Tag Archives: cannabinoid

The nonpsychoactive Cannabis constituent cannabidiol is a wake-inducing agent.

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“Cannabidiol (CBD) is a constituent of Cannabis sativa that induces nonpsychotropic effects, and some of its biological actions in sleep have been described by the authors’ group.

 Here, the authors report that when administered 10 or 20 microg/1 microl during the lights-on period directly into either lateral hypothalamus (LH) or dorsal raphe nuclei (DRN), which are wake-inducing brain areas, CBD enhanced wakefulness and decreased slow wave sleep and REM sleep. Furthermore, CBD increased alpha and theta power spectra but diminished delta power spectra. Additionally, CBD increased c-Fos expression in LH or DRN.

These findings suggest that this cannabinoid is a wake-inducing compound that presumably activates neurons in LH and DRN.”

http://www.ncbi.nlm.nih.gov/pubmed/19045957

[The modulatory role of endocannabinoids in sleep].

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“The endogenous cannabinoid, or endocannabinoid, system is present in the central nervous system (CNS) of rodents and humans. This system includes receptors, endogenous ligands and enzymes. The presence of cannabinoid receptors, called CB1, in the CNS has been reported in the cerebral cortex, the hippocampus, the cerebellum and the brain stem. This neuroanatomical location suggests that this receptor could modify several physiological functions, such as the consolidation of memory, motor control and the generation of sleep.

 

Recent reports have described the presence of lipids in the CNS that bind to the CB1 receptor. Administration of said molecules induces cannabimimetic effects, and hence it has been suggested that these lipids are endogenous cannabinoids or endocannabinoids. Anandamide, 2-arachidonylglycerol, virodhamine, noladin ether and N-arachidonyldopamine are molecules that belong to the endocannabinoid family. Anandamide has received more attention from researchers because it was the first endocannabinoid to be reported. Pharmacological experiments have shown that this endocannabinoid induces several different intracellular and behavioural changes.

CONCLUSIONS:

In this study, we review the most important pharmacological aspects of exogenous cannabinoids and the neurobiological role played by the endocannabinoid system, including endogenous and exogenous ligands and receptors. We also examine their pharmacological effects on different behaviours, with particular attention given to the modulation of sleep.”

http://www.ncbi.nlm.nih.gov/pubmed/18297624

Proof of Concept Trial of Dronabinol in Obstructive Sleep Apnea

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“… Δ9-TetraHydroCannabinol (Δ9THC) stabilizes autonomic output during sleep, reduces spontaneous sleep-disordered breathing, and blocks serotonin-induced exacerbation of sleep apnea. On this basis, we examined the safety, tolerability, and efficacy of dronabinol (Δ9THC), an exogenous Cannabinoid type 1 and type 2 (CB1 and CB2) receptor agonist in patients with Obstructive Sleep Apnea (OSA)…

Conclusion: Dronabinol treatment is safe and well-tolerated in OSA patients at doses of 2.5–10mg daily and significantly reduces AHI in the short-term. These findings should be confirmed in a larger study in order to identify sub-populations with OSA that may benefit from cannabimimetic pharmacologic therapy…

This proof of concept study demonstrates that dronabinol is safe, well-tolerated, and reduces AHI by approximately a third over 3 weeks of oral administration. Dronabinol treatment may be a viable alternative or adjunctive therapy in selected patients with OSA.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3550518/

Circulating anandamide and blood pressure in patients with obstructive sleep apnea.

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” OBJECTIVE: Obstructive sleep apnea chronically increases blood pressure through sympathetic nervous system activation. In animals, hypertension and sympathetic activity are restrained by cannabinoid receptor activation. Therefore, we hypothesized that increased blood pressure in patients with obstructive sleep apnea is associated with increased circulating endocannabinoid concentrations.

 

CONCLUSION: Obstructive sleep apnea patients show positive correlations between blood pressure and venous anandamide concentrations independent of confounding factors. Our data suggest a previously not recognized role of the endocannabinoid system for blood pressure regulation in patients with high risk for hypertension and cardiovascular disease.”

http://www.ncbi.nlm.nih.gov/pubmed/23032139

[A study on the endogenous cannabinoid system synthetic and catabolic enzyme levels in patients with obstructive sleep apnea].

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“OBJECTIVE: To observe the differences of endogenous cannabinoid system (ECS) synthetic and catabolic enzyme levels between the obstructive sleep apnea syndrome (OSA) patients and the control subjects.

 

CONCLUSION: OSA altered the expression of the ECS synthetic and catabolic enzymes, leading to an increase in endogenous cannabinoid substances.”

 

http://www.ncbi.nlm.nih.gov/pubmed/21729625

Expression of the cannabinoid type I receptor and prognosis following surgery in colorectal cancer.

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“The cannabinoid system has been considered to be a potential target of colorectal carcinoma therapy. The aim of this study was to address the correlation between cannabinoid type 1 (CB1) receptor expression and disease severity/outcomes in patients with colorectal cancer (CRC).”

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 “…The high immunoreactivity of the cannabinoid type 1 receptor is a significant prognostic factor following surgery in stage IV CRC…

The effect of cannabinoids in colorectal cancer (CRC) has been demonstrated in in vitro experiments and animal models, which indicate the antiproliferative, apoptotic and antimetastatic actions of cannabinoid agonists…

Antineoplastic effects are mediated by the activation of cannabinoid type I (CB1), type 2 (CB2) or a non-cannabinoid receptor-mediated mechanism…”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576207/

AM404 attenuates reinstatement of nicotine seeking induced by nicotine-associated cues and nicotine priming but does not affect nicotine- and food-taking.

