Tag Archives: THC

Pharmacotherapy of Apnea by Cannabimimetic Enhancement, the PACE Clinical Trial: Effects of Dronabinol in Obstructive Sleep Apnea.

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Oxford University Press

“There remains an important and unmet need for fully effective and acceptable treatments in obstructive sleep apnea (OSA). At present, there are no approved drug treatments. Dronabinol has shown promise for OSA pharmacotherapy in a small dose-escalation pilot study.

Here, we present initial findings of the Phase II PACE (Pharmacotherapy of Apnea by Cannabimimetic Enhancement) trial, a fully-blinded parallel groups, placebo-controlled randomized trial of dronabinol in patients with moderate or severe OSA.

These findings support the therapeutic potential of cannabinoids in patients with OSA. In comparison to placebo, dronabinol was associated with lower AHI, improved subjective sleepiness and greater overall treatment satisfaction. Larger scale clinical trials will be necessary to clarify the best potential approach(es) to cannabinoid therapy in OSA”   https://www.ncbi.nlm.nih.gov/pubmed/29121334

“These findings support the therapeutic potential of cannabinoids in patients with obstructive sleep apnea (OSA).” https://academic.oup.com/sleep/article-abstract/doi/10.1093/sleep/zsx184/4600041?redirectedFrom=fulltext

“Cannabinoid May Be First Drug for Sleep Apnea” https://www.medscape.com/viewarticle/891821

Efficacy and safety of cannabis for treating children with refractory epilepsy.

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Nursing Children and Young People

“The aim of this literature review was to examine the evidence base for the safety and efficacy of cannabis in treating children with refractory epilepsy. Clinical and medical databases were searched and four articles were included in the final analysis, which included retrospective reviews and open-label trials with a total sample size of 424. One clinical trial included administration of cannabidiol, the non-psychoactive compound of cannabis, while the other three articles stated that the compound administered to participants contained tetrahydrocannabidiol, the psychoactive constituent of cannabis.

Cannabis may reduce seizures in some children and young people with refractory epilepsy, however, its success may be affected by aetiology of the epilepsy or concomitant anti-epileptic drug use, and a therapeutic dose has not been found. Positive side effects were also found including improved sleep, alertness and mood. More research is needed on this subject, including randomised controlled trials. Nurses who are aware of patients and families wishing to trial cannabis for refractory epilepsy should have full and frank discussions.”

https://www.ncbi.nlm.nih.gov/pubmed/29115760

https://journals.rcni.com/nursing-children-and-young-people/efficacy-and-safety-of-cannabis-for-treating-children-with-refractory-epilepsy-ncyp.2017.e907

Anti-migraine effect of ∆9-tetrahydrocannabinol in the female rat.

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European Journal of Pharmacology

“Current anti-migraine treatments have limited efficacy and many side effects. Although anecdotal evidence suggests that marijuana is useful for migraine, this hypothesis has not been tested in a controlled experiment. Thus, the present study tested whether administration of ∆9-tetrahydrocannabinol (THC) produces anti-migraine effects in the female rat.

These data suggest that: 1) THC reduces migraine-like pain when administered at the right dose (0.32mg/kg) and time (immediately after AITC); 2) THC’s anti-migraine effect is mediated by CB1 receptors; and 3) Wheel running is an effective method to assess migraine treatments because only treatments producing antinociception without disruptive side effects will restore normal activity.

These findings support anecdotal evidence for the use of cannabinoids as a treatment for migraine in humans and implicate the CB1 receptor as a therapeutic target for migraine.”

https://www.ncbi.nlm.nih.gov/pubmed/29111112

http://www.sciencedirect.com/science/article/pii/S0014299917307239?via%3Dihub

Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation.

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“Cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC) have well documented immunomodulatory effects in vitro, but not following oral administration in humans. Here we show that oral co-administration of cannabinoids with lipids can substantially increase their intestinal lymphatic transport in rats. Moreover, immune cells from MS patients were more susceptible to the immunosuppressive effects of cannabinoids than those from healthy volunteers or cancer patients. Therefore, administering cannabinoids with a high-fat meal or in lipid-based formulations has the potential to be a therapeutic approach to improve the treatment of MS, or indeed other autoimmune disorders.”  https://www.ncbi.nlm.nih.gov/pubmed/29109461

“Cannabis sativa has a very long history of medical use. In summary, it has been demonstrated in this work that oral co-administration of cannabis or cannabis-based medicines with lipids results in extremely high levels of lipophilic cannabinoids in the intestinal lymphatic system and prominent immunomodulatory effects. Therefore, administering cannabinoids with a high-fat meal, as cannabis-containing food, or in lipid-based formulations has the potential to be a therapeutic approach to improve the treatment of MS, or indeed other autoimmune disorders.”  https://www.nature.com/articles/s41598-017-15026-z

Reversal of age-related cognitive impairments in mice by an extremely low dose of tetrahydrocannabinol.

