate (MIA; 3mg). On day 14 (end stage OA), joint afferent mechanosensitivity was assessed using in vivo electrophysiology while pain behaviour was measured by von Frey hair algesiometry and dynamic incapacitance. To investigate acute joint inflammation, blood flow and leukocyte trafficking were measured on day 1 post-MIA. Joint nerve myelination was calculated by G-ratio analysis. The therapeutic and prophylactic effects of peripheral CBD (100-300μg) were assessed. In end stage OA, CBD dose-dependently decreased joint afferent firing rate, and increased withdrawal threshold and weight bearing (p<0.0001; n=8). Acute, transient joint inflammation was reduced by local CBD treatment (p<0.0001; n=6). Prophylactic administration of CBD prevented the development of MIA-induced joint pain at later time points (p<0.0001; n=8), and was also found to be neuroprotective (p<0.05; n=6-8). The data presented here indicate that local administration of CBD blocked OA pain. Prophylactic CBD treatment prevented the later development of pain and nerve damage in these OA joints. These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
PMID: 28885454 [PubMed – as supplied by publisher]
A randomised controlled cross-over double-blind pilot study protocol on THC:CBD oromucosal spray efficacy as an add-on therapy for post-stroke spasticity.
BMJ Open. 2017 Sep 07;7(9):e016843
Authors: Marinelli L, Balestrino M, Mori L, Puce L, Rosa GM, Giorello L, Currà A, Fattapposta F, Serrati C, Gandolfo C, Abbruzzese G, Trompetto C
INTRODUCTION: Stroke is the most disabling neurological disorder and often causes spasticity. Transmucosal cannabinoids (tetrahydrocannabinol and cannabidiol (THC:CBD), Sativex) is currently available to treat spasticity-associated symptoms in patients with multiple sclerosis. Cannabinoids are being considered useful also in the treatment of pain, nausea and epilepsy, but may bear and increased risk for cardiovascular events. Spasticity is often assessed with subjective and clinical rating scales, which are unable to measure the increased excitability of the monosynaptic reflex, considered the hallmark of spasticity. The neurophysiological assessment of the stretch reflex provides a precise and objective method to measure spasticity. We propose a novel study to understand if Sativex could be useful in reducing spasticity in stroke survivors and investigating tolerability and safety by accurate cardiovascular monitoring.
METHODS AND ANALYSIS: We will recruit 50 patients with spasticity following stroke to take THC:CBD in a double-blind placebo-controlled cross-over study. Spasticity will be assessed with a numeric rating scale for spasticity, the modified Ashworth scale and with the electromyographical recording of the stretch reflex. The cardiovascular risk will be assessed prior to inclusion. Blood pressure, heart rate, number of daily spasms, bladder function, sleep disruption and adverse events will be monitored throughout the study. A mixed-model analysis of variance will be used to compare the stretch reflex amplitude between the time points; semiquantitative measures will be compared using the Mann-Whitney test (THC:CBD vs placebo) and Wilcoxon test (baseline vs treatment).
ETHICS AND DISSEMINATION: The study was registered on the EudraCT database with number 2016-001034-10 and approved by both the Italian Medicines Agency (Agenzia Italiana del Farmaco) and local Ethics Committee ‘Comitato Etico Regionale della Liguria’. Data will be made anonymous and uploaded to a open access repository. Results will be disseminated by presentations at national and international conferences and by publication in journals of clinical neuroscience and neurology.
Authors: Mori MA, Meyer E, Soares LM, Milani H, Guimarães FS, de Oliveira RM
This study investigated the effects of cannabidiol (CBD), a non-psychotomimetic phytochemical present in Cannabis sativa, on the cognitive and emotional impairments induced by bilateral common carotid artery occlusion (BCCAO) in mice. Using a multi-tiered behavioral testing battery during 21days, we found that BCCAO mice exhibited long-lasting functional deficits reflected by increase in anxiety-like behavior (day 9), memory impairments (days 12-18) and despair-like behavior (day 21). Short-term CBD 10mg/kg treatment prevented the cognitive and emotional impairments, attenuated hippocampal neurodegeneration and white matter (WM) injury, and reduced glial response that were induced by BCCAO. In addition, ischemic mice treated with CBD exhibited an increase in the hippocampal brain derived neurotrophic factor (BDNF) protein levels. CBD also stimulated neurogenesis and promoted dendritic restructuring in the hippocampus of BCCAO animals. Collectively, the present results demonstrate that short-term CBD treatment results in global functional recovery in ischemic mice and impacts multiple and distinct targets involved in the pathophysiology of brain ischemic injury.
