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

The positive link between executive function and lifetime cannabis use in schizophrenia is not explained by current levels of superior social cognition.

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Psychiatry Research Home

“There has been a growing link between a history of cannabis use and neurocognitive performance in patients with schizophrenia. Fewer neurocognitive deficits may be a marker of the superior social cognition needed to obtain illicit substances, or cannabis use may indicate a distinct path to schizophrenia with less neurocognitive vulnerability. This study sought to determine whether the relationship of cannabis use and executive function exists independently of social cognition.

Eighty-seven patients with schizophrenia were administered measures of social cognition and executive function. Social cognition was assessed using the Bell-Lysaker Emotion Recognition Test to measure affect recognition, and the Eyes and Hinting Tests to measure theory of mind. Executive function was assessed by the Mental Flexibility component of the Delis-Kaplan Executive Functioning Scale. The relations between the variables were examined with structural equation modeling.

Cannabis use positively related to executive function, negatively related to affect recognition, and had no relationship with theory of mind. There were no indirect effects of other illicit substances on amount of regular cannabis use. Alcohol use was related to worse affect recognition. The relationship between cannabis use and better executive function was supported and was not explained by superior social cognition.”

https://www.ncbi.nlm.nih.gov/pubmed/28152399

http://www.psy-journal.com/article/S0165-1781(16)31861-3/fulltext

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

Cannabinoids offer alternatives to opioids for pain relief, experts say.

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“Alternatives to opioids can be used alone or in combination with opioids for pain relief, to help prevent medical exposure to narcotics being an entry point to misuse, said experts at a medical education forum in Washington, DC on 3 November.

Endocannabinoid compounds found in marijuana can greatly enhance the potency of opioids in relieving pain.

The synergy from using these drugs together can result in more effective pain relief from lower doses of opioids,”

https://www.ncbi.nlm.nih.gov/pubmed/29113969

http://www.bmj.com/content/359/bmj.j5140.full

New ACE inhibitory peptides from hemp seed (Cannabis sativa L.) proteins.

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Journal of Agricultural and Food Chemistry

“An hemp seed protein isolate, prepared from defatted hemp seed meals by alkaline solubilization/acid precipitation, was subjected to extensive chemical hydrolysis under acid conditions (6 M HCl). The resulting hydrolysate was fractionated by semipreparative RP-HPLC and the purified fractions were tested as inhibitors of angiotensin converting enzyme (ACE). Mono- and bi-dimensional NMR experiments and LC-MS/MS analyses led to the identification of four potentially bioactive peptides, i.e. GVLY, IEE, LGV, and RVR. They were prepared by solid-phase synthesis, and tested for ACE-inhibitory activity. The IC50 values were GVLY 16 ± 1.5 µM, LGV 145 ± 13 µM, and RVR 526 ± 33 µM, confirming that hemp seed may be a valuable source of hypotensive peptides.”

 https://www.ncbi.nlm.nih.gov/pubmed/29112398
http://pubs.acs.org/doi/abs/10.1021/acs.jafc.7b04522

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

Masturbation to Orgasm Stimulates the Release of the Endocannabinoid 2-Arachidonoylglycerol in Humans.

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The Journal of Sexual Medicine - Click here to go back to the homepage

“Endocannabinoids are critical for rewarding behaviors such as eating, physical exercise, and social interaction. The role of endocannabinoids in mammalian sexual behavior has been suggested because of the influence of cannabinoid receptor agonists and antagonists on rodent sexual activity. However, the involvement of endocannabinoids in human sexual behavior has not been studied.

AIM:

To investigate plasma endocannabinoid levels before and after masturbation in healthy male and female volunteers.

OUTCOMES:

Plasma levels of the endocannabinoids 2-arachidonoylglycerol (2-AG), anandamide, the endocannabinoid-like lipids oleoyl ethanolamide and palmitoyl ethanolamide, arachidonic acid, and cortisol before and after masturbation to orgasm.

METHODS:

In study 1, endocannabinoid and cortisol levels were measured before and after masturbation to orgasm. In study 2, masturbation to orgasm was compared with a control condition using a single-blinded, randomized, 2-session crossover design.

RESULTS:

In study 1, masturbation to orgasm significantly increased plasma levels of the endocannabinoid 2-AG, whereas anandamide, oleoyl ethanolamide, palmitoyl ethanolamide, arachidonic acid, and cortisol levels were not altered. In study 2, only masturbation to orgasm, not the control condition, led to a significant increase in 2-AG levels. Interestingly, we also found a significant increase of oleoyl ethanolamide after masturbation to orgasm in study 2.

CLINICAL TRANSLATION:

Endocannabinoids might play an important role in the sexual response cycle, leading to possible implications for the understanding and treatment of sexual dysfunctions.

STRENGTHS AND LIMITATIONS:

We found an increase of 2-AG through masturbation to orgasm in 2 studies including a single-blinded randomized design. The exact role of endocannabinoid release as part of the sexual response cycle and the biological significance of the finding should be studied further. Cannabis and other drug use and the attainment of orgasm were self-reported in the present study.

