“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. 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.” https://www.ncbi.nlm.nih.gov/pubmed/28885454 https://insights.ovid.com/crossref?an=00006396-900000000-99152]]>
Tag Archives: cannabidiol
Cannabis constituent synergy in a mouse neuropathic pain model.
“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.”
Intra-cerebral cannabidiol infusion-induced neuroprotection is partly associated with the TNF-α/TNFR1/NF-кB pathway in transient focal cerebral ischaemia.
“Stroke is a neurological disease, which, in addition to high mortality, imposes many financial and mental burdens on families and the society. The main objective of this study was to investigate the effect of cannabidiol (CBD) on one of the major inflammatory pathways in cerebral ischaemia.
RESULTS:
Administration of CBD (100 and 200 ng/rat) caused a significant reduction in infarction, brain oedema, and BBB permeability compared with the vehicle-received group. Down-regulation of TNF-α, TNFR1, and NF-кB expression was also observed by CBD.CONCLUSION:
The results achieved in this study support the idea that CBD has a cerebroprotective effect (partly through suppression of TNF-α, TNFR1, and NF-кB) on ischaemic injury.” https://www.ncbi.nlm.nih.gov/pubmed/28872345 http://www.tandfonline.com/doi/abs/10.1080/02699052.2017.1358397?journalCode=ibij20]]>Cannabidiol inhibits priming-induced reinstatement of methamphetamine in REM sleep deprived rats.
“Methamphetamine (METH) is a widely abused and a severely addictive psychostimulant. Relapse is the main cause of concern when treating addiction. It could manifest after a long period of abstinence. Previous studies showed that there is a strong connection between sleep impairment and relapse. Also, it has been reported that cannabidiol might be a potential treatment for drug craving and relapse. In this study, we used conditioned place preference (CPP) to investigate whether Cannabidiol (CBD), a phytocannabinoid, can prevent METH-induced reinstatement in Rapid Eye Movement Sleep Deprived (RSD) rats. In conclusion, the administration of CBD 10μg/5μl effectively prevents METH-induced CPP, even in a condition of stress. CBD can be considered an agent that reduces the risk of the relapse; however, this requires more investigation.” https://www.ncbi.nlm.nih.gov/pubmed/28870635 http://www.sciencedirect.com/science/article/pii/S027858461730218X?via%3Dihub]]>
Clinical and Pre-Clinical Evidence for Functional Interactions of Cannabidiol and Δ9-Tetrahydrocannabinol.
“The plant Cannabis sativa, commonly called cannabis or marijuana, has been used for its psychotropic and mind-altering side effects for millennia. There has been growing attention in recent years on its potential therapeutic efficacy as municipalities and legislative bodies in the United States, Canada, and other countries grapple with enacting policy to facilitate the use of cannabis or its constituents for medical purposes. There are over 550 chemical compounds and over 100 phytocannabinoids isolated from cannabis, including Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD). THC is thought to produce the main psychoactive effects of cannabis, while CBD does not appear to have similar effects. Studies conflict as to whether CBD attenuates or exacerbates the behavioral and cognitive effects of THC. This includes effects of CBD on THC induced anxiety, psychosis and cognitive deficits. In this article, we review the available evidence on the pharmacology and behavioral interactions of THC and CBD from pre-clinical and human studies particularly with reference to anxiety and psychosis like symptoms. Both THC and CBD, as well as other cannabinoid molecules, are currently being evaluated for medicinal purposes, separately and in combination. Future cannabis-related policy decisions should include consideration of scientific findings including the individual and interactive effects of CBD and THC.” https://www.ncbi.nlm.nih.gov/pubmed/28875990 https://www.nature.com/npp/journal/vaop/naam/abs/npp2017209a.html]]>
A selective review of medical cannabis in cancer pain management.
“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.”
https://www.ncbi.nlm.nih.gov/pubmed/28866904
http://apm.amegroups.com/article/view/16199
“Introduction: The endocannabinoid system (ECS) plays an important role in food reward. For example, in humans, liking of palatable foods is assumed to be modulated by endocannabinoid activity. Studies in rodents suggest that the ECS also plays a role in sweet taste intensity perception, but it is unknown to what extent this can be extrapolated to humans. Therefore, this study aimed at elucidating whether Δ9-tetrahydrocannabinol (THC) or cannabidiol (CBD) affects sweet taste intensity perception and liking in humans, potentially resulting in alterations in food preferences.
Results: Inhalation of the Cannabis preparations did not affect sweet taste intensity perception and liking, ranking order, or ad libitum consumption of the favorite drink. In addition, food preferences were not influenced by the interventions. Reported fullness was lower, whereas desire to eat was higher throughout the THC compared to the CBD condition.
Conclusions: These results suggest that administration of Cannabis preparations at the low doses tested does not affect sweet taste intensity perception and liking, nor does it influence food preferences in humans.”
“Introduction: Cannabidiol (CBD) is a nonpsychoactive constituent of whole plant cannabis that has been reported to reduce anxiety-like behaviors in both pre-clinical and human laboratory studies. Yet, no controlled clinical studies have demonstrated its ability to reduce negative mood or dampen responses to negative emotional stimuli in humans. The objective of this study was to investigate the effects of CBD on responses to negative emotional stimuli, as a model for its potential anxiety-reducing effects.
Discussion: CBD did not dampen responses to negative emotional stimuli and did not affect feelings of social rejection. The high dose of CBD (900 mg) marginally reduced attentional bias toward happy and sad facial expressions, and produced a slight increase in late-session heart rate. CBD did not produce detectable subjective effects or alterations in mood or anxiety.
Conclusion: These findings indicate that CBD has minimal behavioral and subjective effects in healthy volunteers, even when they are presented with emotional stimuli. Further research into the behavioral and neural mechanisms of CBD and other phytocannabinoids is needed to ascertain the clinical function of this drug.”
“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.”