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Neurobiology of Aging

“This study was designed to test our hypothesis that an ultra-low dose of delta-9 tetrahydrocannabinol (THC) reverses age-dependent cognitive impairments in old mice and to examine the possible biological mechanisms that underlie this behavioral effect. These findings suggest that extremely low doses of THC that are devoid of any psychotropic effect and do not induce desensitization may provide a safe and effective treatment for cognitive decline in aging humans.”  https://www.ncbi.nlm.nih.gov/pubmed/29107185

“Cognitive decline is an integral aspect of aging. The idea that age-related cognitive decline can be reversed and that the old brain can be revitalized is not new. It has been previously suggested that the endocannabinoid system is part of an antiaging homeostatic defense system.  In previous studies, we have shown that ultra-low doses of tetrahydrocannabinol (THC, the main psychotropic ingredient in cannabis) protected young mice from cognitive impairments that were evoked by various insults. In the present study, we tested our hypothesis that a single ultra-low dose of THC can reverse age-dependent cognitive decline in mice. Here, we show that a single extremely low dose of THC devoid of any psychotropic activity can trigger an endogenous compensatory mechanism that improves cognitive functioning in old mice and that this effect lasts for at least several weeks. Since THC in high doses (dronabinol, 1–10 mg) is already approved for medical treatments in humans, and since its safety profile is well characterized, we believe that the initiation of clinical trials with ultra-low doses of THC designed to reverse cognitive decline in elderly patients should be straightforward.”  http://www.sciencedirect.com/science/article/pii/S0197458017303214

“Reversal of age-related cognitive impairments in mice by an extremely low dose of tetrahydrocannabinol. These findings suggest that extremely low doses of THC that are devoid of any psychotropic effect and do not induce desensitization may provide a safe and effective treatment for cognitive decline in aging humans.”   http://www.neurobiologyofaging.org/article/S0197-4580(17)30321-4/fulltext

Neurobiology of Aging Home

Chronic Adolescent Δ9-Tetrahydrocannabinol Treatment of Male Mice Leads to Long-Term Cognitive and Behavioral Dysfunction, Which Are Prevented by Concurrent Cannabidiol Treatment.

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Mary Ann Liebert, Inc. publishers

“The current study examined the immediate and long-term behavioral consequences of THC, CBD, and their combination in a mouse model of adolescent cannabis use.

All THC-induced behavioral abnormalities were prevented by the coadministration of CBD+THC,

These data suggest that chronic exposure to THC during adolescence leads to some of the behavioral abnormalities common in schizophrenia. Interestingly, CBD appeared to antagonize all THC-induced behavioral abnormalities.

These findings support the hypothesis that adolescent THC use can impart long-term behavioral deficits; however, cotreatment with CBD prevents these deficits.”

https://www.ncbi.nlm.nih.gov/pubmed/29098186

http://online.liebertpub.com/doi/10.1089/can.2017.0034

THC inhibits the expression of ethanol-induced locomotor sensitization in mice.

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Cover image Alcohol

“The motivational circuit activated by ethanol leads to behavioral changes that recruit the endocannabinoid system (ECS). Case reports and observational studies suggest that the use of Cannabis sp. mitigates problematic ethanol consumption in humans.

Here, we verified the effects of the two main phytocannabinoid compounds of Cannabis sp., cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), in the expression of ethanol-induced locomotor sensitization in mice.

Our findings showing that phytocannabinoid treatment prevents the expression of behavioral sensitization in mice provide insight into the potential therapeutic use of phytocannabinoids in alcohol-related problems.”

https://www.ncbi.nlm.nih.gov/pubmed/29084627

http://www.sciencedirect.com/science/article/pii/S0741832916302877?via%3Dihub

Anti-Inflammatory Activity in Colon Models Is Derived from Δ9-Tetrahydrocannabinolic Acid That Interacts with Additional Compounds in Cannabis Extracts.

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“Inflammatory bowel diseases (IBDs) include Crohn’s disease, and ulcerative colitis. Cannabis sativa preparations have beneficial effects for IBD patients. However, C. sativa extracts contain hundreds of compounds. Although there is much knowledge of the activity of different cannabinoids and their receptor agonists or antagonists, the cytotoxic and anti-inflammatory activity of whole C. sativa extracts has never been characterized in detail with in vitro and ex vivo colon models.

Material and Methods: The anti-inflammatory activity of C. sativa extracts was studied on three lines of epithelial cells and on colon tissue. C. sativa flowers were extracted with ethanol, enzyme-linked immunosorbent assay was used to determine the level of interleukin-8 in colon cells and tissue biopsies, chemical analysis was performed using high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance and gene expression was determined by quantitative real-time PCR.

Results: The anti-inflammatory activity of Cannabis extracts derives from D9-tetrahydrocannabinolic acid (THCA) present in fraction 7 (F7) of the extract. However, all fractions of C. sativa at a certain combination of concentrations have a significant increased cytotoxic activity. GPR55 receptor antagonist significantly reduces the anti-inflammatory activity of F7, whereas cannabinoid type 2 receptor antagonist significantly increases HCT116 cell proliferation. Also, cannabidiol (CBD) shows dose dependent cytotoxic activity, whereas anti-inflammatory activity was found only for the low concentration of CBD, and in a bell-shaped rather than dose-dependent manner. Activity of the extract and active fraction was verified on colon tissues taken from IBD patients, and was shown to suppress cyclooxygenase-2 (COX2) and metalloproteinase-9 (MMP9) gene expression in both cell culture and colon tissue.