CONCLUSION:

Our data indicate that the endocannabinoid 2-AG is involved in the human sexual response cycle and we hypothesize that 2-AG release plays a role in the rewarding consequences of sexual arousal and orgasm.”

https://www.ncbi.nlm.nih.gov/pubmed/29110806

http://www.jsm.jsexmed.org/article/S1743-6095(17)31443-1/fulltext

Perinatal maternal high-fat diet induces early obesity and sex-specific alterations of the endocannabinoid system in white and brown adipose tissue of weanling rat offspring.

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“Perinatal maternal high-fat (HF) diet programmes offspring obesity. Obesity is associated with overactivation of the endocannabinoid system (ECS) in adult subjects, but the role of the ECS in the developmental origins of obesity is mostly unknown. The ECS consists of endocannabinoids, cannabinoid receptors (cannabinoid type-1 receptor (CB1) and cannabinoid type-2 receptor (CB2)) and metabolising enzymes.

We hypothesised that perinatal maternal HF diet would alter the ECS in a sex-dependent manner in white and brown adipose tissue of rat offspring at weaning in parallel to obesity development.

Maternal HF diet induced early obesity, white adipocyte hypertrophy and increased lipid accumulation in brown adipose tissue associated with sex-specific changes of the ECS’s components in weanling rats. In male pups, maternal HF diet decreased CB1 and CB2 protein in subcutaneous adipose tissue. In female pups, maternal HF diet increased visceral and decreased subcutaneous CB1. In brown adipose tissue, maternal HF diet increased CB1 regardless of pup sex. In addition, maternal HF diet differentially changed oestrogen receptor across the adipose depots in male and female pups.

The ECS and oestrogen signalling play an important role in lipogenesis, adipogenesis and thermogenesis, and we observed early changes in their targets in adipose depots of the offspring. The present findings provide insights into the involvement of the ECS in the developmental origins of metabolic disease induced by inadequate maternal nutrition in early life.”

https://www.ncbi.nlm.nih.gov/pubmed/29110748

https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/perinatal-maternal-highfat-diet-induces-early-obesity-and-sexspecific-alterations-of-the-endocannabinoid-system-in-white-and-brown-adipose-tissue-of-weanling-rat-offspring/6BA3A77DE45A1537E0BC182E83EF07F0

Characterization of endocannabinoids and related acylethanolamides in the synovial fluid of dogs with osteoarthritis: a pilot study.

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“Cannabis-based drugs have been shown to be effective in inflammatory diseases.

A number of endocannabinoids including N- arachidonoylethanolamide (anandamide, AEA) and 2-arachidonyl glycerol (2-AG) with activity at the cannabinoidreceptors (CBR) CBR1 and CBR2, have been identified. Other structurally related endogenous fatty acid compounds such as oleoylethanolamide (OEA) and palmitoyl ethanolamide (PEA) have been identified in biological tissues.

These compounds do not bind to CBR but might be involved in facilitating the actions of directly acting endocannabinoids and thus are commonly termed “entourage” compounds due to their ability to modulate the endocannabinoid system.

The aim of this study was to evaluate the presence of endocannabinoids and entourage compounds in the synovial fluid of dogs with osteoarthritis subjected to arthrotomy of the knee joint. Cytokines and cytology were studied as well.

AEA, 2-AG, OEA and PEA were all present in the synovial fluid of arthritic knees and in the contralateral joints; in addition, a significant increase of OEA and 2AG levels were noted in SF from OA knees when compared to the contralateral joints.

The identification and quantification of endocannabinoids and entourage compounds levels in synovial fluids from dogs with OA of the knee is reported for the first time. Our data are instrumental for future studies involving a greater number of dogs. Cannabinoids represent an emerging and innovative pharmacological tool for the treatment of OA and further studies are warranted to evaluate the effectiveness of cannabinoids in veterinary medicine.”

https://www.ncbi.nlm.nih.gov/pubmed/29110674

“The ECS can be exploited as a potential therapeutic option for OA. We have demonstrated the presence of AEA, 2-AG, OEA and PEA in the SF of dogs with OA. Our data open the avenue to future studies involving a higher number of dogs and aimed at defining the role played by these compounds in OA of the dogs. Both plant-derived and synthetic agonists of CBRs represent an emerging and innovative pharmacological tool for the treatment of OA. ” https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-017-1245-7

Binding and Signaling Studies Disclose a Potential Allosteric Site for Cannabidiol in Cannabinoid CB2 Receptors.

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“The mechanism of action of cannabidiol (CBD), the main non-psychotropic component of Cannabis sativa L., is not completely understood. First assumed that the compound was acting via cannabinoid CB2 receptors (CB2Rs) it is now suggested that it interacts with non-cannabinoid G-protein-coupled receptors (GPCRs); however, CBD does not bind with high affinity to the orthosteric site of any GPCR.

To search for alternative explanations, we tested CBD as a potential allosteric ligand of CB2R. Radioligand and non-radioactive homogeneous binding, intracellular cAMP determination and ERK1/2 phosphorylation assays were undertaken in heterologous systems expressing the human version of CB2R.

These results may help to understand CBD mode of action and may serve to revisit its therapeutic possibilities.”

https://www.ncbi.nlm.nih.gov/pubmed/29109685

https://www.frontiersin.org/articles/10.3389/fphar.2017.00744/full