In 2016, a new journal Cannabis and Cannabinoid Research published a paper suggesting that non-psychoactive cannabidiol (CBD) converts to psychoactive tetrahydrocannabinol (THC) in the stomach. The controversial paper was coauthored by several scientists employed by Zynerba Pharmaceuticals in Devin, Pennsylvania. It was not the first time that researchers addressed this issue.
In considering whether CBD converts to THC in the stomach, there are three major kinds of data that scientists examine:
The first involves blood samples and physiological tests of humans who have ingested CBD, which demonstrates if they are actually exposed to THC and if they experience THC-like effects after CBD administration.
The second kind of data involves studies that examine excreted metabolites after ingestion of CBD. Excretion studies may not prove that a particular metabolite is physiologically relevant, but they could prove if these breakdown metabolites are formed.
And the third and least significant type of data derives from experimental organ models—such as artificial gastric fluid or extracted liver microsomes—that might demonstrate the possibility of a CBD-to-THC conversion, but does not necessarily translate into human experience.
The recent article by John Merrick et. al. (2016) that sparked renewed interest in CBD’s potential conversion to THC falls into the third category. It raised concerns among patients, physicians and policymakers about possible adverse side effects that might limit CBD’s otherwise formidable therapeutic utility and market potential. Misinformation regarding the consequences of oral CBD administration could skew public policy and regulatory decisions at a time when cannabinoid therapies are gaining favor among health professionals and the general public.
There have been extensive clinical trials demonstrating that ingested CBD—even doses above 600 mg—does not cause THC-like effects.1 The lack of THC-like effects was discussed in detail by Grotenhermen et. al. (2017) in a response to Merrick’s publication. The lack of such effects strongly suggests that CBD does not trigger significant CB1 receptor activity in the brain, which would cause a THC-like “high.” One clinical study examined the blood concentration of THC and its active metabolites after 16 men ingested 600 mg of CBD; the resulting change in the concentration of THC metabolites was statistically meaningless. To the extent that THC is formed from orally ingested CBD, it is physiologically insignificant.
There are a few human studies indicating that very small amounts of THC are excreted in urine after someone ingests CBD. Less than 1% of the total CBD is excreted as ∆9-THC, and between 1-2% is excreted as ∆8-THC. These studies demonstrate that a small amount of ingested CBD does isomerize to THC, but this in and of itself has no practical significance. The clinical evidence demonstrating that CBD does not cause THC-like effects subsumes any imagined physiological consequences associated with this data.
Two studies have explored the conversion of CBD to THC in artificial gastric fluid: One performed by Watanabe et. al. (2007) and the recent publication by Merrick and colleagues. Although Merrick cites Watanabe’s work to build the case for CBD-to-THC conversion in the stomach, Merrick’s experiment is strikingly inconsistent with Watanabe’s data. In Watanabe’s simulated gastric fluid study, 15.4% of the CBD was converted into four compounds: ∆9-THC, CBN, 8-OH-iso-HHC, and 9a-OH–HHC. (The major product, 8-OH-iso-HHC, is approximately 15 times less potent than THC). Less than 3% of the CBD was actually converted to THC in this experiment, which lasted 20 hours—much longer than CBD remains in the stomach. Yet the article by Merrick proposed that 85% of CBD will break down in a single hour. In other words, the reaction that occurred in Merrick’s study was over 200 times faster than the reaction in Watanabe’s study.2 This discrepancy may be due to different stomach fluid models, and it raises questions about the validity of both models. Moreover, it should be noted that Watanabe explicitly states: “In biological systems, there have been no reports on the conversion of CBD to ∆9-THC itself.”
In Merrick et. al. the discussion following the presentation of test data far outpaces the minor implications of their work. They propose an equation to estimate “THC exposure” after CBD ingestion. What does this equation do for the reader? It provides the reader with information that is at best wildly speculative, and at worst totally wrong. But what does it do for the authors? It inflates the minimal significance of their simulated gastric fluid experiment and conveys a misleading impression that they have discovered something truly important about the use of oral cannabinoid medicine.
From Bad to Worse
The weakest aspect of Merrick’s research is found in the authors’ response (Bonn-Miller et. al. 2017) to cogent criticism about their methodology and conclusion. Published in the same journal, Bonn-Miller’s response is replete with subtle distortions and demonstrable falsehoods, including misrepresentation of the studies they reference to back up their initial report.