Conclusions: It is suggested that the anti-inflammatory activity of Cannabis extracts on colon epithelial cells derives from a fraction of the extract that contains THCA, and is mediated, at least partially, via GPR55 receptor. The cytotoxic activity of the C. sativa extract was increased by combining all fractions at a certain combination of concentrations and was partially affected by CB2 receptor antagonist that increased cell proliferation. It is suggested that in a nonpsychoactive treatment for IBD, THCA should be used rather than CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/29082314
http://www.liebertpub.com/manuscript/can

Selective activation of cannabinoid receptor-2 reduces neuroinflammation after traumatic brain injury via alternative macrophage polarization.

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“Inflammation is an important mediator of secondary neurological injury after traumatic brain injury (TBI). Endocannabinoids, endogenously produced arachidonate based lipids, have recently emerged as powerful anti-inflammatory compounds, yet the molecular and cellular mechanisms underlying these effects are poorly defined. Endocannabinoids are physiological ligands for two known cannabinoid receptors, CB1R and CB2R. In the present study, we hypothesized that selective activation of CB2R attenuates neuroinflammation and reduces neurovascular injury after TBI. Taken together, our findings support the development of selective CB2R agonists as a therapeutic strategy to improve TBI outcomes while avoiding the psychoactive effects of CB1R activation.”   https://www.ncbi.nlm.nih.gov/pubmed/29079445   http://www.sciencedirect.com/science/article/pii/S0889159117304774

“The Cannabinoid CB2 Receptor as a Target for Inflammation-Dependent Neurodegeneration. The first approved cannabinoid drugs were analogues of Δ9-tetrahydrocannabinol (Δ9-THC). Dronabinol is a natural isomer of THC that is found in the cannabis plant” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2435344/

“Cannabinoid Receptor CB2 Is Involved in Tetrahydrocannabinol-Induced Anti-Inflammation against Lipopolysaccharide in MG-63 Cells. These results suggested that CB2 is involved in the THC-induced anti-inflammation”  https://www.hindawi.com/journals/mi/2015/362126/

“Cannabinoids as novel anti-inflammatory drugs. Manipulation of endocannabinoids and/or use of exogenous cannabinoids in vivo can constitute a potent treatment modality against inflammatory disorders.  For several centuries, marijuana has been used as an alternative medicine in many cultures and, recently, its beneficial effects have been shown”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614/

“Cannabinoids as neuroprotective agents in traumatic brain injury.  Cannabinoids of all classes have the ability to protect neurons from a variety of insults that are believed to underlie delayed neuronal death after traumatic brain injury (TBI), including excitotoxicity, calcium influx, free radical formation and neuroinflammation.” https://www.ncbi.nlm.nih.gov/pubmed/15281893

“Effect of marijuana use on outcomes in traumatic brain injury. A positive THC screen is associated with decreased mortality in adult patients sustaining TBI.”  https://www.ncbi.nlm.nih.gov/pubmed/25264643

Dronabinol Is a Safe Long-Term Treatment Option for Neuropathic Pain Patients.

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Logo European Neurology

“Treatment of neuropathic pain (NP) symptoms associated with multiple sclerosis (MS) is frequently insufficient. Yet, cannabis is still rarely offered for treatment of pain. This clinical trial aimed at showing the positive benefit-risk ratio of dronabinol. Two hundred forty MS patients with central NP entered a 16-weeks placebo-controlled phase-III study followed by a 32-weeks open-label period. One hundred patients continued therapy for overall up to 119 weeks. Primary endpoint was change of pain intensity on the 11-point Numerical Rating Scale over a 16-weeks treatment period. Safety was assessed on the basis of adverse reactions (ARs), signs of dependency and abuse. Pain intensity during 16-weeks dronabinol and placebo treatment was reduced by 1.92 and 1.81 points without significant difference in between (p = 0.676). Although the proportion of patients with ARs was higher under dronabinol compared to placebo (50.0 vs. 25.9%), it decreased during long-term use of dronabinol (26%). No signs of drug abuse and only one possible case of dependency occurred. The trial results demonstrate that dronabinol is a safe long-term treatment option.” https://www.ncbi.nlm.nih.gov/pubmed/29073592

“Overall, this trial demonstrated the long-lasting therapeutic potential, the good tolerability and favourable safety profile of dronabinol – especially in terms of drug abuse and dependency. Based on the presented results, there is no special focus on the harm caused by dronabinol treatment. Although the statistical proof of efficacy for dronabinol versus placebo treatment is pending, physicians should consider the potential benefits of the multifactorial effects of dronabinol.” https://www.karger.com/Article/FullText/481089