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“Multiple studies suggest a pivotal role of the endocannabinoid system in the regulation of the reinforcing effects of various substances of abuse. Different approaches have been used to modulate endocannabinoid neurotransmission including the use of endogenous cannabinoid anandamide reuptake inhibitors.

 Previously, the effects of one of them, N-(4-hydroxyphenyl)-arachidonamide (AM404), have been explored in rodents trained to self-administer ethanol and heroin, producing some promising results. Moreover, AM404 attenuated the development and reinstatement of nicotine-induced conditioned place preference (CPP). In this study, we used the nicotine intravenous self-administration procedure to assess the effects of intraperitoneal administration of 0, 1, 3 and 10 mg/kg AM404 on nicotine-taking and food-taking behaviors under fixed-ratio and progressive-ratio schedules of reinforcement, as well as on reinstatement of nicotine-seeking induced by nicotine priming and by presentation of nicotine-associated cues. The ability of AM404 to produce place preference was also evaluated. AM404 did not produce CPP and did not modify nicotine-taking and food-taking behaviors. In contrast, AM404 dose-dependently attenuated reinstatement of nicotine-seeking behavior induced by both nicotine-associated cues and nicotine priming.

Our results indicate that AM404 could be a potential promising therapeutic option for the prevention of relapse to nicotine-seeking in abstinent smokers.”

http://www.ncbi.nlm.nih.gov/pubmed/23427192

[Cannabinoids for symptomatic therapy of multiple sclerosis].

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“Spasticity represents a common troublesome symptom in patients with multiple sclerosis (MS). Treatment of spasticity remains difficult, which has prompted some patients to self-medicate with and perceive benefits from cannabis. Advances in the understanding of cannabinoid biology support these anecdotal observations.

Various clinical reports as well as randomized, double-blind, placebo-controlled studies have now demonstrated clinical efficacy of cannabinoids for the treatment of spasticity in MS patients. Sativex is a 1:1 mix of delta-9-tetrahydocannabinol and cannabidiol extracted from cloned Cannabis sativa chemovars, which recently received a label for treating MS-related spasticity in Germany.

The present article reviews the current understanding of cannabinoid biology and the value of cannabinoids as a symptomatic treatment option in MS.”

http://www.ncbi.nlm.nih.gov/pubmed/22080198

A new multiple sclerosis spasticity treatment option: effect in everyday clinical practice and cost-effectiveness in Germany.

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“Sativex(®) (GW Pharmaceuticals PLC, Porton Down, UK; Laboratorios Almirall, SA, Barcelona, Spain), a cannabinoid oromucosal spray containing a 1:1 ratio of 9-δ-tetrahydrocannabinol and cannabidiol, has been licensed in Germany since July 2011 as add-on therapy for moderate-to-severe multiple sclerosis (MS) treatment-resistant spasticity symptoms.

The ‘MOVE 2′ study evaluated clinical outcomes, treatment satisfaction, quality of life (QoL) and provision of care in MS patients with spasticity receiving Sativex in everyday clinical practice. Data from 300 patients were collected from 42 specialized MS centers across Germany and were available for this analysis. Assessments, including the MS spasticity 0-10 numerical rating scale, modified Ashworth scale, patients’ and physicians’ clinical impressions, and QoL scales were rated at baseline and at 1 and 3 months after starting treatment with Sativex.

 Sativex provided relief of MS-related spasticity in the majority of patients who were previously resistant to treatment. In addition, clear improvements were noted in MS spasticity-associated symptoms (e.g., sleep quality, bladder function and mobility), activities of daily living and QoL. Sativex was generally well tolerated. The majority of patients (84%) reported no adverse events, and there was only a limited risk of serious adverse reactions.

Furthermore, based on data from Sativex clinical trials, a Markov model-based analysis has shown that Sativex is a cost-effective treatment option for patients with MS spasticity in Germany.”

http://www.ncbi.nlm.nih.gov/pubmed/23369055

Endocannabinoid system modulator use in everyday clinical practice in the UK and Spain.

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“Spasticity is a disabling complication of multiple sclerosis. Some commonly used oral medications include baclofen, tizanidine, anticonvulsants and benzodiazepines, but their benefits are modest.

Sativex(®) (GW Pharmaceuticals PLC, Porton Down, UK; Laboratorios Almirall, SA, Barcelona, Spain) is a unique cannabinoid-based medicine with two main active ingredients; 9-δ-tetrahydrocannabinol, which acts mainly on cannabinoid 1 receptors in the CNS and plays a key role in the modulation of spasticity and spasms, and cannabidiol, which has different properties, including minimization of the psychoactivity associated with 9-δ-tetrahydrocannabinol. Sativex is indicated for symptomatic improvement in adult patients with moderate-to-severe multiple sclerosis-related spasticity who have not responded adequately to other first- or second-line antispasticity medications, and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy.

Over the past couple of years, Sativex has been approved for use in a number of European countries and ongoing postmarketing studies are evaluating the possible risks associated with Sativex treatment by systematically collecting all suspected adverse reactions that occur in patients from the start of treatment. Interim data from the UK as well as Spanish Sativex safety registries confirm that clinical benefit is maintained over the longer term despite the expected trend for deterioration owing to disease progression.

 Even after more than 2 years of use, no new safety/tolerability signals have emerged with Sativex, including no evidence of driving impairment and no relevant incidence of falls or other adverse events of concern, such as psychiatric or nervous system events.

Sativex appears to be a well-tolerated and useful add-on therapy in patients who have not achieved an adequate response with traditional antispastic agents.”

http://www.ncbi.nlm.nih.gov/pubmed/23369054