In one particularly egregious example, the authors state that “studies documented… poor motor and cognitive performance after administration of oral CBD,” citing an article by Consroe (1979). The actual study by Consroe states that “alcohol and alcohol + CBD, but not CBD given singly, produce decrements of motor and cognitive responses [emphasis added].”
In an attempt to discredit one of the two human studies demonstrating that ingested CBD does not convert to THC to a significant degree, Merrick and his coauthors assert that a chart included in a paper by Martín-Santos et. al. (2012) shows an increase in THC metabolites after CBD administration. But the trend shown in the chart is not only statistically insignificant, it is so minuscule as to be clinically irrelevant.
Other claims in the article, while not outright falsehoods, misrepresent the work of other authors. The conversion of CBD to THC, previously documented by Gaoni and Mechoulam (1968), did not occur in simulated gastric conditions, but rather was performed in a highly unnatural setting with CBD dissolved in sulfuric acid and methanol. This reaction is entirely valid in the realm of chemical synthesis, but it has little to do with real-life human experience.
Merrick and his cohorts also suggest that a recent review by István Ujváry and Lumir Hanuš (2016) “highlighted” the “consistent findings of CBD conversion to THC.” But only a single sentence in this review mentions the conversion of CBD to THC, and this sentence was accompanied by a figure caption indicating that ∆9-THC was a “minor (<1%) urinary metabolite.” Ujváry and Hanuš also note the presence of a small amount of ∆8-THC, which is less psychoactive than ∆9-THC.
It is unclear if the journal Cannabis and Cannabinoid Research peer-reviewed the response to criticism of Merrick’s article, as the response does not appear to meet the standards of scientific reporting. The purpose of peer-review is for scientists to confirm the validity of a paper before publication so that others can read it without questioning the accuracy of its contents. In publishing this response by Bonn-Miller et. al., Cannabis and Cannabinoid Research seems to have failed that goal.3
But the authors may have succeeded in advancing the agenda of Zynerba Pharmaceuticals, the company that funded their research. Zynerba disclosed in a press release (April 12, 2016) that it was developing a transdermal delivery system that “avoids the gastrointestinal tract and potential stomach acid degradation of CBD into THC (associated with psychoactive effects).” In other words, Zynerba has a financial interest in depicting oral CBD, which is well tolerated in clinical research, as potentially harmful.
While purporting to solve a problem that doesn’t actually exist may not amount to much scientifically, Zynerba isn’t the only company making erroneous claims about CBD converting to THC in the stomach. Ananda Scientific, a privately-held Delaware corporation, tried to one-up its competitors by asserting that its hemp-derived CBD formulation is “protected from being transformed, after it is ingested, into THC which is a risk factor in other existing [hemp CBD] products.”
Copyright, Project CBD. May not be reprinted without permission.
1 There are, of course, many effects common to both THC and CBD. The “tetrad” test that is used to assay CB1 receptor activity involves measuring catalepsy, hypothermia, hypomotility, and analgesia. Ingested CBD consistently evokes analgesia, but is inactive on other measures of the tetrad.
2 The rate constant from Merrick’s study was -3.1 * 10^-2 per min, while it was -1.4 * 10^-4 per min in Watanabe’s study. The rate constant for Watanabe’s experiment can be calculated as follows. If we assume first-order kinetics – which makes sense for the degradation of a molecule – then [CBD] / [initial CBD] = exp(-k * t), where k is the rate constant, and […] indicates we are considering concentrations. Since 15.4% of the CBD had degraded at 20 hours (1200 min), the left side of the equation is 1-0.154 = 0.846 when ‘t’ on the right side is 1200 min. Solving for k, we see that k = -ln(0.846)/1200 min ≈ -1.4 * 10^-4/min. If we then compare these rate constants, we see that k_Merrick/k_Watanabe = 222, meaning that CBD degraded 222 times faster in Merrick’s experiment than in Watanabe’s.
3 A coauthor of Grotenhermen’s article told Project CBD that their critical commentary was peer-reviewed before publication. But when asked by Project CBD, the editor of Cannabis and Cannabinoid Research did not comment on whether or not Bonn-Miller (2017) was peer-reviewed. Dr. Bonn-Miller, who was the first author of the response to criticism but was not an author on Merrick’s initial publication, is on the editorial board of Cannabis and Cannabinoid Research.
Bergamaschi MM, Queiroz RHC, Zuardi AW, Crippa JAS. Safety and Side Effects of Cannabidiol, a Cannabis sativa Constituent. Current Drug Safety. 2011, 6:237-249.
Bonn-Miller M, Banks SL, Sebree T. Conversion of Cannabidiol Following Oral Administration: Authors’ Response to Grotenhermen et al. Cannabis and Cannabinoid Research. January 2017, 2(1): 5-7.
Consroe P, Carlini EA, Zwicker AP, Lacerda LA. Interaction of Cannabidiol and Alcohol in Humans. Psychopharmacology. 1979, 66:45-50.
Gaoni Y and Mechoulam R. The iso-tetrahydrocannabinols. Israeli Journal of Chemistry. 1968, 6:679-690.
Grotenhermen F, Russo E, Zuardi AW. Even High Doses of Oral Cannabidiol do not Cause THC-like Effects in Humans: Comment on Merrick et al. Cannabis and Cannabinoid Research. January 2017, 2(1): 1-4.
Martín-Santos R, Crippa JA, Batalla A, Bhattacharyya S, Atakan Z, Borgwardt S, Allen P, Seal M, Langohr K, Farré M, Zuardi AW, McGuire PK. Acute Effects of a Single, Oral Dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers. Current Pharmaceutical Design. 2012, 18:4966-4979.
Merrick J, Lane B, Sebree T, Yaksh T, O’Neill C, and Banks SL. Identification of Psychoactive Degradants of Cannabidiol in Simulated Gastric and Physiological Fluid. Cannabis and Cannabinoid Research. April 2016, 1(1): 102-112.
Ujváry I and Hanuš L. Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy. Cannabis and Cannabinoid Research. March 2016, 1(1): 90-101.
Watanabe K, Itokawa Y, Yamaori S, Funahashi T, Kimura T, Kaji T, Usami N, Yamamoto I. Conversion of cannabidiol to ∆9-tetrahydrocannabinol and related cannabinoids in artificial gastric juice, and their pharmacological effects in mice. Forensic Toxicology. 2007 25:16-21.
Solomon, Shoshanna, “Israeli cannabis-based nanotech droplets start US sales,” The Times of Israel, Dec. 5, 2016.
Zynerba Pharmaceuticals, Inc., “Cannabis and Cannabinoid Research Publishes Data Demonstrating the Degradation of Cannabidiol to Psychoactive Cannabinoids when Exposed to Simulated Gastric Fluid,” press release, April 12, 2016.
A selective review of medical cannabis in cancer pain management.
Ann Palliat Med. 2017 Aug 23;:
Authors: Blake A, Wan BA, Malek L, DeAngelis C, Diaz P, Lao N, Chow E, O’Hearn S
Insufficient management of cancer-associated chronic and neuropathic pain adversely affects patient quality of life. Patients who do not respond well to opioid analgesics, or have severe side effects from the use of traditional analgesics are in need of alternative therapeutic op-tions. Anecdotal evidence suggests that medical cannabis has potential to effectively manage pain in this patient population. This review presents a selection of representative clinical studies, from small pilot studies conducted in 1975, to double-blind placebo-controlled trials conducted in 2014 that evaluated the efficacy of cannabinoid-based therapies containing tetrahydrocannabinol (THC) and cannabidiol (CBD) for reducing cancer-associated pain. A review of literature published on Medline between 1975 and 2017 identified five clinical studies that evaluated the effect of THC or CBD on controlling cancer pain, which have been reviewed and summarised. Five studies that evaluated THC oil capsules, THC:CBD oromucosal spray (nabiximols), or THC oromucosal sprays found some evidence of cancer pain reduction associated with these therapies. A variety of doses ranging from 2.7-43.2 mg/day THC and 0-40 mg/day CBD were administered. Higher doses of THC were correlated with increased pain relief in some studies. One study found that significant pain relief was achieved in doses as low as 2.7-10.8 mg THC in combination with 2.5-10.0 mg CBD, but there was conflicting evidence on whether higher doses provide superior pain relief. Some reported side effects include drowsiness, hypotension, mental clouding, and nausea and vomiting. There is evidence suggesting that medical cannabis reduces chronic or neu-ropathic pain in advanced cancer patients. However, the results of many studies lacked statistical power, in some cases due to limited number of study subjects. Therefore, there is a need for the conduct of further double-blind, placebo-controlled clinical trials with large sample sizes in order to establish the optimal dosage and efficacy of different cannabis-based therapies.
PMID: 28866904 [PubMed – as supplied by publisher]
A Conversion of Oral Cannabidiol to Delta9-Tetrahydrocannabinol Seems Not to Occur in Humans.
Cannabis Cannabinoid Res. 2017;2(1):81-86
Authors: Nahler G, Grotenhermen F, Zuardi AW, Crippa JAS
Cannabidiol (CBD), a major cannabinoid of hemp, does not bind to CB1 receptors and is therefore devoid of psychotomimetic properties. Under acidic conditions, CBD can be transformed to delta9-tetrahydrocannabinol (THC) and other cannabinoids. It has been argued that this may occur also after oral administration in humans. However, the experimental conversion of CBD to THC and delta8-THC in simulated gastric fluid (SGF) is a highly artificial approach that deviates significantly from physiological conditions in the stomach; therefore, SGF does not allow an extrapolation to in vivo conditions. Unsurprisingly, the conversion of oral CBD to THC and its metabolites has not been observed to occur in vivo, even after high doses of oral CBD. In addition, the typical spectrum of side effects of THC, or of the very similar synthetic cannabinoid nabilone, as listed in the official Summary of Product Characteristics (e.g., dizziness, euphoria/high, thinking abnormal/concentration difficulties, nausea, tachycardia) has not been observed after treatment with CBD in double-blind, randomized, controlled clinical trials. In conclusion, the conversion of CBD to THC in SGF seems to be an in vitro artifact.
An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies.
Cannabis Cannabinoid Res. 2017;2(1):139-154
Authors: Iffland K, Grotenhermen F
Introduction: This literature survey aims to extend the comprehensive survey performed by Bergamaschi et al. in 2011 on cannabidiol (CBD) safety and side effects. Apart from updating the literature, this article focuses on clinical studies and CBD potential interactions with other drugs. Results: In general, the often described favorable safety profile of CBD in humans was confirmed and extended by the reviewed research. The majority of studies were performed for treatment of epilepsy and psychotic disorders. Here, the most commonly reported side effects were tiredness, diarrhea, and changes of appetite/weight. In comparison with other drugs, used for the treatment of these medical conditions, CBD has a better side effect profile. This could improve patients’ compliance and adherence to treatment. CBD is often used as adjunct therapy. Therefore, more clinical research is warranted on CBD action on hepatic enzymes, drug transporters, and interactions with other drugs and to see if this mainly leads to positive or negative effects, for example, reducing the needed clobazam doses in epilepsy and therefore clobazam’s side effects. Conclusion: This review also illustrates that some important toxicological parameters are yet to be studied, for example, if CBD has an effect on hormones. Additionally, more clinical trials with a greater number of participants and longer chronic CBD administration are still lacking.
Authors: Hill KP, Palastro MD, Johnson B, Ditre JW
Introduction: Cannabis has been used for medical purposes across the world for centuries. As states and countries implement medical and recreational cannabis policies, increasing numbers of people are using cannabis pharmacotherapy for pain. There is a theoretical rationale for cannabis’ efficacy for pain management, although the subjective pain relief from cannabis may not match objective measurements of analgesia. As more patients turn to cannabis for pain relief, there is a need for additional scientific evidence to evaluate this increase. Materials and Methods: Research for this review was performed in the PubMed/National Library of Medicine database. Discussion: Preclinical studies demonstrate a narrow therapeutic window for cannabis as pharmacotherapy for pain; the body of clinical evidence for this indication is not as extensive. A recent meta-analysis of clinical trials of cannabis and cannabinoids for pain found modest evidence supporting the use of cannabinoid pharmacotherapy for pain. Recent epidemiological studies have provided initial evidence for a possible reduction in opioid pharmacotherapy for pain as a result of increased implementation of medical cannabis regimens. Conclusion: With increased use of medical cannabis as pharmacotherapy for pain comes a need for comprehensive risk-benefit discussions that take into account cannabis’ significant possible side effects. As cannabis use increases in the context of medical and recreational cannabis policies, additional research to support or refute the current evidence base is essential to attempt to answer the questions that so many healthcare professionals and patients are asking.
Acudimos a CBDnetwork buscando un aceite de calidad para uno de nuestros familiares, afectado de cáncer.
Su evolución ha sido muy positiva, usando el aceite junto con el tratamiento del hospital.
Damos las gracias a todo CBDnetwork, ánimo y seguid así.
Acudimos a CBDnetwork buscando un aceite de calidad para uno de nuestros familiares, afectado de cáncer.
Su evolución ha sido muy positiva, usando el aceite junto con el tratamiento del hospital.
Damos las gracias a todo CBDnetwork, ánimo y seguid así.